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Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer

  1. Sebastiaan L Knijnenburg1,*,
  2. Renée L Mulder2,
  3. Antoinette YN Schouten-Van Meeteren2,
  4. Arend Bökenkamp3,
  5. Hester Blufpand3,
  6. Eline van Dulmen-den Broeder4,
  7. Margreet A Veening4,
  8. Leontien CM Kremer2,
  9. Monique WM Jaspers1

Editorial Group: Cochrane Childhood Cancer Group

Published Online: 8 OCT 2013

Assessed as up-to-date: 20 MAY 2012

DOI: 10.1002/14651858.CD008944.pub2


How to Cite

Knijnenburg SL, Mulder RL, Schouten-Van Meeteren AYN, Bökenkamp A, Blufpand H, van Dulmen-den Broeder E, Veening MA, Kremer LCM, Jaspers MWM. Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD008944. DOI: 10.1002/14651858.CD008944.pub2.

Author Information

  1. 1

    Academic Medical Center, Medical Informatics, Amsterdam, Netherlands

  2. 2

    Emma Children's Hospital / Academic Medical Center, Department of Paediatric Oncology, Amsterdam, Netherlands

  3. 3

    VU University Medical Center, Department of Pediatric Nephrology, Amsterdam, Netherlands

  4. 4

    VU University Medical Center, Department of Pediatrics, Division of Oncology/Hematology, Amsterdam, Netherlands

*Sebastiaan L Knijnenburg, Medical Informatics, Academic Medical Center, P.O. Box 22660, Amsterdam, 1100 DD, Netherlands. s.l.knijnenburg@amc.uva.nl.

Publication History

  1. Publication Status: New
  2. Published Online: 8 OCT 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

Great improvements in diagnostics and treatment for malignant disease in childhood have led to a major increase in survival, with five-year survival reaching 80% in Europe (Gatta 2009). Despite this rise in five-year survival, childhood cancer survivors (CCS) are at high risk of developing late effects caused by their cancer therapies. Three large cohort studies found that up to 88% of all survivors suffer from at least one long-term effect after follow-up of 30, 17 and 7 years, respectively (Oeffinger 2006; Geenen 2007; Wasilewski-Masker 2010).

Nephrotoxicity is a known side effect of certain childhood cancer therapies, resulting in a decline in glomerular filtration rate (GFR), deterioration of tubular function, development of albuminuria and/or (renovascular) hypertension during or after treatment (Jones 2008). Potentially nephrotoxic agents include ifosfamide and the platinum compounds cisplatin and carboplatin (Womer 1985; English 1999; Rossi 1999; Jones 2008). Recent studies have shown that ifosfamide and platinum toxicities persist during follow-up even up to 10 years after treatment, with prevalence of renal adverse effects ranging from 0% to 45% depending on the study group and the measured outcome variable (Oberlin 2009; Skinner 2009). Abdominal and total body irradiation may cause radiation nephropathy, characterised by hypertension, a decline in GFR and (intermittent) proteinuria (Breitz 2004). Kidney surgery may also play a role in the long-term course of renal function, for example, by causing hyperfiltration in unilateral nephrectomised survivors, which may ultimately lead to hypertension and glomerular impairment (Schell 1995; De Graaf 1996).

Several risk factors for the development of late renal effects have been mentioned in the literature, but these effects were often examined in small, selected study populations and produced inconsistent results. Risk factors such as cumulative chemotherapy and radiotherapy doses, age at diagnosis, duration of follow-up and infusion schemes have all been investigated, but conclusive evidence is missing. For example, both Pietilä et al and Loebstein et al reported the cumulative cisplatin dose to be a risk factor for impaired renal function, whereas Brock et al and Schell et al did not find any relationship (Brock 1991; Schell 1995; Loebstein 1999; Pietilä 2005). The use of multimodal nephrotoxic cancer treatment may also increase the risk of renal dysfunction: In one study, glomerular function of nephrectomised Wilms' tumour (WT) survivors was significantly lower among participants who received radiation therapy and chemotherapy in comparison with those given chemotherapy alone (De Graaf 1996). Systematic review and meta-analysis of the literature may elucidate which risk factors are associated with renal impairment and which are not.

In 2008, Jones et al published an evidence summary for the American Childhood Oncology Group (COG), delineating exposure-based risks of potentially nephrotoxic treatment modalities accompanied by health screening recommendations and considerations for the treatment/management of associated late effects (Jones 2008). The focus of management of nephrotoxicity lies in blood pressure control, electrolyte supplementation and, when needed, consultation with or referral to the nephrologist. The COG evidence summary served as a basis for the COG Long-Term Follow-up Guidelines. Skinner published two overviews of the literature regarding nephrotoxicity during and after treatment for childhood cancer (Skinner 2010a; Skinner 2011). To reduce the number of (long-term) nephrotoxic events in CCS, treatment and screening protocols should be adjusted. A systematic review of the literature is required to gain evidence-based insight into the role of these treatments in early and long-term function of the kidneys.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of and associated risk factors for renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with healthy controls or CCS treated without potentially nephrotoxic treatment.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Criteria for considering studies for this review

 

Types of studies

All study designs, except case reports and case series, examining the effects of (multimodal) treatment of childhood cancer on renal adverse effects.

 

Types of participants

CCS diagnosed between the ages of 0 and 18 years with a mean or median survival of at least one year after the end of treatment and related healthy controls, if available. If no follow-up time after the end of treatment was stated, at least 90% of the study group had to be off treatment. Studies had to include at least 20 survivors who received potentially nephrotoxic therapies.

 

Types of interventions

Treatment with cisplatin, carboplatin, ifosfamide, radiotherapy involving the kidney including total body irradiation and/or surgery involving the kidney.

 

Types of outcome measures

We decided to limit included outcome measures to those reported most often and that were most consistent and had the greatest clinical relevance. Included outcome measurements were chronic kidney disease (CKD)/renal insufficiency, (estimated) GFR, proteinuria, serum phosphate/hypophosphataemia, tubular phosphate regulation parameters (tubular phosphate threshold and fractional phosphate excretion), serum magnesium/hypomagnesaemia and finally blood pressure. We did not impose any restrictions on the outcome definitions. Studies that reported on composite outcome measures that included one of the aforementioned outcomes were included. Studies investigating blood pressure as part of a cardiovascular assessment or metabolic syndrome were excluded.

 

Search methods for identification of studies

The objective of the literature search was to identify all studies reporting on renal adverse effects of potentially nephrotoxic treatment modalities in CCS, with the exception of case reports and case series; hence randomised controlled trials, case control studies and cohort studies were included.

We did not impose language restrictions.

 

Electronic searches

We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2011), MEDLINE/PubMed (from 1945 to December 2011) and EMBASE/Ovid (from 1980 to December 2011).

We provide the search strategies for the different electronic databases (using a combination of controlled vocabulary and text words) in the appendices (Appendix 1, Appendix 2, Appendix 3).

 

Data collection and analysis

 

Selection of studies

After performing the search strategy described previously, two review authors independently selected studies meeting the inclusion criteria on the basis of title and/or abstract. Full-text papers were obtained for closer inspection of any study that seemed to meet the inclusion criteria on the basis of title and/or abstract. We resolved discrepancies between review authors by consensus. If this proved impossible, final resolution was achieved by consulting a third review author. Details of reasons for exclusion of any study considered for this review are provided in the Characteristics of excluded studies.

 

Data extraction and management

Two review authors performed data extraction independently using standardised data extraction forms. We retrieved data on the following items.

  1. Study characteristics.
    1. Study design;
    2. Number of participants in the original cohort;
    3. Number of participants in the described study group;
    4. Number of participants in the study group of interest;
    5. Number of participants tested for renal adverse effects; and
    6. Number of controls.
  2. Study participants.
    1. Age at diagnosis or at treatment;
    2. Time period diagnosis/treatment;
    3. Age at follow-up;
    4. Duration of follow-up;
    5. Completion of follow-up;
    6. Sex; and
    7. Tumour type.
  3. Interventions.
    1. Number of participants treated with ifosfamide, cisplatin and carboplatin;
    2. Cumulative doses of ifosfamide, cisplatin and carboplatin;
    3. Number of participants treated with other types of chemotherapy;
    4. Number of participants treated with radiotherapy including the kidney region;
    5. Cumulative radiotherapy dose; and
    6. Number of participants treated with (partial) unilateral or bilateral nephrectomy.
  4. Outcome measurements as defined by the authors of the original studies.
  5. Risk factors for nephrotoxicity as defined by the authors of the original studies.

The participants in the original cohort represent the whole group of CCS. The described study group encompasses CCS from the original cohort included in the study. The study group of interest consists of the CCS within the original cohort who received potentially nephrotoxic treatment. Finally, the study group tested for renal adverse effects is made up of the CCS who were assessed for renal function as well.

In cases of disagreement, both review authors re-assessed the abstracts and full-text articles and discussed until consensus was achieved. If consensus was not achieved, we consulted a third review author for resolution.

 

Assessment of risk of bias in included studies

The risk of bias assessment was based on earlier described checklists for observational studies based on evidence-based medicine criteria (Grimes 2002; Laupacis 1994), as adapted by Mulder 2010. Two review authors independently assessed all included studies on the risk of bias related to the composition of the study population, the follow-up assessments and the outcome assessments, as well as the methods used to assess risk factors for nephrotoxicity in each study. The criteria for the risk of bias assessment are presented in  Table 1. To ensure a well-defined study group, chemotherapy and radiotherapy dosages were assessed as relevant when a study explicitly stated that potentially nephrotoxic therapy was part of the study's treatment protocol. For the risk of bias assessment in case control studies, we used adapted criteria related to the selection of cases and controls: Selection of cases and controls had to be based on similar participant characteristics (i.e. age, sex and cancer treatment). For randomised controlled trials (RCTs) and non-randomised controlled trials (CCTs), we will use the criteria put forth by the Childhood Cancer Group (Module CCG).

In cases of disagreement between two review authors, both re-assessed the abstracts and full-text articles to achieve consensus. If this proved impossible, a third review author was consulted for resolution.

 

Measures of treatment effect

Prevalence, cumulative incidence, mean difference, risk ratio, odds ratio, attributable risk and other associated risk measures.

 

Assessment of heterogeneity

Heterogeneity was assessed by visual inspection of the forest plots and by the I2 statistic-the formal statistical test for heterogeneity. Substantial heterogeneity was defined as I² > 50% (Higgins 2011). Cases of substantial heterogeneity were reported.

 

Assessment of reporting biases

We planned to make funnel plots to assess possible publication bias. Heterogeneity prevented us from performing any meta-analysis; therefore, it was not possible to construct any funnel plot.

 

Data synthesis

Data were entered into Review Manager 5 and were analysed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We used random-effects models throughout the review. We used the generic inverse variance function of RevMan to analyse the prevalence of renal adverse effects. Pooling was not possible, so we provided descriptive results of the studies. Because of the substantial heterogeneity, it was not feasible to perform multivariate meta-regression analyses on any of the outcome variables. We had planned to perform subgroup analyses of studies based on age at diagnosis and follow-up duration and of studies that reported on a single treatment modality (cisplatin, carboplatin, ifosfamide, nephrectomy or radiotherapy). However, it was not feasible to perform these analyses, again because of the high degree of heterogeneity and the variety of treatment regimens given within the included studies.

 

Sensitivity analysis

Pooling of study outcomes was not possible for any of the included outcomes; therefore, sensitivity analysis was not performed.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification.

We identified 5504 references by searches of the electronic databases of CENTRAL, MEDLINE (PubMed) and EMBASE (Ovid). After initial screening of the titles and abstracts, we excluded 5138 references that clearly did not meet all inclusion criteria defined for this systematic review. We obtained 366 articles in full text for further screening. Of these 366, another 293 were excluded for not meeting the inclusion criteria. The reasons for exclusion are described in the Characteristics of excluded studies section. Another sixteen studies are not yet classified because we are awaiting the translation, because we were not able to retrieve the full-text study, or because no full-text study was available yet (Cohen 2010; Cozzi 2010; D'Angio 1978; Eckstein 2010; Janda 1993; Kieran 2010; Li 2006; Madden 2010; Matsuyama 2002; Pugachev 2004; Radvansky 2010; Sakellari 2010; Schwartz 2001; Sierota 2005; Stronska 2003; Terenziani 2010). The details of these studies can be found in the Characteristics of studies awaiting classification table. As a result, we were able to include 57 studies on renal adverse effects after potentially nephrotoxic treatment for childhood cancer. The characteristics of these studies are summarised below and are provided in the Characteristics of included studies table. One other study was added to the Characteristics of studies awaiting classification section during the review process because it was suggested by a review author. This study will be included in the first update of the review. Based on the author lists and study and treatment characteristics, readers should take note that there may be potential overlap of participants in the studies of Geenen 2010, Van Dijk 2010, Aronson 2011 and Cardous-Ubbink 2010; the studies of Stefanowicz 2009, Stefanowicz 2010 and Stefanowicz 2011; the studies of Frisk 2002 and Frisk 2007; the studies of Di Tullio 1996 and Indolfi 2001 and all studies of Rossi and colleagues (Rossi 1993; Rossi 1994; Rossi 1994a; Rossi 1994b; Rossi 1997; Rossi 1999).

A total of 23 prospective cohort studies were identified, as well as 12 retrospective cohort studies, 13 cross-sectional cohort studies and 7 cohort studies for which the direction of inclusion was unclear. Additionally, one nested case control study (Cardous-Ubbink 2010) and one medical record linkage study (Breslow 2005) were obtained. Diagnosis or treatment periods of included participants started as early as 1931 (Kantor 1989) and went on until 2009 (Bolling 2010), with a median enrolment period of 15 years per study. Thirteen studies did not report the diagnosis or treatment period of included participants. The earliest study was published in 1986 (Wikstad 1986) and the latest ones in 2011 (Aronson 2011; Hamilton 2011; Stefanowicz 2011).

The total number of participants of interest described in 55 studies was 13,338, and the numbers were not mentioned in two studies (Bardi 2004; Cardous-Ubbink 2010). Of these 13,338 participants of interest, at least 6516 participants from 50 studies underwent renal function testing. In seven studies, the number of participants who underwent renal function tests was not mentioned (Breslow 2005; Cosentino 1993; Hamilton 2011; Laverdiere 2005; Loebstein 1999; Van Dijk 2010; Weirich 2004). Study sizes ranged from 23 (English 1999; Kubiak 2004; Trahair 2007 ) to 5910 participants (Breslow 2005). Twenty-six studies included only survivors of unilateral or bilateral WT (Aronson 2011; Breslow 2005; Chevallier 1997; Cosentino 1993; Cozzi 2005; de Graaf 1996; Di Tullio 1996; Finklestein 1993; Geenen 2010; Hamilton 2011; Indolfi 2001; Kantor 1989; Kubiak 2004; Makipernaa 1991; Mancini 1996; Mpofu 1992; Othman 2002; Paulino 2000; Sasso 2010; Srinivas 1998; Stefanowicz 2010; Stefanowicz 2011; Trobs 2001; Van Dijk 2010; Weirich 2004; Wikstad 1986). Furthermore, seven studies included only survivors with a sarcoma (Ferrari 2005; Oberlin 2009; Prasad 1996; Rossi 1997; Skinner 2010; Stohr 2007; Stohr 2007a), three studies included only participants with neuroblastoma (Bergeron 2005; Laverdiere 2005; Trahair 2007), one study included only participants with hepatoblastoma (von Schweinitz 1997), two studies included only participants with leukaemia and/or lymphoma (Frisk 2002; Frisk 2007) and 17 studies included participants with diagnoses of miscellaneous tumours. One study did not mention the types of tumours that were included (Rossi 1993).

Fifty studies mentioned the median or mean participant age at diagnosis, which ranged from 4.7 months (Bergeron 2005) to 16 years (Ferrari 2005). Median or mean participant age at follow-up was reported in only 24 studies and ranged from 3.6 years (de Graaf 1996) to 29 years (Kantor 1989). Follow-up duration of survivors also varied widely, from a median less than 1 year (Schell 1995) up to 25 years (Kantor 1989). Follow-up duration was better reported than participant age at follow-up: all but three studies mentioned the follow-up duration. The sex distribution was reported in 41 studies. The percentage of included male participants ranged from 28% to 69%, but the median percentage of male participants in the 41 studies that reported sex was 52%.

Treatment

In 23 of 57 studies, participants were treated with cisplatin, in 21 studies it was clear that participants did not receive cisplatin and in 13 studies it was unclear whether participants did or did not receive cisplatin. At least 1049 participants were treated with cisplatin. The percentage of participants treated with cisplatin varied widely from 2% (Mancini 1996) to 100% (Brock 1991; Ferrari 2005; von Schweinitz 1997); one study did not mention the exact number of participants treated with cisplatin (Bardi 2004). Median or mean doses were reported in 18 of the 23 studies including cisplatin and ranged from 80 mg/m2 (Trahair 2007) to 4000 mg/m2 (Loebstein 1999), although most studies reported a mean or median cumulative cisplatin dose prescription of between 300 and 500 mg/m2 (Brock 1991; Fujieda 2009; Rossi 1993; Rossi 1994; Rossi 1994a; Rossi 1994b; Rossi 1999; Schell 1995; Skinner 2009; Stohr 2007; Stohr 2007a).

Carboplatin was used in 16 studies for at least 447 participants. Twenty-six studies did not use carboplatin and 15 studies did not mention carboplatin usage. The average percentage of participants treated with carboplatin was 36%, although this varied widely from 3% (Mancini 1996) to 100% (Bergeron 2005; English 1999) and was not reported in three studies (Bardi 2004; Stefanowicz 2011; Trobs 2001). Cumulative carboplatin dose was reported in all but four studies (Bardi 2004; Stefanowicz 2011; Trobs 2001; Weirich 2004). Median carboplatin cumulative doses ranged from 267 mg/m2 to 2590 mg/m2.

Thirty-one of the 57 studies reported prescription of ifosfamide for at least 2147 participants, 16 studies did not use ifosfamide and in 10 studies ifosfamide usage was unclear. In 13 of the 31 ifosfamide studies, all participants received ifosfamide (Ferrari 2005; Fujieda 2009; Loebstein 1999; Oberlin 2009; Prasad 1996; Rossi 1994; Rossi 1994a; Rossi 1994b; Rossi 1997; Rossi 1999; Skinner 2010; Stohr 2007; von Schweinitz 1997). Median cumulative dose varied between 10 g/m2 (Patzer 2001) and 106 g/m2 (Skinner 2010) in 19 studies and was not reported in 12 studies.

Radiotherapy was used in the treatment regimen of at least 1736 participants and in 41 of the 57 studies. Four studies did not include participants who received radiotherapy, and prescription of radiotherapy was unclear in 12 studies. Radiotherapy included solely total body irradiation (TBI) in 5 studies (Frisk 2002; Frisk 2007; Patzer 2001; Trahair 2007; Van Why 1991) and solely abdominal irradiation in 25 studies. Four studies included both participants treated with TBI and participants treated with abdominal irradiation (Skinner 2010; Hoffmeister 2010; Laverdiere 2005; Schell 1995), and the field was not mentioned in seven other studies. Median doses ranged between 7.5 Gy and 13.2 Gy for the TBI group and between 15 Gy and 45 Gy for the abdominal irradiation group. Eighteen studies did not report the radiation dose.

A total of 40 studies included nephrectomised participants, 10 studies did not and in seven studies, this information was unclear. In most (24) of the 40 studies, 100% of the included participants were treated with a nephrectomy (Aronson 2011; Breslow 2005; Chevallier 1997; Cozzi 2005; de Graaf 1996; Di Tullio 1996; Finklestein 1993; Geenen 2010; Indolfi 2001; Kantor 1989; Kubiak 2004; Makipernaa 1991; Mancini 1996; Mpofu 1992; Othman 2002; Paulino 2000; Schell 1995; Srinivas 1998; Stefanowicz 2010; Stefanowicz 2011; Trobs 2001; Van Dijk 2010; Weirich 2004; Wikstad 1986). In all but one of these 24 studies, nephrectomy was performed for WT. Eight studies mentioned that they also included participants who underwent bilateral surgery in cases of bilateral disease (Aronson 2011; Breslow 2005; Hamilton 2011; Kantor 1989; Mancini 1996; Paulino 2000; Trobs 2001; Weirich 2004).

In 45 of the 57 studies, other chemotherapeutics were described; 12 studies did not report on other treatments. Types of other chemotherapy varied widely between studies; detailed descriptions per study can be found in the Characteristics of included studies.

We divided the included studies into subgroups on the basis of the combination of treatments described in the paper, as the five different included treatments can be given in various combinations. When a study included at least one participant who was given a certain treatment, we considered the study to include participants with that treatment. When it was unclear whether a study prescribed a certain treatment, we considered the study to exclude participants with that treatment. The subgroups and the studies per subgroup are provided in  Table 2.

Outcome definitions

A total of 225 adverse renal outcomes were reported in the 57 studies. As profound heterogeneity was noted in the reported outcome measurements, we limited this review to the following outcome parameters: CKD/renal insufficiency, (estimated) GFR, proteinuria, serum phosphate, tubular phosphate parameters, serum magnesium and blood pressure. Even in these selected outcome measurements, great differences were observed in defined cut-off points for abnormal test results. Also, studies differed in reporting dichotomous or continuous outcome variables.

Chronic kidney disease/renal insufficiency
Ten studies reported only the prevalence of (chronic) renal insufficiency or end-stage renal disease without specifying the cut-off value used to assess the GFR (Aronson 2011; Bardi 2004; Breslow 2005; Cosentino 1993; Geenen 2010; Hamilton 2011; Laverdiere 2005; Paulino 2000; Sasso 2010; Stefanowicz 2011).

(Estimated) glomerular filtration rate
(Estimated) GFR was the most frequently assessed outcome parameter (32 studies). However, great methodological variation was noted in the assessment of this outcome parameter. Studies assessed the GFR directly by 51Cr-EDTA clearance (Brock 1991; English 1999; Frisk 2002; Frisk 2007; Makipernaa 1991; Skinner 2009; Skinner 2010), inulin clearance (Chevallier 1997; Patzer 2001; Schell 1995; Wikstad 1986), Tc-99m clearance (Srinivas 1998; Stefanowicz 2011) or 125-I-iothalamate clearance (de Graaf 1996), or they used GFR estimation formulae, including the Schwartz formula (Bergeron 2005; Hoffmeister 2010; Kubiak 2004; Mpofu 1992; Oberlin 2009; Rossi 1993; Rossi 1994; Rossi 1994a; Rossi 1994b; Stefanowicz 2009; Stefanowicz 2010; Stefanowicz 2011; Stohr 2007a), the Cockroft-Gault formula (Oberlin 2009), the Modification of Diet in Renal Disease (MDRD) formula (Hoffmeister 2010), the Filler formula (Stefanowicz 2009; Stefanowicz 2011) or the Counahan formula (Bardi 2004). Two studies used more than one method to assess the GFR: Stefanowicz 2009 compared the Schwartz and Filler formulae for GFR estimation, whereas Stefanowicz 2011 compared Tc-99m clearance with the Filler formula, the old Schwartz formula and the new Schwartz formula. Five studies investigated the GFR but did not mention the assessment methods used (Di Tullio 1996; Ferrari 2005; Indolfi 2001; Mancini 1996; von Schweinitz 1997). Studies also varied in the defined cut-off point for glomerular dysfunction: values of 90, 80 and 70 mL/min/1.73m2 were used.

Proteinuria
Proteinuria was reported in 19 manuscripts and was investigated by a variety of urinary protein measurements. Five studies reported on microalbuminuria (Bardi 2004; Di Tullio 1996; Indolfi 2001; Mancini 1996; Srinivas 1998) and used cut-off points of 20 mg/24 h (Di Tullio 1996; Indolfi 2001), 30 mg/24 h (Srinivas 1998) or 20 mg/L (Bardi 2004; Mancini 1996). Seven studies reported urinary albumin-to-creatinine ratios (Bergeron 2005; Chevallier 1997; Cozzi 2005; Mpofu 1992; Rossi 1994b; Stefanowicz 2009; Stefanowicz 2011) and used cut-off points of 2 g/mol (Bergeron 2005; Chevallier 1997; Cozzi 2005), 20 mg/mmol (Mpofu 1992), 30 mg/g (Stefanowicz 2011) and 38 mg/g (Rossi 1994b). One study did not mention a cut-off value for the urinary albumin-to-creatinine ratio (Stefanowicz 2009). Four studies reported urinary albumin levels (Makipernaa 1991; Patzer 2001; Stefanowicz 2011; Wikstad 1986). Makipernaa 1991 used a cut-off value of 20 mg/24 h, Stefanowicz 2011 used 20 mg/L, Patzer 2001 used age-specific reference values and Wikstad 1986 did not present a cut-off value. Two studies reported more than one proteinuria measure: Bardi 2004 reported on urine dipsticks and microalbuminuria in 24-hour urine samples, whereas Stefanowicz 2011 reported on the urinary albumin-to-creatinine ratio and the urinary albumin level. Four studies did not further specify how proteinuria was measured (Fujieda 2009; Laverdiere 2005; Oberlin 2009; Schell 1995), and two studies did not provide a prevalence for proteinuria (Patzer 2001; Wikstad 1986).

Serum phosphate/hypophosphataemia
Seven studies reported on serum phosphate levels (Frisk 2007; Fujieda 2009; Mancini 1996; Oberlin 2009; Othman 2002; Schell 1995; Skinner 2010). The cut-off value for hypophosphataemia was age-dependent in two studies (Frisk 2007; Oberlin 2009), < 0.90 mmol/L in one study (Skinner 2010) and < 2.9 mg/dL in one study (Fujieda 2009); it was not mentioned in the last three (Mancini 1996; Othman 2002; Schell 1995).

Tubular phosphate regulation parameters
Eleven studies reported on an outcome measure related to tubular phosphate regulation. Four studies reported on the renal tubular phosphate threshold (Bergeron 2005; Ferrari 2005; Oberlin 2009; Skinner 2010). The low cut-off value for the renal tubular phosphate threshold was < 1.0 mmol/L in two studies (Bergeron 2005; Ferrari 2005) and < 0.99 mmol/L in one study (Skinner 2010), and in another study a cut-off value of < -2 standard deviations (SD) below the expected tubular phosphate threshold for age was used (Oberlin 2009). Seven studies reported the fractional phosphate reabsorption (Chevallier 1997; Rossi 1993; Rossi 1994; Rossi 1994a; Rossi 1994b; Rossi 1997; Rossi 1999). Two studies compared the fractional phosphate reabsorption with previously established normal data (Rossi 1993; Rossi 1994), two studies used < 1.07 mmol/L as a cut-off value (Rossi 1994a; Rossi 1994b), one study used < 1.0 mmol/L (Rossi 1999) and two studies did not report a cut-off value (Chevallier 1997; Rossi 1997).

Serum magnesium/hypomagnesaemia
Hypomagnesaemia was assessed by serum magnesium measurements in 8 studies (Bergeron 2005; Brock 1991; English 1999; Fujieda 2009; Oberlin 2009; Othman 2002; Skinner 2009; Stohr 2007a). Two studies used an age-dependent cut-off to define hypomagnesaemia (Brock 1991; Skinner 2009), two studies used a cut-off of < 0.70 mmol/L (Oberlin 2009; Stohr 2007a), Fujieda 2009 used < 1.9 mg/dL, Othman 2002 used < 0.80 mmol/L and two studies did not report the used cut-off value (Bergeron 2005; English 1999).

Blood pressure
Twenty-six studies investigated the blood pressure of CCS (Bergeron 2005; Cardous-Ubbink 2010; Chevallier 1997; Cozzi 2005; Di Tullio 1996; Finklestein 1993; Geenen 2010; Hoffmeister 2010; Indolfi 2001; Kantor 1989; Kubiak 2004; Laverdiere 2005; Makipernaa 1991; Mancini 1996; Mpofu 1992; Paulino 2000; Sasso 2010; Schell 1995; Srinivas 1998; Stefanowicz 2009; Stefanowicz 2010; Stefanowicz 2011; Trobs 2001; Van Dijk 2010; Van Why 1991; Wikstad 1986). Twenty-four studies reported hypertension prevalence, and the other two studies provided only mean/median blood pressure measurements (Mancini 1996; Wikstad 1986).

Composite outcome measures
Five studies reported on composite outcome measures that included at least one of the six outcome measures mentioned previously (Bolling 2010; Loebstein 1999; Stohr 2007; Weirich 2004; von Schweinitz 1997). Three of those used a composite outcome to capture general renal function by defining their own grading system (Bolling 2010; Loebstein 1999) or by using a set of predefined criteria (Weirich 2004). Two studies used a composite outcome to report on renal tubular function (Stohr 2007; von Schweinitz 1997). Both studies used their own definitions, combining hypophosphataemia, glycosuria and proteinuria (Stohr 2007) or tubular phosphate reabsorption and amino acid reabsorption (von Schweinitz 1997). Detailed descriptions of the composite outcome measures can be found in the Characteristics of included studies table.

 

Risk of bias in included studies

Data on the risk of bias of the included studies are reported in the Characteristics of included studies section and are summarised in Figure 1 and Figure 2. The criteria for the risk of bias assessment are listed in  Table 1.

 FigureFigure 1. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

To determine the internal validity of the included studies, we assessed the risks of selection bias, attrition bias, detection bias and confounding.

Risk of selection bias was low in only 19 of the 57 (33.3%) included studies (Bolling 2010; Chevallier 1997; de Graaf 1996; Finklestein 1993; Frisk 2002; Geenen 2010; Hamilton 2011; Kubiak 2004; Loebstein 1999; Paulino 2000; Rossi 1999; Sasso 2010; Skinner 2009; Skinner 2010; Trahair 2007; Van Dijk 2010; Van Why 1991; von Schweinitz 1997; Weirich 2004). These studies provided enough information for the review authors to conclude that they consisted of a representative study group, including > 90% of the original cohort or a random sample of the original cohort. Twenty studies (35.1%) included < 90% of the original cohort, and this group did not represent a random sample, and the other 18 studies (31.6%) did not report the size of their original cohort, so the risk of selection bias could not be assessed for these studies.

Most included studies (46/57; 80.7%) had good follow-up, defined as assessment of outcome parameters in > 90% of the study group. For four additional studies (7%), follow-up was adequate and was defined as an outcome assessment for 60% to 90% of the study group (Bolling 2010; Finklestein 1993; Indolfi 2001; von Schweinitz 1997). No study assessed the outcome parameter in < 60% of the study group. The risk of attrition bias was unclear in seven other studies (12.3%) that did not mention the size of the study group or the number of participants who underwent an outcome assessment (Breslow 2005; Cosentino 1993; Hamilton 2011; Laverdiere 2005; Loebstein 1999; Van Dijk 2010; Weirich 2004).

The risk of detection bias, defined as outcomes assessment by blinded investigators, could not be determined in any of the 57 studies (0%). Although most of the reported outcomes were not at risk for detection bias, as they represent only objective laboratory measurements, some outcomes (e.g. blood pressure, echographic measurements) could have been influenced by non-blinded outcome assessors.

Forty-three studies assessed possible risk factors for the development of early or late renal adverse effects (75.4%). Only 11 of these 43 studies (25.6%) adjusted their risk factor analyses for potential confounders (Cardous-Ubbink 2010; Frisk 2002; Geenen 2010; Hoffmeister 2010; Kantor 1989; Oberlin 2009; Rossi 1994a; Stohr 2007; Stohr 2007a; Van Dijk 2010; Van Why 1991). One of these 11 studies did not report potential risk factors but did adjust for potential confounders in their analysis (Van Why 1991). Thirty-one of the 43 studies (72.1%) that did perform some risk factor analysis did not adjust for possible confounders and hence were scored as having a high risk of potential bias. For only one of the 43 studies (2.3%) that assessed potential risk factors, it was unclear whether the analyses were adjusted for confounders (English 1999). The remaining fourteen studies did not assess and hence could not correct for confounding (Breslow 2005; Cosentino 1993; Frisk 2007; Hamilton 2011; Kubiak 2004; Laverdiere 2005; Loebstein 1999; Othman 2002; Paulino 2000; Srinivas 1998; Trahair 2007; Trobs 2001; von Schweinitz 1997; Weirich 2004). This means that the risk for confounding could not be excluded for 46 of 57 studies (80.7%).

To determine the external validity, we assessed four aspects of possible reporting bias in the included studies.

As a first requirement, studies had to adequately describe the treatment regimen, including cumulative doses of the chemotherapeutic agents of interest (cisplatin, carboplatin and/or ifosfamide), as well as (cumulative) doses of radiotherapy, as long as these therapies were part of the study's main treatment protocol. Thirty-one studies (54.4%) met this criterion. Twenty-six studies (45.6%) provided partial or no information on the treatment regimen provided and were regarded to have a high risk of reporting bias regarding the included study group (Aronson 2011; Bardi 2004; Bolling 2010; Breslow 2005; Cardous-Ubbink 2010; Cosentino 1993; Finklestein 1993; Fujieda 2009; Geenen 2010; Hamilton 2011; Kantor 1989; Kubiak 2004; Mancini 1996; Mpofu 1992; Othman 2002; Prasad 1996; Rossi 1994b; Sasso 2010; Srinivas 1998; Stefanowicz 2010; Stefanowicz 2011; Trobs 2001; Van Dijk 2010; Van Why 1991; von Schweinitz 1997; Weirich 2004).

The second requirement was mention of the follow-up duration for the study group of interest. This was reported better than the treatment regimen, with only four studies (7.0%) not reporting the follow-up period (Cosentino 1993; Finklestein 1993; Othman 2002; Trobs 2001). All of the other 53 studies (93.0%) mentioned a minimum, a median or a mean follow-up period.

Outcome definitions had to be objective and precise and had to include a description of the upper or lower limits of the reported outcome. Studies had to provide their outcome definitions for more than 50% of their included outcomes. Although the outcome definitions were highly heterogeneous, outcomes were described objectively and precisely in 38 of the 57 studies (66.7%). The other 19 studies (33.3%) did not provide outcome definitions for most of their included outcomes, or the given definitions were not objective and precise (Bardi 2004; Bolling 2010; Chevallier 1997; Cosentino 1993; De Graaf 1996; English 1999; Hamilton 2011; Indolfi 2001; Loebstein 1999; Mancini 1996; Othman 2002; Paulino 2000; Rossi 1997; Sasso 2010; Schell 1995; Stohr 2007; Trobs 2001; von Schweinitz 1997; Wikstad 1986).

The last criterion for the external validity assessment was that studies had to provide relevant risk measures for more than 90% of the study group. Forty-three studies (75.4%) investigated potential risk factors for the development of early or late renal adverse effects. Of these 43 studies, seven failed to provide any relevant risk measure for the assessed risk factors (Bergeron 2005; Bolling 2010; Ferrari 2005; Finklestein 1993; Rossi 1993; Sasso 2010; Wikstad 1986). One other study did perform multivariate logistic regression but did not present any relevant risk measures (Van Why 1991). This means that 35 studies (61.4%) had a well-defined risk estimation and eight studies (14.0%) had a high risk of bias regarding the definition of their statistical analyses. Fourteen studies (24.6%) did not investigate potential risk factors and hence were scored as having an unclear risk of bias.

 

Effects of interventions

Chronic kidney disease/renal insufficiency

Chronic renal disease (or renal insufficiency) was reported by ten studies (Aronson 2011; Bardi 2004; Breslow 2005; Cosentino 1993; Geenen 2010; Hamilton 2011; Laverdiere 2005; Paulino 2000; Sasso 2010; Stefanowicz 2011). Six studies specifically evaluated renal function in WT survivors treated with a unilateral nephrectomy and found prevalences ranging from 0.5% to 18.8% (Breslow 2005; Cosentino 1993; Geenen 2010; Paulino 2000; Sasso 2010; Stefanowicz 2011). The study by Geenen et al also assessed CKD/renal insufficiency in 63 healthy siblings of survivors and found a prevalence of 0% (Geenen 2010). Three studies investigated renal function after a bilateral WT and reported a prevalence range for renal insufficiency of 10.7% to 32% (Aronson 2011; Breslow 2005; Hamilton 2011). Breslow et al also investigated the prevalence of end-stage renal disease (ESRD) in unilateral and bilateral nephrectomised WT survivors with specific tumour disposition syndromes and genitourinary malformations, which ranged from 3.2% to 70% (Breslow 2005). The study by Laverdiere et al reported on CKD as defined by the Common Terminology Criteria for Adverse Events (CTCAE) criteria in 63 survivors of neuroblastoma and found only 1 participant with mild CKD (Laverdiere 2005). The study by Bardi et al reported that one of the 115 included survivors had been put on chronic haemodialysis for end-stage renal failure (Bardi 2004). Pooling of data regarding CKD/renal insufficiency proved not feasible because of the high heterogeneity (I2 = 94%). See also  Analysis 1.1 and Figure 3.

 FigureFigure 3. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.1 Chronic kidney disease/renal insufficiency as defined by authors.

(Estimated) glomerular filtration rate
Twelve studies used a cut-off value of 90 mL/min/1.73 m2 to assess the (estimated) GFR. Reported prevalences ranged from 2.3% in CCS treated with cisplatin, carboplatin, ifosfamide or nephrectomy (Stefanowicz 2009) up to 50% in CCS treated with ifosfamide and radiotherapy involving the kidney region (Skinner 2010). Because of profound heterogeneity (I2 = 91%) pooling of study results was not feasible. Only Oberlin et al investigated possible risk factors for glomerular dysfunction defined as GFR < 90 in multivariate analyses (Oberlin 2009). They showed that older age at treatment and longer follow-up duration were significantly associated with glomerular dysfunction, whilst no relationship could be established between GFR and higher cumulative ifosfamide dose. See also  Analysis 1.2, Figure 4 and  Table 3.

 FigureFigure 4. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.2 (Estimated) glomerular filtration rate < 90 ml/min/1.73m2. The outcome presented for Stefanowicz 2009 is the estimated GFR using the Schwartz formula, for Stefanowicz 2011 the GFR measured by Tc-99m clearance.

Seven studies used a cut-off value of 80 mL/min/1.73 m2 to assess the GFR. Reported prevalences ranged from 0.0% in CCS treated with nephrectomy and radiotherapy involving the kidney region (Srinivas 1998) to 42.5% in CCS treated with cisplatin (Brock 1991). Heterogeneity made it impossible to pool these study results as well (I2 = 79%). See also  Analysis 1.3 and Figure 5.

 FigureFigure 5. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.3 (Estimated) glomerular filtration rate < 80 mL/min/1.73 m2.

Only one study used a cut-off value of 70 mL/min/1.73 m2 to assess GFR. Frisk et al found a prevalence of 27% in 26 survivors treated with TBI as a conditioning regimen for an autologous bone marrow transplantation (Frisk 2002). Combined treatment with aminoglycosides and intravenous vancomycin was significantly related to the decrease in GFR among survivors treated with TBI, whereas age had no influence. In survivors treated without TBI, no relationship was observed between concomitant treatment with aminoglycosides and intravenous vancomycin and a lower GFR. See also  Analysis 1.4, Figure 6 and  Table 3.

 FigureFigure 6. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.4 (Estimated) glomerular filtration rate < 70 mL/min/1.73 m2.

One other study used a GFR cut-off value of 50 mL/min/1.73 m2. Van Why et al investigated survivors treated with a bone marrow transplant and found a prevalence of 14% (Van Why 1991). In this study, treatment with TBI, amphotericin B and cyclosporin A after 60 days was an independent predictor of late renal insufficiency, whilst early renal insufficiency and chemotherapy conditioning had no predictive value. See also  Analysis 1.5, Figure 7 and  Table 3.

 FigureFigure 7. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.5 (Estimated) glomerular filtration rate < 50 mL/min/1.73 m2.

One study did not report any exact cut-off values for GFR but used the CTCAE v3 grading criteria to assess glomerular function impairment in sarcoma survivors treated with cisplatin and/or carboplatin (Stohr 2007a). However, estimation of the GFR using the Schwartz formula proved to be inappropriate in this cohort, especially during the first year after treatment, as > 40% of all survivors had an estimated GFR above the upper limit of normal, indicating considerable overestimation of the GFR.

Four studies reported a mean GFR at follow-up in comparison with controls (Bardi 2004; Schell 1995; Stefanowicz 2009; Wikstad 1986). All four studies investigated WT survivors who received a unilateral nephrectomy. The most profound decrease in GFR was note by Bardi et al after a median follow-up of 7 years (Bardi 2004). WT survivors had a mean GFR of 71 mL/min/1.73 m2 at follow-up-a decrease of 61 mL/min/1.73 m2 in comparison with healthy controls (P < 0.05). Schell et al used a control group of only six children who received a unilateral nephrectomy for non-malignant disease, and found an insignificant difference of 6 mL/min/1.73 m2 (Schell 1995). In the study by Stefanowicz et al, it was possible to compare survivors with oncohaematological disease treated without potentially nephrotoxic therapy with survivors treated for WT or other solid tumours treated with potentially nephrotoxic therapy, who had a mean difference in GFR of -20.0 mL/min/1.73 m2(Stefanowicz 2009). Wikstad et al reported a similar difference between WT survivors and healthy controls (-18.9 mL/min/1.73 m2), as well as a significant difference between WT survivors and children nephrectomised for hydronephrosis (-10.6 mL/min/1.73 m2; Wikstad 1986). Pooling of these study results was not feasible (I2 = 86%). See also  Analysis 2.1 and Figure 8.

 FigureFigure 8. Forest plot of comparison: 2 Mean glomerular filtration rate in mL/min/1.73 m2 at least 1 year after diagnosis, outcome: 2.1 Mean (estimated) GFR in studies that included internal or healthy controls. The outcome presented for Stefanowicz 2009 is the estimated GFR using the Schwartz formula.

Three studies investigated risk factors for glomerular dysfunction whilst correcting for possible confounders (Frisk 2002; Oberlin 2009; Van Why 1991).  Table 3 gives an overview of which risk factors were investigated and which were or were not significantly associated with GFR in multivariate analyses.

Proteinuria
The prevalence of proteinuria was reported in 17 studies (Bardi 2004; Bergeron 2005; Chevallier 1997; Cozzi 2005; Di Tullio 1996; Fujieda 2009; Indolfi 2001; Laverdiere 2005; Makipernaa 1991; Mancini 1996; Mpofu 1992; Oberlin 2009; Rossi 1994b; Schell 1995; Srinivas 1998; Stefanowicz 2009; Stefanowicz 2011). The lowest prevalence (0%) was found in a study focusing on carboplatin nephrotoxicity (Bergeron 2005), the highest prevalence (84%) in a study on renal function after nephrectomy for WT (Srinivas 1998). It should be noted that the 16 studies that reported proteinuria used 5 different methods of proteinuria assessment. Median follow-up duration varied from 1 to 19.2 years, and median age at follow-up varied widely, from 6 to 21.8 years. Because of high heterogeneity, it was not possible to pool results (I2 = 93%). No studies investigated risk factors for proteinuria whilst correcting for possible confounders. See also  Analysis 1.6 and Figure 9.

 FigureFigure 9. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.6 Proteinuria as defined by authors.

Serum phosphate/hypophosphataemia
Seven studies investigated serum phosphate levels (Frisk 2007; Fujieda 2009 Mancini 1996; Oberlin 2009; Othman 2002; Schell 1995; Skinner 2010). In four studies, the prevalence of hypophosphataemia was 0% (Frisk 2007; Mancini 1996; Othman 2002; Schell 1995). The studies by Oberlin et al and Skinner et al specifically evaluated ifosfamide toxicity after a follow-up duration of approximately 10 years and reported prevalences of 1.1% and 8.0%, respectively (Oberlin 2009; Skinner 2010). Fujieda et al also reported hypophosphataemia prevalence of 47.6% after ifosfamide (in combination with cisplatin or carboplatin) but after a much shorter median follow-up period of 14 months (Fujieda 2009). All hypophosphataemia prevalences are presented in  Analysis 1.7 and Figure 10. No study used multivariate analysis to assess possible risk factors for hypophosphataemia. Again, variation in outcome definitions, study populations and follow-up durations resulted in profound heterogeneity (I2 = 90%), making pooling of results not feasible.

 FigureFigure 10. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.7 Serum phosphate/hypophoshataemia as defined by the authors.

Tubular phosphate regulation parameters
Eleven studies investigated the phosphate reabsorption capacity of the renal tubuli, using fractional phosphate reabsorption or the tubular phosphate threshold as an outcome measure. Two studies found a relatively low prevalence of impaired tubular function of 3.3% and 0% (Bergeron 2005; Chevallier 1997). All other studies found a prevalence between 24.4% and 62.5% (see  Analysis 1.8 and Figure 11). It should be noted that the five studies investigating tubular phosphate function by Rossi et al may have included the same participants in multiple studies (Rossi 1994; Rossi 1994a; Rossi 1994b; Rossi 1997; Rossi 1999). Again, variation in outcome definitions, study populations and follow-up durations resulted in profound heterogeneity (I2 = 90%), making pooling of results not feasible.

 FigureFigure 11. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.8 Tubular phosphate regulation parameters as defined by the authors.

Two studies used multivariate regression analysis to analyse possible risk factors for tubular dysfunction (Oberlin 2009; Rossi 1994a). Oberlin et al found that the cumulative ifosfamide dose and the follow-up duration were significant predictors of the tubular phosphate threshold, whilst age at treatment was not significant (Oberlin 2009). Rossi et al performed stepwise logistic regression on a combined outcome (low phosphate reabsorption AND low amino acid reabsorption) in survivors treated with ifosfamide and found that concomitant treatment with cisplatin and a nephrectomy were significant risk factors (Rossi 1994a). Methotrexate, gentamicin, mesna and age had no influence. See  Table 4 for additional details on the multivariate analyses.

Serum magnesium/hypomagnesaemia
Hypomagnesaemia prevalences in CCS were reported in eight studies (Bergeron 2005; Brock 1991; English 1999; Fujieda 2009; Oberlin 2009; Othman 2002; Stohr 2007a; Skinner 2009), as shown in  Analysis 1.9 and Figure 12. The study of Skinner 2009 could not be included in Figure 12 because the number of tested participants was missing. Six of these eight studies included survivors treated with cisplatin and/or carboplatin (Bergeron 2005; Brock 1991; English 1999; Fujieda 2009; Stohr 2007a; Skinner 2009). The studies of Bergeron et al and English et al investigated survivors treated only with carboplatin as a potentially nephrotoxic agent and found prevalences of 0% and 4.4% after follow-up durations of 7 years and 1 year, respectively (Bergeron 2005; English 1999). The carboplatin-only subgroup of the study by Stohr et al revealed a similar prevalence of 3.3% after 1.9 years (Stohr 2007a), whilst Skinner et al reported a prevalence of 17% ten years after treatment (Skinner 2009). The studies by Stohr et al and Skinner et al also reported the prevalence of hypomagnesaemia in survivors treated with both cisplatin and carboplatin, which was 9% in both studies (Stohr 2007a; Skinner 2009). Hypomagnesaemia in survivors treated only with cisplatin was reported to be 2.3% (Stohr 2007a), 32% (Skinner 2009) and 29% (Brock 1991).

 FigureFigure 12. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.7 Serum magnesium/hypomagnesaemia as defined by the authors. The study of Skinner 2009 was not included in the figure due to missing numbers of included survivors.

Two additional studies investigated serum magnesium as an outcome measure for tubular function in participants treated without cisplatin and/or carboplatin (Oberlin 2009; Othman 2002). Oberlin et al investigated the nephrotoxic effects of ifosfamide and found 2 of 171 survivors (1.2%) to be hypomagnesaemic (Oberlin 2009). Othman et al investigated serum magnesium in WT survivors treated with nephrectomy and radiotherapy (in 15/31 survivors only) and found a prevalence of 25.8% (Othman 2002). As with all other outcomes, it was not possible to pool the results of these studies because of heterogeneity (I2 = 79%).

Only one study investigated possible risk factors for hypomagnesaemia whilst taking into account appropriate measures to prevent confounding (Stohr 2007a). Investigators found that sarcoma survivors treated with carboplatin (P = 0.0102) and/or cisplatin (P = 0.0005) had significantly lower serum magnesium levels than sarcoma survivors treated without these therapies. They did not find a significant effect of abdominal radiotherapy, ifosfamide or follow-up duration nor any interaction of these risk factors with time (see also  Table 5).

Blood pressure
Twenty-four studies reported the prevalence of hypertension (high blood pressure as defined by the authors) in survivors treated with potentially nephrotoxic therapy (Bergeron 2005; Cardous-Ubbink 2010; Chevallier 1997; Cozzi 2005; Di Tullio 1996; Finklestein 1993; Geenen 2010; Hoffmeister 2010; Indolfi 2001; Kantor 1989; Kubiak 2004; Laverdiere 2005; Makipernaa 1991; Mpofu 1992; Paulino 2000; Sasso 2010; Schell 1995; Srinivas 1998; Stefanowicz 2009; Stefanowicz 2010; Stefanowicz 2011; Trobs 2001; Van Dijk 2010; Van Why 1991). Prevalence of hypertension ranged from 0% (Chevallier 1997; Di Tullio 1996; Indolfi 2001; Schell 1995; Srinivas 1998) to 18.2% (Kubiak 2004). Especially studies that included only radiotherapy and nephrectomy as potentially nephrotoxic treatments investigated hypertension (see  Analysis 1.10 and Figure 13). One study compared hypertension prevalence between 62 WT survivors and 69 healthy sibling controls and found that survivors treated with radiotherapy and chemotherapy had a significantly higher hypertension prevalence than their siblings (prevalence 21.6% vs 1.4%; Geenen 2010). Overall the differences in outcome definition, study population and follow-up duration caused profound heterogeneity, making it impossible to pool the results (I2 = 89%).

 FigureFigure 13. Forest plot of comparison: 1 Prevalence of renal dysfunction, outcome: 1.10 Blood pressure.

Four studies reported risk factors for hypertension as a result of multivariate analysis (Cardous-Ubbink 2010; Geenen 2010; Hoffmeister 2010; Kantor 1989).  Table 6 lists the risk factors reported in these studies. Two studies that investigated a higher body mass index in relation to hypertension found it to be a significant risk factor (Cardous-Ubbink 2010; Hoffmeister 2010). All other investigated risk factors were assessed in a single study only, or inconsistent results were reported between studies. One determinant significantly decreased the risk of hypertension: previous hepatitis C infection (hazard ratio 0.52, 95% confidence interval (CI) 0.3 to 0.9; Hoffmeister 2010). All other significant risk factors increased the risk of hypertension.

Composite outcome measures
Three studies reported on the prevalence of renal toxicity by using a composite outcome that incorporated one of the included outcome measures for this review (Bolling 2010; Loebstein 1999; Weirich 2004). Bolling et al assessed radiation nephropathy in 74 survivors and found 5 of 74 (6.8%) survivors with signs of renal toxicity (Bolling 2010). The study by Loebstein et al investigated ifosfamide toxicity in 174 participants after a mean follow-up duration of 5.3 years (Loebstein 1999); 7 of 174 had developed severe nephrotoxicity, of whom 2 survivors showed progressive deterioration of GFR followed by ESRD. One study used the CTCAE v2 criteria to assess renal and urinary dysfunction and found 28 of 385 (7.2%) WT survivors with toxicity. Fifteen survivors (3.9%) needed treatment for renal or urinary system impairment (Weirich 2004). Two studies used a composite outcome measure to report on renal tubular function. Stohr et al assessed ifosfamide toxicity in 593 German sarcoma survivors and reported on the prevalence of tubular dysfunction, defined as having at least two of the three following criteria: hypophosphataemia, glycosuria and/or proteinuria (Stohr 2007). Eighteen of the 593 survivors (30.4%) were diagnosed with a tubulopathy after a median follow-up period of 12.6 months. Von Schweinitz et al defined a tubulopathy as impaired tubular phosphate reabsorption and/or impaired amino acid reabsorption (von Schweinitz 1997), although cut-off values for both measurements were not stated. Of 41 assessed hepatoblastoma survivors, five had a mild tubulopathy (12%) and two had a more severe tubulopathy (5%) after a median follow-up duration of 5.3 years.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

In this systematic review of the literature, we evaluated all available evidence on the prevalence of and risk factors for renal dysfunction in CCS treated with potentially nephrotoxic treatments (i.e. ifosfamide, carboplatin, cisplatin, radiotherapy involving the kidney region and nephrectomy). We were able to include 57 studies. The prevalence of renal adverse effects ranged from 0% to 84%. This variation can be explained in part by variation in included malignancies, variation in prescribed treatments, variation in reported outcome measurements and variation in the methodological quality of available evidence. Gaps in evidence remain regarding which specific nephrotoxic treatments put CCS at greatest risk of developing early or late renal adverse effects.

The prevalence of CKD/renal insufficiency was low, ranging between 0.5% and 3% in unilaterally nephrectomised WT survivors without specific syndromes or genitourinary congenital malformations. When survivors received a bilateral (partial) nephrectomy or suffered from syndromes such as Denys-Drash or WAGR, the prevalence was higher (11% to 71%). Follow-up in these studies ranged from 7 to 25 years. The studies that investigated an impaired (estimated) GFR (regardless of the used cut-off value) showed higher prevalences, ranging from 0% to 50%. This raises the suspicion that glomerular function, with renal insufficiency as the ultimate stage, deteriorates slowly over time. The decline in GFR is a physiological process as well: During the normal aging process, glomerular function slowly declines. However, a GFR below 90 mL/min/1.73 m2 usually does not manifest until late adulthood (Hoang 2003), whilst most of the included studies show an increased prevalence of impaired GFR in a relatively very young population. No evidence indicates which nephrotoxic treatments place CCS at greatest risk for glomerular dysfunction. Very long-term follow-up (> 25 years) studies have not yet been performed, in part because of the low survival rates for paediatric malignancies up until 25 years ago. Future studies should assess glomerular function in these aging survivors over time, especially in relation to glomerular function in the normal population.

A matter of concern was the large variation in the methods used to determine or estimate the GFR. The studies included in this review used more than ten different measures to express the GFR by obtaining renal clearance measurements or by estimating the GFR using estimation formulae. Two studies by Stefanowicz et al showed that there may be large differences in the GFR that are based on which method or formula is used (Stefanowicz 2009; Stefanowicz 2011). Depending on the method, these differences were as large as 35.6 mL/min/1.73 m2, causing variation in the prevalence of participants with a GFR < 90 mL/min/1.73 m2 between 0% and 43.8% in the same study. Effort should be put into (international) guideline harmonisation for the follow-up of glomerular function after childhood cancer to facilitate comparability between studies.

Proteinuria is one of the early and sensitive markers for CKD, and it is an independent predictor of mortality in the general population (Matsushita 2010; National Kidney Foundation 2002). In the sixteen studies that measured proteinuria, prevalence ranged between 0% and 84%. This heterogeneity may have been caused by several measurements that were available to assess proteinuria: The sixteen studies reported at least five different proteinuria measurements. Because of this heterogeneity and the fact that no study corrected its proteinuria analyses for potential confounders, it was not possible to draw any conclusions regarding prevalence or risk factors for proteinuria. More valid research is needed regarding proteinuria in CCS, as it is can be a valuable and cheap tool for screening purposes.

Hypophosphataemia in CCS is most often associated with impairment of proximal tubular reabsorption of phosphate caused by ifosfamide toxicity. Hypomagnesaemia and hypokalaemia are associated with renal phosphate wasting and phosphate depletion as well (Liamis 2010). Impairment of proximal tubular phosphate reabsorption may be accompanied by impaired reabsorption of bicarbonate, glucose, amino acids and uric acid, possibly resulting in metabolic acidosis, hypouricaemia, aminoaciduria and/or glycosuria (Pratt 1991). Hypophosphataemia prevalence ranged between 1.1% and 8.0% 10 years after diagnosis in survivors treated with ifosfamide (Oberlin 2009; Skinner 2010). Impaired tubular phosphate regulation parameters were more prevalent in these two studies, with prevalences of 24.4% and 62.5%, respectively. The prevalence of impaired tubular phosphate regulation parameters in all other studies that solely investigated ifosfamide survivors ranged between these two percentages. The difference between the prevalence of hypophosphataemia and impaired phosphate reabsorption may be explained by sufficient dietary intake or adequate phosphate supplementation. Still, the high prevalence of impaired tubular phosphate regulation parameters emphasises the need for longitudinal follow-up to prevent the development of hypophosphataemia, loss of bone mineral density and ultimately hypophosphataemic rickets. Especially survivors treated with higher cumulative ifosfamide doses and with ifosfamide in combination with cisplatin or a nephrectomy should be considered for follow-up.

Damage to the proximal and distal tubulus of the kidney, associated with platinum toxicity caused by cisplatin and/or carboplatin treatment, can cause (chronic) tubular magnesium wasting, leading to hypomagnesaemia (Lajer 1999). The prevalence of hypomagnesaemia among participants in the included studies varied between 0% and 29%. The variation in prevalence was not consistent with the variation in treatment modality or the time between cancer diagnosis and serum magnesium testing at follow-up; nor did it reflect the definitions of abnormal values provided. The only way to gain valid insight into potential risk factors for hypomagnesaemia is to perform multivariate analysis to control for potential confounders such as cumulative chemotherapy dose, follow-up duration and age at diagnosis. Only Stöhr et al used appropriate measures to prevent confounding and found that treatment with cisplatin and carboplatin significantly reduced serum magnesium, whereas abdominal irradiation and duration of follow-up had no significant influence (Stohr 2007a). Longitudinal studies with repeated serum magnesium measurements, preferably in a cohort of CCS that included all malignancies and treatments, would provide the opportunity for investigators to assess in greater detail risk factors for hypomagnesaemia and its course.

Uncontrolled hypertension is the number one risk factor associated with high mortality rates throughout the world, as high blood pressure is closely correlated with coronary heart disease and stroke (Beevers 2007; World Health Organization 2002). Many CCS are already at risk for cardiovascular disease, for example, that due to anthracycline- or radiation-induced cardiotoxicity (Kremer 2002; van Dalen 2006; van der Pal 2012). In the studies included in this review, the prevalence of renal-related hypertension varied between 0% and 18.2%. Substantial heterogeneity among studies prevented us from performing a meta-analysis. The studies that corrected for possible confounders for hypertension were not concordant either: Only two of the four studies showed a significant negative effect of radiation therapy, whilst the two other studies could not confirm this effect. The study by Hoffmeister et al reported that survivors with hepatitis C virus (HCV) infection were almost 50% less likely to develop hypertension than their HCV-negative counterparts (Hoffmeister 2010). Although they did not have an explanation for this phenomenon, investigators in a large study of 171,665 veterans reported a similar finding (Butt 2009). Two studies that performed multivariate analyses showed that higher body mass index (BMI) was a significant risk factor for hypertension in CCS (Cardous-Ubbink 2010; Hoffmeister 2010). Targeting obesity and its related life-style factors may be an important approach in preventing cardiovascular events and subsequently renal late adverse effects in this population. Additionally, future studies should always correct for BMI when assessing treatment-related risk factors for hypertension in CCS.

The risk of bias assessment of all included studies showed that all studies suffered from methodological limitations. Not a single study stated that investigators blinded the outcome assessor to the treatment exposure. Of course this may not be applicable to simple laboratory tests, but assessment of blood pressure or renal ultrasound would be susceptible to detection bias, for example. Apart from this bias, the methodological quality of studies varied widely. Only one study had a low risk of bias on all seven remaining criteria (Frisk 2002). In addition, eight studies had a low risk of bias when only six items were taken into account (Geenen 2010; Hoffmeister 2010; Oberlin 2009; Rossi 1994a; Rossi 1999; Skinner 2009; Skinner 2010; Stohr 2007a). One study had an unclear or high risk of bias on all eight criteria (Cosentino 1993).

We assessed the internal validity of the included studies by applying criteria for selection bias, attrition bias, detection bias and confounding. Selection bias could not be excluded in 67% of the studies. Selection bias may lead to distortion of the observed effects in a study in relationship to the 'real' effect. When a study includes only a non-random subsample of the original cohort, the risk that selection of survivors is based on factors related to the specific outcome of interest is substantial. The results of these studies should be interpreted with caution, as reported prevalences and risk factors may overestimate or underestimate the real prevalence. If selection bias can be ruled out, attrition bias (incomplete follow-up) poses an additional threat to the validity of the study. The risk for attrition bias was low in all but seven studies.

The last criterion related to the internal validity of studies was confounding: Did studies take important (confounding) variables into account in the analysis of possible risk factors for renal adverse outcomes? For most studies, the answer was no; only 11 studies used multivariate analysis to correct for possible confounders. This poses a problem for the interpretation of risk factor analyses in the other 46 studies. Without control for potential confounders, the results of (univariate) risk factor analysis may overestimate or underestimate the real effect.

To a considerable extent, external validity determines the generalisability of study results to other populations or to individual participants. We assessed external validity by applying four criteria of study reporting: the characteristics of the study group, the follow-up duration, the outcome definition and the statistical analysis. Although the follow-up duration was mentioned in most studies, reporting of the other three items was limited. If substantial information is missing regarding the treatment that participants received, the definition of the outcome measured or the statistical relevance of the results, it is difficult to interpret the results of the study correctly. To improve the external validity of studies, authors should adhere to published guidelines regarding high-quality reporting, such as the STROBE statement (von Elm 2007).

This systematic review may have some limitations as well. Although we used a comprehensive search strategy, because of time constraints we were unable to comply with Cochrane guidelines on handsearching conference proceedings, reference lists of included studies and reference lists of relevant reviews. As a result, we cannot affirm that we did not miss certain relevant studies for inclusion, and we must state that selection bias based on the search strategy may be present. Additionally, we are still awaiting translation of some of the relevant studies that were not published in English. These language limitations may have resulted in language bias, as it is known that authors of studies are more likely to publish in English if their results are significant (Egger 1997). Selection of outcome measurements that had the highest clinical relevance and were reported most often and most consistently also may have introduced reporting bias, as reporting of a certain outcome may be related to the nature and direction of study results. This may have caused selection of outcome measures that show the most desirable or significant results. However, selection of the outcome measures for this review was based predominantly on clinical relevance and existing screening guidelines for renal function in childhood cancer survivors, such as the guidelines of Skinner 1991.

In conclusion, this systematic review shows that the prevalence of renal adverse effects after treatment for childhood cancer varies widely, from 0% to 84%. Variations in study populations, outcome measurements, follow-up duration and methodological quality may explain this heterogeneity. New research projects should focus particularly on complete data collection and well-defined outcome measurements and especially on multivariate analysis methods. Evidence on renal adverse effects is not conclusive; therefore, all CCS treated with cisplatin, carboplatin, ifosfamide, kidney or TBI and/or nephrectomy should be included in prospective, longitudinal follow-up programmes to allow researchers to gain insight into the prevalence of, and especially the risk factors for, kidney disease.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

 

Implications for practice

This systematic review shows that childhood cancer survivors (CCS) are at risk for developing early and late renal adverse effects, including chronic kidney disease/renal insufficiency, impaired (estimated) glomerular filtration rate, proteinuria, hypomagnesaemia, hypophosphataemia, impaired tubular phosphate regulation and hypertension. CCS should be screened for these adverse effects, preferably according to systematic, prespecified protocols based on the treatment modalities provided. Because current evidence is not conclusive regarding possible risk factors for renal adverse effects, we believe that all CCS who receive potentially nephrotoxic therapy should receive renal function testing at fixed time intervals. Increasing follow-up duration was a risk factor in several studies; therefore, regardless of the investigated outcome, screening should continue during adulthood. However, recommendations about the exact time interval for renal function surveillance cannot be made on the basis of current evidence. When additional evidence becomes available, treatment regimens and follow-up protocols can be adjusted. Until then, alternatives for nephrotoxic treatment should be explored without compromising the high childhood cancer survival rates. CCS should receive life-style counselling on topics such as avoidance of tobacco use, excessive non-steroidal anti-inflammatory drug (NSAID) use, excessive alcohol use and dehydration, to minimise the risk of developing kidney disease and/or hypertension (Jones 2008; Nathan 2009).

 
Implications for research

All studies included in this review showed methodological limitations. Future research on the prevalence of and risk factors for renal dysfunction after childhood cancer should be designed as prospective cohort studies, preferably in large and complete cohorts with large and complete study groups. Very little evidence is available on the development of renal function over time in CCS. Study investigators should perform longitudinal analyses of renal function and, if possible, should include an age-matched control population (preferably siblings) because normative data on glomerular and tubular function in healthy children and in young adults are scarce. As the development of renal adverse effects after childhood cancer can have several causes and pathways, studies should always use multivariate analysis to assess risk factors and to correct for possible confounders. As the reporting quality of many of the included studies was inadequate, we recommend that all authors adhere to one of the existing reporting guidelines for clinical studies, such as the STROBE checklist (von Elm 2007).

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

We would like to thank Edith Leclercq for developing and running the search strategies for the different databases, and peer reviewers R. Skinner, E. Bárdi and D.P. Jones for their constructive comments on the manuscript.

The editorial base of the Cochrane Childhood Cancer Group is funded by Kinderen Kankervrij (KiKa).

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
Download statistical data

 
Comparison 1. Prevalence of renal dysfunction

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Chronic kidney disease / renal insufficiency as defined by authors10Prevalence (Random, 95% CI)Totals not selected

    1.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.3 Ifosfamide, radiotherapy and/or nephrectomy
3Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.4 Radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.5 Unilateral nephrectomy for Wilms' tumour
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.6 Unilateral nephrectomy for Wilms' tumour (Denys-Drash syndrome)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.7 Unilateral nephrectomy for Wilms' tumour (WAGR syndrome)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.8 Unilateral nephrectomy for Wilms' tumour (genitourinary anomalies)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.9 Bilateral (partial) nephrectomy for Wilms' tumour
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.10 Bilateral (partial) nephrectomy for Wilms' tumour (Denys-Drash syndrome)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.11 Bilateral (partial) nephrectomy for Wilms' tumour (WAGR syndrome)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    1.12 Bilateral (partial) nephrectomy for Wilms' tumour (genitourinary anomalies)
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 2 (Estimated) glomerular filtration rate < 90 mL/min/1.73m212Prevalence (Random, 95% CI)Totals not selected

    2.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.2 Cisplatin, carboplatin, ifosfamide and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.3 Cisplatin, carboplatin and/or radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.4 Cisplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.5 Cisplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.6 Carboplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.7 Carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.8 Ifosfamide and/or radiotherapy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.9 Ifosfamide and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.10 Ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    2.11 Radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 3 (Estimated) glomerular filtration rate < 80 mL/min/1.73m27Prevalence (Random, 95% CI)Totals not selected

    3.1 Cisplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    3.2 Cisplatin, ifosfamide and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    3.3 Cisplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    3.4 Cisplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    3.5 Radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 4 (Estimated) glomerular filtration rate < 70 mL/min/1.73m21Prevalence (Random, 95% CI)Totals not selected

    4.1 Radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 5 (Estimated) glomerular filtration rate < 50 mL/min/1.73 m21Prevalence (Random, 95% CI)Totals not selected

    5.1 Radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 6 Proteinuria as defined by authors17Prevalence (Random, 95% CI)Totals not selected

    6.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
3Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.2 Cisplatin, carboplatin, ifosfamide and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.3 Cisplatin, carboplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.4 Cisplatin, carboplatin, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.5 Cisplatin, ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.6 Cisplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.7 Carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.8 Carboplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.9 Ifosfamide and/or radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.10 Radiotherapy and/or nephrectomy
4Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    6.11 Nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 7 Serum phosphate / hypophoshataemia as defined by the authors7Prevalence (Random, 95% CI)Totals not selected

    7.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    7.2 Cisplatin, carboplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    7.3 Cisplatin, carboplatin, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    7.4 Ifosfamide and/or radiotherapy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    7.5 Radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    7.6 Radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 8 Tubular phosphate regulation parameters as defined by the authors11Prevalence (Random, 95% CI)Totals not selected

    8.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.2 Cisplatin, ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.3 Cisplatin, ifosfamide and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.4 Cisplatin and/or ifosfamide
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.5 Carboplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.6 Ifosfamide and/or radiotherapy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    8.7 Ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 9 Serum magnesium / hypomagnesaemia as defined by the authors7Prevalence (Random, 95% CI)Totals not selected

    9.1 Cisplatin, carboplatin, ifosfamide and/or radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    9.2 Cisplatin, carboplatin and/or ifosfamide
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    9.3 Cisplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    9.4 Carboplatin
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    9.5 Ifosfamide and/or radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    9.6 Radiotherapy and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 10 Blood pressure24Prevalence (Random, 95% CI)Totals not selected

    10.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.2 Cisplatin, carboplatin, and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.3 Cisplatin, ifosfamide, radiotherapy and/or nephrectomy
3Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.4 Carboplatin, ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.5 Carboplatin
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.6 Ifosfamide, radiotherapy and/or nephrectomy
2Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.7 Ifosfamide and/or nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.8 Radiotherapy and/or nephrectomy
10Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.9 Radiotherapy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

    10.10 Nephrectomy
1Prevalence (Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Mean (estimated) glomerular filtration rate in mL/min/1.73m2 at least 1 year after diagnosis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Mean (estimated) glomerular filtration rate in studies that included internal or healthy controls4Mean Difference (Random, 95% CI)Totals not selected

    1.1 Cisplatin, carboplatin, ifosfamide, radiotherapy and/or nephrectomy
2Mean Difference (Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Cisplatin, carboplatin, ifosfamide and/or nephrectomy
1Mean Difference (Random, 95% CI)0.0 [0.0, 0.0]

    1.3 Radiotherapy and/or nephrectomy
1Mean Difference (Random, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Appendix 1. Search strategy for Cochrane Central Register of Controlled Trials (CENTRAL)

1. ForIfosfamide the following text words were used:

ifosfamide OR iphosphamide OR iso-endoxan OR iso endoxan OR isophosphamide OR isofosfamide OR holoxan OR asta z 4942 OR NSC-109,724 OR NSC 109,724 OR NSC109,724 OR NSC 109724 OR NSC-109724 OR NSC109724 OR cyclic p-oxides OR ethylamines OR oxazines OR ifosfa* OR iphospha* OR isofosfa* OR isophospha* OR “br cl fosfamide” OR cyfos OR ifex OR “ifo-cell” OR ifolem OR ifomide OR ifosfamidum OR ifosforamide mustard OR ifoxan OR ipambr OR iphosphamid OR isophosphoramide bromide mustard OR isophosphoramide mustard OR mitoxana OR mjf 9325 OR naxamide OR seromida OR tronoxal OR z 4942

2. ForCarboplatin and cisplatin the following text words were used:

Platinum OR Platinum Compounds OR cis-diamminedichloroplatinum* OR cis-platinum OR cis platinum OR biocisplatinum OR dichlorodiammineplatinum OR nsc-119875 or NSC 119875 or NSC119875 OR platidiam OR platino OR platinol OR platinum* OR CDDP OR CACP OR cisplatin OR carboplatin OR abiplatin OR paraplatin OR CBDCA OR cis-DDP OR neoplatin OR platidiam OR cis-Diamminedichloroplatinum OR cis Diamminedichloroplatinum OR cis-Dichlorodiammineplatinum(II) OR platinum diamminodichloride OR Platinum Diamminodichloride OR 15663-27-1 OR cis-Diammine(cyclobutanedicarboxylato)platinum II OR Carbosin OR Pharmachemie Brand of Carboplatin OR Carbotec OR Columbia Brand of Carboplatin OR Ercar OR Almirall Brand of Carboplatin OR JM-8 OR JM 8 OR JM8 OR Neocarbo OR Neocorp Brand of Carboplatin OR NSC-241240 OR NSC 241240 OR NSC241240 OR Bristol-Myers Squibb Brand of Carboplatin OR Carboplat OR Paraplatine OR Platinwas OR Chiesi Brand of Carboplatin OR Ribocarbo OR ribosepharm Brand of Carboplatin OR Blastocarb OR Lemery Brand of Carboplatin OR Nealorin OR Prasfarma Brand of Carboplatin OR 41575-94-4

3. ForRadiotherapy the following text words were used:

Radiotherapy OR radiotherapies OR Targeted Radiotherapies OR Targeted Radiotherapy OR radiother* OR (radiation AND therapy) OR "radiation therapy" OR "x ray therapy" OR ("x-ray" AND therapy) OR total body irradiation OR TBI OR whole-body irradiation OR Whole Body Irradiation OR Whole-Body Radiation OR Whole Body Radiation OR Whole-Body Radiations OR Total Body Irradiations OR Whole-Body Irradiations

4. ForNephrectomy the following text words were used:

Nephrectomy OR nephrectomies OR nephrect* OR nephron-sparing surgery

5. ForChildren the following text words were used:

infant OR infan* OR newborn OR newborn* OR new-born* OR baby OR baby* OR babies OR neonat* OR perinat* OR postnat* OR child OR child* OR schoolchild* OR schoolchild OR school child OR school child* OR kid OR kids OR toddler* OR adolescent OR adoles* OR teen* OR boy* OR girl* OR minors OR minors* OR underag* OR under ag* OR juvenil* OR youth* OR kindergar* OR puberty OR puber* OR pubescen* OR prepubescen* OR prepuberty* OR pediatrics OR pediatric* OR paediatric* OR peadiatric* OR schools OR nursery school* OR preschool* OR pre school* OR primary school* OR secondary school* OR elementary school* OR elementary school OR high school* OR highschool* OR school age OR schoolage OR school age* OR schoolage* OR infancy

6. For Childhood cancer the following text words were used:

leukemia OR leukemi* OR leukaemi* OR childhood ALL OR AML OR lymphoma OR lymphom* OR hodgkin OR hodgkin* OR T-cell OR B-cell OR non-hodgkin OR sarcoma OR sarcom* OR Ewing* OR osteosarcoma OR osteosarcom* OR wilms tumor OR wilms* OR nephroblastom* OR neuroblastoma OR neuroblastom* OR rhabdomyosarcoma OR rhabdomyosarcom* OR teratoma OR teratom* OR hepatoma OR hepatom* OR hepatoblastoma OR hepatoblastom* OR PNET OR medulloblastoma OR medulloblastom* OR PNET* OR primitive neuroectodermal tumors OR retinoblastoma OR retinoblastom* OR meningioma OR meningiom* OR glioma OR gliom* OR pediatric oncology OR paediatric oncology OR childhood cancer OR childhood tumor OR childhood tumors OR brain tumor* OR brain tumour* OR brain neoplasms OR central nervous system neoplasm OR central nervous system neoplasms OR central nervous system tumor* OR central nervous system tumour* OR brain cancer* OR brain neoplasm* OR intracranial neoplasm* OR acute lymphocytic leukemia

7. ForCancer the following text words were used:

cancer OR oncology OR oncolog* OR neoplasms OR neoplas* OR carcinoma OR carcinom* OR tumor OR tumour OR tumor* OR tumour* OR cancer* OR malignan* OR hematooncological OR hemato oncological OR hemato-oncological OR hematologic neoplasms OR hematolo* OR bone marrow transplantation OR bone marrow transplant* OR leukemia OR leukaemia OR lymphoma

8. ForNephrotoxicity the following text words were used:

glomerular filtration rate OR GFR OR Glomerular Filtration Rates OR glomerular OR glomerul* OR tubular OR tubula* OR renal tubular acidosis OR RTA OR Distal Renal Tubular Acidosis OR Classic Distal Renal Tubular Acidosis OR Proximal Renal Tubular Acidosis OR Type II Renal Tubular Acidosis OR renal acidosis OR renal insufficiency OR Renal Insufficiencies OR Kidney Insufficiency OR Kidney Insufficiencies OR microalbuminuria OR microalbumin*OR hypophosphatemia OR hypophosphataemia OR hypophospha* OR hypomagnes* OR hypomagnesemia OR hypomagnesaemia OR magnesium OR 7439-95-4 OR phosphate OR phosphates OR Inorganic Phosphates OR Phosphates, Inorganic OR Orthophosphate OR phosphorus OR Hyponatremia OR Hyponatremias OR hyponatraemia OR hyponatraemias OT hyponatrem* OR hyponatraem* OR Hypocitraturia OR Hypocitraturias OR Hypocitraturi* OR Potassium OR Potassium Ion Level OR Ion Level, Potassium OR Level, Potassium Ion OR 7440-09-7 OR Hypokalemia OR Hypokalemias OR Hypopotassemia OR Hypopotassemias OR hypokalemic OR hypokalem* OR hypokalaemic OR hypokalaem* OR Hypocalcemia OR hypocalcemias OR hypocalciuria OR hypocalciuri* OR hypocalcem* OR hypocalc* OR “hypocarbia” OR Proteinuria OR proteinurias OR proteinuri* OR albuminuria OR albuminurias OR albuminuri* OR Aminoaciduria OR Renal Aminoaciduria OR Renal Aminoacidurias OR Aminoacidurias, Renal OR Aminoaciduria, Renal OR aminoacidur* OR Glucosuria OR glucosurias OR glucosur* OR glycosuria OR glycosurias OR glycosuria, renal OR Fanconi syndrome OR Syndrome, Fanconi OR Renal Fanconi Syndrome OR Proximal Renal Tubular Dysfunction OR Fanconi Renotubular Syndrome OR Syndrome, Fanconi Renotubular OR De Toni-Debre-Fanconi Syndrome OR De Toni Debre Fanconi Syndrome OR Syndrome, De Toni-Debre-Fanconi OR Lignac-Fanconi Syndrome OR Lignac Fanconi Syndrome OR Syndrome, Lignac-Fanconi OR low molecular weight OR LMW OR alpha 1 microglobulin OR a1 microglobulin OR beta 2 microglobulin OR b2 microglobulin OR 2-Microglobulin, beta OR Thymotaxin OR retinol binding protein OR RBP OR Retinol Binding Proteins OR Binding Proteins, Retinol OR Retinoid Binding Proteins OR Binding Proteins, Retinoid OR Retinoid Binding Protein, F-Type OR Retinoid Binding Protein, F Type OR creatinine OR Krebiozen OR Creatinine Sulfate Salt OR Salt, Creatinine Sulfate OR Sulfate Salt, Creatinine OR 60-27-5 OR inulin OR 9005-80-5 OR "(51) Cr EDTA" OR 51chromium edetic acid OR “(99) Tc DTPA” OR Tc DTPA OR 65454-61-7[rn] OR Technetium Tc 99m Pentetate OR (99m)Tc-DMSA OR 99mTc(V)DMSA OR DMSA OR dimercaptosuccinic acid OR Technetium Tc 99m Dimercaptosuccinic Acid OR 65438-08-6 OR 99Tc-Succimer OR 99Tc Succimer OR 99mTc-Dimercaptosuccinate OR 99mTc Dimercaptosuccinate OR renal scan OR “kidney size” OR cystatin c OR gamma-Trace OR gamma Trace OR Post-gamma-Globulin OR Post gamma Globulin OR Cystatin 3 OR Neuroendocrine Basic Polypeptide OR Basic Polypeptide, Neuroendocrine OR CST3 gene OR cystatins OR cystatin* OR renal failure OR kidney failure OR Failure, Kidney OR Failures, Kidney OR Kidney Failures OR Failure, Renal OR Failures, Renal OR Renal Failures OR renal plasma flow OR Plasma Flow, Renal OR Flow, Renal Plasma OR RPF OR ERPF OR Renal clearance OR reabsorption OR re-absorption OR nephrotoxicity OR nephrotox* OR rickets OR rickets* OR Hypertension OR hypertens* OR hypertension, renal OR Hypertensions, Renal OR Renal Hypertension OR Renal Hypertensions OR Blood Pressure, High OR Blood Pressures, High OR High Blood Pressure OR High Blood Pressures OR blood pressure OR blood pressures OR blood pressur* OR diastolic pressure OR systolic pressure

9. Final search (1 or 2 or 3 or 4) and 5 and (6 or 7) and 8

The search was performed in title, abstract or keywords

[* = 1 or more characters]

 

Appendix 2. Search strategy for MEDLINE/PubMed

1. ForIfosfamide the following MeSH headings and text words were used:

ifosfamide OR iphosphamide OR iso-endoxan OR iso endoxan OR isophosphamide OR isofosfamide OR holoxan OR asta z 4942 OR NSC-109,724 OR NSC 109,724 OR NSC109,724 OR NSC 109724 OR NSC-109724 OR NSC109724 OR cyclic p-oxides OR ethylamines OR oxazines OR ifosfa* OR iphospha* OR isofosfa* OR isophospha* OR “br cl fosfamide” OR cyfos OR ifex OR “ifo-cell” OR ifolem OR ifomide OR ifosfamidum OR ifosforamide mustard OR ifoxan OR ipambr OR iphosphamid OR isophosphoramide bromide mustard OR isophosphoramide mustard OR mitoxana OR mjf 9325 OR naxamide OR seromida OR tronoxal OR z 4942

2. For Carboplatin and cisplatin the following MeSH headings and text words were used:

Platinum OR Platinum Compounds OR cis-diamminedichloroplatinum* OR cis-platinum OR cis platinum OR biocisplatinum OR dichlorodiammineplatinum OR nsc-119875 or NSC 119875 or NSC119875 OR platidiam OR platino OR platinol OR platinum* OR CDDP OR CACP OR cisplatin OR carboplatin OR abiplatin OR paraplatin OR CBDCA OR cis-DDP OR neoplatin OR platidiam OR cis-Diamminedichloroplatinum OR cis Diamminedichloroplatinum OR cis-Dichlorodiammineplatinum(II) OR platinum diamminodichloride OR Platinum Diamminodichloride OR Diamminodichloride, Platinum OR 15663-27-1 OR cis-Diammine(cyclobutanedicarboxylato)platinum II OR Carbosin OR Pharmachemie Brand of Carboplatin OR Carbotec OR Columbia Brand of Carboplatin OR Ercar OR Almirall Brand of Carboplatin OR JM-8 OR JM 8 OR JM8 OR Neocarbo OR Neocorp Brand of Carboplatin OR NSC-241240 OR NSC 241240 OR NSC241240 OR Bristol-Myers Squibb Brand of Carboplatin OR Carboplat OR Paraplatine OR Platinwas OR Chiesi Brand of Carboplatin OR Ribocarbo OR ribosepharm Brand of Carboplatin OR Blastocarb OR Lemery Brand of Carboplatin OR Nealorin OR Prasfarma Brand of Carboplatin OR 41575-94-4

3. ForRadiotherapy the following MeSH headings and text words were used:

Radiotherapy OR radiotherapy[sh] OR radiotherapies OR Radiotherapy, Targeted OR Radiotherapies, Targeted OR Targeted Radiotherapies OR Targeted Radiotherapy OR radiother* OR ("radiation"[All Fields] AND "therapy"[All Fields]) OR "radiation therapy"[All Fields] OR "x ray therapy"[All Fields] OR "x-ray therapy"[MeSH Terms] OR ("x-ray"[All Fields] AND "therapy"[All Fields]) OR "x-ray therapy"[All Fields] OR total body irradiation OR TBI OR whole-body irradiation OR Whole Body Irradiation OR Radiation, Whole-Body OR Radiation, Whole Body OR Whole-Body Radiation OR Radiations, Whole-Body OR Whole Body Radiation OR Whole-Body Radiations OR Irradiation, Total Body OR Irradiations, Total Body OR Total Body Irradiations OR Irradiation, Whole-Body OR Irradiation, Whole Body OR Irradiations, Whole-Body OR Whole-Body Irradiations

4. ForNephrectomy the following MeSH headings and text words were used:

Nephrectomy OR nephrectomies OR nephrect* OR nephron-sparing surgery

5. For Children the following MeSH headings and text words were used:

infant OR infan* OR newborn OR newborn* OR new-born* OR baby OR baby* OR babies OR neonat* OR perinat* OR postnat* OR child OR child* OR schoolchild* OR schoolchild OR school child OR school child* OR kid OR kids OR toddler* OR adolescent OR adoles* OR teen* OR boy* OR girl* OR minors OR minors* OR underag* OR under ag* OR juvenil* OR youth* OR kindergar* OR puberty OR puber* OR pubescen* OR prepubescen* OR prepuberty* OR pediatrics OR pediatric* OR paediatric* OR peadiatric* OR schools OR nursery school* OR preschool* OR pre school* OR primary school* OR secondary school* OR elementary school* OR elementary school OR high school* OR highschool* OR school age OR schoolage OR school age* OR schoolage* OR infancy OR schools, nursery OR infant, newborn

6. For Childhood cancer the following MeSH headings and text words were used:

leukemia OR leukemi* OR leukaemi* OR ALL OR AML OR lymphoma OR lymphom* OR hodgkin OR hodgkin* OR T-cell OR B-cell OR non-hodgkin OR sarcoma OR sarcom* OR sarcoma, Ewing's OR Ewing* OR osteosarcoma OR osteosarcom* OR wilms tumor OR wilms* OR nephroblastom* OR neuroblastoma OR neuroblastom* OR rhabdomyosarcoma OR rhabdomyosarcom* OR teratoma OR teratom* OR hepatoma OR hepatom* OR hepatoblastoma OR hepatoblastom* OR PNET OR medulloblastoma OR medulloblastom* OR PNET* OR neuroectodermal tumors, primitive OR retinoblastoma OR retinoblastom* OR meningioma OR meningiom* OR glioma OR gliom* OR pediatric oncology OR paediatric oncology OR childhood cancer OR childhood tumor OR childhood tumors OR brain tumor* OR brain tumour* OR brain neoplasms OR central nervous system neoplasm OR central nervous system neoplasms OR central nervous system tumor* OR central nervous system tumour* OR brain cancer* OR brain neoplasm* OR intracranial neoplasm* OR leukemia lymphocytic acute OR leukemia, lymphocytic, acute[mh]

7. For Cancer the following MeSH headings and text words were used:

cancer OR cancers OR cancer* OR oncology OR oncolog* OR neoplasm OR neoplasms OR neoplasm* OR carcinoma OR carcinom* OR tumor OR tumour OR tumor* OR tumour* OR tumors OR tumours OR malignan* OR malignant OR hematooncological OR hemato oncological OR hemato-oncological OR hematologic neoplasms OR hematolo*

8. For Nephrotoxicity the following MeSH headings and text words were used:

glomerular filtration rate OR GFR OR Filtration Rate, Glomerular OR Filtration Rates, Glomerular OR Glomerular Filtration Rates OR Rate, Glomerular Filtration OR Rates, Glomerular Filtration OR glomerular OR glomerul* OR tubular OR tubula* OR renal tubular acidosis OR RTA OR Acidosis, Renal Tubular OR Renal Tubular Acidosis, Type I OR Type I Renal Tubular Acidosis OR Distal Renal Tubular Acidosis OR Acidosis, Renal Tubular, Type I OR Classic Distal Renal Tubular Acidosis OR Renal Tubular Acidosis, Distal, Autosomal Dominant OR Renal Tubular Acidosis, Type II Acidosis, Renal Tubular, Type II OR Renal Tubular Acidosis, Proximal, with Ocular Abnormalities OR Proximal Renal Tubular Acidosis OR Type II Renal Tubular Acidosis OR renal acidosis OR renal insufficiency OR Renal Insufficiencies OR Kidney Insufficiency OR Insufficiency, Kidney OR Kidney Insufficiencies OR microalbuminuria OR microalbumin* OR hypophosphatemia OR hypophosphataemia OR hypophospha* OR hypomagnes* OR hypomagnesemia OR hypomagnesaemia OR magnesium OR 7439-95-4[rn] OR phosphate OR phosphates OR Inorganic Phosphates OR Phosphates, Inorganic OR Orthophosphate OR phosphorus OR Hyponatremia OR Hyponatremias OR hyponatraemia OR hyponatraemias OR hyponatrem* OR hyponatraem* OR Hypocitraturia OR Hypocitraturias OR Hypocitraturi* OR Potassium OR Potassium Ion Level OR Ion Level, Potassium OR Level, Potassium Ion OR 7440-09-7[rn] OR Hypokalemia OR Hypokalemias OR Hypopotassemia OR Hypopotassemias OR hypokalemic OR hypokalem* OR hypokalaemic OR hypokalaem* OR Hypocalcemia OR hypocalcemias OR hypocalciuria OR hypocalciuri* OR hypocalcem* OR hypocalc* OR “hypocarbia” OR Proteinuria OR proteinurias OR proteinuri* OR albuminuria OR albuminurias OR albuminuri* OR Aminoaciduria OR Renal Aminoaciduria OR Renal Aminoacidurias OR Aminoacidurias, Renal OR Aminoaciduria, Renal OR aminoacidur* OR Glucosuria OR glucosurias OR glucosur* OR glycosuria OR glycosurias OR glycosuria, renal OR Fanconi syndrome OR Syndrome, Fanconi OR Renal Fanconi Syndrome OR Proximal Renal Tubular Dysfunction OR Fanconi Renotubular Syndrome OR Syndrome, Fanconi Renotubular OR De Toni-Debre-Fanconi Syndrome OR De Toni Debre Fanconi Syndrome OR Syndrome, De Toni-Debre-Fanconi OR Lignac-Fanconi Syndrome OR Lignac Fanconi Syndrome OR Syndrome, Lignac-Fanconi OR low molecular weight OR LMW OR alpha 1 microglobulin OR a1 microglobulin OR beta 2 microglobulin OR b2 microglobulin OR 2-Microglobulin, beta OR Thymotaxin OR retinol binding protein OR RBP OR Retinol Binding Proteins OR Binding Proteins, Retinol OR Retinoid Binding Proteins OR Binding Proteins, Retinoid OR Retinoid Binding Protein, F-Type OR Retinoid Binding Protein, F Type OR creatinine OR Krebiozen OR Creatinine Sulfate Salt OR Salt, Creatinine Sulfate OR Sulfate Salt, Creatinine OR 60-27-5[rn] OR inulin OR 9005-80-5[rn] OR "(51) Cr EDTA" OR 51chromium edetic acid OR “(99) Tc DTPA” OR Tc DTPA OR 65454-61-7[rn] OR Technetium Tc 99m Pentetate OR (99m)Tc-DMSA OR 99mTc(V)DMSA OR DMSA OR dimercaptosuccinic acid OR Technetium Tc 99m Dimercaptosuccinic Acid OR 65438-08-6[rn] OR 99Tc-Succimer OR 99Tc Succimer OR 99mTc-Dimercaptosuccinate OR 99mTc Dimercaptosuccinate OR renal scan OR “kidney size” OR cystatin c OR gamma-Trace OR gamma Trace OR Post-gamma-Globulin OR Post gamma Globulin OR Cystatin 3 OR Neuroendocrine Basic Polypeptide OR Basic Polypeptide, Neuroendocrine OR CST3 gene OR cystatins OR cystatin* OR renal failure OR kidney failure OR Failure, Kidney OR Failures, Kidney OR Kidney Failures OR Failure, Renal OR Failures, Renal OR Renal Failures OR renal plasma flow OR Plasma Flow, Renal OR Flow, Renal Plasma OR RPF OR ERPF OR Renal clearance OR reabsorption OR re-absorption OR nephrotoxicity OR nephrotox* OR rickets OR rickets* OR Hypertension OR hypertens* OR hypertension, renal OR Hypertensions, Renal OR Renal Hypertension OR Renal Hypertensions OR Blood Pressure, High OR Blood Pressures, High OR High Blood Pressure OR High Blood Pressures OR blood pressure OR blood pressures OR blood pressur* OR diastolic pressure OR systolic pressure

9. Final search (1 OR 2 OR 3 OR 4) AND 5 AND (6 OR 7) AND 8

[* = 1 or more characters; mh = MeSH heading; rn = registry number]

 

Appendix 3. Search strategy for Embase (OVID)

1. ForIfosfamide the following Emtree terms and text words were used:

1. exp ifosfamide/
2. (ifosfamide or iphosphamide or iso-endoxan or iso endoxan or isophosphamide or isofosfamide or holoxan or asta z 4942 or NSC-109,724 or NSC 109,724 or NSC109,724 or NSC 109724 or NSC-109724 or NSC109724 or cyclic p-oxides or ethylamines or oxazines or ifosfa$ or iphospha$ or isofosfa$ or isophospha$).mp.
3. (br cl fosfamide or cyfos or ifex or ifo-cell or ifolem or ifomide or ifosfamidum or ifosforamide mustard or ifoxan or ipambr or iphosphamid or isophosphoramide bromide mustard or isophosphoramide mustard or mitoxana or mjf 9325 or naxamide or seromida or tronoxal or z 4942).mp.
4. 3778-73-2.rn.
5. or/1-4

2. ForCarboplatin and cisplatin the following Emtree terms and text words were used:

1. exp platinum/ or platinum.mp.
2. Platinum Compounds.mp. or exp platinum derivative/
3. (cis-diamminedichloroplatinum or cis diamminedichloroplatinum or cis-diamminedichloroplatinum$).mp.
4. cis-diamminedichloroplatinum II.mp. or exp cisplatin/
5. (cis-platinum or cis platinum or biocisplatinum).mp.
6. (dichlorodiammineplatinum or NSC-119875 or NSC 119875 or NSC119875).mp.
7. (platidiam or platino or platinol or platinum$).mp.
8. (CDDP or CACP or CBDCA or cis-DDP).mp.
9. (cisplatin or carboplatin or abiplatin or paraplatin or neoplatin or platidiam).mp.
10. (platinum diamminodichloride or Platinum Diamminodichloride).mp.
11. 15663-27-1.rn.
12. (cis-Diammine cyclobutanedicarboxylato platinum II or Carbosin).mp.
13. (carbotec or ercar or JM-8 or JM 8 or JM8 or neocarbo or NSC-241240 or NSC 241240 or NSC241240 or carboplat or paraplatine or platinwas or blastocarb or nealorin).mp.
14. 41575-94-4.rn.
15. or/1-14

3. ForRadiotherapy the following Emtree terms and text words were used:

1. exp radiotherapy/ or exp cancer radiotherapy/ or radiotherapy.mp.
2. radiotherapy.sh.
3. (radiotherapies or targeted radiotherapies or targeted radiotherapy or radiother$).mp.
4. ((radiation and therapy) or (radiation and x ray therapy)).mp.
5. (x ray therapy or (x ray and therapy)).mp
6. (total body irradiation or TBI).mp.
7. whole-body irradiation.mp. or exp whole body radiation/
8. (whole body irradiation or whole body radiation).mp.
9. (whole-body radiation or whole-body radiations or whole body radiations).mp.
10. (whole-body irradiations or Total Body Irradiation or Total Body Irradiations).mp.
11. or/1-10

4. ForNephrectomy the following Emtree terms and text words were used:

1. exp partial nephrectomy/ or exp nephrectomy/ or nephrectomy.mp.
2. (nephrectomies or nephrect$).mp.
3. nephron sparing surgery.mp. or exp nephron sparing surgery/
4. or/1-3

5. ForChildren the following Emtree terms and text words were used:

1. infant/ or infancy/ or newborn/ or baby/ or child/ or preschool child/ or school child/
2. adolescent/ or juvenile/ or boy/ or girl/ or puberty/ or prepuberty/ or pediatrics/
3. primary school/ or high school/ or kindergarten/ or nursery school/ or school/
4. or/1-3
5. (infant$ or newborn$ or (new adj born$) or baby or baby$ or babies or neonate$ or perinat$ or postnat$).mp.
6. (child$ or (school adj child$) or schoolchild$ or (school adj age$) or schoolage$ or (pre adj school$) or preschool$).mp.
7. (kid or kids or toddler$ or adoles$ or teen$ or boy$ or girl$).mp.
8. (minors$ or (under adj ag$) or underage$ or juvenil$ or youth$).mp.
9. (puber$ or pubescen$ or prepubescen$ or prepubert$).mp.
10. (pediatric$ or paediatric$ or peadiatric$).mp.
11. (school or schools or (high adj school$) or highschool$ or (primary adj school$) or (nursery adj school$) or (elementary adj school) or (secondary adj school$) or kindergar$).mp.
12. or/5-11
13. 4 or 12

6. ForChildhood cancer the following Emtree terms and text words were used:

1. (leukemia or leukemi$ or leukaemi$ or (childhood adj ALL) or acute lymphocytic leukemia).mp.
2. (AML or lymphoma or lymphom$ or hodgkin or hodgkin$ or T-cell or B-cell or non-hodgkin).mp.
3. (sarcoma or sarcom$ or Ewing$ or osteosarcoma or osteosarcom$ or wilms tumor or wilms$).mp.
4. (nephroblastom$ or neuroblastoma or neuroblastom$ or rhabdomyosarcoma or rhabdomyosarcom$ or teratoma or teratom$ or hepatoma or hepatom$ or hepatoblastoma or hepatoblastom$).mp.
5. (PNET or medulloblastoma or medulloblastom$ or PNET$ or neuroectodermal tumors or primitive neuroectodermal tumor$ or retinoblastoma or retinoblastom$ or meningioma or meningiom$ or glioma or gliom$).mp.
6. (pediatric oncology or paediatric oncology).mp.
7. ((childhood adj cancer) or (childhood adj tumor) or (childhood adj tumors) or childhood malignancy or (childhood adj malignancies) or childhood neoplasm$).mp.
8. ((pediatric adj malignancy) or (pediatric adj malignancies) or (paediatric adj malignancy) or (paediatric adj malignancies)).mp.
9. ((brain adj tumor$) or (brain adj tumour$) or (brain adj neoplasms) or (brain adj cancer$) or brain neoplasm$).mp.
10. (central nervous system tumor$ or central nervous system neoplasm or central nervous system neoplasms or central nervous system tumour$).mp.
11. intracranial neoplasm$.mp.
12. LEUKEMIA/ or LYMPHOMA/ or brain tumor/ or central nervous system tumor/ or teratoma/ or sarcoma/ or osteosarcoma/
13. nephroblastoma/ or neuroblastoma/ or rhabdomyosarcoma/ or hepatoblastoma/ or medulloblastoma/ or neuroectodermal tumor/ or retinoblastoma/ or meningioma/ or glioma/ or childhood cancer/
14. or/1-13

7. ForCancer the following Emtree terms and text words were used:

1. (cancer or cancers or cancer$).mp.
2. (oncology or oncolog$).mp. or exp oncology/
3. (neoplasm or neoplasms or neoplasm$).mp. or exp neoplasm/
4. (carcinoma or carcinom$).mp. or exp carcinoma/
5. (tumor or tumour or tumor$ or tumour$ or tumors or tumours).mp. or exp tumor/
6. (malignan$ or malignant).mp.
7. (hematooncological or hemato oncological or hemato-oncological or hematologic neoplasms or hematolo$).mp. or exp hematologic malignancy/
8. or/1-7

8. For Nephrotoxicity the following Emtree terms and text words were used:

1. glomerular filtration rate.mp. or exp glomerulus filtration rate/
2. (GFR or glomerular filtration rates).mp.
3. (glomerular or glomerul$).mp.
4. (tubular or tubula$).mp.
5. exp tubular dysfunction/ or tubular.mp.
6. renal tubular acidosis.mp. or exp kidney tubule acidosis/
7. (RTA or renal tubular acidosis or type I renal tubular acidosis or distal renal tubular acidosis or classic distal renal tubular acidosis).mp.
8. (type II renal tubular acidosis or proximal renal tubular acidosis or renal acidosis).mp.
9. renal insufficiency.mp.
10. (renal insufficiencies or kidney insufficiency or kidney insufficiencies).mp.
11. (microalbuminuria or microalbumin$).mp.
12. exp microalbuminuria/
13. hypophosphatemia.mp. or exp hypophosphatemia/
14. (hypophosphataemia or hypophospha$).mp.
15. hypomagnesemia.mp. or exp hypomagnesemia/
16. (hypomagnes$ or hypomagnesaemia or magnesium).mp. or 7439-95-4.rn.
17. phosphate.mp. or exp phosphate/
18. (phosphates or inorganic phosphates or orthophosphate or phosphorus).mp.
19. Hyponatremia.mp. or exp hyponatremia/
20. (hyponatremias or hyponatraemia or hyponatraemias or hyponatrem$ or hyponatraem$).mp.
21. exp hypocitraturia/ or hypocitraturia.mp.
22. (hypocitraturias or hypocitraturi$).mp.
23. exp potassium/ or Potassium.mp.
24. Potassium Ion Level.mp. or 7440-09-7.rn.
25. Hypokalemia.mp. or exp hypokalemia/
26. (hypokalemias or hypopotassemia or hypopotassemias or hypokalemic or hypokalem$ or hypokalaemic or hypokalaem$).mp.
27. Hypocalcemia.mp. or exp hypocalcemia/
28. (hypocalcemias or hypocalciuria or hypocalciuri$ or hypocalcem$ or hypocalc$ or hypocarbia).mp.
29. Proteinuria.mp. or exp proteinuria/
30. (proteinurias or proteinuri$).mp.
31. albuminuria.mp. or exp albuminuria/
32. (albuminurias or albuminuri$).mp.
33. aminoaciduria.mp. or exp aminoaciduria/
34. (Renal Aminoaciduria or Renal Aminoacidurias or aminoacidur$).mp.
35. glucosuria.mp. or exp glucosuria/
36. (glucosurias or glucosur$ or glycosuria or glycosurias).mp.
37. Fanconi syndrome.mp. or exp Fanconi renotubular syndrome/
38. (renal Fanconi syndrome or proximal renal tubular dysfunction or Fanconi renotubular syndrome).mp.
39. (De Toni-Debre-Fanconi Syndrome or De Toni Debre Fanconi Syndrome or Lignac-Fanconi Syndrome or Lignac Fanconi Syndrome).mp.
40. (low molecular weight or LMW or alpha 1 microglobulin or a1 microglobulin or beta 2 microglobulin or b2 microglobulin or thymotaxin).mp.
41. retinol binding protein.mp. or exp retinol binding protein/
42. (RBP or retinol binding proteins or retinoid binding proteins or F type retinoid binding protein).mp.
43. creatinine.mp. or exp creatinine/
44. (krebiozen or creatinine sulfate salt).mp. or 60-27-5.rn.
45. exp inulin clearance/ or exp inulin/ or inulin.mp. or 9005-80-5.rn.
46. (51 Cr EDTA or 51chromium edetic acid or 99 Tc DTPA or Tc DTPA).mp. or 65454-61-7.rn.
47. Technetium Tc 99m Pentetate.mp. or exp pentetate technetium tc 99m/
48. exp succimer tc 99m/ or exp succimer/ or (99m Tc-DMSA or 99mTc V DMSA or DMSA).mp.
49. (dimercaptosuccinic acid or Technetium Tc 99m Dimercaptosuccinic Acid).mp. or 65438-08-6.rn.
50. (99Tc-Succimer or 99Tc Succimer or 99mTc-Dimercaptosuccinate or 99mTc Dimercaptosuccinate).mp.
51. (renal scan or kidney size).mp.
52. cystatin.mp. or exp cystatin/
53. (gamma-Trace or gamma Trace or Post-gamma-Globulin or Post gamma Globulin or Cystatin 3 or Neuroendocrine Basic Polypeptide).mp.
54. (CST3 gene or cystatins or cystatin$).mp.
55. renal failure.mp. or exp kidney failure/
56. (kidney failure or kidney failures or renal failures).mp.
57. renal plasma flow.mp. or exp kidney plasma flow/
58. (RPF or ERPF or Renal clearance or reabsorption or re-absorption or nephrotoxicity or nephrotox$ or rickets or rickets$).mp.
59. exp hypertension/ or (Hypertension or hypertens$).mp.
60. (Renal Hypertension or Renal Hypertensions or Renal Hypertension$).mp. or exp renovascular hypertension/
61. (High Blood Pressure or High Blood Pressures or High Blood Pressure$).mp.
62. (blood pressure or blood pressures or blood pressure$).mp. or exp blood pressure/
63. (diastolic pressure or systolic pressure).mp.
64. or/1-63

9. Final search (1 or 2 or 3 or 4) and 5 and (6 or 7) and 8

[mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name; rn = registry number; $ = 1 or more characters; / = Emtree term]

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

Sebastiaan Knijnenburg designed the study and wrote the protocol. He identified studies meeting the inclusion criteria (both by initial screening of the titles and abstract and by screening of the full-text articles). He performed data extraction and the risk of bias assessment of included studies, analysed the data and interpreted the results. He wrote and revised the manuscript.

Renée L Mulder designed the study and critically reviewed the protocol. She identified studies meeting the inclusion criteria (part of the initial screening and all full-text articles). She performed data extraction and the risk of bias assessment of included studies. She critically revised the manuscript.

Antoinette Schouten-Van Meeteren critically reviewed the protocol. She identified parts of studies that met the inclusion criteria. She critically reviewed the manuscript.

Arend Bökenkamp critically reviewed the protocol. He identified parts of studies that met the inclusion criteria. He critically reviewed the manuscript.

Hester Blufpand identified parts of studies that met the inclusion criteria. She critically reviewed the manuscript.

Eline van Dulmen-den Broeder identified parts of studies that met the inclusion criteria. She critically reviewed the manuscript.

Margreet A Veening identified parts of studies that met the inclusion criteria. She critically reviewed the manuscript.

Leontien CM Kremer designed the study and critically reviewed the protocol. She identified parts of studies that met the inclusion criteria and contributed to the interpretation of results. She critically reviewed the manuscript.

Monique WM Jaspers critically reviewed the protocol. She identified parts of studies that met the inclusion criteria. She critically reviewed the manuscript.

All authors approved the final version of the manuscript.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

Leontien CM Kremer is author of several studies included in this review.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms
 

Internal sources

  • Dutch Cochrane Centre, Netherlands.

 

External sources

  • Tom Voûte Fund, Netherlands.
    Financial support

 

Differences between protocol and review

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

The protocol stated that we would include all renal outcome measurements as reported by the authors. During the data synthesis of this review, it became clear that the heterogeneity in reported outcomes of all included studies was very high. After careful deliberation about whether it would be useful to report on all these outcomes, we decided that this would add too little information. Instead, we focused on outcomes that were reported most often and that had the highest clinical relevance. We added a sentence to state that we included studies reporting on composite outcome measures covering one of the included outcomes. Additionally, we included only studies investigating hypertension when they had a clear focus on renal function, to prevent the inclusion of studies focusing on metabolic abnormalities.

In the Data Extraction section, we removed two points in comparison with the protocol: The number of participants treated with a specific combination of potentially nephrotoxic treatment (point 3.f. in the protocol) and the number of participants treated with potentially nephrotoxic antibiotics (point 3.g. in the protocol) were both reported so sporadically that systematic extraction had no use.

Some changes regarding the risk of bias assessment were made. We added the word "relevant" to the definition of a well-defined study group in  Table 1: "if the treatment regimen was specified, including relevant cumulative chemotherapy and radiotherapy doses." Chemotherapy and radiotherapy dosages were assessed as relevant when a study explicitly stated that that potentially nephrotoxic therapy was part of the study's treatment protocol. For the definition of a well-defined outcome, we added "for more than 50% of the included outcomes."

We stated that we would (hand)search the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2005 to 2010), the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (from 2004 to 2010) and the European Symposium on Late Complications After Childhood Cancer 2009 (from 2007 to 2009). We also started to search for information about trials not registered in MEDLINE, EMBASE or CENTRAL, published or unpublished, by searching the reference lists of relevant articles and review articles and by scanning the International Standard Randomised Controlled Trials Number (ISRCTN) register and the National Institutes of Health (NIH) register for ongoing trials: http://www.controlled-trials.com. However, because of the sheer volume of references retrieved from the online databases, we did not have resources available to search the aforementioned sources.

We adapted the risk of bias assessment criteria for an adequate follow-up and for a well-defined outcome. The original definition of low risk of follow-up bias was as follows: if the outcome was assessed at the end date of the study for 60% to 90% of the study group, or if the outcome was assessed for more than 90% of the study group but with an unknown end date. Because no straightforward definition is available for the end date of the study, we decided to change this risk of bias item. The new definition of low risk of follow-up bias is as follows: if the outcome was assessed for more than 90% of the study group of interest (++), or if the outcome was assessed for 60% to 90% of the study group of interest (+). In the protocol we had not yet specified the definition of a well-defined outcome. The definition is as follows: if the outcome definition was objective and precise, that is, if the upper or lower limits of normal for renal function tests were described in the definition of renal adverse effects.

 

Index terms

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Contributions of authors
  12. Declarations of interest
  13. Sources of support
  14. Differences between protocol and review
  15. Index terms

Medical Subject Headings (MeSH)

*Survivors; Antineoplastic Agents [*adverse effects]; Carboplatin [adverse effects]; Cisplatin [adverse effects]; Glomerular Filtration Rate [drug effects; physiology; radiation effects]; Hypertension [epidemiology; etiology]; Hypophosphatemia [epidemiology; etiology]; Ifosfamide [adverse effects]; Magnesium Deficiency [epidemiology; etiology]; Nephrectomy [*adverse effects]; Proteinuria [epidemiology; etiology]; Radiotherapy [*adverse effects]; Renal Insufficiency, Chronic [epidemiology; *etiology]; Risk Factors

MeSH check words

Adult; Child; Humans

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Aronson 2011 {published data only}
Bardi 2004 {published data only}
Bergeron 2005 {published data only}
Bolling 2010 {published data only}
  • Bolling T, Ernst I, Pape H, Martini C, Rube C, Timmermann B, et al. Dose-volume analysis of radiation nephropathy in children: preliminary report of the RiSK Consortium. International Journal of Radiation Oncology, Biology and Physics 2010;80(3):840-4.
Breslow 2005 {published data only}
  • Breslow NE, Collins AJ, Ritchey ML, Grigoriev YA, Peterson SM, Green DM. End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. Journal of Urology 2005;174:1972-5.
Brock 1991 {published data only}
Cardous-Ubbink 2010 {published data only}
  • Cardous-Ubbink MC, Geenen MM, Schade KJ, Heinen RC, Caron HN, Kremer LC, et al. Hypertension in long-term survivors of childhood cancer: a nested case-control study. European Journal of Cancer 2010;46:782-90.
Chevallier 1997 {published data only}
  • Chevallier C, Hadj-Aissa A, Brunat-Mentigny M, Faraj G, Schell M, Cochat P. Renal function after nephrectomy for Wilms' tumor [Fonction rénale après néphrectomie pour tumeur de Wilms]. Archives de Pediatrie 1997;4:639-44.
Cosentino 1993 {published data only}
  • Cosentino CM, Raffensperger JG, Luck SR, Reynolds M, Sherman JO, Reyes-Mugica M. A 25-year experience with renal tumors of childhood. Journal of Pediatric Surgery 1993;28:1350-4.
Cozzi 2005 {published data only}
  • Cozzi F, Schiavetti A, Morini F, Zani A, Gambino M, Donfrancesco C, et al. Renal function adaptation in children with unilateral renal tumors treated with nephron sparing surgery or nephrectomy. Journal of Urology 2005;174:1404-8.
de Graaf 1996 {published data only}
  • de Graaf SS, van Gent H, Reitsma-Bierens WC, van Luyk WH, Dolsma WV, Postma A. Renal function after unilateral nephrectomy for Wilms' tumour: the influence of radiation therapy. European Journal of Cancer 1996;32A:465-9.
Di Tullio 1996 {published data only}
English 1999 {published data only}
Ferrari 2005 {published data only}
  • Ferrari S, Pieretti F, Verri E, Tolentinis L, Cesari M, Versari M, et al. Prospective evaluation of renal function in pediatric and adult patients treated with high-dose ifosfamide, cisplatin and high-dose methotrexate. Anticancer Drugs 2005;16(7):733-8.
Finklestein 1993 {published data only}
  • Finklestein JZ, Norkool P, Green DM, Breslow N, D'Angio GJ. Diastolic hypertension in Wilms' tumor survivors: a late effect of treatment? A report from the National Wilms' Tumor Study Group. American Journal of Clinical Oncology 1993;16(3):201-5.
Frisk 2002 {published data only}
  • Frisk P, Bratteby LE, Carlson K, Lonnerholm G. Renal function after autologous bone marrow transplantation in children: a long-term prospective study. Bone Marrow Transplantation 2002;29(2):129-36.
Frisk 2007 {published data only}
Fujieda 2009 {published data only}
  • Fujieda M, Matsunaga A, Hayashi A, Tauchi H, Chayama K, Sekine T. Children's toxicology from bench to bed-Drug-induced renal injury (2): nephrotoxicity induced by cisplatin and ifosfamide in children. Journal of Toxicological Science 2009;34(Suppl 2):251-7.
Geenen 2010 {published data only}
Hamilton 2011 {published data only}
  • Hamilton TE, Ritchey ML, Haase GM, Argani P, Peterson SM, Anderson JR, et al. The management of synchronous bilateral Wilms tumor: a report from the National Wilms Tumor Study Group. Annals of Surgery 2011;253(5):1004-10.
Hoffmeister 2010 {published data only}
  • Hoffmeister PA, Hingorani SR, Storer BE, Baker KS, Sanders JE. Hypertension in long-term survivors of pediatric hematopoietic cell transplantation. Biology of Blood and Marrow Transplantion 2010;16(4):515-24.
Indolfi 2001 {published data only}
Kantor 1989 {published data only}
  • Kantor AF, Li FP, Janov AJ, Tarbell NJ, Sallan SE. Hypertension in long-term survivors of childhood renal cancers. Journal of Clinical Oncology 1989;7(7):912-5.
Kubiak 2004 {published data only}
  • Kubiak R, Gundeti M, Duffy PG, Ransley PG, Wilcox DT. Renal function and outcome following salvage surgery for bilateral Wilms' tumor. Journal of Pediatric Surgery 2004;39(11):1667-72.
Laverdiere 2005 {published data only}
Loebstein 1999 {published data only}
  • Loebstein R, Atanackovic G, Bishai R, Wolpin J, Khattak S, Hashemi G, et al. Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children. Journal of Clinical Pharmacology 1999;39(5):454-61.
Makipernaa 1991 {published data only}
Mancini 1996 {published data only}
  • Mancini AF, Rosito P, Salmi S, Rondelli R, Alvisi P, Leopardi G, et al. Renal function in patients previously treated for Wilms tumor in infancy. Rivista Italiana di Pediatria 1996;22:882-8.
Mpofu 1992 {published data only}
Oberlin 2009 {published data only}
  • Oberlin O, Fawaz O, Rey A, Niaudet P, Ridola V, Orbach D, et al. Long-term evaluation of Ifosfamide-related nephrotoxicity in children. Journal of Clinical Oncology 2009;27(32):5350-5.
Othman 2002 {published data only}
Patzer 2001 {published data only}
  • Patzer L, Ringelmann F, Kentouche K, Fuchs D, Zintl F, Brandis M, et al. Renal function in long-term survivors of stem cell transplantation in childhood. A prospective trial. Bone Marrow Transplantion 2001;27(3):319-27.
Paulino 2000 {published data only}
  • Paulino AC, Wen BC, Brown CK, Tannous R, Mayr NA, Zhen WK, et al. Late effects in children treated with radiation therapy for Wilms' tumor. International Journal of Radiation Oncology, Biology and Physics 2000;46(5):1239-46.
Prasad 1996 {published data only}
Rossi 1993 {published data only}
  • Rossi R, Ehrich JH. Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. European Journal of Clinical Pharmacology 1993;44 Suppl 1:S43-5.
Rossi 1994 {published data only}
Rossi 1994a {published data only}
  • Rossi R, Godde A, Kleinebrand A, Riepenhausen M, Boos J, Ritter J, et al. Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients. Journal of Clinical Oncology 1994;12(1):159-65.
Rossi 1994b {published data only}
Rossi 1997 {published data only}
  • Rossi R, Schafers P, Pleyer J, Postler C, Boos J, Jurgens H. The influence of short versus continuous ifosfamide infusion on the development of renal tubular impairment. International Journal of Pediatric Hematology/Oncology 1997;4:393-9.
Rossi 1999 {published data only}
Sasso 2010 {published data only}
  • Sasso G, Greco N, Murino P, Sasso FS. Late toxicity in Wilms tumor patients treated with radiotherapy at 15 years of median follow-up. Journal of Pediatric Hematology and Oncology 2010;32(7):e264-7.
Schell 1995 {published data only}
  • Schell M, Cochat P, Hadj-Aissa A, Bouffet E, Dubourg L, Brunat-Mentigny M. Renal function following unilateral nephrectomy for neuroblastoma and Wilms' tumour. Pediatric Nephrology 1995;9:579-82.
Skinner 2009 {published data only}
  • Skinner R, Parry A, Price L, Cole M, Craft AW, Pearson AD. Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors. European Journal of Cancer 2009;45(18):3213-9.
Skinner 2010 {published data only}
Srinivas 1998 {published data only}
  • Srinivas M, Agarwala S, Padhy AK, Gupta AK, Bajpai M, Bhatnagar V, et al. Somatic growth and renal function after unilateral nephrectomy for Wilms' tumor. Pediatric Surgery International 1998;14(3):185-8.
Stefanowicz 2009 {published data only}
  • Stefanowicz J, Owczuk R, Sierota D, Kaczorowska-Hac B, Balcerska A. Does antineoplasm treatment decrease the glomerular filtration rate in children?. Kidney and Blood Pressure Research 2009;32:194-9.
Stefanowicz 2010 {published data only}
Stefanowicz 2011 {published data only}
  • Stefanowicz J, Kosiak M, Romanowicz G, Owczuk R, Adamkiewicz-Drozynska E, Balcerska A. Glomerular filtration rate and prevalence of chronic kidney disease in Wilms' tumour survivors. Pediatric Nephrology 2011;26(5):759-66.
Stohr 2007 {published data only}
Stohr 2007a {published data only}
Trahair 2007 {published data only}
  • Trahair TN, Vowels MR, Johnston K, Cohn RJ, Russell SJ, Neville KA, et al. Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation. Bone Marrow Transplantation 2007;40(8):741-6.
Trobs 2001 {published data only}
  • Trobs RB, Hansel M, Friedrich T, Bennek J. A 23-year experience with malignant renal tumors in infancy and childhood. European Journal of Pediatric Surgery 2001;11(2):92-8.
Van Dijk 2010 {published data only}
  • Van Dijk IWEM, Oldenburger F, Cardous-Ubbink MC, Geenen MM, Heinen RC, de Kraker J, et al. Evaluation of late adverse events in long-term Wilms' tumor survivors. International Journal of Radiation Oncology Biology Physics 2010;78:370-8.
Van Why 1991 {published data only}
  • Van Why SK, Friedman AL, Wei LJ, Hong R. Renal insufficiency after bone marrow transplantation in children. Bone Marrow Transplantation 1991;7(5):383-8.
von Schweinitz 1997 {published data only}
  • von Schweinitz D, Byrd DJ, Hecker H, Weinel P, Bode U, Burger D, et al. Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology. European Journal of Cancer 1997;33(8):1243-9.
Weirich 2004 {published data only}
  • Weirich A, Ludwig R, Graf N, Abel U, Leuschner I, Vujanic GM, et al. Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity. Annals of Oncology 2004;15(5):808-20.
Wikstad 1986 {published data only}

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Abboud 2009 {published data only}
  • Abboud I, Porcher R, Robin M, de Latour RP, Glotz D, Socie G, et al. Chronic kidney dysfunction in patients alive without relapse 2 years after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation 2009;15:1251-7.
Abd-El-Aal 2005 {published data only}
  • Abd-El-Aal HH, Mokhtar MM, Habib EE, El-Kashef AT, Fahmy ES. Medulloblastoma: conventional radiation therapy in comparison to chemo radiation therapy in the post-operative treatment of high-risk patients. Journal of the Egyptian National.Cancer Institute 2005;17:301-7.
Abedi 1990 {published data only}
  • Abedi MR, Backman L, Bostrom L, Lindback B, Ringden O. Markedly increased serum erythropoietin levels following conditioning for allogeneic bone marrow transplantation. Bone Marrow Transplantation 1990;6:121-6.
Aksnes 2009 {published data only}
Aleksa 2001 {published data only}
Aleksa 2004 {published data only}
  • Aleksa K, Ito S, Koren G. Renal-tubule metabolism of ifosfamide to the nephrotoxic chloroacetaldehyde: pharmacokinetic modeling for estimation of intracellular levels. Journal of Laboratory and Clinical Medicine 2004;143:159-62.
Amato 1995 {published data only}
Anderson 1979 {published data only}
  • Anderson T, Javadpour N, Schilsky R, Barlock A, Young RC. Chemotherapy for testicular cancer: current status of the National Cancer Institute Combined Modality Trial. Cancer Treatment Reports 1979;63:1687-92.
Anderson 2010 {published data only}
Antman 1989 {published data only}
  • Antman KH, Ryan L, Elias A, Sherman D, Grier HE. Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma. Journal of Clinical Oncology 1989;7:126-31.
Arai 1998 {published data only}
  • Arai A, Sakamaki H, Tanikawa S, Akiyama H, Onozawa Y, Okamoto R, et al. [Hemolytic uremic syndrome after bone marrow transplantation]. Rinsho Ketsueki 1998;39:422-6.
Arakelyan 2010 {published data only}
Argueso 1992 {published data only}
  • Argueso LR, Ritchey ML, Boyle ET Jr, Milliner DS, Bergstralh EJ, Kramer SA. Prognosis of children with solitary kidney after unilateral nephrectomy. Journal of Urology 1992;148:747-51.
Ariceta 1997 {published data only}
Arjmandi-Rafsanjani 2008 {published data only}
  • Arjmandi-Rafsanjani K, Hooman N, Vosoug P. Renal function in late survivors of Iranian children with cancer: single centre experience. Indian Journal of Cancer 2008;45:154-7.
Arndt 1997 {published data only}
  • Arndt C, Tefft M, Gehan E, Anderson J, Jenson M, Link M, et al. A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study. Journal of Pediatric Hematology and Oncology 1997;19:124-9.
Arndt 1999 {published data only}
Arriagada 2009 {published data only}
Ashraf 1994 {published data only}
Bacci 2002 {published data only}
  • Bacci G, Ferrari S, Longhi A, Picci P, Mercuri M, Alvegard TA, et al. High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study. Journal of Chemotherapy 2002;14:198-206.
Baker 2010 {published data only}
  • Baker KS, Bresters D, Sande JE. The burden of cure: long-term side effects following hematopoietic stem cell transplantation (HSCT) in children. Pediatric Clinics of North America 2010;57:323-42.
Barahmani 2009 {published data only}
  • Barahmani N, Carpentieri S, Li XN, Wang T, Cao Y, Howe L, et al. Glutathione S-transferase M1 and T1 polymorphisms may predict adverse effects after therapy in children with medulloblastoma. Neuro-Oncology 2009;11:292-300.
Bardi 2004a {published data only}
  • Bardi E, Bobok I, Olah AV, Olah E, Kappelmayer J, Kiss C. Cystatin C is a suitable marker of glomerular function in children with cancer. Pediatric Nephrology 2004;19:1145-7.
Bardi 2007 {published data only}
  • Bardi E, Bobok I, Olah V, Kappelmayer J, Kiss C. Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer. Pathology & Oncology Research 2007;13:249-53.
Bashir 2007 {published data only}
Baudoin 1993 {published data only}
Berg 2006 {published data only}
Beyzadeoglu 2008 {published data only}
  • Beyzadeoglu M, Arpaci F, Surenkok S, Ozyigit G, Oysul K, Caglar K, et al. Acute renal toxicity of 2 conditoning regimens in patients undergoing autologous peripheral blood stem-cell transplantation: Total body irradiation-cyclophosphamide versus ifosfamide, carboplatin, etoposide. Saudi Medical Journal 2008;29:832-6.
Bhatia 2003 {published data only}
Bhisitkul 1991 {published data only}
Boddy 1996 {published data only}
  • Boddy AV, English M, Pearson AD, Idle JR, Skinner R. Ifosfamide nephrotoxicity: limited influence of metabolism and mode of administration during repeated therapy in paediatrics. European Journal of Cancer 1996;32A:1179-84.
Bodei 2008 {published data only}
  • Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. European Journal of Nuclear Medicine and Molecular Imaging 2008;35:1847-56.
Bonsib 2010 {published data only}
  • Bonsib SM, Pei Y. The non-neoplastic kidney in tumor nephrectomy specimens: what can it show and what is important?. Advances in Anatomic Pathology 2010;17:235-50.
Bosl 1988 {published data only}
  • Bosl GJ, Geller NL, Bajorin D, Leitner SP, Yagoda A, Golbey RB, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. Journal of Clinical Oncology 1988;6:1231-8.
Brade 1991 {published data only}
Bradley 1998 {published data only}
  • Bradley J, Reft C, Goldman S, Rubin C, Nachman J, Larson R, et al. High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications. International Journal of Radiation Oncology Biology Physics 1998;40:391-6.
Brock 1992 {published data only}
  • Brock PR, Yeomans EC, Bellman SC, Pritchard J. Cisplatin therapy in infants: short and long-term morbidity. British Journal of Cancer 1992;Suppl 18:S36-40.
Bunjes 2002 {published data only}
Bürger 1985 {published data only}
  • Bürger D, Moorman-Voestermans CG, Mildenberger H, Lemerle J, Voute PA, Tournade MF, et al. The advantages of preoperative therapy in Wilms' tumour. A summarised report on clinical trials conducted by the International Society of Paediatric Oncology (SIOP). Zeitschrift für Kinderchirurgie 1985;40:170-5.
Burk 1990 {published data only}
Cachat 1996 {published data only}
  • Cachat F, Guignard J-P. Chemotherapy in children and renal side-effects. Revue Medicale de la Suisse Romande 1996;116:985-93.
Cai 2010 {published data only}
  • Cai J-Y, Tang J-Y, Pan C, Xu M, Xue H-L, Zhou M, et al. Results of RS-99 protocol for childhood solid tumors. World Journal of Pediatrics 2010;6:43-9.
Carlson 1993 {published data only}
  • Carlson K, Smedmyr B, Hagberg H, Oberg G, Simonsson B. Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, ara-C, cyclophosphamide) +/- TBI and autologous BMT for malignant lymphomas. Bone Marrow Transplantation 1993;11:205-8.
Castleberry 1991 {published data only}
  • Castleberry RP, Kun LE, Shuster JJ, Altshuler G, Smith IE, Nitschke R, et al. Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma. Journal of Clinical Oncology 1991;9:789-95.
Chen 2007 {published data only}
  • Chen XF, Zhou FJ, Han H, Qin ZK, Liu ZW, Yu SL, et al. [Transabdominal radical nephrectomy for renal cell carcinoma: an experience on 155 patients]. Ai.Zheng 2007;26:528-32.
Cheng 2008 {published data only}
  • Cheng JC, Schultheiss TE, Wong JY. Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation. International Journal of Radiation Oncology, Biology, Physics 2008;71:1436-43.
Chow 2007 {published data only}
Chow 2010 {published data only}
  • Chow EJ, Simmons JH, Roth CL, Baker KS, Hoffmeister PA, Sanders JE, et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biology of Blood and Marrow Transplantation 2010;16(12):1674-81.
Chow 2011 {published data only}
  • Chow EJ, Mueller BA, Baker KS, Cushing-Haugen KL, Flowers ME, Martin PJ, et al. Cardiovascular hospitalizations and mortality among recipients of hematopoietic stem cell transplantation. Annals of Internal Medicine 2011;155(1):21-32.
Cohen 1995 {published data only}
Cohen 2008 {published data only}
  • Cohen EP, Irving AA, Drobyski WR, Klein JP, Passweg J, Talano JA, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. International Journal of Radiation Oncology, Biology, Physics 2008;70:1546-51.
Cole 1994 {published data only}
Conn 1972 {published data only}
  • Conn JW, Cohen EL, McDonald WJ, Blough WM Jr, Lucas CP, Mayor GH, et al. The syndrome of hypertension, hyperreninemia and secondary aldosteronism associated with renal juxtaglomerular cell tumor (primary reninism). Transactions of the Association of American Physicians 1972;85:353-68.
Cosset 1994 {published data only}
  • Cosset JM, Socie G, Dubray B, Girinsky T, Fourquet A, Gluckman E. Single dose versus fractionated total body irradiation before bone marrow transplantation: radiobiological and clinical considerations. International Journal of Radiation Oncology, Biology, Physics 1994;30:477-92.
Couto-Silva 2001 {published data only}
  • Couto-Silva AC, Trivin C, Thibaud E, Esperou H, Michon J, Brauner R. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplantation 2001;28:67-75.
Coze 1997 {published data only}
  • Coze C, Hartmann O, Michon J, Frappaz D, Dusol F, Rubie H, et al. NB87 induction protocol for stage 4 neuroblastoma in children over 1 year of age: a report from the French Society of Pediatric Oncology. Journal of Clinical Oncology 1997;15:3433-40.
Cozzi 1997 {published data only}
Cozzi 2001 {published data only}
Cozzi 2007 {published data only}
  • Cozzi F, Zani A, Schiavetti A, Morini F, DeGaetano V, Matrunola M, et al. Compensatory renal growth in children with unilateral renal tumor treated by nephron-sparing surgery or nephrectomy. European Journal of Pediatric Surgery 2007;17:382-6.
Crist 2001 {published data only}
  • Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. Journal of Clinical Oncology 2001;19:3091-102.
Crom 1981 {published data only}
Culine 1994 {published data only}
  • Culine S, Lhomme C, Kattan J, Duvillard P, Michel G, Droz J-P. Long-term results of two VAB-like regimens (vinblastine + actinomycin-D + bleomycin + cyclophosphamide + cisplatin) in malignant germ cell tumours of the ovary. European Journal of Cancer Part A: General Topics 1994;30:1239-44.
Curigliano 2009 {published data only}
  • Curigliano G, Spitaleri G, Magni E, Lorizzo K, De Cobelli O, Locatelli M, et al. Cisplatin, etoposide and continuous infusion bleomycin in patients with testicular germ cell tumors: efficacy and toxicity data from a retrospective study. Journal of Chemotherapy 2009;21:687-92.
D'Angio 1976 {published data only}
D'Aoust 1979 {published data only}
De Gislain 1990 {published data only}
  • De Gislain C, Dumas M, D'Athis P, Chapuis T, Mayer F, Fargeot P, et al. Plasma creatinine evolution in long term cisplatin therapy. Influence of drug addosications. Therapie 1990;45:423-7.
de Kraker 1989 {published data only}
  • de Kraker J, Voute PA. Experience with ifosfamide in paediatric tumours. Cancer Chemotherapy and Pharmacology 1989;24 Suppl 1:S28-9.
Delpassand 2008 {published data only}
  • Delpassand ES, Sims-Mourtada J, Saso H, Azhdarinia A, Ashoori F, Torabi F, et al. Safety and efficacy of radionuclide therapy with high-activity In-111 pentetreotide in patients with progressive neuroendocrine tumors. Cancer Biotherapy and Radiopharmaceuticals 2008;23:292-300.
Demchak 1991 {published data only}
  • Demchak PA, Mier JW, Robert NJ, O'Brien K, Gould JA, Atkins MB. Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. Journal of Clinical Oncology 1991;9:1821-30.
Detaille 2007 {published data only}
  • Detaille T, Anslot C, de Clety SC. Acute kidney injury in paediatric bone marrow patients. Acta Clinica Belgica 2007;2 Suppl:401-4.
Dhaliwal 1980 {published data only}
  • Dhaliwal RS, Adelman RD, Turner E, Russo JC, Ruebner B. Radiation nephritis with hypertension and hyperreninemia following chemotherapy: cure by nephrectomy. Journal of Pediatrics 1980;96:68-70.
Diavolitsis 2010 {published data only}
  • Diavolitsis VM, Rademaker A, Boyle J, Kang Z, Kiel K, Mulcahy M, et al. Change in creatinine clearance over time following upper abdominal irradiation: a dose-volume histogram multivariate analysis. American Journal of Clinical Oncology 2010;34(1):53-7.
Dome 1993 {published data only}
  • Dome JS, Huff V. Wilms tumor overview. In: Pagon RA,  Bird TD,  Dolan CR,  Stephens K,  Adam MP editor(s). GeneReviews™. Seattle, USA: University of Washington, 1993.
Doz 1994 {published data only}
Druley 2009 {published data only}
  • Druley TE, Hayashi R, Mansur DB, Zhang QJ, Barnes Y, Trinkaus K, et al. Early outcomes after allogeneic hematopoietic SCT in pediatric patients with hematologic malignancies following single fraction TBI. Bone Marrow Transplantation 2009;43:307-14.
Dunkel 2007 {published data only}
Edgar 2009 {published data only}
  • Edgar AB, Morris EMM, Kelnar CJH, Wallace HB. Endocrinopathy after childhood cancer treatment. Long-term Follow-up of Survivors of Childhood Cancer. Basel: S Karger AG, 2009:159-80.
Eghbali 1994 {published data only}
  • Eghbali H, Catry-Thomas I, Soubeyran P, Bonnel C, Hoerni B. Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients [Association d'etoposide, de cisplatine et d'ifosfamide (VPH) dans la chimiotherapie de "rattrapage" des lymphomes malins agressifs en progression ou en rechute. Etude sur 51 patients]. Bulletin du Cancer 1994;81:800-7.
Ehrlich 1974 {published data only}
Eklof 1976 {published data only}
  • Eklof O, Ringertz H. Kidney size and growth in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. Acta Radiologica: Diagnosis (Stockholm) 1976;17(5A):601-8.
Emminger 1992 {published data only}
  • Emminger W, Emminger-Schmidmeier W, Peters C, Hawliczek R, Hocker P, Gadner H. Limited tolerance of intensified conditioning regimens in children receiving methotrexate/cyclosporin A for graft-versus-host disease prophylaxis. Pediatric Hematology and Oncology 1992;9:1-9.
England 2011 {published data only}
Escobar 2006 {published data only}
  • Escobar MA, Grosfeld JL, Powell RL, West KW, Scherer LR III, Fallon RJ, et al. Long-term outcomes in patients with stage IV neuroblastoma. Journal of Pediatric Surgery 2006;41:377-81.
Esiashvili 2009 {published data only}
  • Esiashvili N, Chiang K-Y, Hasselle MD, Bryant C, Riffenburgh RH, Paulino AC. Renal toxicity in children undergoing total body irradiation for bone marrow transplant. Radiotherapy and Oncology 2009;90:242-6.
Feig 2009 {published data only}
Ferrari 2005a {published data only}
  • Ferrari S, Smeland S, Mercuri M, Bertoni F, Longhi A, Ruggieri P, et al. Neoadjuvant chemotherapy with high-dose Ifosfamide, high-dose methotrexate, cisplatin, and doxorubicin for patients with localized osteosarcoma of the extremity: a joint study by the Italian and Scandinavian Sarcoma Groups. Journal of Clinical Oncology 2005;23:8845-52.
Feusner 2008 {published data only}
Feyer 1989 {published data only}
  • Feyer P, Hoffmann FA, Standke E, Kubel M, Helbig W. Acute and late effects in the course of and after total body irradiation with following bone marrow transplantation in patients with different forms of leukaemia. Folia Haematologica 1989;116:487-91.
Flentje 1998 {published data only}
  • Flentje M, Weirich A, Graf N, Potter R, Zimmerman H, Ludwig R. Abdominal irradiation in unilateral nephroblastoma and its impact on local control and survival. International Journal of Radiation Oncology, Biology, Physics 1998;40:163-9.
Fouladi 2009 {published data only}
Friedman 2007 {published data only}
Gallegos-Castorena 2007 {published data only}
  • Gallegos-Castorena S, Martinez-Avalos A, Mohar-Betancourt A, Guerrero-Avendano G, Zapata-Tarres M, Medina-Sanson A. Toxicity prevention with amifostine in pediatric osteosarcoma patients treated with cisplatin and doxorubicin. Pediatric Hematology and Oncology 2007;24:403-8.
Galsky 2007 {published data only}
Garaventa 1994 {published data only}
  • Garaventa A, Hartmann O, Bernard JL, Zucker JM, Pardo N, Castel V, et al. Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry. Medical and Pediatric Oncology 1994;22:11-4.
Gaynon 1994 {published data only}
Geenen 2007 {published data only}
  • Geenen MM, Cardous-Ubbink MC, Kremer LCM, Van Den Bos C, Van Der Pal HJH, Heinen RC, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. Journal of the American Medical Association 2007;297:2705-15.
Gerke 2000 {published data only}
  • Gerke P, Filejski W, Robins HI, Wiedemann GJ, Steinhoff J. Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia. Journal of Cancer Research and Clinical Oncology 2000;126:173-7.
Gerstein 2009 {published data only}
  • Gerstein J, Meyer A, Sykora KW, Fruhauf J, Karstens JH, Bremer M. Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Strahlentherapie und Onkologie 2009;185(11):751-5.
Gillis 2007 {published data only}
  • Gillis AM, Sutton E, Dewitt KD, Matthay KK, Weinberg V, Fisch BM, et al. Long-term outcome and toxicities of intraoperative radiotherapy for high-risk neuroblastoma. International Journal of Radiation Oncology, Biology, Physics 2007;69:858-64.
Gobel 1993 {published data only}
  • Gobel U, Calaminus G, Teske C, Bamberg M, Bokkerink JP, Haas RJ, et al. BEP/VIP in children and adolescents with malignant non-testicular germ cell tumors. A comparison of the results of treatment of therapy studies MAKEI 83/86 and 89P/89 [BEP/VIP bei Kindern und Jugendlichen mit malignen nichttestikularen Keimzelltumoren. Ein Vergleich der Behandlungsergebnisse der Therapiestudien MAKEI 83/86 und 89P/89]. Klinische Pädiatrie 1993;205:231-40.
Goren 1986 {published data only}
Goren 2003 {published data only}
Goyal 2011 {published data only}
  • Goyal J, Sidana A, Georgiades CS, Rodriguez R. Renal function and oncologic outcomes after cryoablation or partial nephrectomy for tumors in solitary kidneys. Korean Journal of Urology 2011;52(6):384-9.
Graf 2003 {published data only}
  • Graf N, Reinhard H. Wilms tumors. Diagnosis and therapy. Urologe A 2003;42:391-409.
Gratton 2006 {published data only}
Green 1995 {published data only}
Green 2008 {published data only}
  • Green DM. Chemotherapy for the treatment of children and adolescents with malignant germ cell tumors. Journal of Clinical Oncology 2008;26:3297-8.
Gronroos 2008 {published data only}
  • Gronroos MH, Jahnukainen T, Irjala K, Harkonen R, Hurme S, Mottonen M, et al. Comparison of glomerular function tests in children with cancer. Pediatric Nephrology 2008;23:797-803.
Gunes 2010 {published data only}
  • Gunes AM, Can E, Saglam H, Ilcol YO, Baytan B. Assessment of bone mineral density and risk factors in children completing treatment for acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology 2010;32:e102-7.
Haddy 2009 {published data only}
Hadley 2006 {published data only}
Hanly 2009 {published data only}
Hanna 2008 {published data only}
Hartmann 2000 {published data only}
  • Hartmann JT, Fels LM, Knop S, Stolt H, Kanz L, Bokemeyer C. A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors. Investigational New Drugs 2000;18:281-9.
Hayashi 2009 {published data only}
  • Hayashi K, Tsuchiya H, Yamamoto N, Shirai T, Yamauchi K, Takeuchi A, et al. Impact of serum caffeine monitoring on adverse effects and chemotherapeutic responses to caffeine-potentiated chemotherapy for osteosarcoma. Journal of Orthopaedic Science 2009;14:253-8.
Hayes-Jordan 2010 {published data only}
  • Hayes-Jordan A, Green H, Fitzgerald N, Xiao L, Anderson P. Novel treatment for desmoplastic small round cell tumor: hyperthermic intraperitoneal perfusion. Journal of Pediatric Surgery 2010;45:1000-6.
Hazar 2009 {published data only}
Hegde 2009 {published data only}
Heikens 1998 {published data only}
  • Heikens J, Somers R, Behrendt H, Oldenburger F, Langeveld NE, Bakker PJ. Late sequelae of oncologic treatment in children [Late gevolgen van oncologische behandeling bij kinderen]. Nederlands Tijdschrift voor Geneeskunde 1998;142:2191-5.
Heikens 2000 {published data only}
Helenglass 1988 {published data only}
  • Helenglass G, Powles RL, McElwain TJ, Lakhani A, Milan S, Gore M, et al. Melphalan and total body irradiation (TBI) versus cyclophosphamide and TBI as conditioning for allogeneic matched sibling bone marrow transplants for acute myeloblastic leukaemia in first remission. Bone Marrow Transplantation 1988;3:21-9.
Henderson 2008 {published data only}
  • Henderson T, Patel S, Levine J, Oeffinger KC. Follow-up of childhood cancer survivors: the role of the primary care physician. Consultant 2008;48:438-42.
Hingorani 2008 {published data only}
Horwich 1991 {published data only}
  • Horwich A, Dearnaley DP, Nicholls J, Jay G, Mason M, Harland S, et al. Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors. Journal of Clinical Oncology 1991;9:62-9.
Hovi 1989 {published data only}
Hudson 2008 {published data only}
Iida 2008 {published data only}
  • Iida S, Kondo T, Amano H, Nakazawa H, Ito F, Hashimoto Y, et al. Minimal effect of cold ischemia time on progression to late-stage chronic kidney disease observed long term after partial nephrectomy. Urology 2008;72:1083-8.
Ippolito 2006 {published data only}
Janeway 2010 {published data only}
Jereb 1997 {published data only}
  • Jereb B. Radiotherapy in nephroblastoma. Pre- and postoperative combination treatment. Radiotherapy in localized (stage II, III, IV) and metastatic disease. Actue and long-term side effects. Radiology and Oncology 1997;31:48-53.
Jones 1995 {published data only}
  • Jones DP, Chesney RW. Renal toxicity of cancer chemotherapeutic agents in children: ifosfamide and cisplatin. Current Opinion in Pediatrics 1995;7:208-13.
Jones 2008 {published data only}
Kantarjian 1996 {published data only}
  • Kantarjian HM, Beran M, O'Brien S, Robertson L, Siddik Z, Yoshida M, et al. Evaluation of CI-973, a platinum analogue, in refractory or relapsed acute leukemia. Leukemia 1996;10:396-401.
Katzenstein 2009 {published data only}
Keaney 2005 {published data only}
  • Keaney CM, Springate JE. Cancer and the kidney. Adolescent Medicine Clinics 2005;16:121-48.
Kenney 2010 {published data only}
Kibirige 1988 {published data only}
Kim 1980 {published data only}
Kim 2009 {published data only}
  • Kim A, Gillespie A, Dombi E, Goodwin A, Goodspeed W, Fox E, et al. Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas. Neurology 2009;73:1273-9.
Kirch 1997 {published data only}
Kist-van Holthe 2002 {published data only}
  • Kist-van Holthe JE, Goedvolk CA, Brand R, van Weel MH, Bredius RG, van Oostayen JA, et al. Prospective study of renal insufficiency after bone marrow transplantation. Pediatric Nephrology 2002;17:1032-7.
Kist-van Holthe 2005 {published data only}
Koren 2007 {published data only}
Kourti 2005 {published data only}
  • Kourti M, Tragiannidis A, Makedou A, Papageorgiou T, Rousso I, Athanassiadou F. Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy. Journal of Pediatric Hematology/Oncology 2005;27:499-501.
Kremens 2002 {published data only}
  • Kremens B, Gruhn B, Klingebiel T, Hasan C, Laws HJ, Koscielniak E, et al. High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma. Bone Marrow Transplantation 2002;30:893-8.
Kremers 2003 {published data only}
  • Kremers A, Langer T, Stohr W, Beck JD, Rascher W. Late effects of oncological therapy in children. Padiatrische Praxis 2003;64:47-64.
Kumar 1996 {published data only}
  • Kumar M, Kedar A, Neiberger RE. Kidney function in long-term pediatric survivors of acute lymphoblastic leukemia following allogeneic bone marrow transplantation. Pediatric Hematology and Oncology 1996;13:375-9.
Kung 1995 {published data only}
  • Kung FH, Desai SJ, Dickerman JD, Goorin AM, Harris MB, Inoue S, et al. Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of childhood: a Pediatric Oncology Group Phase I/II study. Journal of Pediatric Hematology/Oncology 1995;17:265-9.
Kurt 2008 {published data only}
Kusumi 2008 {published data only}
  • Kusumi E, Kami M, Hara S, Hoshino J, Yamaguchi Y, Murashige N, et al. Postmortem examination of the kidney in allogeneic hematopoietic stem cell transplantation recipients: possible involvement of graft-versus-host disease. International Journal of Hematology 2008;87:225-30.
Landier 2008 {published data only}
Langer 2004 {published data only}
Leahey 1999 {published data only}
  • Leahey AM, Teunissen H, Friedman DL, Moshang T, Lange BJ, Meadows AT. Late effects of chemotherapy compared to bone marrow transplantation in the treatment of pediatric acute myeloid leukemia and myelodysplasia. Medical and Pediatric Oncology 1999;32:163-9.
Le Bourgeois 1979 {published data only}
  • Le Bourgeois JP, Meignan M, Parmentier C, Tubiana M. Renal consequences of irradiation of the spleen in lymphoma patients. British Journal of Radiology 1979;52:56-60.
Lee 2001 {published data only}
Levi 1993 {published data only}
  • Levi JA, Raghavan D, Harvey V, Thompson D, Sandeman T, Gill G, et al. The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group. Journal of Clinical Oncology 1993;11:1300-5.
Liesner 1994 {published data only}
  • Liesner RJ, Leiper AD, Hann IM, Chessells JM. Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood. Journal of Clinical Oncology 1994;12:916-24.
Lonnerholm 1991 {published data only}
  • Lonnerholm G, Carlson K, Bratteby LE, Backlund L, Hagberg H, Rikner G, et al. Renal function after autologous bone marrow transplantation. Bone Marrow Transplantation 1991;8:129-34.
Ludwig 1992 {published data only}
  • Ludwig R, Weirich A, Potter R, Harms D, Burger D, Michaelis J, et al. Preoperative chemotherapy of nephroblastoma. Preliminary results of the SIOP-9/GPO therapy study [Praoperative Chemotherapie des Nephroblastoms. Vorlaufige Ergebnisse der Therapiestudie SIOP-9/GPO.]. Klinische Pediatrie 1992;204:204-13.
Macklis 1991 {published data only}
Macleod 1988 {published data only}
Majhail 2009 {published data only}
  • Majhail NS, Challa TR, Mulrooney DA, Baker KS, Burns LJ. Hypertension and diabetes mellitus in adult and pediatric survivors of allogeneic hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation 2009;15:1100-7.
Makari 2010 {published data only}
  • Makari JH, Ramachandra P, Ferrer FA. Pediatric urologic oncology: organ-sparing surgery in kidney and testis. Urologic Clinics of North America 2010;37:287-98.
Mandell 1999 {published data only}
  • Mandell LR, Kadota R, Freeman C, Douglass EC, Fontanesi J, Cohen ME, et al. There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. International Journal of Radiation Oncology, Biology, Physics 1999;43:959-64.
Marina 1994 {published data only}
  • Marina NM, Wilimas JA, Meyer WH, Jones DP, Douglass EC, Pratt CB. Refining therapeutic strategies for patients with resistant Wilm's tumor. American Journal of Pediatric Hematology/Oncology 1994;16:296-300.
Marina 2000 {published data only}
  • Marina NM, Poquette CA, Cain AM, Jones D, Pratt CB, Meyer WH. Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas. Journal of Pediatric Hematology/Oncology 2000;22:112-8.
Marina 2004 {published data only}
Mashhadi 2011 {published data only}
  • Mashhadi MA, Sanadgol H, Keikhaei M. Ifosfamide nephropathy in patients with sarcoma. Iranian Journal of Kidney Disease 2011;5(4):238-41.
Massimi 2007 {published data only}
McCune 2004 {published data only}
McCune 2009 {published data only}
  • McCune JS, Batchelder A, Guthrie KA, Witherspoon R, Appelbaum FR, Phillips B, et al. Personalized dosing of cyclophosphamide in the total body irradiation-cyclophosphamide conditioning regimen: a phase II trial in patients with hematologic malignancy. Clinical Pharmacology & Therapeutics 2009;85:615-622.
McDonald 1993 {published data only}
  • McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Annals of Internal Medicine 1993;118:255-67.
Meacham 2010 {published data only}
  • Meacham LR, Chow EJ, Ness KK, Kamdar KY, Chen Y, Yasui Y, et al. Cardiovascular risk factors in adult survivors of pediatric cancer-a report from the childhood cancer survivor study. Cancer Epidemiology, Biomarkers and Prevention 2010;19:170-81.
Meadows 1985 {published data only}
Meck 2006 {published data only}
Mendez 2006 {published data only}
  • Mendez Romero A, Wunderink W, Hussain SM, De Pooter JA, Heijmen BJ, Nowak PC, et al. Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I-II study. Acta Oncologica 2006;45:831-7.
Mertens 1997 {published data only}
Meyer 2006 {published data only}
Millar 2011 {published data only}
  • Millar AJ, Davidson A, Rode H, Numanoglu A, Hartley PS, Desai F. Nephron-sparing surgery for bilateral Wilms' tumours: a single-centre experience with 23 cases. African Journal of Paediatric Surgery 2011;8(1):49-56.
Miralbell 1996 {published data only}
  • Miralbell R, Bieri S, Mermillod B, Helg C, Sancho G, Pastoors B, et al. Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. Journal of Clinical Oncology 1996;14:579-85.
Miralbell 2004 {published data only}
  • Miralbell R, Sancho G, Bieri S, Carrio I, Helg C, Brunet S, et al. Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment. International Journal of Radiation Oncology, Biology, Physics 2004;58:809-16.
Mitchell 2009 {published data only}
  • Mitchell C, Hall G, Clarke RT. Acute leukaemia in children: diagnosis and management. British Medical Journal 2009;338:1491-5.
Moghrabi 1998 {published data only}
  • Moghrabi A, Friedman HS, Ashley DM, Bottom KS, Kerby T, Stewart E, et al. Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurgical Focus 1998;4:e3.
Mohammadianpanah 2004 {published data only}
Morris 1991 {published data only}
  • Morris Jones PH. The late effects of cancer therapy in childhood. British Journal of Cancer 1991;64:1-2.
Naguib 2008 {published data only}
  • Naguib SF, El Haddad A, El Badawy SA, Zaghloul AS. Multidisciplinary approach to wilms' tumor: a retrospective analytical study of 53 patients. Journal of the Egyptian National Cancer Institute 2008;20:410-23.
Nath 2007 {published data only}
Niethammer 1998 {published data only}
  • Niethammer D, Mayer E. Long-term survivors: an overview on late effects, sequelae and second neoplasias. Bone Marrow Transplantation 1998;21:S61-3.
Nieto 2005 {published data only}
  • Nieto B, Martin Aguado MJ, Verdu J, Canals A, Martin Hortiguela ME, Mira J, et al. Study of renal function and compensatory changes in children with single kidney [Determinacion de funcion renal y cambios compensadores en ninos con rinon unico]. Cirugía Pediátrica 2005;18:151-5.
Nogueira 1998 {published data only}
  • Nogueira PCK, Hadj-Aissa A, Schell M, Dubourg L, Brunat-Mentigny M, Cochat P. Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma. Pediatric Nephrology 1998;12:572-5.
Nunez 2007 {published data only}
  • Nunez SB, Mulrooney DA, Laverdiere C, Hudson MM. Risk-based health monitoring of childhood cancer survivors: a report from the Children's Oncology Group. Current Oncology Reports 2007;9:440-52.
Oeffinger 2001 {published data only}
  • Oeffinger KC, Buchanan GR, Eshelman DA, Denke MA, Andrews TC, Germak JA, et al. Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology 2001;23:424-30.
Oeffinger 2009 {published data only}
  • Oeffinger KC, Adams-Huet B, Victor RG, Church TS, Snell PG, Dunn AL, et al. Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. Journal of Clinical Oncology 2009;27:3698-704.
Ota 1993 {published data only}
  • Ota K. [Cisplatinum compounds]. Gan To Kagaku Ryoho 1993;20:50-8.
Pahernik 2007 {published data only}
Parigi 2003 {published data only}
  • Parigi GB, Beluffi G, Corbella F, Matteotti C, Ramella B, Bragheri R. Long-term follow-up in children treated for retroperitoneal malignant tumours. European Journal of Pediatric Surgery 2003;13:240-4.
Parisi 1999 {published data only}
Patte 1991 {published data only}
  • Patte C, Philip T, Rodary C, Zucker JM, Behrendt H, Gentet JC, et al. High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. Journal of Clinical Oncology 1991;9:123-32.
Patzer 1997 {published data only}
Paulides 2008 {published data only}
  • Paulides M, Mergenthaler A, Peeters J, Beck JD, Langer T, Kaatsch P. Major organ-related long-term effects of chemotherapy and secondary malignancies. Medizinische Welt 2008;59:105-9.
Pectasides 2010 {published data only}
  • Pectasides D, Pectasides E, Papaxoinis G, Xiros N, Kamposioras K, Tountas N, et al. Methotrexate, paclitaxel, ifosfamide, and cisplatin in poor-risk nonseminomatous germ cell tumors. Urologic Oncology 2010;28(6):617-23.
Pentheroudakis 2007 {published data only}
Pereira 2005 {published data only}
Petersen 1992 {published data only}
  • Petersen FB, Deeg HJ, Buckner CD, Appelbaum FR, Storb R, Clift RA, et al. Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide-a phase I trial. International Journal of Radiation Oncology, Biology, Physics 1992;23:1027-32.
Petersen 1999 {published data only}
Phillips 2008 {published data only}
  • Phillips RS, Tyerman K, Al-Kassim MI, Picton S. A systematic review of the accuracy and utility of early markers of Ifosfamide-induced proximal tubulopathy in survivors of childhood cancers. Pediatric Hematology and Oncology 2008;25:107-13.
Pietila 2005 {published data only}
Pietila 2009 {published data only}
Pinter 2003 {published data only}
Plowman 1999 {published data only}
  • Plowman PN. Survivors of cancer: organ preservation and reducing the morbidity of treatment in paediatric genitourinary oncology. British Journal of Urology International 1999;83 Supp:51-60.
Pochedly 1973 {published data only}
Ponisch 2006 {published data only}
Poon 2007 {published data only}
  • Poon RT, Tso WK, Pang RW, Ng KK, Woo R, Tai KS, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clinical Gastroenterology and Hepatology 2007;5:1100-8.
Pratt 1981 {published data only}
  • Pratt CB, Hayes A, Green AA, Evans WE, Senzer N, Howarth CB, et al. Pharmacokinetic evaluation of cisplatin in children with malignant solid tumors: a phase II study. Cancer Treatment Reports 1981;65:1021-6.
Pratt 1991 {published data only}
Pratt 1996 {published data only}
Raney 1994 {published data only}
  • Raney B, Ensign LG, Foreman J, Khan F, Newton W, Ortega J, et al. Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor. American Journal of Pediatric Hematology/Oncology 1994;16:286-95.
Regazzoni 1998 {published data only}
  • Regazzoni BM, Genton N, Pelet J, Drukker A, Guignard JP. Long-term followup of renal functional reserve capacity after unilateral nephrectomy in childhood. Journal of Urology 1998;160:844-8.
Reisi 2009 {published data only}
  • Reisi N, Azhir A, Hashemipour M, Raeissi P, Amini A, Moafi A. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran. Journal of Research in Medical Sciences 2009;14:111-6.
Renal tumours and hypertension {published data only}
  • No authors listed. Renal tumours and hypertension. British Medical Journal 1968;3(5614):327-8.
Ritchey 1996 {published data only}
Ritchey 2008 {published data only}
Roback 1971 {published data only}
  • Roback SA, Nesbit ME Jr, Sharp HL, D'Angio GJ, Leonard AS. Portal hypertension following surgery, x-radiation, and actinomycin D therapy of nephroblastoma. Journal of Pediatrics 1971;78:1031-4.
Robert 1995 {published data only}
Romanini 1981 {published data only}
  • Romanini A, Galli G, D'Errico G, Carlesimo M, De Renzis C. Radioisotopic study of some organs after radiotherapy of the upper abdomen (author's translation) [Studio radioisotopico di alcuni organi dopo radioterapia dell'addome superiore]. Radiologia Medica 1981;67:757-61.
Rossi 1999a {published data only}
Saddadi 2009 {published data only}
  • Saddadi F, Hakemi M, Najafi I, Moghadam K, Ghavamzadeh A, Jahani M, et al. Chronic kidney disease after hematopoietic cell transplantation: frequency, risk factors, and outcomes. Transplantation Proceedings 2009;41:2895-7.
Saez 1995 {published data only}
  • Saez RA, Slease RB, Strnad C, Selby GB, Confer DL, Epstein RB. High-dose carboplatin, etoposide and cyclophosphamide with autologous bone marrow transplantation for the treatment of advanced malignancies: a phase I study. Bone Marrow Transplantation 1995;16:507-14.
Sagerman 1969 {published data only}
  • Sagerman RH, Berdon WE, Baker DH. Renal atrophy without hypertension following abdominal irradiation in infants and children [Atrophie renale sans hypertension apres irradiation de l'abdomen chez le nourrisson et chez l'enfant]. Annales de Radiologie 1969;12:278-84.
Sagstuen 2005 {published data only}
Sakellari 2010a {published data only}
  • Sakellari I, Bamichas G, Barbouti A, Mallouri D, Fragidis S, Apostolou C, et al. Older age, the number of preceded events of acute kidney injury and the in vivo t cell depletion are risk factors for kidney injury after hematopoietic cell transplantation. Haematologica 2010:447.
Sastry 2005 {published data only}
  • Sastry J, Kellie SJ. Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatric Hematology and Oncology 2005;22:441-5.
Schenkein 1994 {published data only}
  • Schenkein DP, Dixon P, Desforges JF, Berkman E, Erban JK, Ascensao JL, et al. Phase I/II study of cyclophosphamide, carboplatin, and etoposide and autologous hematopoietic stem-cell transplantation with posttransplant interferon alfa-2b for patients with lymphoma and Hodgkin's disease. Journal of Clinical Oncology 1994;12:2423-31.
Schiff 1977 {published data only}
Schmidt 2010 {published data only}
  • Schmidt D, Anderson L, Bingen K, Hoag J, Kupst MJ, Warwick AB. Late effects in adult survivors of childhood cancer: considerations for the general practitioner. Wisconsin Medical Journal 2010;109:98-108.
Schmoll 2003 {published data only}
  • Schmoll HJ, Kollmannsberger C, Metzner B, Hartmann JT, Schleucher N, Schoffski P, et al. Long-term results of first-line sequential high-dose etoposide, ifosfamide, and cisplatin chemotherapy plus autologous stem cell support for patients with advanced metastatic germ cell cancer: an extended phase I/II study of the German Testicular Cancer Study Group. Journal of Clinical Oncology 2003;21:4083-91.
Schwartz 2007 {published data only}
Shamash 2000 {published data only}
  • Shamash J, O'Doherty CA, Oliver RT, Kelsey S, Gupta RK, Gallagher CJ, et al. Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?. Acta Oncologica 2000;39:857-63.
Shirasaki 2004 {published data only}
Shirasaki 2004a {published data only}
Shnorhavorian 2009 {published data only}
  • Shnorhavorian M, Friedman DL, Koyle MA. Genitourinary long-term outcomes for childhood cancer survivors. Current Urology Reports 2009;10:134-7.
Sieber 2004 {published data only}
  • Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, et al. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Annals of Oncology 2004;15:276-82.
Silberzweig 1992 {published data only}
Simpson 2002 {published data only}
  • Simpson AB, Calvert PM, Sludden JA, Boddy AV, Griffin MJ, Schatzlein A, et al. Topotecan in combination with carboplatin: Phase I trial evaluation of two treatment schedules. Annals of Oncology 2002;13:399-402.
Skinner 1991 {published data only}
  • Skinner R, Pearson AD, Coulthard MG, Skillen AW, Hodson AW, Goldfinch ME, et al. Assessment of chemotherapy-associated nephrotoxicity in children with cancer. Cancer Chemotherapy and Pharmacology 1991;28:81-92.
Skinner 1992 {published data only}
  • Skinner R, Pearson AD, Price L, Coulthard MG, Craft AW. The influence of age on nephrotoxicity following chemotherapy in children. British Journal of Cancer 1992;18:S30-5.
Skinner 1993 {published data only}
Skinner 2000 {published data only}
  • Skinner R, Cotterill SJ, Stevens MC. Risk factors for nephrotoxicity after ifosfamide treatment in children: a UKCCSG Late Effects Group study. United Kingdom Children's Cancer Study Group. British Journal of Cancer 2000;82:1636-45.
Skinner 2003 {published data only}
Skinner 2010a {published data only}
  • Skinner R. Nephrotoxicity of cancer treatment in children. Pediatric Health 2010;4:519-38.
Skinner 2011 {published data only}
Sloetjes 2000 {published data only}
  • Sloetjes KG, van den Bergh JP, Wesseling P, Otten BJ, Pieters GF, Hermus AR. Clinical presentation, treatment, and follow-up of 32 patients with a primary intracranial germinoma, registered during the previous 15 years in the Dutch Pathological-Anatomical National Automated Archive (PALGA) [Kliniek, behandeling en follow-up van 32 patienten met een primair intracranieel germinoom uit de afgelopen 15 jaar, geregistreerd in het Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)]. Nederlands Tijdschrift voor Geneeskunde 2000;144:2264-8.
Smith 1998 {published data only}
  • Smith GR, Thomas PR, Ritchey M, Norkool P. Long-term renal function in patients with irradiated bilateral Wilms tumor. National Wilms' Tumor Study Group. American Journal of Clinical Oncology 1998;21(1):58-63.
Sonn 2008 {published data only}
Spira 2009 {published data only}
  • Spira EM, Jacobi C, Frankenschmidt A, Pohl M, von Schnakenburg C. Sonographic long-term study: paediatric growth charts for single kidneys. Archives of Disease in Childhood 2009;94:693-8.
Springate 1997 {published data only}
  • Springate JE. Toxic nephropathies. Current Opinion in Pediatrics 1997;9:166-9.
Stava 2007 {published data only}
  • Stava CJ, Jimenez C, Vassilopoulou-Sellin R. Endocrine sequelae of cancer and cancer treatments. Journal of Cancer Survivorship 2007;1:261-74.
Steinbach 1995 {published data only}
  • Steinbach F, Novick AC, Zincke H, Miller DP, Williams RD, Lund G, et al. Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study. Journal of Urology 1995;153:1812-6.
Stern 2002 {published data only}
Suarez 1991 {published data only}
  • Suarez A, McDowell H, Niaudet P, Comoy E, Flamant F. Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report. Journal of Clinical Oncology 1991;9(12):2177-82.
Sukarochana 1972 {published data only}
Talvensaari 1996 {published data only}
Talvensaari 1997 {published data only}
Tamaro 1997 {published data only}
  • Tamaro P. Wilms' tumor: reached progress and future prospects [Il tumore di Wilms: progressi ottenuti e prospettive future]. Archivio Italiano di Urologia, Andrologia 1997;69:227-32.
Taylor 1997 {published data only}
  • Taylor RE. Morbidity from abdominal radiotherapy in the First United Kingdom Children's Cancer Study Group Wilms' Tumour Study. United Kingdom Children's Cancer Study Group. Clinical Oncology 1997;9:381-4.
Taylor 2003 {published data only}
  • Taylor RE, Bailey CC, Robinson K, Weston CL, Ellison D, Ironside J, et al. Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: the International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study. Journal of Clinical Oncology 2003;21:1581-91.
Tefft 1977 {published data only}
Thomas 1983 {published data only}
Tichelli 1991 {published data only}
  • Tichelli A, Gratwohl A, Uhr M, Dazzi H, Hoffmann T, Stebler Gysi C, et al. [Health status and late complications following allogeneic bone marrow transplantation. A review] [Gesundheitszustand und Spatkomplikationen nach allogener Knochenmarktransplantation. Eine Ubersicht]. Schweizerische Medizinische Wochenschrift 1991;121:1473-81.
Tokuc 1997 {published data only}
  • Tokuc G, Yalciner A, Kebudi R, Dogan S, Gorgun O, Ayan I. Renal dysfunctions secondary to ifosfamide treatment in children. Journal of Experimental & Clinical Cancer Research 1997;16:227-30.
Trimis 2007 {published data only}
  • Trimis G, Moschovi M, Papassotiriou I, Chrousos G, Tzortzatou-Stathopoulou F. Early indicators of dysmetabolic syndrome in young survivors of acute lymphoblastic leukemia in childhood as a target for preventing disease. Journal of Pediatric Hematology/Oncology 2007;29:309-14.
Turna 2008 {published data only}
  • Turna B, Frota R, Kamoi K, Lin Y-C, Aron M, Desai MM, et al. Risk factor analysis of postoperative complications in laparoscopic partial nephrectomy. Journal of Urology 2008;179:1289-95.
van Waas 2010 {published data only}
  • van Waas M, Neggers SJ, Van Der Lelij A-J, Pieters R, Van Den Heuvel-Eibrink MM. The metabolic syndrome in adult survivors of childhood cancer, a review. Journal of Pediatric Hematology/Oncology 2010;32:171-9.
van Waas 2010a {published data only}
  • van Waas M, Neggers SJ, Pieters R, van den Heuvel-Eibrink MM. Components of the metabolic syndrome in 500 adult long-term survivors of childhood cancer. Annals of Oncology 2010;21:1121-6.
Veringa 2011 {published data only}
Vio 1970 {published data only}
  • Vio A, Reggiani A. Hypertension in Wilms' tumors [L'ipertensione nei tumori di Wilms]. Archivio Italiano di Urologia, Nefrologia, Andrologia 1970;43:155-62.
Von Der Weid 1999 {published data only}
  • Von Der Weid NX, Erni BM, Mamie C, Wagner HP, Bianchetti MG. Cisplatin therapy in childhood: renal follow up 3 years or more after treatment. Nephrology Dialysis Transplantation 1999;14:1441-4.
Voute 1992 {published data only}
  • Voute PA, de Kraker J. Ifosfamide in pediatric oncology. Seminars in Oncology 1992;19:2-6.
Voute 1996 {published data only}
  • Voute PA, van den Berg H, Behrendt H, Michiels E, de Kraker J. Ifosfamide in the treatment of pediatric malignancies. Seminars in Oncology 1996;23:8-11.
Weijl 2004 {published data only}
  • Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink Bakker A, Zwinderman AH, et al. Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. European Journal of Cancer 2004;40:1713-23.
Welch 1987 {published data only}
Wistow 1979 {published data only}
  • Wistow BW, McAfee JG, Sagerman RH, Thomas FD, Grossman ZD. Renal uptake of Tc-99m methylene diphosphonate after radiation therapy. Journal of Nuclear Medicine 1979;20:32-4.
Womer 1985 {published data only}
Wright 2009 {published data only}
Wu 2005 {published data only}
Yanagisawa 2009 {published data only}
  • Yanagisawa R, Nakazawa Y, Sakashita K, Tanaka M, Shikama N, Kamijo T, et al. Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies. Pediatric Transplantation 2009;13:737-45.
Yao 1997 {published data only}
  • Yao MS, Mehta MP, Boyett JM, Li H, Donahue B, Rorke LB, et al. The effect of M-stage on patterns of failure in posterior fossa primitive neuroectodermal tumors treated on CCG-921: a phase III study in a high-risk patient population. International Journal of Radiation Oncology, Biology, Physics 1997;38:469-76.
Yaris 2005 {published data only}
  • Yaris N, Sozen E, Erduran E, Okten A, Orem A, Cakirbay H. Bone mineral metabolism and its relationship to leptin levels in survivors of childhood leukemia and lymphoma. Pediatric Hematology and Oncology 2005;22:489-98.
Yoshimura 1997 {published data only}
  • Yoshimura K, Yamauchi T, Maeda H, Kawai T. Cisplatin, vincristine, methotrexate, peplomycin, etoposide (COMPE) therapy for disseminated germ cell testicular tumors. International Journal of Urology 1997;4:47-51.
Zagars 1987 {published data only}
Zerin 1996 {published data only}
Zielinska 2003 {published data only}
  • Zielinska E, Zubowska M, Bodalski J. Polymorphism at the glutathione S-transferase pi locus as a risk factor for ifosfamide nephrotoxicity in children [Polimorfizm genu kodujacego transferaze S-glutationowa klasy P1 jako czynnik ryzyka nefrotoksycznego dzialania ifosfamidu u dzieci]. Polski Merkuriusz Lekarski 2003;14:295-8.
Zorn 2007 {published data only}
  • Zorn KC, Gong EM, Orvieto MA, Gofrit ON, Mikhail AA, Msezane LP, et al. Comparison of laparoscopic radical and partial nephrectomy: effects on long-term serum creatinine. Urology 2007;69:1035-40.

References to studies awaiting assessment

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Bailey 2002 {published data only}
  • Bailey S,  Roberts A,  Brock C,  Price L,  Craft AW,  Kilkarni R,  et al. Nephrotoxicity in survivors of Wilms' tumours in the North of England. British Journal of Cancer 2002;87:1092-8.
Cohen 2010 {published data only}
  • Cohen E, Fish BL, Moulder J. Mitigation of radiation nephropathy. Radiotherapy and Oncology 2010:S109.
Cozzi 2010 {published data only}
  • Cozzi D, Ceccanti S, Mele E, Frediani S, Iaconelli R, Schiavetti A, et al. Renal function outcomes after nephrectomy or nephron-sparing surgery for unilateral renal tumor in childhood. Pediatric Blood and Cancer 2010:793.
D'Angio 1978 {published data only}
  • D'Angio GJ, Tefft M, Breslow N, Meyer JA. Radiation therapy of Wilms' tumor: results according to dose, field, post-operative timing and histology. International Journal of Radiation Oncology, Biology, Physics 1978;4:769-80.
Eckstein 2010 {published data only}
  • Eckstein OS, O'Hear CE, Chi S, Lehmann LE, Duncan CN. High-dose chemotherapy with autologous stem-cell rescue in pediatric patients with CNS tumors: toxicity and outcomes. Biology of Blood and Marrow Transplantation. 2010:S247.
Janda 1993 {published data only}
  • Janda J, Koutecky J, Lukes M, Lukesova M, Malis J. The solitary kidney in patients after nephrectomy in Wilm's tumor. Ceskoslovenska Pediatrie 1993;48:577-80.
Kieran 2010 {published data only}
  • Kieran K, Giel DW, Davidoff AM, Williams MA. Urolithiasis in patients treated for childhood cancer: does altered calcium metabolism play a role?. Journal of Urology. 2010:e409.
Li 2006 {published data only}
  • Li MJ, Huang Y, Tang DX, Zhou YB, Tang HF, Liang JF. [Treatment of advanced Wilms' tumor]. Zhonghua Zhong Liu Za Zhi 2006;28:791-5.
Madden 2010 {published data only}
  • Madden JR, Hemenway M, Dorneman L, Strecker R, Foreman N. Outpatient cisplatin for average risk medulloblastoma: 15 year experience. Neuro-Oncology. 2010:ii111.
Matsuyama 2002 {published data only}
  • Matsuyama T, Kato K, Hanada R, Kawa K, Okamura J, Tsuchida M, et al. [Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia]. Rinsho Ketsueki 2002;43:527-37.
Pugachev 2004 {published data only}
  • Pugachev AG. Conservative surgery-a basic principle of childhood urology [Organosokhraniaiushchie Operatsii Osnovnoe Napravlenie v Detskoi Urologii]. Urologiia 2004;4:3-5.
Radvansky 2010 {published data only}
  • Radvansky J, Slaby K, Radvanska J, Malis J, Eckschalger T, Sulc J, et al. Late effect of treatment of nephroblastoma in patients treated in 1980-2001 in a single centre [Pozdni nasledky Wilmsova tumoru a jeho lecby u pacientu lecenych v letech 1980-2001 na jedinem pracovisti.]. Klinikal Onkologie 2010;23:245-55.
Sakellari 2010 {published data only}
  • Sakellari I, Bamichas G, Barbouti A, Mallouri D, Fragidis S, Yannaki E, et al. Kidney injury as an early complication after haematopoietic cell transplantation: incidence, risk factors and outcome. Bone Marrow Transplantation 2010:S107.
Schwartz 2001 {published data only}
Sierota 2005 {published data only}
  • Sierota D, Stefanowicz J, Aleszewicz-Baranowska J, Birkholz D, Kosiak W, Adamkiewicz-Drozynska E, et al. Late side-effects of treatment in patients with nephroblastoma [Odlegle nastepstwa leczenia przeciwnowotworowego u dzieci z rozpoznaniem nerczaka zarodkowego]. Medycyna Wieku Rozwojowego 2005;9:517-22.
Stronska 2003 {published data only}
  • Stronska E, Zwolinska D, Sawicz-Birkowska K, Makulska I, Magier K, Czernik J. Assessment of function of the only kidney in children after nephrectomy due to Wilms tumor [Ocena czynnosci jedynej nerki u dzieci po nefrektomii z powodu guza Wilmsa.]. Polski Merkuriusz Lekarski 2003;14:311-4.
Terenziani 2010 {published data only}
  • Terenziani M, Indolfi P, Ardissino G, Bianchi M, Biasoni D, Catania S, et al. Bilateralwilms tumour (stage V): a report from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) Wilms Tumour 2003 Cooperative Protocol. Pediatric Blood and Cancer 2010:883.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Differences between protocol and review
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. References to studies awaiting assessment
  20. Additional references
Beevers 2007
  • Beevers G, Lip GY, O'Brien E. ABC of Hypertension. 5th Edition. London, United Kingdom: BMJ Books, 2007.
Breitz 2004
Butt 2009
De Graaf 1996
  • De Graaf SS, Van Gent H, Reitsma-Bierens WC, Van Luyk WH, Dolsma WV, Postma A. Renal function after unilateral nephrectomy for Wilms' tumour: the influence of radiation therapy. European Journal of Cancer 1996;32A(3):465-9.
Egger 1997
  • Egger M,  Zellweger-Zähner T,  Schneider M,  Junker C,  Lengeler C,  Antes G. Language bias in randomised controlled trials published in English and German. The Lancet 1997;350(9074):326-9.
Gatta 2009
  • Gatta G,  Zigon G,  Capocaccia R,  Coebergh JW,  Desandes E,  Kaatsch P,  et al. Survival of European children and young adults with cancer diagnosed 1995–2002. European Journal of Cancer 2009;45(6):992-1005.
Grimes 2002
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011.
Hoang 2003
  • Hoang K, Tan JC,  Derby G, Blouch KL, Masek M, Ma I, et al. Determinants of glomerular hypofiltration in aging humans. Kidney International 2003;64(4):1417–24.
Kremer 2002
  • Kremer LC, van Dalen EC, Offringa M, Voûte PA. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Annals of Oncology 2002;13(4):503-12.
Lajer 1999
Laupacis 1994
  • Laupacis A, Wells G, Richardson WS, Tugwell P. Users' guides to the medical literature. V. How to use an article about prognosis. Evidence-Based Medicine Working Group. Journal of the American Medical Association 1994;272:234-7.
Liamis 2010
Matsushita 2010
  • Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. The Lancet 2010;375:2073-81.
Mulder 2010
Nathan 2009
  • Nathan PC,  Ford JS,  Henderson TO,  Hudson MM,  Emmons KM,  Casillas JN, et al. Health behaviors, medical care, and interventions to promote healthy living in the Childhood Cancer Survivor Study cohort. Journal of Clinical Oncology 2009;27(14):2363-73.
National Kidney Foundation 2002
  • National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Disease 2002;39:S1-S266.
Oeffinger 2006
  • Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. New England Journal of Medicine 2006;355:1572-82.
Pietilä 2005
van Dalen 2006
  • van Dalen EC,  van der Pal HJ,  Kok WE,  Caron HN,  Kremer LC. Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. European Journal of Cancer 2006;42(18):3191-8.
van der Pal 2012
  • van der Pal HJ,  van Dalen EC,  van Delden E,  van Dijk IW,  Kok WE,  Geskus RB,  et al. High risk of symptomatic cardiac events in childhood cancer survivors. Journal of Clinical Oncology 2012;30(13):1429-37.
von Elm 2007
  • von Elm E,  Altman DG,  Egger M,  Pocock SJ,  Gøtzsche PC,  Vandenbroucke JP,  STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Annals of Internal Medicine 2007;147(8):573-77.
Wasilewski-Masker 2010
  • Wasilewski-Masker K, Mertens AC, Patterson B, Meacham LR. Severity of health conditions identified in a pediatric cancer survivor program. Pediatric Blood and Cancer 2010;54(7):976-82.
World Health Organization 2002
  • World Health Organization. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organization, 2002.