Description of the condition
Ureteric-pelvic junction obstruction (UPJO) adversely effects kidney development and function. UPJO is defined as impeded normal urine outflow from the renal pelvis to the nearest ureter (Koff 2008). Its incidence is 0.5 to 1/1000 births and is most often unilateral (60% to 80%). Children with UPJO have increased incidence of associated urological anomalies (Karnak 2008).
Unilateral UPJO is the most common cause of pre- and postnatal obstructive uropathy, which can lead to development of chronic kidney disease (CKD) (Mesrobian 2012; Williams 2007). UPJO is generally detected at pre- or neonatal ultrasound screening (Clayton 2012), but before ultrasonographic screening was widespread, it was often detected on investigation of clinical symptoms secondary to urinary outflow obstruction (Sutherland 1997). UPJO aetiology is multifactorial (Chen 2009; Chevalier 2010), and pathophysiology is limited to animal model findings (Chevalier 2010; Thornhill 2007).
Three primary pathophysiologic processes - mural, intramural and extramural changes - are associated with anatomic or functional UPJO (Chen 2009). Mural obstruction is the most common diagnosis, and results from either dysfunctional or adynamic ureteral peristalsis caused by abnormal distribution of smooth muscle, collagen fibres and innervation, or from incomplete re-canalisation during development. Intramural changes, such as fibroepithelial polyps or stones, are rare in children. Extramural anomalies such as crossing vessels, kinks, bands, adhesions, high insertion of the ureter, or abnormal rotation of the kidney can cause intermittent impairment in urine flow with dilatation of the pelvicaliceal system.
The pathogenetic consequences on kidney maturation, growth and histomorphology are dependent on the child's developmental stage when obstruction occurs, and the degree and duration of urinary tract obstruction on the non-obstructed kidney (Rosen 2008; Vaughan 2004).
UPJO evaluation requires kidney ultrasound and scintigraphy (Riccabona 2009). UPJO presents on ultrasound as a dilated renal pelvis without ureter dilatation. It is commonly assessed using the Society for Fetal Urology grading system and the anterior-posterior diameter (APD) of the renal pelvis in the transverse plane (Nguyen 2010). Renal scintigraphy using
Investigations of MRI and proteome analysis from urinary polypeptides have been suggested as promising non-invasive alternatives to diagnose UPJO in the future (Cerwinka 2010; Mesrobian 2010; Muthusami 2013).
Although kidney imaging techniques are often used to investigate need for surgical intervention, they are not good predictors to determine pathophysiological consequences of kidney function (Riccabona 2009).
The changing and dynamic nature of urinary outflow obstruction, individual compensatory processes, and the child's developmental stage at which the obstruction occurs elucidate the clinical variability of consequences on kidney development, function and urodynamics in children with similar degrees of urinary tract dilatation on kidney imaging (Davenport 2013). Therefore, urinary tract dilatation does not necessarily equate to the presence of urinary flow obstruction (Mesrobian 2012).
Description of the intervention
Both surgical and non-surgical interventions are essential therapeutic strategies for children with unilateral UPJO (Csaicsich 2004; Gallo 2009; Mei 2011). There are three main surgical procedures undertaken for the management of children with UPJO:
- open approach (such as Anderson-Hynes pyeloplasty)
- endoscopic approach (antegrade or retrograde)
The type of surgical approach is determined by factors including the specific anatomical abnormality, the child's age and clinical presentation (Herndon 2009; Williams 2007). Conservative non-surgical wait-and-see strategy with and without prophylactic antibiotics and nephroprotective ACE-inhibitors requires serial kidney ultrasound and scintigraphy imaging to monitor for early kidney deterioration in children with UPJO (Csaicsich 2004; Malki 2012).
How the intervention might work
Surgical intervention aims to resolve obstruction and provide adequate drainage of the affected kidney (Mei 2011; Thornhill 2007; Williams 2007). Although it has been suggested that optimal kidney function improvement results from surgery performed during the first year of life, others argue that delayed surgical intervention offers better outcomes (King 1984). The gold standard of open dismembered pyeloplasty has a reported success rate of 90% to 99% and a 13% complication rate (Williams 2007). Other surgical procedures have varying success (56% to 98%) and complication rates (3.6% to 25%) often resulting from applied techniques and limited experience in children (Mei 2011; Weikert 2005).
However, unilateral UPJO may improve or even resolve spontaneously without surgical intervention, and can persist without significant impairment of split kidney function (Dhillon 1998; Palmer 1998). Only around 25% of children with UPJO develop clinical problems or evidence of deteriorating kidney function that requires surgical intervention following conservative management (Malki 2012; Ransley 1990). Full recovery of impaired split kidney function after surgical procedure was reported for most of these children (Dhillon 1998).
Why it is important to do this review
Despite the epidemiological relevance of UPJO, optimal management remains controversial and practice varies widely (Csaicsich 2004; Ingraham 2011; NAPRTC 2008). Although early surgical intervention aims to prevent kidney function impairment (King 1984; Perez 1991), several studies have challenged this therapeutic approach, and recommend conservative management with close monitoring and serial kidney imaging (Dhillon 1998; Malki 2012; Palmer 1998). It is therefore essential to establish a common therapeutic approach in children with unilateral UPJO that balances the risks and costs of surgery with harms associated with excessive imaging and risk of kidney deterioration (Csaicsich 2004). The purpose of this review is to inform practice through the examination of evidence from randomised controlled trials (RCTs) comparing surgical and conservative management for children with UPJO.
This review will evaluate the available evidence for benefits and harms of the currently available surgical and non-surgical treatment options for children with unilateral UPJO.
Criteria for considering studies for this review
Types of studies
All RCTs and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) which evaluated any treatment for unilateral ureteric-pelvic junction obstruction will be included. We will include only parallel group, cluster and cross-over RCTs.
Types of participants
We will include boys and girls aged up to 18 years with unilateral ureteric-pelvic junction obstruction (UPJO, delayed urinary outflow) diagnosed postnatally by renal scintigraphy (with or without administration of diuretics) or any other appropriate cross-sectional imaging method, such as magnetic resonance imaging (MRI).
We will exclude:
- Patients with unilateral UPJO and diminished or no contralateral kidney function (e.g. multicystic-dysplastic kidney, kidney transplant)
- Patients with acute clinical symptoms or extended degree of hydronephrosis at diagnosis (e.g. stones, sepsis) leading to immediate surgery
- Patients with nephrostomy and/or stenting.
Types of interventions
We will compare surgical interventions for treating UPJO (open, antegrade and retrograde endoscopic and laparoscopic with or without robotic-assisted techniques) with conservative (non-surgical) management with or without antibiotic prophylaxis of any duration excluding stenting and/or nephrostomy.
Types of outcome measures
- Numbers of patients with improved (≥ +5%) split kidney function based on any appropriate imaging test
- Numbers of patients whose split kidney function deteriorated (≥ -5%) and/or was unchanged, based on any appropriate imaging test.
- Numbers with regressive, persistent or progressive upper urinary tract dilatation diagnosed by postnatal ultrasound
- Numbers with presentation of UPJO-associated clinical symptoms (e.g. stone formation, febrile urinary tract infection)
- Numbers with secondary surgical intervention following progressive kidney impairment
- Numbers with postoperative complications
- Numbers who progressed to CKD and end-stage kidney disease
- Differences in renal scintigraphy and any other appropriate imaging tests
- Costs of interventions
- Quality of life.
Search methods for identification of studies
We will search the Cochrane Renal Group's Specialised Register for the review through contact with the Trials Search Co-ordinator using search terms relevant to this review. The Cochrane Renal Group’s Specialised Register contains studies identified from:
- Quarterly searches of the Cochrane Central Register of Controlled Trials CENTRAL
- Weekly searches of MEDLINE OVID SP
- Handsearching of renal-related journals and the proceedings of major renal conferences
- Searching of the current year of EMBASE OVID SP
- Weekly current awareness alerts for selected renal journals
- Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the Specialised Register section of information about the Cochrane Renal Group.
See Appendix 1 for search terms used in strategies for this review.
Searching other resources
- Reference lists of clinical practice guidelines, review articles and relevant studies.
- Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.
Data collection and analysis
Selection of studies
The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. Titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable; however, studies and reviews that might include relevant data or information on studies will be retained initially. Two authors will independently assess retrieved abstracts, and if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria.
Data extraction and management
Data extraction will be carried out independently by two authors using standard data extraction forms. Studies reported in non-English and non-German language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions these data will be used. Any discrepancy between published versions will be highlighted. Any disagreements will be resolved by discussion and consensus.
Assessment of risk of bias in included studies
- Was there adequate sequence generation (selection bias)?
- Was allocation adequately concealed (selection bias)?
- Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?
- Participants and personnel
- Outcome assessors
- Were incomplete outcome data adequately addressed (attrition bias)?
- Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
- Was the study apparently free of other problems that could put it at a risk of bias?
Measures of treatment effect
For dichotomous outcomes results will be expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment, such as split kidney function, the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used. Where summary statistics are missing, they will be derived from accompanying P values.
Number needed to treat estimates will be calculated to compare the benefits and harms of each active treatment.
Unit of analysis issues
We will include only parallel group RCTs, cluster RCTs and cross-over RCTs. Where parallel group designs include three or more treatment groups, we will segment the control group ensuring that the total number adds up to the original size of the group.
Dealing with missing data
Any further information required from the original author will be requested by written correspondence (e.g. emailing and/or writing to corresponding author/s) and any relevant information obtained in this manner will be included in the review. Evaluation of important numerical data such as screened, randomised patients as well as intention-to-treat, as-treated and per-protocol population will be carefully performed. Attrition rates, for example drop-outs, losses to follow-up and withdrawals will be investigated. Issues of missing data and imputation methods (for example, last-observation-carried-forward) will be critically appraised (Higgins 2011).
Assessment of heterogeneity
Heterogeneity will be analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² test (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.
Assessment of reporting biases
If possible, funnel plots will be used to assess for the potential existence of small study bias (Higgins 2011).
Data will be pooled using the random-effects model but the fixed-effect model will also be used to ensure robustness of the model chosen and susceptibility to outliers.
Subgroup analysis and investigation of heterogeneity
Subgroup analysis will be used to explore possible sources of heterogeneity:
- age at diagnosis of UPJO
- grade of presentation of upper urinary tract dilatation (according ultrasound classification grade 0, 1, 2, 3, 4)
- grade of urinary outflow obstruction at time of diagnosis
- grade of split kidney function at time of diagnosis
- pathophysiologic origin of UPJO (intramural, mural, extramural)
- type of surgical intervention (open, endoscopic and robotic-assisted techniques)
- administration of antibiotic prophylaxis (yes/no)
- association of other urological abnormalities (vesicoureteral reflux)
Adverse effects will be tabulated and assessed with descriptive techniques, as they are likely to be different for the various agents used. Where possible, the risk difference with 95% CI will be calculated for each adverse effect, either compared with no treatment or another agent.
We will perform sensitivity analyses in order to explore the influence of the following factors on effect size:
- repeating the analysis excluding unpublished studies
- repeating the analysis taking account of risk of bias
- repeating the analysis excluding any very long or large studies to establish how much they dominate the results
- repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country
- repeating the analysis excluding studies that were stopped early for efficacy.
We would like to thank the Cochrane Renal Group and referees for their assistance, comments and feedback.
Appendix 1. Electronic search strategies
Appendix 2. Risk of bias assessment tool
Contributions of authors
- Draft the protocol: MW, DB
- Study selection: MW, ST
- Extract data from studies: MW, ST
- Enter data into RevMan: MW, ST
- Carry out the analysis: MW, ST
- Interpret the analysis: MW, ST
- Draft the final review: MW, ST
- Disagreement resolution: MW, DB, ST
- Update the review: MW, ST, DB
Declarations of interest