Surgery versus non-surgical management for unilateral ureteric-pelvic junction obstruction in children

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

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.

Background

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 99mTc-MAG3 provides useful information on split kidney function and isotope clearance (Riccabona 2009). Administration of diuretics, such as frusemide 0.5 to 1.0 mg/kg body weight, is aimed to differentiate between obstruction and the immediate drainage of non-obstructive urinary tract dilatation caused by a reservoir effect (Riccabona 2009).

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:

  1. open approach (such as Anderson-Hynes pyeloplasty)

  2. endoscopic approach (antegrade or retrograde)

  3. laparoscopic approach with or without robotic assistance (Mei 2011; Vemulakonda 2008).

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.

Objectives

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.

Methods

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

Inclusion criteria

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).

Exclusion criteria

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

Primary outcomes
  • 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.

Secondary outcomes
  • 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

Electronic searches

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:

  1. Quarterly searches of the Cochrane Central Register of Controlled Trials CENTRAL

  2. Weekly searches of MEDLINE OVID SP

  3. Handsearching of renal-related journals and the proceedings of major renal conferences

  4. Searching of the current year of EMBASE OVID SP

  5. Weekly current awareness alerts for selected renal journals

  6. 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

  1. Reference lists of clinical practice guidelines, review articles and relevant studies.

  2. 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

The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (Appendix 2).

  • 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 synthesis

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.

Sensitivity analysis

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.

Acknowledgements

We would like to thank the Cochrane Renal Group and referees for their assistance, comments and feedback.

Appendices

Appendix 1. Electronic search strategies

DatabaseSearch terms
CENTRAL
  1. MeSH descriptor Ureteral Obstruction, this term only

  2. MeSH descriptor Kidney Pelvis explode all trees

  3. pelvic-ureteric junction obstruction:ti,ab,kw or pelvicureteric junction obstruction:ti,ab,kw in Clinical Trials

  4. (uretero-pelvic junction obstruction ):ti,ab,kw or (ureteropelvic junction obstruction):ti,ab,kw in Clinical Trials

  5. (upjo):ti,ab,kw or (pujo):ti,ab,kw in Clinical Trials

  6. (#1 OR #2 OR #3 OR #4 OR #5)

MEDLINE (OVID SP)
  1. Ureteral Obstruction/

  2. exp Kidney Pelvis/

  3. (pelvic-ureteric junction obstruction$ or pelvicureteric junction obstruction).tw.

  4. (uretero-pelvic junction obstruction or ureteropelvic junction obstruction).tw.

  5. (UPJO or PUJO).tw.

  6. or/1-5

EMBASE (OVID SP)
  1. ureteropelvic junction obstruction/

  2. pelvic-ureteric junction obstruction$.tw.

  3. ureteropelvic junction obstruction$.tw.

  4. PUJO.tw.

  5. or/1-4

Appendix 2. Risk of bias assessment tool

Potential source of bias Assessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence

Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random)
High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention
Unclear: Insufficient information about the sequence generation process to permit judgement

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment

Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes)
High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure
Unclear: Randomisation stated but no information on method used is available

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study

Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken
High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding
Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.

Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken
High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding
Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.

Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods
High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation
Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting

Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon)
High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study
Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table

Low risk of bias: The study appears to be free of other sources of bias
High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem
Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias

Contributions of authors

  1. Draft the protocol: MW, DB

  2. Study selection: MW, ST

  3. Extract data from studies: MW, ST

  4. Enter data into RevMan: MW, ST

  5. Carry out the analysis: MW, ST

  6. Interpret the analysis: MW, ST

  7. Draft the final review: MW, ST

  8. Disagreement resolution: MW, DB, ST

  9. Update the review: MW, ST, DB

Declarations of interest

None known

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