Abstract
Background
Unilateral ureteric‐pelvic junction obstruction (UPJO) is the most common cause of obstructive uropathy and may lead to renal impairment and loss of renal function. The current diagnostic approach with renal imaging cannot reliably determine which newborns and infants less than two years of age have a significant obstruction and are at risk for permanent kidney damage. There is therefore no consensus on optimal therapeutic management of unilateral UPJO.
Objectives
To assess the effects of surgical versus non‐surgical treatment options for newborns and infants less than two years of age with unilateral UPJO.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2016), MEDLINE/Ovid, and EMBASE/Ovid databases from their inception to 13 June 2016. We searched the reference lists of potentially relevant studies without using any language restriction. We also searched the following trial registers for relevant registered studies: www.clinicaltrials.gov/; ISRCTN registry (controlled‐trials.com/); www.trialscentral.org/; apps.who.int/trialsearch/; www.drks.de/; and www.anzctr.org.au/trialSearch.aspx.
Selection criteria
We selected randomised and quasi‐randomised controlled trials comparing surgical with non‐surgical interventions for the treatment of unilateral UPJO.
Data collection and analysis
Two review authors independently assessed study eligibility and risk of bias of included studies and extracted data. In case of disagreements we consulted a third review author. The data reported in the two included studies did not allow us to perform a meta‐analysis.
Main results
We found only two studies at high risk of bias that were eligible for inclusion in this review. The total sample size, including both trials, was small (n = 107 participants less than six months of age from the UK and USA), and not all prespecified outcome measures were assessed. Reported measures only accounted for the short‐term follow‐ups. The mean split renal function was not statistically different between the surgical and non‐surgical group at the six‐month or one‐year time point (very low‐quality evidence). The surgical group showed a significantly less obstructed drainage pattern and a lower urinary tract dilatation than the non‐surgical group (very low‐quality evidence). Transfer from the non‐surgical group to the surgical group was reported for about one out of five participants. Split renal function after secondary surgical intervention was reported with variable results, but most of the participants reverted to pre‐deteriorated values. The studies either provided no or insufficient data on the following outcome measures: postoperative complications, UPJO‐associated clinical symptoms, costs of interventions, radiation exposure, quality of life, and adverse effects.
Authors' conclusions
We found limited evidence assessing the benefits and harms of surgical compared to non‐surgical treatment options for newborns and infants less than two years of age with unilateral UPJO. The majority of participants in the non‐surgical treatment group did not experience any significant deterioration of split renal function, and only about 20% of them underwent secondary surgical intervention, with minor risk of permanent deteriorated split renal function. The study follow‐up period was too short to assess the long‐term effects on split renal function in both treatment groups. We need further randomised controlled trials with sufficient statistical power and an adequate follow‐up period to determine the optimal therapy for newborns and infants less than two years of age with unilateral UPJO.
Keywords: Female; Humans; Infant; Infant, Newborn; Male; Kidney Pelvis; Kidney Pelvis/surgery; Randomized Controlled Trials as Topic; Sample Size; Ureteral Obstruction; Ureteral Obstruction/surgery; Ureteral Obstruction/therapy
Plain language summary
Surgery versus non‐surgical management for unilateral ureteric‐pelvic junction obstruction in newborns and infants less than two years of age
Review question
Do children with unilateral ureteric‐pelvic junction obstruction do better with or without surgery?
Background
Some newborn and infants less than two years of age are shown using ultrasound to have an enlargement of the pelvis of the kidney. This is the anatomical structure where the urine collects before it is transported down the ureter to the bladder. Enlargement of the pelvis of the kidney is a concern due to possible blockage of urine flow, not unlike how a river widens in front of a dam.
Longer‐term blockage of the urine flow for months and years may damage the kidney and lead to other problems such as urinary tract infections or kidney stones. Surgery can remove a blockage if it occurs, but it also has downsides including risks of complications. It is unclear whether these operations are necessary.
Results
We searched for studies up to 13 June 2016 and found two trials that compared groups of newborns and infants less than two years of age, including a total of 107 children who had surgery or no surgery and were followed for up to five years. Based on very low‐quality evidence, we found that short‐term kidney function (after six and 12 months) was similar in the two groups. Very low‐quality evidence also showed that after surgery, the pelvis of the kidney was smaller and urine seemed to flow better from the kidney down the ureter. However, due to the methods and size and of the studies, we are very uncertain about these results. There was insufficient evidence to determine whether one group of participants did better longer term, had fewer complications, or had better quality of life.
Summary of findings
Summary of findings for the main comparison. Surgical compared to non‐surgical management for UPJO.
| Surgical compared to non‐surgical management for UPJO | |||
| Patient or population: newborns and infants < 2 years of age with unilateral ureteric‐pelvic junction obstruction Intervention: surgical management Comparison: non‐surgical management | |||
| Outcomes | Anticipated absolute effects | № of participants (studies) | Quality of the evidence (GRADE) |
| Split renal function (SRF; assessed with any appropriate imaging test) |
After 6 months Mean SRF is reported to not be significantly different between groups at 6 months' follow‐up |
17 (1 study) |
⊕⊝⊝⊝ VERY LOW 1 2 3 |
|
After 12 months Mean SRF is reported to not be significantly different between groups at 12 months' follow‐up |
89 (2 studies) |
||
| Drainage pattern (assessed with scintigraphy or MRI) |
After 6 months After 6 months, all non‐surgical participants still exhibited obstruction, while all surgical participants showed no obstruction |
57a (2 studies) |
⊕⊝⊝⊝ VERY LOW 1 2 3 |
|
After 12 months One study reported only the drainage pattern of the surgical group. These participants had an improved drainage pattern. The other study reported no obstruction in all surgical participants, but no change in obstruction for the non‐surgical group, except for 1 participant with indeterminate obstruction |
55a (2 studies) |
||
| Upper urinary tract dilatation (assessed with ultrasound) |
After 6 months Only one study reported the mean grade of urinary tract dilatation for each treatment group. 6 months after enrolment, it was not changed in the non‐surgical group (3.6) and decreased from 3.7 to 2.6 in the surgical group |
15 (1 study) |
⊕⊝⊝⊝ VERY LOW 1 3 |
|
After 12 months While one study reported essentially unchanged mean grade of urinary tract dilatation for the non‐surgical group, the other study describes dilatation improvement in 16.7% of non‐surgical participants. In the surgical groups of these studies a lowering in hydronephrosis was observed, dropping further to a mean grade of 2.1 or showing a reduction in mean pelvic diameter from 25 to 11 mm. |
88 (2 studies) |
||
| UPJO‐associated clinical symptoms | One study reported only the absence of urinary tract infections, yet the number of participants for this evaluation remains unclear | ‐ | ⊕⊝⊝⊝ VERY LOW 1 3 |
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | |||
1Lack of blinding of participants and personnel (risk of performance bias) and unclear blinding of outcome assessors in one study (risk of detection bias). In addition, a large proportion of participants were not accounted for in the analysis (loss to follow‐up; risk of attrition bias). Therefore downgraded by 2 levels for risk of bias.
2Diagnostic assessment and therapeutic management of patients has changed considerably since the time trials were conducted. Therefore downgraded by 1 level for indirectness.
3Sample size of trials (in particular number of analysed participants) small; although there is insufficient detail for formal assessment, clinically relevant differences cannot be excluded or confirmed. Therefore downgraded by 1 level for imprecision.
aThe total number of participants could be slightly different, because reporting of the number of participants assessed at each stage is imprecise in Palmer 1998.
Background
Description of the condition
Ureteric‐pelvic junction obstruction (UPJO) adversely affects 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 per 1000 births, and it is most often unilateral (60% to 80%). People with unilateral UPJO have increased incidence of associated urological anomalies (Karnak 2008).
Unilateral UPJO is the most common cause of pre‐ and postnatal obstructive uropathy (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, and research on pathophysiology is limited to animal model findings (Chen 2009; 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 infants. 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 stage at which the obstruction occurs in the child's development, and the degree and duration of urinary tract obstruction on the kidney (Rosen 2008; Vaughan 2004).
UPJO evaluation requires kidney ultrasound, renal scintigraphy, or any other appropriate imaging test, such as magnetic resonance imaging (MRI) (Cerwinka 2010; Muthusami 2013; 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 Tc‐99m MAG3 or MRI provide mandatory information on split renal function and urinary outflow impediment (Riccabona 2009). Administration of diuretics, such as furosemide 0.5 to 1.0 mg/kg body weight, aims to differentiate between obstruction and the immediate drainage of non‐obstructive urinary tract dilatation caused by a reservoir effect (Riccabona 2009).
Proteome analysis from urinary polypeptides is a potentially promising future non‐invasive alternative in the diagnosis of UPJO (Mesrobian 2010).
Although kidney imaging techniques are often used to investigate and assess the need for a surgical intervention, they are not adequate predictors in determining pathophysiological consequences of impeded kidney function (Riccabona 2009).
The dynamic nature of urinary outflow obstruction, individual compensatory processes, and the stage at which the obstruction occurs in the child's development all contribute to the clinical variability of consequences on kidney development, their function, and urinary outflow impediment in children with similar degrees of urinary tract dilatation on kidney imaging (Davenport 2013). Urinary tract dilatation therefore does not necessarily equate to the presence of urinary outflow obstruction (Mesrobian 2012).
Description of the intervention
Both surgical and non‐surgical interventions are common therapeutic strategies for newborns and infants less than two years of age with unilateral UPJO (Csaicsich 2004; Gallo 2009; Mei 2011). Three main surgical procedures are used for the management of UPJO:
open approach (such as Anderson‐Hynes pyeloplasty);
laparoscopic approach (with or without robotic assistance);
endoscopic approach as a salvage procedure (antegrade or retrograde).
Multiple factors usually determine the type of surgical approach chosen, including the specific anatomical abnormality, the child's age and clinical presentation (Herndon 2009; Williams 2007). The non‐surgical wait‐and‐see strategy with and without prophylactic antibiotics requires serial kidney ultrasound examinations and renal scintigraphy or MRI in order to screen for early kidney deterioration in newborns and infants less than two years of age with unilateral UPJO (Csaicsich 2004; Malki 2012).
How the intervention might work
The aim of surgical intervention is to resolve obstruction and provide adequate drainage of the affected kidney (Mei 2011; Thornhill 2007; Williams 2007). Although it has been suggested that surgery performed during the first year of life leads to optimal kidney function improvement, others argue that secondary 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%) (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 a few newborns and infants less than two years of age with unilateral UPJO develop clinical problems or evidence of deteriorating kidney function that requires surgical intervention following non‐surgical management (Malki 2012; Ransley 1990). Full recovery of impaired split kidney function after secondary surgical procedure was reported for most of these children (Dhillon 1998).
Why it is important to do this review
Despite its relevance, optimal management of UPJO 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, recommending non‐surgical management with close monitoring and serial kidney imaging (Dhillon 1998; Malki 2012; Palmer 1998). It is therefore essential to have informed decision‐making in newborns and infants less than two years of age 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 was to better inform practice through the examination of evidence from randomised controlled trials (RCTs) comparing surgical and non‐surgical management of unilateral UPJO in newborns and infants less than two years of age.
Objectives
To assess the effects of surgical versus non‐surgical treatment options for newborns and infants less than two years of age with unilateral UPJO.
Methods
Criteria for considering studies for this review
Types of studies
We considered 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) for inclusion in this review. We included only parallel‐group RCTs, cluster RCTs, and cross‐over RCTs. We included studies regardless of their publication status or language of publication.
Types of participants
Inclusion criteria
We included newborns and infants of both genders less than two years of age with unilateral 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 MRI.
Exclusion criteria
We excluded:
newborns and infants less than two years of age with unilateral UPJO and diminished or no contralateral kidney function (e.g. multicystic‐dysplastic kidney, kidney transplant);
newborns and infants less than two years of age with acute clinical symptoms or extended degree of hydronephrosis at diagnosis (e.g. stones, sepsis) leading to immediate surgery;
newborns and infants less than two years of age with nephrostomy or stenting, or both.
Types of interventions
We compared surgical interventions for treating UPJO (open, laparoscopic with or without robotic‐assisted techniques, or antegrade and retrograde endoscopic) with non‐surgical management with or without antibiotic prophylaxis of any duration excluding stenting and/or nephrostomy.
Types of outcome measures
We included studies that measured any of the outcomes assessed in this review.
Primary outcomes
Split renal function based on any appropriate imaging test
Secondary outcomes
Number of newborns and infants less than two years of age with regressive, persistent, or progressive upper urinary tract dilatation
Number of newborns and infants less than two years of age with regressive, persistent, or progressive drainage pattern
Number of newborns and infants less than two years of age with secondary surgical intervention following progressive kidney impairment
Number of newborns and infants less than two years of age with presentation of UPJO‐associated clinical symptoms (e.g. stone formation, febrile urinary tract infection)
Number of newborns and infants less than two years of age with postoperative complications
Radiation exposure
Costs of interventions
Quality of life
Adverse effects
Main outcomes for 'Summary of findings' table
We assessed the following main outcomes in their order of importance for the narrative 'Summary of findings' table.
Split renal function
Number of newborns and infants less than two years of age with regressive, persistent, or progressive drainage pattern
Number of newborns and infants less than two years of age with regressive, persistent, or progressive upper urinary tract dilatation
Number of newborns and infants less than two years of age with presentation of UPJO‐associated clinical symptoms
Search methods for identification of studies
Electronic searches
The initial search strategy for this review was developed and carried out by the Cochrane Renal Group in 2012. For the latest version of the strategy, we searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2016); MEDLINE/Ovid (1945 to 13 June 2016); and EMBASE/Ovid (1980 to 13 June 2016). The search strategies for the different electronic databases are shown in Appendix 1. In order to restrict the search to RCTs and quasi‐RCTs, we applied the Cochrane Highly Sensitive Search Strategy as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).
We also searched the following clinical trials registries for ongoing or recently completed trials, and for locating potential links to other related databases and resources, on 14 October 2015. We used a regular search with keywords ('hydronephrosis', 'obstruction', 'junction', 'ureteric‐pelvic', 'ureteropelvic', 'pelvi‐ureteric', 'ureteral obstruction', 'pyeloplasty') alone or in combination, where applicable. We applied no time restrictions and did not limit the search to trials of children less than 18 years of age.
ClinicalTrials.gov (www.clinicaltrials.gov/)
ISRCTN registry (controlled‐trials.com/)
Trials Central (www.trialscentral.org/) (search under the subheading 'urinary tract, sexual organs, and pregnancy conditions')
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/)
Internet Portal of the German Clinical Trials Register (DRKS) (www.drks.de/)
Australian New Zealand Clinical Trials Registry (ANZCTR) (www.anzctr.org.au/trialSearch.aspx)
We contacted study authors of identified trials to clarify information or to request additional data, as necessary.
Searching other resources
We searched the conference proceedings of the following societies electronically (either with regular or advanced search, using the keywords 'hydronephrosis', 'obstruction', 'junction', 'ureteric‐pelvic', 'ureteropelvic', 'pelvi‐ureteric', 'ureteral obstruction', and 'pyeloplasty') or, if unavailable, by hand on 20 October 2015. Source links for electonic searches are provided in Appendix 2.
Society for Pediatric Urology (SPU) (2010 to 2015)
European Society for Paediatric Urology (ESPU) (2010 to 2015)
American Academy of Pediatrics (AAP) (2010 to 2015)
European Academy of Paediatrics (EAP) (2012 to 2015)
American Urological Association (AUA) (2010 to 2015)
European Association of Urology (EAU) (2010 to 2015)
American Society of Pediatric Nephrology (ASPN) (2010 to 2015)
European Society for Paediatric Nephrology (ESPN) (2010 to 2015)
We searched the reference lists of relevant articles and review articles. We sent letters seeking information on unpublished or incomplete studies to investigators known to be involved in previous studies. We contacted specialists in the field to ask for potential unpublished data.
Data collection and analysis
Selection of studies
The literature search strategy described above was developed and performed in order to identify eligible studies. Two review authors (MW, SP) independently screened the titles and abstracts of references identified by the search. We retrieved the full texts of references considered relevant by at least one of the review authors. Two review authors (MW, SP) screened the full‐text papers against the inclusion criteria. We resolved any disagreements on the eligibility of studies through discussion and consensus or through arbitration by a third review author (DB).
Data extraction and management
Two review authors (MW, SP) independently performed data extraction using a data extraction form developed by the review authors. Any disagreements on data extraction and management issues were resolved through discussion and consensus, or by consulting a third review author (GFL). We obtained further information from the study authors by written correspondence, and included any relevant information acquired in this manner in the review. We extracted the following data.
Characteristics of included studies (MW, SP): These included study design, country, study execution date, date of publication, population characteristics, setting, detailed nature of experimental intervention, detailed nature of comparator intervention, detailed nature of outcomes, funding sources, and declarations of interest of the study authors. A key purpose of extracting this data was to define unexpected clinical heterogeneity in included studies independently of analysis of results.
Results of included studies with respect to outcomes listed under Types of outcome measures: MW and SP carefully recorded reasons why an included study did not contribute data on a particular outcome and considered the possibility of selective reporting of results on particular outcomes.
Assessment of risk of bias in included studies
Two review authors (MW, SP) independently assessed the following domains using the Cochrane 'Risk of bias' tool (Higgins 2011a).
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants and personnel (performance bias)
Blinding of outcome assessment (detection bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other sources of bias
We judged 'Risk of bias' domains as 'low risk', 'high risk', or 'unclear risk' and evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). Two review authors (MW and SP or DB) independently assessed the risk of bias of studies to be included without blinding to authorship or journal of publication. Discrepancies were resolved by consensus and when necessary by discussion with GFL. We further summarised the risk of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome. We reported the 'Risk of bias' table as part of the table of Characteristics of included studies and presented a 'Risk of bias' graph and summary (Figure 1 and Figure 2) that detailed all of the judgements made for all studies included in the review (Higgins 2011a). For each included study, we assessed the selective reporting bias by comparing the methods and results section of the individual studies. We resolved any disagreements on the 'Risk of bias' assessment through discussion and consensus, or if necessary by consulting a third party (MW and SP, or GFL) and planned to explore the impact of the level of bias by undertaking sensitivity analyses (see Sensitivity analysis). For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we aimed to evaluate the risk of bias separately for each outcome where possible. We also assessed attrition bias (incomplete outcome data) on an outcome‐specific basis, and grouped outcomes with like judgements when reporting our findings in the 'Risk of bias' tables.
1.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Measures of treatment effect
We planned to express results for dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment, such as split kidney function, we planned to use the mean difference (MD) with 95% CI, or the standardised mean difference (SMD) with 95% CI if different scales had been used. Where summary statistics were missing, we planned to derive them from accompanying P values. We intended to estimate the number needed to treat for an additional beneficial outcome and number needed to treat for an additional harmful oucome in order to compare the benefits and harms of each active treatment.
Unit of analysis issues
We planned to include only parallel‐group RCTs, cluster RCTs, and cross‐over RCTs. In case of parallel‐group designs with three or more treatment groups, we planned to segment the control group into several parts, ensuring that the total number adds up to the original size of the group.
Dealing with missing data
We requested any further information required from the study authors by written correspondence (for example by emailing or writing to corresponding authors, or both), and included any relevant information obtained in this manner in the review. We intended to perform careful evaluation of important numerical data such as screened, randomised participants as well as intention‐to‐treat, as‐treated, and per‐protocol population. We investigated attrition rates, for example dropouts, losses to follow‐up, and withdrawals, and carefully appraised issues of missing data and imputation methods (for example last observation carried forward) (Higgins 2011b). We planned to conduct an intention‐to‐treat analysis if data on all participants were available. If participant data were missing, we performed available‐case analyses (analysing participants in the groups to which they were randomised) and addressed the potential impact of missing data on the findings of the review in the Discussion section.
Assessment of heterogeneity
We planned to assess heterogeneity using a Chi2 test on N‐1 degrees of freedom, with an alpha of 0.1 used for statistical significance and with the I2 statistic (Higgins 2003). I2 values of ≥ 25%, ≥ 50% and ≥ 75% were to correspond to low, medium, and high levels of heterogeneity.
Assessment of reporting biases
We minimised the likelihood of publication bias by using a comprehensive search strategy without language restrictions. This search strategy included searching the abstracts of conference proceedings (see Searching other resources) and various trial registries (see Electronic searches) in order to identify unpublished trials. We also contacted experts in the field and questioned them about any unpublished trials. We planned to use funnel plots to assess the existence of small‐study bias (Higgins 2011b). We attempted to obtain study protocols to assess for reporting bias, however no study protocols were received.
Data synthesis
We intended to pool data using the random‐effects and fixed‐effect models to ensure robustness of the model chosen and susceptibility to outliers. We planned to list all adverse effects detected within the included studies and assess them in a descriptive manner.
Subgroup analysis and investigation of heterogeneity
We planned to explore possible sources of heterogeneity through the following subgroup analyses.
Age at diagnosis of UPJO
Grade of presentation of upper urinary tract dilatation (according to ultrasound classification grade 0, 1, 2, 3, 4)
Grade of urinary outflow obstruction at time of diagnosis
Grade of split renal function at time of diagnosis
Pathophysiologic origin of UPJO (intramural, mural, extramural)
Type of surgical intervention (open, robotic‐assisted techniques, and endoscopic)
Administration of antibiotic prophylaxis (yes/no)
Association of other urological abnormalities (vesico‐ureteral reflux)
Sensitivity analysis
We intended to 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 into account the risk of bias (e.g. excluding studies at high or unclear risk of bias, or both)
Repeating the analysis excluding any very long or large studies to establish to what degree they dominate the results
Repeating the analysis excluding studies that were stopped early for efficacy
Due to the limited data available, we performed no sensitivity analysis.
'Summary of findings' table
We summarised the evidence using a 'Summary of findings’ table, which we created using the GRADEpro Guideline Development Tool (www.guidelinedevelopment.org) (Guyatt 2011). We rated the quality of evidence per outcome using the GRADE approach, considering five factors that can decrease the quality of evidence (that is risk of bias, inconsistency, indirectness, imprecision, and publication bias) and three factors that can increase the quality of evidence (that is large effect, dose‐response relationship, and opposing confounding) (Balshem 2011).
Results
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies.
Results of the search
The initial search yielded 1101 articles in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/Ovid, and EMBASE/Ovid (Figure 3). After removing duplicates, we screened 847 titles and abstracts. A total of 844 articles were not eligible and were therefore excluded. We screened three full‐text articles. One manuscript describes a retrospective cohort study (see Characteristics of excluded studies). The other manuscripts describe RCTs. Our search of the references of review articles identified no additional RCTs.
3.
Study flow diagram.
Our search of other resources did not reveal any eligible studies. There is currently one registered clinical trial comparing surgical versus non‐surgical intervention for unilateral UPJO in newborns and infants less than two years of age (NCT00444431). We contacted the primary investigators and were informed that the trial was closed prior to recruitment and had not been deleted from the ClinicalTrials.gov trial registry.
We included a total of two studies in the review. All index reports were in English.
Included studies
The two included studies enrolled a total of 107 newborns and infants less than two years of age with unilateral UPJO. Details of the included studies are presented in the Characteristics of included studies table.
Dhillon 1998: This was a single‐centre study in the UK. Infants between three and six months of age (n = 75) with unilateral UPJO (ultrasonographic hydronephrosis less than or equal to 15 mm anteroposterior diameter) and renal scintigraphy (diethylene triamine pentaacetic acid) with a split renal function of less than 40% on the ipsilateral side were randomised either to the surgical (dismembered pyeloplasty, not further specified) or non‐surgical group. Imaging (ultrasound/renal scintigraphy) was done in the surgical group after three months, one year, and five years and in the non‐surgical group after three months, one year, two years, three years, four years, and five years. The indication for secondary surgical intervention was a deterioration of split renal function of the hydronephrotic kidney by less than 10% (renal scintigraphy) or to less than 40%. Outcome criteria were mean pelvic diameter (ultrasound) and split renal function (renal scintigraphy). Information on the funding source was not given.
Palmer 1998: This was a multicentre study in the USA including infants less than six months of age (n = 32) with unilateral UPJO (ultrasonographic hydronephrosis less than or equal to grade 3 according to the grading system of the Society for Fetal Urology and renal scintigraphy with a split renal function of at least 40% on the ipsilateral side). Infants were randomised to either the surgical (dismembered pyeloplasty, not further specified) or non‐surgical group. Imaging (ultrasound/renal scintigraphy) was done after six months, one year, two years, and three years in the surgical group and after six months, one year, two years, and three years in the non‐surgical group. The indication for secondary surgical intervention was a deterioration of split renal function less than 10% (renal scintigraphy) or hydronephrosis (ultrasound) of the ipsilateral side, or both. Outcome criteria were mean pelvic diameter (ultrasound), split renal function and drainage pattern (renal scintigraphy). Information on the funding source was not given.
Excluded studies
Heinlen 2009: This was a single‐centre, retrospective study.
Risk of bias in included studies
We assessed the risk of bias of the included studies according to the seven domains outlined in the Cochrane 'Risk of bias' tool. We extracted the methodological details of the studies from the published data and by contacting the primary authors. However, we received a response from only one primary author (Dhillon 1998). No study protocols were made available for us to further assess the risk of bias for both included studies.
Allocation
Random sequence generation
Randomisation to one of the study groups was done using a computer‐generated random number sequence in Palmer 1998, resulting in a judgement of low risk of bias for this domain. As no allocation information was provided in Dhillon 1998, we judged the risk of bias to be unclear.
Allocation concealment
In both studies allocation concealment was not clearly described. We judged the risk of bias to be unclear.
Blinding
We assessed blinding on an outcome‐specific basis.
Blinding of participants and personnel
Split renal function, upper urinary tract dilatation, drainage pattern, secondary surgical intervention, UPJO‐associated clinical symptoms, postoperative complications
Due to the nature of the study (surgical versus non‐surgical treatment), participants could not be blinded. One study reported absence of blinding of primary investigators (Palmer 1998), whereas the other study did not mention blinding (Dhillon 1998). We therefore judged the risk of bias due to blinding of participants and personnel to be high for Palmer 1998 and unclear for Dhillon 1998 across all assessed outcomes.
Radiation exposure, costs of intervention, quality of life
Neither of the studies covered these outcomes. Assessment of risk of bias was not applicable.
Blinding of outcome assessment
Split renal function, upper urinary tract dilatation, drainage pattern
Blinded reviewers confirmed imaging assessment for the three outcomes split renal function, urinary tract dilatation, and drainage pattern in Palmer 1998, resulting in a judgement of low risk of bias. As Dhillon 1998 did not report blinding of investigator, we judged the risk of bias to be unclear for these three outcomes.
Secondary surgical intervention, UPJO‐associated clinical symptoms, postoperative complications
As assessment was based solely on medical records, we judged the risk of bias to be low in both studies.
Radiation exposure, costs of intervention, quality of life
Neither of the studies covered these outcomes. Assessment of risk of bias was not applicable.
Incomplete outcome data
We assessed risk of bias for incomplete outcome data on an outcome‐specific basis.
Split renal function, upper urinary tract dilatation, drainage pattern, secondary surgical intervention, UPJO‐associated clinical symptoms, postoperative complications
There were no participants reported lost to follow‐up in Dhillon 1998, but it was not clearly stated how many participants were initially enrolled in the study. This applies to all assessed outcomes, therefore we judged the risk of bias to be unclear. The study authors of Palmer 1998 reported a loss to follow‐up of 12 out of 36 participants (33%) due to parental refusal to continue the protocol or inability to contact. It is not mentioned whether the excluded participants were balanced across intervention groups. Due to this high loss of follow‐up rate, we judged the risk of bias to be high for all assessed outcomes.
Radiation exposure, costs of intervention, quality of life
Neither of the studies covered these outcomes. Assessment of risk of bias was not applicable.
Selective reporting
In both studies it is unclear whether all prespecified outcomes that were assessed were reported, and we were not able to obtain original trial protocols. We attempted to contact the corresponding author of each study, but only received a response to our inquiry (with limited information) from one author (Dhillon 1998).
In the Dhillon 1998 study, outcomes were reported only at the one‐year time point despite the fact that prespecified time points included three months and five years. Only the lack of five‐year data is justified, since not all participants had completed the whole study period at the time of publication. Furthermore, Dhillon 1998 did not report data for hydronephrosis for the participants with secondary surgical intervention, as well as drainage pattern for the non‐surgical group. We therefore judged the risk of bias to be high.
Palmer 1998 reported 32 randomised participants, however in the manuscript the study authors subsequently refer to only 31 participants. The study authors reported a loss to follow‐up of 12 participants, however this number is not consistent with the number of participants assessed at each time point, and it is not clear if this was due to loss to follow‐up or selective reporting. For instance, 16 participants had completed one year in the trial, but data was only provided for 13 on urinary tract dilatation and for 14 on split renal function. We therefore considered the risk of bias to be high.
Other potential sources of bias
It remains unclear how participants with secondary surgical intervention from the non‐surgical group were analysed. Both studies presented only preliminary results, with pending results for participants at different time points. It is not mentioned whether analyses were done per protocol or intention to treat. In both studies it is unclear whether adjustment for multiple testing was done. For all of these reasons we judged the risk of bias to be high in both studies.
Effects of interventions
See: Table 1
Surgical versus non‐surgical management
The data reported in the two included studies was not sufficient for the performance of meta‐analyses. The study authors did not present the results in a common format (mean and standard deviation) or in one that could be easily converted. Furthermore, due to lack of data we could carry out no preplanned subgroup analyses. The overall risk of bias across domains is identical for all outcomes and across studies and must be considered to be high. The relative importance of the ‘reporting bias’ domain was the most influential for this judgement, because selective reporting is a major decisive factor for implications and conclusions that can or cannot be drawn from the reported results.
Primary outcomes
Split renal function based on any appropriate imaging test
Both trials used renal scintigraphy to determine split renal function. The renal scintigraphy was carried out with Tc‐99m DTPA (diethylene triamine pentaacetic acid) without administration of furosemide and Tc‐99m MAG3 (mercaptoacetyltriglycine) with administration of furosemide after complete filling of the renal collecting system (Dhillon 1998; Palmer 1998). The presented results for split renal function were given as percentage differential function of the affected hydronephrotic kidney in both trials, but the evidence must be considered to be of very low quality (see Table 1) due to the small sample size of both studies and unclear risk of selection and detection bias, as well as high risk of selective outcome reporting. Dhillon 1998 reported results for split renal function only one year postoperatively. However, it remains unclear how the time point of assessment of this outcome was determined in the non‐surgical group. The study by Palmer et al. presented statistical analysis for the time points of six months and one year (Palmer 1998). The number of participants in that study did not allow for statistical analysis at the time points of two years (surgical group: n = 3; non‐surgical group: n = 3) and three years (surgical group: n = 2; non‐surgical group: n = 2). The number of participants at different imaging time points was unclear due to varying information within the manuscript. In Dhillon 1998, one year after surgery, there was no difference in split renal function between the treatment groups. The mean (range) split renal function was 50% (38% to 65%) for the surgical group and 50% (39% to 60%) for the non‐surgical group (total number of participants unclear). In the study by Palmer et al., there was no significant difference between the two groups in mean split renal function at six months (surgical group: n = 7; non‐surgical group: n = 10) and one year (surgical group: n = 8; non‐surgical group: n = 6) (Palmer 1998).
Secondary outcomes
Number of newborns and infants less than two years of age with regressive, persistent, or progressive upper urinary tract dilatation diagnosed by postnatal ultrasound
The study by Dhillon et al. did not mention any comparison of ultrasound imaging between the randomised groups or present the number of regressive, persistent, or progressive hydronephrosis (Dhillon 1998). Instead, the study reports mean pelvic diameter for the surgical group at entry into the trial as 25 mm (range 15 to 55 mm) and at the one‐year time point as 11 mm (range 3 to 27 mm). Data for participants in the non‐surgical group were only reported for the one‐year follow‐up, with five having complete resolution and 12 only mild hydronephrosis. The mean grade of urinary tract dilatation was significantly lower in the surgical group than in the non‐surgical group at the time points of six months (n = 15) and one year (n = 13) in the study by Palmer et al. (Palmer 1998). In contrast, there was no significant difference in mean polar lengths of the affected kidneys between the randomised groups at six‐months and one‐year imaging (number of cases unknown). For the subsequent time points (two years and three years), the number of participants was reported as being too small for statistical analysis. Overall, the quality of data for upper urinary tract dilatation must be considered to be very low (see Table 1), since selection and detection bias are unclear, and again, the risk for selective reporting is high and the sample size very low for both studies.
Number of newborns and infants less than two years of age with regressive, persistent, or progressive drainage pattern
All participants in both trials showed obstructive drainage pattern at randomisation. In addition to the Tc‐99m DTPA imaging, Dhillon et al. performed a Whitaker test prior to randomisation of the participants (Dhillon 1998; Jaffe 1980). Only the study by Palmer et al. provided information about the definition of obstructed drainage pattern, following the recommendation made by Conway et al. (Conway 1992; Palmer 1998). The study by Dhillon et al. did not compare drainage patterns between the randomised groups, but reported it as being not obstructed in all participants of the surgical group at one year (n = 39) (Dhillon 1998). Regarding drainage pattern in the study by Palmer et al., participants who underwent surgery showed significantly less obstruction than participants who did not undergo surgery at six‐months and one‐year imaging intervals (number of participants unclear) (Palmer 1998). Again, the number of participants did not allow for statistical analyses at the subsequent time points (two years and three years). We considered the evidence for both studies to be of very low quality, as they are based on a very small sample size and the risk of bias for allocation concealment and partially for blinding of outcome assessment is unclear and in the case of selective reporting is high.
Number of newborns and infants less than two years of age with secondary surgical intervention following progressive kidney impairment
Both studies reported on secondary surgical intervention in non‐surgical group participants (Dhillon 1998; Palmer 1998). The proportion of secondary surgery was 7 out of 36 participants (19.4%) in Dhillon 1998 and 4 out of 16 participants (25%) in Palmer 1998. It must be noted that the percentage of secondary surgical intervention in Palmer 1998 is probably higher than 25%, since 16 participants were initially enrolled per treatment group, but an unreported number of these were lost to follow‐up. Dhillon 1998, reported that six out of seven cases with secondary surgical intervention (85.7%) had full recovery of split renal function. No recovery of split renal function despite surgical intervention was seen in one out of seven participants (14.3%) at one‐year imaging (Dhillon 1998). This child had a reduced split renal function of 39% compared to 45% at randomisation and 36% at time of secondary surgical intervention. No change in urinary tract dilatation or drainage pattern was reported. In Palmer 1998, imaging data was only available for two of the four participants with secondary surgical intervention at the six‐months time point postoperatively. For the other participants and time points, imaging results were pending at the time of publication of the study report. Reduction of split renal function despite surgical intervention was seen in both of these participants, with diminished split renal function of 29% (53% at randomisation; 40% at secondary surgery) and 24% (45% at randomisation; 30% at secondary surgery). Decreased hydronephrosis was seen in both participants from grade 4 to grade 3, whereas drainage pattern was unchanged in one child and no signs of obstruction present in the other.
Number of newborns and infants less than two years of age with presentation of UPJO‐associated clinical symptoms (for example stone formation, febrile urinary tract infection)
All participants in the study of Dhillon 1998 received antibiotic prophylaxis (trimethoprim 2 mg/kg nightly) until one year of age. The study did not report on the indications for antibiotic prophylaxis (for example vesico‐ureteral reflux following voiding cystourethrography) on urinary tract infection in association with UPJO as an outcome. No antibiotic prophylaxis was administered in the study of Palmer 1998; in this study no urinary tract infection occurred in any of the intervention groups. Neither of the studies reported on other potential UPJO‐associated clinical symptoms (for example stones). The evidence for this outcome was of very low quality, mostly due to the high risk of selective reporting in both studies, but also because of unclear risk of detection and selection bias and the very small sample size.
Number of newborns and infants less than two years of age with postoperative complications
Dhillon 1998 did not report this outcome. Palmer 1998 reported no associated surgical complications after pyeloplasty. However, the criteria for postoperative complication was not defined.
Radiation exposure
We found no mention of this outcome.
Costs of interventions
We found no mention of this outcome.
Quality of life
We found no mention of this outcome.
Adverse effects
We found no mention of this outcome apart from those already defined as secondary outcomes above.
Subgroup analysis
We performed no subgroup analyses because of the limited number of studies included in this review and because no meta‐analysis was conducted.
Discussion
Summary of main results
We included a total of two studies in this review. Both published RCTs are not in total agreement regarding the main outcomes, with partially conflicting results despite comparable study design, study methods, and participants’ characteristics. The overall quality of evidence for the reported main outcomes split renal function, drainage pattern, upper urinary tract dilatation, and UPJO‐associated clinical symptoms was very low (Table 1). Mean split renal function was not significantly different between the surgical and the non‐surgical group in both studies. Only one study reported the outcome drainage pattern, with significant improvement in the surgical group compared to the non‐surgical group. One study reported less upper urinary tract dilatation in the surgical group compared to the non‐surgical group, whereas the other study described only changes in upper urinary tract dilatation within both groups without comparing them to each other. Information was not available for the remaining main outcome of UPJO‐associated clinical symptoms.
Overall completeness and applicability of evidence
The two included studies examined clinically important populations that were representative of patients seen in routine clinical practice. These participants and the assessed interventions directly conformed to the review question. However, several points must be considered regarding the applicability of evidence. Both studies included only participants with split renal function greater than 40%. In addition, the mean split renal function was within the normal range in both comparison groups. The findings are therefore restricted to the particular group of newborns and infants less than two years of age without significant deterioration of split renal function at time of diagnosis. Moreover, the outcomes are only reported for the short‐term follow‐up because the number of participants was either too small for statistical analysis at later follow‐up or pending (and later not published) at time of publication of the trial. For this reason, there is a lack of evidence for the more important long‐term impact of both intervention strategies on split renal function. The interpretation of the results for the outcome drainage pattern may be influenced by the postoperative use of ureteral stents in some participants of the surgery group. The available data on newborns and infants less than two years of age with secondary surgical intervention following progressive impairment of split renal function are scarce. Neither of the studies provided information on the origin of unilateral UPJO (for example crossing vessels), which hampers the assessment of outcomes between both comparison groups. It is therefore not possible to clarify whether the aetiology of UPJO represents an independent risk factor for deterioration of split renal function. The included studies did not specify the type of surgery applied. For these reasons, we could not evaluate whether the type of surgical approach affects outcomes. Both studies did not or only partially addressed outcomes that were relevant to clinical decision‐making, such as postoperative complications, radiation exposure, or UPJO‐associated complications, between intervention groups. Especially for the non‐surgical group, it may be hypothesised that there is an increasing risk for radiation exposure following serial long‐term imaging or UPJO‐associated clinical symptoms (for example stone formation, febrile urinary tract infection). At the time of the studies' publication (1998), diagnostic methods other than ultrasound and renal scintigraphy were not commonly used. For this reason, it remains unclear whether other appropriate diagnostic methods (for example MRI or proteome analysis) would be superior to the imaging methods described in the studies. We could undertake no prespecified subgroup analyses because of the paucity of data. The overall evidence encountered in this review therefore has little applicability.
Quality of the evidence
Results of the two studies included in this review may reflect pre‐2001 CONSORT (Consolidated Standards of Reporting Trials) conditions (www.consort‐statement.org/), which can have a large effect on study results (Schulz 1995). We assessed risk of bias in both studies as being either unclear or high, with the exception of the adequate randomisation method in one study (Palmer 1998), as well as blinding of outcome assessment for some outcomes. Neither study reported sufficient information on allocation concealment and only one on blinding of primary investigators. Lack of adequate allocation concealment and blinding in studies can lead to overestimation of treatment effects and bias the results of the original studies, influencing the overall results of a systematic review (Moher 1998; Schulz 1995). Blinding of primary investigators would have been feasible and could have been expected in the included studies. It is conceivable that particular outcomes without precise clinical definition such as drainage pattern are influenced by lack of blinding. The effects of the intervention may therefore have been overestimated (Als‐Nielsen 2004; Pildal 2007; Wood 2008). The results of both studies were based on data for which risk for selective reporting was high, and in both studies the analysis of the participants with secondary surgical intervention was not explained in detail. Studies without an intention‐to‐treat analysis can exaggerate the efficacy of the experimental treatment (Hollis 1999). Both studies reported the point estimate of the results but not the standard deviation or 95% confidence interval. For this reason, we could not combine the results across both studies in meta‐analysis. Also, we could not use funnel plots because of the limited number of studies for each intervention (Egger 1997). Conflicts of interest are a possibility in the two included studies, as the trial authors provided no disclosure statement. Conflicts of interest are common in the field of urology and may introduce a risk of bias (Hampson 2012; Meerpohl 2010; Ramm 2012). Overall, we identified several limitations during our 'Risk of bias' assessment causing us to downgrade the quality of evidence to very low for all main outcomes, specifically small sample size of trials (in particular number of analysed participants), as well as unclear or lack of blinding of participants and personnel, and outcome assessors. Most importantly, a high risk of selective outcome reporting in both studies and unclear or high risk of attrition bias were present (Table 1).
Potential biases in the review process
Limitations of the review at the review level
The applied literature search was extensive enough to identify all relevant published studies. Inaccurate information contained in this systematic review may still be present due to incomplete reporting of studies. Two review authors independently screened information provided in the reports of the included studies. We requested supplementary information from authors of identified studies where applicable, but this yielded no additional data. This review therefore summarises the overall current and accessible evidence on published RCTs.
Limitations of the review at the study or outcome level
Data gathered from peer‐reviewed publications might be limited by the following aspects:
both trials did not include newborns and infants less than two years of age with already significant deterioration of split renal function of less than 40%;
only results for the short‐term follow‐up were reported, and the more relevant long‐term effects of each intervention on split renal function remain unclear;
not all prespecified or relevant outcomes were reported, either because they were not measured during the trial or not mentioned in the studies;
the number of participants at several time points of one study varied due to reported loss of follow‐up data from participants exceeding 20% (Palmer 1998).
Limitations of the review related to detection of serious or rare adverse events, or both
Apart from the RCTs considered in this review, it might also be useful to screen non‐randomised studies (controlled clinical trials, cohort studies, case‐control studies) in order to evaluate serious and rare adverse effects. Greater external validity might be achieved with observational studies, which rely on larger databases than RCTs (Gartlehner 2008). Additionally, small sample size and the highly selected group of participants in RCTs could underestimate rare but serious adverse effects, leading to bias (Chou 2010).
Agreements and disagreements with other studies or reviews
To our knowledge, the assessment of the comparative effects of surgical versus non‐surgical treatment options in children with unilateral UPJO have not been the subject of any previous Cochrane review. Existing narrative reviews describe retrospective studies of people with either surgical or non‐surgical treatment (for example Csaicsich 2004) and focus on reporting the proportion of people who were safely monitored without secondary surgical intervention or compare immediate surgery with delayed surgical intervention. The reviews are in agreement with the studies included in this review, unanimously reporting mostly positive outcomes for surgical interventions as well as possible observational management in a certain proportion of cases. Although these conclusions are clinically highly relevant, they do not discuss and evaluate surgical versus non‐surgical therapy.
Authors' conclusions
Implications for practice.
We cannot make recommendations in favour or against non‐surgical treatment of UPJO in newborns and infants less than two years of age based solely on the two identified studies. Evidence for the main outcomes was of very low quality due to small to very small sample size, unclear allocation concealment, unclear blinding of outcome assessors in some cases, and a high risk of selective outcome reporting. We obtained the following results, but these must be considered with caution and require rigorous verification through further RCTs. The presented studies show that early surgical management is associated with maintenance of split renal function, and this outcome improves to pre‐deteriorating values in the majority of children with secondary surgical intervention. Up to 80% of children can be safely observed with retention of split renal function. It remains to be determined if this holds true for long‐term follow‐up periods. Early surgical management is always associated with improved drainage pattern and decreased urinary tract dilatation. The development of obstruction and dilatation after secondary surgical intervention is less clear, as it differed between studies. A certain proportion of participants may experience a spontaneous improvement of hydronephrosis. Adequate data from RCTs were not available to determine postoperative complications, risk of developing chronic kidney insufficiency, UPJO‐associated clinical symptoms, differences in imaging tests, radiation exposure, costs of intervention, quality of life, and additional adverse effects.
Implications for research.
Future studies should take the following considerations into account:
precise description of the patient population (including pathophysiologic origin of UPJO and association of other urological abnormalities, split renal function, grade of presentation of upper urinary tract dilatation, and drainage pattern at time of diagnosis);
detailed information on used imaging methods and interpretation of the results at any time point of the investigation;
type of applied surgical method with success rate and postoperative complications;
specification of the use of supportive therapy (e.g. antibiotic prophylaxis, stents);
information on non‐surgical‐associated adverse effects (e.g. radiation exposure of serial imaging, febrile urinary tract infections, stone formation);
incorporation of other relevant outcomes (e.g. costs of intervention, quality of life);
an adequate follow‐up period beyond one year to clarify the risks and harms of both treatment strategies, especially for the non‐surgical group and the group with secondary surgical intervention (e.g. within the scope of a hybrid design of RCT with a non‐surgical cohort allowing later linkage with longer‐term follow‐up data);
adequately powered and well‐designed RCTs fulfilling reporting standards as established by the CONSORT group (Schulz 2010).
Acknowledgements
The review authors thank the Cochrane Urology Group for their valuable comments and support. We would also like to thank the Trials Search Co‐ordinator of the Cochrane Renal Group and Mrs Christina Walter of the University of Tuebingen for developing and running the essential search strategies throughout different databases. Helpful comments and suggestions from L Braga, J Wiener, C Nelson, J Lewis, and the other reviewers are greatly appreciated and were a tremendous help in the revision process and improvement of the manuscript.
Appendices
Appendix 1. Electronic search strategies
| Database | Search terms |
| CENTRAL |
|
| MEDLINE (OVID SP) |
|
| EMBASE (OVID SP) |
|
Appendix 2. Conference proceedings search links
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Dhillon 1998.
| Methods | Study design: parallel‐group, randomised controlled trial Country: UK Setting: single‐centre trial at a tertiary hospital in the UK Power analysis: not reported Duration: Enrolling time 5 years. Study time 5 years. Study dates: Participants’ enrolment commenced in April 1998 and continued for 5 years |
|
| Participants | INCLUSIONS Age: 3 to 6 months of age Ultrasound: unilateral hydronephrosis ≥ 15 mm (anteroposterior diameter) Renal scintigraphy (DTPA): split renal function of > 40% on the ipsilateral side Intravenous pyelogram: calyceal dilatation Prophylactic antibiotics: trimethoprim 2 mg/kg nightly until 1 year of age Total participants: 75 (22 F) with hydronephrosis on the left side (49) SURGICAL GROUP Number: 39 Mean age: 3.63 months (range 3 to 6) Mean pelvic diameter: 25 mm (15 to 55 mm) Mean split renal function: 48% (range 40 to 57) NON‐SURGICAL GROUP Number: 36 Mean age: 3.65 months of age (range 3 to 6) Mean pelvic diameter: 23 mm (15 to 50 mm) Mean split renal function: 49% (range 41 to 49) EXCLUSION Abnormal findings of the contralateral kidney |
|
| Interventions | SURGICAL GROUP: Dismembered pyeloplasty without further specification with imaging (ultrasound/renal scintigraphy) after 3 months; 1 year, 5 years NON‐SURGICAL GROUP: No intervention with imaging (ultrasound/renal scintigraphy) after 3 months; 1 year, 2 years, 3 years, 4 years, 5 years INDICATION FOR TRANSFER FROM NON‐SURGICAL TO SURGICAL GROUP: Deterioration of split renal function of hydronephrotic kidney by > 10% (renal scintigraphy) or to < 40% |
|
| Outcomes | SPLIT RENAL FUNCTION How measured: renal scintigraphy (DTPA) Reported as: % mean split renal function for surgical and non‐surgical group Timing of measurement: 1 year after surgical or non‐surgical management UPPER URINARY TRACT DILATATION How measured: ultrasound Reported as: % mean pelvic diameter for surgical group; number of children with regressive, persistent, or progressive degree of hydronephrosis for conservative group Timing of measurement: 1 year after surgery or 1, 2, and 3 years after non‐surgical management DRAINAGE PATTERN How measured: renal scintigraphy (DTPA) and Whitaker test at enrolment Time of measurement: 1 year after surgery for surgical group only SECONDARY SURGICAL INTERVENTION FOLLOWING PROGRESSIVE KIDNEY IMPAIRMENT How measured: count of participants with split renal function < 40% or decrease in split renal function > 10% compared to time of randomisation Time of measurement: time period from entry into trial until publication |
|
| Funding sources | No information available | |
| Declarations of interest | No information available | |
| Notes | Definition of drainage pattern: not defined | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No information |
| Allocation concealment (selection bias) | Unclear risk | No information |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Blinding was not reported, so the risk of bias concerning performance remains unclear |
| Blinding of outcome assessment (detection bias) split renal function, upper urinary tract dilatation, drainage pattern | Unclear risk | Blinding was not reported, so the risk of bias during the assessment of these outcomes remains unclear |
| Blinding of outcome assessment (detection bias) Secondary surgical intervention, UPJO‐associated clinical symptoms, postoperative complications | Low risk | Obtained from medical records, therefore risk of bias should be low |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | No loss to follow‐up was reported, but the number of initially enrolled participants is not clearly stated. This affects all outcomes |
| Selective reporting (reporting bias) | High risk | The manuscript does not provide a list of outcomes that the study intended to assess, and we could not obtain a study protocol. Outcome data were not provided for all prespecified time points of assessment |
| Other bias | High risk | 7 participants received secondary surgical treatment because of deterioration of renal function, decreased drainage, and/or an increased urinary tract dilatation. It remains unclear how these participants were analysed. No mention of intention‐to‐treat analysis. The study only includes preliminary results ("the results are presented for the first 75 patients"). Complete results including the 5‐year outcomes have been announced but not yet published |
Palmer 1998.
| Methods | Study design: parallel‐group, randomised controlled trial; 1:1 randomisation Country: USA Setting: multicentre trial performed at 10 sites in the USA Power analysis: not reported Duration: Enrolling time 5 years. Study time 3 years. Study dates: Participants were reported to have been enrolled between 1991 and 1995 |
|
| Participants | INCLUSIONS Age: < 6 months of age Ultrasound: isolated obstructive unilateral hydronephrosis ≥ grade 3 (grading system of the Society for Fetal Urology) Renal scintigraphy: split renal function of at least 40% on the ipsilateral side Total participants: 32 (9 F) with hydronephrosis on the left side (5 F) and on the right side (4 F) SURGICAL GROUP Number: 16 Mean age: 2.5 months NON‐SURGICAL GROUP Number: 16 Mean age: 2.3 months EXCLUSIONS Gross structural anomalies of the urinary tract (e.g. ureterocoele, duplication and solitary kidney) Contralateral renal or ureteral anomalies Systemic diseases influencing renal function (e.g. myelodysplasia) Positive MCUG for vesico‐ureteral reflux, urethral valves, occult spinal dysraphism |
|
| Interventions | SURGICAL GROUP: Pyeloplasty without further specification but potentially including ureteral stents and drains. Imaging (ultrasound/renal scintigraphy) after 6 months; 1 year, 2 years, 3 years NON‐SURGICAL GROUP: No intervention with imaging (ultrasound/renal scintigraphy) after 6 months; 1 year, 2 years, 3 years INDICATION FOR TRANSFER FROM NON‐SURGICAL TO SURGICAL GROUP: Deterioration of split renal function > 10% (renal scintigraphy) or progressive hydronephrosis (ultrasound) of the ipsilateral side, or both |
|
| Outcomes | SPLIT RENAL FUNCTION How measured: renal scintigraphy (MAG3) Reported as: % mean split renal function for surgical and non‐surgical group Timing of measurement: 6 months and 1 year after surgical or non‐surgical management UPPER URINARY TRACT DILATATION How measured: ultrasound Reported as: mean grade of hydronephrosis (grading system of the Society for Fetal Urology) Timing of measurement: 6 months and 1 year after surgical/non‐surgical management DRAINAGE PATTERN How measured: renal scintigraphy (MAG3) Time of measurement: 6 months and 1 year after surgical/non‐surgical management SECONDARY SURGICAL INTERVENTION FOLLOWING PROGRESSIVE KIDNEY IMPAIRMENT How measured: count of participants with decrease in split renal function > 10% compared to time of randomisation Time of measurement: undefined PRESENTATION OF UPJO‐ASSOCIATED CLINICAL SYMPTOMS How measured: not reported Reported as: number of participants with urinary tract infection Time of measurement: not reported POSTOPERATIVE COMPLICATIONS How measured: not reported Time of measurement: not reported |
|
| Funding sources | No information available | |
| Declarations of interest | No information available | |
| Notes | Definition of progressive hydronephrosis: not defined Definition of drainage pattern: not defined |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: “...randomized to 1 of the 2 study groups ... using a computer generated random number sequence...” Comment: Probably done |
| Allocation concealment (selection bias) | Unclear risk | Quote: ”A pharmacist at the center would then randomly allocate the child to either management group.” Comment: Unclear allocation concealment. The role of the pharmacist in the study is not further specified |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "...hydronephrosis was initially assessed by the participating pediatric urologist..." "Test interpretation and analysis were done by the participating nuclear medicine physician..." Comment: Contrary to the final test assessments, the blinding of study physicians was not mentioned, resulting in a high risk of bias for their performance |
| Blinding of outcome assessment (detection bias) split renal function, upper urinary tract dilatation, drainage pattern | Low risk | Quote: "All ultrasound and well tempered renography studies were reviewed by 2 of the authors who were blinded to the study group assignment." Comment: Blinding for the final assessment of these outcomes, therefore risk of bias should be low |
| Blinding of outcome assessment (detection bias) Secondary surgical intervention, UPJO‐associated clinical symptoms, postoperative complications | Low risk | Obtained from medical records, therefore risk of bias should be low |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: “The remaining 12 patients were lost to followup...” Comment: The number of participants (12 of 32 according to the manuscript) lost to follow‐up is high (37.5%), and information on balance of reasons for missing data and proportion of participants per group with missing data was not given. The high risk applies to all outcomes |
| Selective reporting (reporting bias) | High risk | The manuscript does not provide a list of outcomes that the study intended to assess, and we could not obtain a study protocol. Outcome data are not provided for all randomised participants and for all prespecified time points of assessment |
| Other bias | High risk | 4 participants received secondary surgical treatment because of deterioration of renal function, decreased drainage, and/or an increased grade of urinary tract dilatation. It remains unclear how these participants were analysed. No mention of intention‐to‐treat analysis. Unclear whether adjustment for multiple testing was done. The study only includes preliminary results. Follow‐up for some of the participants is pending |
DTPA: diethylene triamine pentaacetic acid MAG3: mercaptoacetyltriglycine MCUG: micturating cystourethrogram UPJO: ureteric‐pelvic junction obstruction
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Heinlen 2009 | Retrospective analysis of 243 children with grade 3 to 4 hydronephrosis |
Differences between protocol and review
This review was based on a published protocol (Weitz 2013), with differences as described here.
In the Methods section Types of studies, we clarified that we included studies regardless of their language of publication or publication status, in accordance with Cochrane standards. Concerning inclusion criteria, we narrowed down the age for participants from 18 to less than two years of age for several reasons. First, the diagnosis of UPJO without immediate symptoms usually occurs at a prenatal or directly postnatal stage, and the adjusted age better reflects the patient group of interest in the daily clinical routine. Also, this threshold should not lead to a meaningful selection bias of the patients, but still potentially includes children with delayed diagnosis of UPJO.
We combined the two primary outcome measures into just one general measure (termed 'split renal function based on any appropriate imaging test'), because, in our opinion, this definition better describes the objective nature of this continuous variable. A broader definition was not applicable for the outcomes 'drainage pattern' and 'urinary tract dilatation', since these are susceptible to the experience and subjective evaluation of the physician. The included studies have shown that drainage pattern is an important indicator for kidney function in conjunction with split renal function. We therefore added the imaging criterion 'number of newborns and infants less than two years of age with regressive, persistent, or progressive drainage pattern' to the secondary outcomes. We also added 'radiation exposure', even though it was not assessed by the included studies. Especially in terms of long‐term follow‐up, this measure could have a differential impact on patients with surgical and non‐surgical treatment. We added 'adverse effects' as an outcome, as suggested by one of the peer reviewers. We removed 'differences in renal scintigraphy and any other appropriate imaging tests' and 'numbers who progressed to chronic kidney disease and end‐stage kidney disease' from the secondary outcomes list.
The electronic search for trials and studies was initially developed by the Cochrane Renal Group. We updated and supplemented this search as described in the Methods section, and additionally included the search within the specified conference proceedings.
We performed 'Risk of bias' assessment in accordance with the current version of the Cochrane 'Risk of bias' tool, and we updated the Methods section Assessment of risk of bias in included studies to list the 'Risk of bias' domains assessed with the current Cochrane tool.
Contributions of authors
Designing the review: Marcus Weitz (MW) and Dirk Bassler (DB) Co‐ordinating the review: MW, Suniva Portz (SP) and DB Data extraction: MW and SP Entering data into RevMan: MW and SP Analysis of data: MW, SP, and Joerg J Meerpohl (JJM) Interpretation of data: MW, SP, JJM, and DB Writing the review: MW, SP, JJM, and DB Providing general advice on the review: Guido F Laube (GFL) and JJM
Sources of support
Internal sources
No sources of support supplied, Other.
External sources
The review was supported by Bundesministerium für Bildung und Forschung (BMBF, Federal Ministry of Education and Research) under support code 01KG1501, Germany.
Declarations of interest
MW, SP, GFL, JJM, and DB: none known.
New
References
References to studies included in this review
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