Routine intraoperative ureteric stenting for kidney transplant recipients

  • Review
  • Intervention

Authors


Abstract

Background

Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from the vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting, at the time of graft implantation, to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications and some centres advocate a policy of only stenting selected anastomoses.

Objectives

To examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplant recipients.

Search methods

We searched the Cochrane Renal Group's Specialised Register (up to 8 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria

All RCTs and quasi-RCTs were included in our meta-analysis.

Data collection and analysis

Four reviewers assessed the studies for quality against four criteria (allocation concealment, blinding, intention-to-treat and completeness of follow-up). The primary outcome was the incidence of MUCs. Further outcomes of interest were graft and patient survival and the incidence of adverse events (urinary tract infection (UTI), haematuria, irritative symptoms, pain and stent migration). Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI).

Main results

Seven RCTs (1154 patients) of low or moderate quality were identified. The incidence of MUCs was significantly reduced (RR 0.24, 95% CI 0.07 to 0.77, P = 0.02, NNT 13) by universal prophylactic stenting. This was dependent on whether the same surgeon performed, or was in attendance, during the operations. Two patients lost their grafts to infective urinary tract complications in the stented group. UTIs, in general, were more common in stented patients (RR 1.49, 95% CI 1.04 to 2.15) unless the patients were prescribed cotrimoxazole 480 mg/d: in which case the incidence was equivalent (RR 0.97, 95% CI 0.71 to 1.33). Stents appeared generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration.

Authors' conclusions

Routine prophylactic stenting reduces the incidence of MUCs. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.

摘要

背景

接受腎臟移植患者,手術中的常規置放輸尿管支架的效用

腎臟移植後如產生重大的泌尿系統併發症(MUCs)會造成患者發生併發症及危害到移植腎的功能。絕大多數泌尿系統併發症是發生在由膀胱輸尿管吻合處,而且通常在移植後初期即可能出現。輸尿管支架的置放,可以成功地治療這類併發症。有些移植中心在移植時全面採置放預防支架的策略,以降低尿液滲漏與輸尿管狹窄症的發生率。然而,支架置放與特定併發症有關,所以某些移植中心主張選擇性地使用支架放置。

目標

檢視以常規置放輸尿管支架來預防腎臟移植後之泌尿系統併發症的利與弊。

搜尋策略

搜尋Cochrane對照試驗登錄資料庫(Cochrane資料庫內的CENTRAL)、MEDLINE、EMBASE、文章的參考文獻、書籍與摘要及聯絡公司、作者與專家以確認相關的隨機對照臨床試驗(RCTs)。

選擇標準

所有的隨機對照臨床試驗(RCTs)與半隨機對照臨床試驗(quasiRCTs)皆納入我們的分析。

資料收集與分析

由4位審查者針對4項標準(分配方式的隱密性、是否為雙盲試驗、意向治療、與後續追蹤的完成度),進行試驗的品質評估。主要觀察為主要泌尿系統併發症(MUCs)的發生率為何。感興趣的觀察包括: 移植腎與患者存活率、不良反應的發生率[包括尿道感染(UTI)、血尿、泌尿道刺激的症狀、疼痛、與支架位移等]。利用隨機效應模型進行統計分析,而以95% 信賴區間(CI)的相對風險(RR)表示結果。

主要結論

共有7項屬於低中品質的隨機對照臨床試驗(共1154位患者被確認),全面預防性支架置放可明顯降低主要尿系統併發症(MUCs)的發生率(相對風險0.24,95% 信賴區間0.07 – 0.77,P = 0.02,NNT 13)。不過此結果與手術過程中是否由相同外科醫師進行或僅在場指導有關。在支架組中,有2位患者因為尿道感染併發症而使移植失敗。一般而言,尿道感染(UTIs)常見於裝設支架的患者中(相對風險1.49,95% 信賴區間1.04 – 2.15),除非患者每日服用480毫克的cotrimoxazole;則此病發症的發生率與一般未放置支架者相當(相對風險0.97,95% 信賴區間 0.71 – 1.33).雖然目前研究大多使用較長時間(>6周)且使用較長支架(20公分),顯示有較常出現型成硬塊與位移的問題,但一般而言,支架置放的耐受性通常很好。

作者結論

常規地預防性支架置放可降低主要泌尿系統併發症(MUCs)的發生率,但要比較選擇性支架置放與全面預防支架置放之試驗由於不容易設計與分析,也要考量關於生活品質與經濟支出問題。

翻譯人

本摘要由馬偕醫院郭馨仁翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

接受腎臟移植患者,常規置放預防性輸尿管支架,可以減少主要泌尿系統併發症(MUCs)的發生率。腎臟移植是很多末期腎病變患者治療的選擇之一,可以改善病患生活品質和延長生命。任何可以減少移植後併發症的治療方式,都是在移植領域研究很重要的一環。重大的泌尿系統併發症(MUCs)(如尿液洩漏或阻塞),可以在腎臟移植之後很短時間馬內發生。這篇文章是在檢視以常規置放輸尿管支架來預防腎臟移植後之泌尿系統併發症的利與弊。共有7個臨床試驗(1154位患者)被納入分析。重大的泌尿系統併發症(MUCs)的發生率,在置放預防性輸尿管支架後,明顯下降。然而泌尿道感染在使用預防性輸尿管支架的患者卻明顯增加。但加入預防性抗生素後,泌尿道感染的發生率,在兩組中就沒有差異。在考量生活品質及醫療花費的情況,到底是以選擇性支架置放與全面預防支架置放,則需要更多研究來決定。

Résumé scientifique

Pose de stent urétéral peropératoire de routine pour les receveurs de greffe de rein

Contexte

Les complications urologiques majeures (CUM) suite à une greffe de rein contribuent à la morbidité du patient et mettent en risque la fonction de la greffe. La plupart résulte de l'anastomose vésico-urétérale et se présente précocement après le greffage. Les stents urétéraux ont été utilisés avec succès pour traiter de telles complications. Un nombre de centres a adopté une politique de pose de stent prophylactique universel au moment de transférer le greffon pour réduire l'incidence de fuites d'urine et la sténose urétérale. Les stents sont liés à des complications spécifiques et certains centres préconisent une politique qui consiste à ne poser des stents que sur certaines anastomoses spécifiques.

Objectifs

Examiner les bénéfices et inconvénients de la pose de stents urétéraux de routine pour prévenir les complications urologiques chez les receveurs de greffes de rein.

Stratégie de recherche documentaire

On a cherché le registre spécialisé Cochrane rénal (jusqu’au 8 janvier 2013) par contact avec la recherche de coordonnateur de l’essai en utilisant des termes de recherche pertinents à cet examen.

Critères de sélection

Tous les ECR et quasi-ECR ont été inclus dans notre méta-analyse.

Recueil et analyse des données

Quatre relecteurs ont évalué les études de qualité en suivant quatre critères (assignation secrète, assignation en aveugle, intention de traiter et état complet du suivi). L'incidence des CUM en a été le résultat primaire. La survie du greffon et du patient et l'incidence des événements indésirables (infection des voies urinaires (IVU), hématurie, symptômes d'irritation, douleurs et migration du stent) constituaient des résultats additionnels d'intérêt. Les analyses statistiques ont été réalisées en utilisant le modèle à effets aléatoires et les résultats ont été exprimés sous la forme de risque relatif (RR) avec des intervalles de confiance (IC) à 95%.

Résultats principaux

Sept ECR (1154 patients) d'une qualité faible à modérée ont été identifiés. L'incidence des CUM se réduisit considérablement (RR de 0,24, IC à 95 % de 0,07 à 0,77, P = 0,02, nombre de sujets à traiter : 13) avec la pose d'un stent prophylactique universel. Ces résultats étaient subordonnés à la réalisation de l'opération par le même chirurgien ou de la présence de celui-ci pendant les opérations. Deux patients perdirent leurs greffes suite à des complications causées par des voies urinaires infectieuses au sein du groupe à qui on a posé des stents. En général, les IVU étaient plus fréquentes chez les patients avec stent (RR de 1,49, IC à 95 % de 1,04 à 2,15), sauf lorsque le cotrimoxazole de 480/mg/d leur était prescrit : dans ces cas-là, l'incidence était équivalente (RR de 0,97, IC à 95 % de 0,71 à 1,33) : En règle générale, les stents semblent être bien tolérés, malgré le fait que des études ont indiqué que l'emploi de stents plus longs (≥ 20 cm) pendant une durée plus longue (> 6 semaines) peut causer des problèmes avec l'incrustation et la migration.

Conclusions des auteurs

La pose de stents prophylactiques de routine réduit l'incidence des CUM. Les études comparant la pose de stents sélectifs et la pose de stents prophylactiques universels, bien que difficiles à concevoir et à analyser, pourraient faire face aux questions non résolues de la qualité de vie et des coûts.

Plain language summary

Routine prophylactic stenting reduces the incidence of major urological complications in kidney transplant recipients

Kidney transplantation is the treatment of choice for end-stage kidney disease, improving quality of life and extending the recipient's life expectancy. Interventions aimed at reducing the burden of post-transplant complications are a major area of research amongst the transplant community. Major urological complications (MUCs) (e.g. urine leak, obstruction) can occur in the immediate post-transplant period. This review aimed to determine the benefit and harms of the use of routine stenting in kidney transplant recipients in the prevention of urological complications. Seven studies (1154 patients) were identified. The incidence of MUCs were significantly reduced by the use of prophylactic stenting. Urinary tract infections (UTIs) were more common in stented patients however the addition of antibiotic prophylaxis resulted in no difference in the incidence of UTIs between the two groups. More studies are needed to investigate the use of selective versus universal prophylactic stenting for the unresolved issues of quality of life and cost.

Résumé simplifié

La pose d'un stent prophylactique de routine réduit l'incidence de complications urologiques majeures chez les receveurs de greffe de rein

La greffe de rein est le traitement préféré pour les maladies rénales terminales car elle améliore la qualité de vie et prolonge l'espérance de vie du receveur. Les interventions dont le but consiste à réduire les inconvénients des complications après la greffe sont un des principaux domaines de recherche au sein de la communauté de greffage. Les complications urologiques majeures (CUM) (comme par exemple fuites d'urine, obstructions) peuvent survenir immédiatement après la greffe. Cette revue avait pour but de déterminer les bénéfices et inconvénients de la pose d'un stent de routine chez les receveurs de greffe de rein pour prévenir les complications urologiques. Sept études (1154 patients) ont été identifiées. L'incidence des CUM s'est considérablement réduite avec la pose de stents prophylactiques. Les infections des voies urinaires (IVU) étaient plus fréquentes chez les patients avec stent ; cependant, l'ajout de la prophylaxie antibiotique n'a pas produit de différence dans l'incidence des IVU entre les deux groupes. Des études supplémentaires sont nécessaires pour examiner la pose d'un stent prophylactique sélectif par opposition à un stent universel pour les questions non résolues de qualité de vie et de coûts.

Notes de traduction

Traduit par: French Cochrane Centre 1st November, 2012
Traduction financée par: Instituts de Recherche en Sant� du Canada, Minist�re de la Sant� et des Services Sociaux du Qu�bec, Fonds de recherche du Qu�bec-Sant� et Institut National d'Excellence en Sant� et en Services Sociaux

Background

Kidney transplantation is the treatment of choice for end-stage kidney disease (ESKD). Transplantation improves both quantity and quality of life for recipients. Currently, and for the foreseeable future, kidney graft demand greatly exceeds supply. A large body of research is developing into strategies to expand the donor pool and increase the supply of organs. Concurrently other groups are looking at ways to extend the life of kidney grafts by both reducing the burden of chronic allograft nephropathy and reducing the number of recipients dying with functioning grafts. There remain a small percentage of grafts lost in the early months post-transplantation to acute rejection and technical complications including vascular thrombosis. Major urological complications (MUCs) mostly originate from the vesicoureteric anastomosis, present early after transplantation (within three months) (Kumar 2004) and contribute to patient morbidity, graft loss and mortality (Rigg 1994; Thomalla 1990). The first kidney transplants were anastomosed using a transvesical approach (Merrill 1956). This technique, now more commonly known by the eponym Leadbetter-Politano (L-P)(Politano 1958), has been generally superceded by the extravesical ureteroneocystostomy (Lich-Gregoir) (L-G)(Konnak 1972) which is less technically demanding. Despite this there remains a significant morbidity with a recent review of case control studies reporting mean incidences of between 3% and 5% (Mangus 2004).

vesicoureteric complications present either as urine leaks or collecting system obstruction. In the absence of technical complications, ureteric ischaemia (often related to the retrieval procedure) is thought to be chiefly responsible for the early ureteric complications post-transplantation (Karam 2004). Both ureteric leak and obstruction have been successfully treated with "double-J" stent insertion, prompting surgeons to contemplate the use of prophylactic stents (Insall 1995).

Stents have been successfully used in general urological practice for a number of years. The double-J stent consists of a straight tube with anchoring "j" loops at either end. In conventional urological practice the stent is straightened and inserted over a guidewire either via a cystoscope and/or under radiological guidance. Removal of the guidewire causes both ends to curl into their natural anchoring conformation. Placement of a stent during transplantation is a relatively simple procedure and requires no additional instrumentation or imaging. However, a further procedure to remove the stent is always required, may be inadvertently delayed and incurs further healthcare costs.

Conventional native ureteric repairs over stents are widely accepted to have a better outcome (Turner 1982). In addition they have been successfully used in pyeloplasty, ureterovesical reconstruction and in the management of stone disease (Baum 1982; Finney 1978). The therapeutic benefits of stents in transplantation are still disputed but may include simplifying the creation of a watertight ureteric to bladder anastomosis and reduction of anatomical kinking (French 2001; Kumar 2004). The most significant theoretical complication is an increase in the number and severity of urinary tract infections (UTI). Other possible complications include persistent haematuria and bladder discomfort, stent migration, breakage, encrustation and complications during removal.

A number of centres have adopted a policy of prophylactic stent insertion with endoscopic removal at a designated time post-transplantation in an effort to reduce the MUCs rate (Lin 1993). However, it has been suggested that a tension-free anastomosis with an intact blood supply is the only effective strategy to avoid both early and late ureteric complications, and the benefits of prophylactic stenting are outweighed by their possible complications. As a consequence many units continue to selectively stent only difficult anastomoses or in circumstances where the vesicoureteric viability may be additionally compromised (Thomalla 1990).

Objectives

This review aimed to examine the benefits and harms of routine ureteric stenting to prevent urological complications in kidney transplants recipients.

Potential benefits

  • Reduction in incidence of MUCs

Potential harms

  • Increase in the incidence of UTI and haematuria

  • Idiosyncratic complications (migration, malposition, irritation, encrustation)

  • Complications from stent removal

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) and quasi-RCTs looking at the use of double-J stents to prevent urological complications.

Types of participants

Inclusion criteria

We included all studies designed to examine the impact of the use of stents in recipients of kidney transplants. Specifically we aimed to include studies regardless of the type of graft (live donor, cadaveric), technique of ureteric implantation (extravesical, transvesical) and patient group (e.g. paediatric, elderly, multiple organ and previous transplant recipients).

Studies were assessed against a number of criteria including the demographics of organ donor, recipient, surgical techniques and medical management to allow comparison and stratification for known MUCs risk factors.

Exclusion criteria

Specific exclusion criteria stipulated by our protocol included studies detailing the analysis of horseshoe kidneys, patients with abnormal bladder function and urinary diversion.

Types of interventions

For a trial to be included one randomised group of graft recipients must have had the vesicoureteric anastomosis stented at the time of implantation with a suitable prosthesis. Our protocol stipulated that the stent must have remained in for at least 14 days to be considered an adequate "treatment period".

Types of outcome measures

  • Urological complications related to the transplant ureter (urine leak/ obstruction) within three months of transplant.

  • Patient survival.

  • Graft survival.

  • Stent complications including pain, haematuria, UTI, migration, irritative symptoms, stone formation, secondary obstruction from crusting.

  • Complications from stent removal.

Search methods for identification of studies

We searched the Cochrane Renal Group's Specialised Register (up to 8 January 2013) 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. Monthly searches of the Cochrane Central Register of Controlled Trials CENTRAL;

  2. Weekly searches of MEDLINE OVID SP;

  3. Handsearching of renal-related journals & 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 & ClinicalTrials.gov

Studies contained in the Specialised register are identified through search strategies for CENTRAL, MEDLINE, 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 nephrology textbooks, review articles and relevant studies.

  2. Letters seeking information about unpublished or incomplete trials to investigators known to be involved in previous studies.

Data collection and analysis

Included and excluded studies

The review was carried out initially by three authors (CHW, AAB, DMM, DAR) and a fourth (DAR) was consulted for a specific urological transplant opinion. The search strategy described was used to obtain titles and abstracts of studies that may have been relevant to the review. The titles and abstracts were screened independently by CHW and AAB who discarded studies that were not applicable. Both primary authors independently assessed the retrieved abstracts and determined which studies satisfied the inclusion criteria. Data extraction was carried out by the same authors independently using standard data extraction forms. Further information required from the original author was requested by written correspondence and relevant information obtained in this manner has been included in the review. The inclusion of studies was then discussed and agreed with the third and fourth authors (DMM and DAR).

Study quality

The quality of studies to be included was assessed independently by CHW and AAB without blinding to authorship or journal using the checklist developed for the Cochrane Renal Group. Discrepancies were resolved by discussion with DMM. The quality items assessed were allocation concealment, blinding, intention-to-treat analysis and completeness to follow-up.

Quality checklist

Allocation concealment
  • Adequate (A): Randomisation method described that would not allow investigator / participant to know or influence intervention group before eligible participant entered in the study.

  • Unclear (B): Randomisation stated but no information on method used is available.

  • Inadequate (C): Method of randomisation used such as alternate medical record numbers or unsealed envelopes; any information in the study that indicated that investigators or participants could influence intervention group

Blinding
  • Blinding of participants: Yes/no/not stated.

  • Blinding of outcome assessor: Yes/no/not stated.

  • Blinding of data analysis: Yes/no/not stated.

Intention-to-treat analysis
  • Yes: Specifically reported by authors that intention-to-treat analysis was undertaken and this was confirmed on study assessment.

  • No: Not reported and lack of intention-to-treat analysis confirmed on study assessment. (Patients who were randomised were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation).

  • Not stated.

Completeness of follow-up

Number of participants loss to follow-up.

Statistical assessment

Outcomes were expressed as risk ratio (RR) with 95% confidence intervals (CI) where appropriate. Absolute risk reductions are given as numbers needed to treat (NNT), a figure that quantifies the number of patients that must be stented to prevent one MUCs. Data was pooled using the random effects model but the fixed effects model was also analysed to ensure robustness of the model chosen, susceptibility to outliers and during sub group analysis. Heterogeneity was analysed using a Chi squared test on N-1 degrees of freedom, with a P value 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. When statistical heterogeneity was present subgroup analysis was to be used to explore possible sources. Adverse effects were collated and reported in tabular form.

Results

Description of studies

Seven RCTs and quasi-RCTs (1154 patients) were identified (Bassiri 1995; Benoit 1996; Dominguez 2000; Guleria 1998; Kumar 1998; Osman 2004; Pleass 1995). All were published as full articles in English language journals. No dual publications or non-English language studies were identified. Three of the seven authors (Dominguez 2000; Osman 2004; Pleass 1995) answered enquiries about study design and results; whilst their assistance was invaluable often original data was unavailable and the basis for their response was personal memory. We did not pursue statistical attempts to identify publication bias.

Risk of bias in included studies

As expected none of the studies attempted to blind patient, investigator or assessor to treatment allocation. Overall the studies were of low or medium quality, however four of the RCTs (Guleria 1998; Kumar 1998; Osman 2004; Pleass 1995) detailed a robust method of randomisation which would be unaffected by physician pre-conceptions. One study (Dominguez 2000) was designed with a treatment group randomised to receive stents universally and one arm receiving stents if the senior surgeon present deemed them necessary, a policy commonly termed "selective" stenting. For two studies the randomisation method was unclear from the paper and the authors did not respond to attempts at clarification (Bassiri 1995; Benoit 1996). Bassiri 1995 and Osman 2004 presented their results censored for either graft loss or patient death unrelated to urological complications or stents, during our meta-analysis these results were adjusted to include the patients as originally randomised. Pleass 1995 randomised patients to four groups: L-G or L-P with or without stent. These results were summated into "with" and "without stent" groups. Only Guleria 1998 detailed a loss to follow-up before three months.

The inclusion and exclusion criteria of each study were difficult to assess. Only one study investigator (Dominguez 2000) reported patients assessed, enrolled or withdrawn prior to randomisation in keeping with modern CONSORT guidelines (Ioannidis 2004). Three studies (Bassiri 1995; Dominguez 2000; Osman 2004) specifically excluded kidneys and recipients with abnormal urinary tracts. One study included multi-visceral recipients (Dominguez 2000) and in three studies (Guleria 1998; Kumar 1998; Osman 2004) the kidneys were only live donor derived. Paediatric recipients were specifically excluded by Osman 2004 and Pleass 1995 whilst in other studies the protocol was unclear. No study reported results on our specific exclusion criteria recipients. The intervention period in Dominguez 2000 was only seven to 10 days, out with our protocol stated minimum period of 14 days.

Benoit 1996, Guleria 1998 and Kumar 1998 stated that the operations reported on were consecutive and detailed no exclusions. None of these authors responded to attempts to contact and the inclusion/ exclusion criteria from their protocols could not be confirmed.

In summary, the study designs were heterogeneous with disparate donors, intervention periods, outcome assessments and statistical analysis, however common themes of randomisation and control were present in all studies and the primary research question of each study followed the principle of this review. After consultation between all four reviewers, we decided to include all the studies in this meta-analysis.

Effects of interventions

Urine leak and obstruction

The MUCs (leak and/or stenosis) incidence ranged between 0 and 4 % in stented patients (median 1.0%) and between 0 and 17.3% (median 7.0 %) in the non-stented patients (additional Table 1 - Incidence of major urological complications (MUCs)) There were significantly fewer events in the stent group (Analysis 1.1.1: RR 0.24, 95% CI 0.07 to 0.77, P = 0.02; NNT 13). This treatment effect appeared uniform for both complications, with urine leak (Analysis 1.1.2: RR 0.29, 0.12 to 0.74, P = 0.009) and ureteric stenosis (Analysis 1.1.3: RR 0.27, 0.09 to 0.81, P = 0.02) similarly reduced.

Table 1. Incidence of major urological complications (MUCs)
StudyEvents (stent)Patients (stent)Incidence (stent)Events (no stent)Patients (no stent)Incidence (no stent)
Bassiri 19950350%3378.1%
Benoit 19961971.0%109710.3%
Dominguez 200051433.5%91376.6%
Guleria 19981541.9%3545.6%
Kumar 19980570%3437.0%
Osman 20042504%0500%
Pleass 199501500%2615017.3%
Total9586median 1.0 (0 - 4.0)54568median 7.0 (0 - 17.3)

As was to be expected with considerable differences in the clinical interventions, diagnostic techniques and donors there was a level of statistical heterogeneity in these outcomes; although this did not reach significance (χ² = 11.48, P = 0.07, I² = 48%).

Subgroup analyses

The most substantial finding during subgroup analysis was the influence of surgeon experience on outcome. In studies where only a single experienced surgeon performed or supervised all the operations, the incidence of MUCs in the control group was lower (median 6.3 % versus 10.3% (Analysis 1.2.1 same surgeon: RR 0.39, 95% CI 0.08 to 1.86; Analysis 1.2.2 many surgeons: RR 0.13, 95% CI 0.01 to 1.16; Table 2 - Influence of surgeon number on incidence of MUCs) and hence the benefit of stent placement was lower (NNT 30 versus 10).

Table 2. Influence of surgeon number on incidence of MUCs
Comparison/ StudyEvents (stent)Patients (stent)Incidence (stent)Events (no stent)Patients (no stent)Incidence (no stent)
Bassiri 19950350%3378.1%
Guleria 19981541.9%3545.6%
Kumar 19980570%3437.0%
Osman 20042504%0500%
Same surgeon (4 studies, 380 patients)3196median 0.95 (0 - 4.0)9184median 6.3 (0 - 8.1)
       
Benoit 19961971.0%109710.3%
Dominguez 200051433.5%91376.6%
Pleass 199501500%2615017.3%
Many surgeons (3 studies, 774 patients)6390median 1.0 (0 - 3.5)45384median 10.3 (6.6 - 17.3)

Of the two studies in which both LP and LG techniques were utilised, only Pleass 1995 reported results on LP procedures separately and showed a significantly greater incidence of MUCs in the unstented LP group, and a concomitantly larger risk reduction with the use of stents. No significant influence of the donor organ type (cadaveric, live, multiorgan) or stent type could be identified in this small number of studies. Similarly we could not identify a correlation with the length of stent placement and the incidence of MUCs.

In Dominguez 2000 (stenting versus selective stenting), six (4.4%) patients in the control group received a prophylactic stent. Despite this, there were more MUCs in the control group than the stent group. Three studies specifically reported better graft function or less MUCs whilst the stent was in situ. Bassiri 1995 reported no MUCs in the first two weeks post-transplant in the stented group versus two in the non-stented group. Benoit 1996 showed a significant difference in kidney function early post-transplant (mean serum creatinine at one week 302 µmol/L versus 388 µmol/L ) and Dominguez 2000 reported no MUCs within 20 days in the group that had been stented, whilst all the patients with MUCs in the non-stented group presented within 13 days.

Patient and graft survival

(Table 3 - Graft loss and patient mortality)

Table 3. Graft loss and patient mortality
  1. NR - not reported

StudyFollow-upStent related lossStent related deathsOverall mortalityOverall graft loss
Bassiri 19952-10 months005 patients total either lost their graft or died (6.5%)-
Benoit 1996Up to 3 years207.8%NR
Dominguez 20003 months00NRNR
Guleria 19986 months0001.9%
Kumar 199816-32 months0093% 1 year survival89% 1 year survival
Osman 20047-16 months000.8%0.8%
Pleass 19953 months00NRNR

No studies directly attributed patient mortality to the use of ureteric stents. Benoit 1996 reported graft loss secondary to use of ureteric stents: two kidneys had to be removed after stent encrustation with corynebacterium could not be eradicated with antibiotics.

UTI

There was considerable heterogeneity in definitions, reported morbidity and relative incidence of UTI. Meta-analysis identified a significant increase in UTI associated with stents (Analysis 1.3: RR 1.49 95% CI 1.04 to 2.15, P = 0.03) with significant statistical heterogeneity (Chi² = 15.32, P = 0.02, I² = 60.8%). This statistic was independent of the diagnostic criteria (Analysis 1.4), with an equivalent RR reported between studies diagnosing infection on the basis of culture alone (Analysis 1.4.1: RR 1.44, 95% CI 0.85 to 2.45) and studies requiring clinical symptoms for confirmation of infection (Analysis 1.4 .2: RR 1.23, 95% CI 0.80 to 1.90). Subgroup analysis identified the risk to be associated with the antibiotic regime (Analysis 1.5). Studies detailing prophylaxis (Bassiri 1995 excluded) with long-term cotrimoxazole 480 mg/d (or 960 mg alternate days) had an equivalent RR for infection between stented and non-stented patients (Analysis 1.5.1: RR 0.97, 95% CI 0.71 to 1.33) compared with other regimes Analysis 1.5.2: RR 1.78, 95% CI 1.45 to 2.21). The cotrimoxazole regime detailed by Dominguez 2000 included only three doses of cotrimoxazole 480 mg/wk.

Haematuria

Graft implantation requires bladder incision and there will always be a level of haematuria after kidney transplantation. As a symptom or clinical finding, haematuria was sporadically reported by investigators and definitions varied widely (additional Table 4 - Incidence of haematuria). Two studies reported cases of ureteric clot retention (Benoit 1996; Dominguez 2000) and only three studies gave specific definitions for haematuria (Bassiri 1995; Osman 2004; Pleass 1995). Of the three studies that gave figures for haematuria, two studies reported more morbidity in the stented group and one the non-stented group. There was no evidence in the six studies that the presence of a stent per se pre-disposed to recurrent or severe haematuria Analysis 1.6: RR 0.74, 95% CI 0.37 to 1.48).

Table 4. Incidence of haematuria
  1. NR - not reported

StudyStentNo Stent
Bassiri 19955.7%0%
Benoit 1996NR1 ureter clot retention (1.0%)
Dominguez 2000NR1 ureter clot retention (0.7%)
Guleria 1998NRNR
Kumar 19980%0%
Osman 20046.0%2.0%
Pleass 19956.0%10.0%

Other complications

(Table 5 - Other stent-related complications)

Table 5. Other stent-related complications
  1. NR - not reported

StudyIrritative symptomsBreakageMigration/malpositioningEncrustationForgottenExpulsion
Bassiri 1995NRNRNR5.7%NR0
Benoit 1996NR2.1%1.0%2.1%NR1.0%
Dominguez 20000%0 %0 %0 %NR0%
Guleria 19985.6%0 %7.4%0 %NR7.4%
Kumar 19985.3%0 %0 %0 %7.0 %0
Osman 2004NR0 %4.0%0 %00
Pleass 1995NR0 %"+""++"NR> 1 patient

The most significant complications reported were the two graft losses by Benoit 1996. Only two stent breakages were reported, both in patients receiving simultaneous pancreas-kidney transplants with bladder exocrine drainage. Encrustation appeared to be a significant problem for stents left in for longer periods (Bassiri 1995; Pleass 1995), although this statistic was not reported in the original paper from Pleass 1995. The highest rate of stent migration and expulsion was reported by Guleria 1998 who used the longest (24 cm) stent. Cases of "forgotten" stents were reported in Kumar 1998, none of these cases was associated with excess morbidity. Stents appeared well tolerated whilst in situ with only two studies reporting an excess of irritative symptoms and pain not associated with infection (Guleria 1998; Kumar 1998). No studies reported complications from routine removal or secondary obstruction from encrustation.

In summary the maximum reported non-infectious complications were irritative symptoms 5.6% (Guleria 1998), breakage 2.0% (Benoit 1996), migration/malposition/expulsion 7.4% (Guleria 1998), encrustation/urolithiasis 5.7% (Bassiri 1995) and "forgotten" stents 7% (Kumar 1998).

Discussion

MUCs require interventions varying in severity from a radiological nephrostomy through to surgical urinary diversion. Consequently any intervention which can safely and cost effectively lower their incidence are to be welcomed. Our analysis demonstrates that universal prophylactic ureteric stenting reduces the incidence of MUCs significantly (RR 0.24, 95% CI 0.07 to 0.77).

A recent review and meta-analysis included only five of the RCTs (796 patients) and reported a similar treatment effect (Mangus 2004). However, there is a significant "caveat" to these conclusions. RCTs with unblinded treatment allocation have been acknowledged to overestimate the beneficial effects of medical interventions by up to 40% (Schulz 1995). Such an overestimate would comprehensively negate the treatment effect described here. Of the studies included, Dominguez 2000, which had a shorter intervention period than our protocol originally allowed and compared universal stenting with selective stenting, would be expected to show the least evidence of effect. This was not born out by his results. It was slightly surprising therefore that despite six of the seven studies showing a reduction in the MUCs incidence, only three of the seven studies recommended universal prophylactic stenting.

One explanation for this may be an "experience" effect. The four studies with a single senior author performing or supervising all the operations had a lower complication rate in the control group when compared with studies where more than one surgical team performed the operations. This has been suggested previously and may explain the conclusions of senior study investigators, cognisant of their considerable personal experience, extolling a policy of selective stenting (French 2001).

We were unable to identify a particular stent design associated with a better outcome as a wide variety of stent designs, calibres and lengths were used. Non-infectious adverse events appeared more common in studies using longer stents (Guleria 1998; Osman 2004) and or longer treatment periods (Bassiri 1995; Pleass 1995), although there was no evidence that haematuria was more common. These idiosyncratic stent-related complications were mostly managed by endoscopic removal of the stent - a minimally invasive procedure - which was unavoidable after initial stent placement and has been successfully combined with other necessary interventions for transplant recipients (e.g. peritoneal and haemodialysis catheter removal). Irritative symptoms and stent-related pain were much less frequent than would be expected from studies examining the use of stents in native ureters after general urological procedures where the incidence may be as high as 80% (Joshi 2003). Kumar 2004 has suggested that the combination of a denervated kidney and the high anterior placement of the stent reduce the combination of vesicoureteric reflux pain and trigonal irritation. However, none of the studies specifically used a validated questionnaire to quantify the urinary symptoms or bother associating with either stent usage or removal and this may well be an underestimate of the morbidity burden.

Two grafts were lost as a result of stent related infectious complications and the pooled results indicated a general increased risk of UTI with their use (RR 1.49, 05% CI 1.04 to 2.15). Cotrimoxazole, at a dose of 480 mg/d or 960 mg every other day, is standard therapy in most units and recommended in published guidelines for all kidney transplant recipients as prophylaxis against Pneumocystis carinii pneumonia (EBPG 2002). Our subgroup analysis data also suggests this regime is effective at reducing the incidence of UTI to levels found in unstented transplant urinary tracts (RR 0.97, 95% CI 0.71 to 1.33). It should be emphasised that this statistic, in common with all the analyses, is based on a small number of studies and open to reporting error.

Only one study reported a cost-benefit analysis and although the morbidity associated with stents appears minimal and the therapeutic benefit sizeable, there remain unanswered questions with regards to economic and quality of life issues. In this respect a study of selective versus universal stenting, utilising a stent specific quality of life instrument , would not only provide the opportunity for a more realistic cost benefit analysis of universal prophylactic stenting but also demonstrate whether surgeons can identify intra-operatively urinary tracts that need to be stented. Such a study would also need to stratify surgeons by experience to have significant worldwide implications for practice.

Authors' conclusions

Implications for practice

Routine prophylactic stenting reduces the incidence of MUCs and is to be recommended on the basis of the currently available RCTs. Stents are associated with specific complications and experienced surgeons may adopt a policy of selective stenting, as opposed to universal stenting, to minimise the potential morbidity of stents. Cotrimoxazole, at a dose of 480 mg/d, effectively reduces the risk of UTIs associated with stent placement. Transplant units currently using this antibiotic regime as prophylaxis for pneumocystis pneumonia should not notice an excess of stent related infections.

Implications for research

The optimal stent calibre, length, design and duration remain to be determined and further studies addressing these issues could be instituted. Well designed studies of stenting versus selective stenting, with appropriate patient selection protocols, randomisation, quality of life questionnaires, cost-benefit analyses and surgeon stratification would answer the more clinically important question of whether it is possible and desirable to identify the appropriate patients to stent at the time of graft implantation.

Acknowledgements

This review has been co-published with Transplantation Oct 2005 (Wilson 2005)
We would also like to thank Dr Nicholas Brooks, Dr David Cranston, Dr Francis Keeley and Dr Petra Macaskill for their editorial advice during the preparation of this review.

Data and analyses

Download statistical data

Comparison 1. Stent versus no stent
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Urine leak and obstruction7 Risk Ratio (M-H, Random, 95% CI)Subtotals only
1.1 Combined - urine leak and obstruction71154Risk Ratio (M-H, Random, 95% CI)0.24 [0.07, 0.77]
1.2 Urine leak71154Risk Ratio (M-H, Random, 95% CI)0.29 [0.12, 0.74]
1.3 Ureteric obstruction71154Risk Ratio (M-H, Random, 95% CI)0.27 [0.09, 0.81]
2 Surgeon number MUC subgroup analysis7 Risk Ratio (M-H, Random, 95% CI)Subtotals only
2.1 Same surgeon4380Risk Ratio (M-H, Random, 95% CI)0.39 [0.08, 1.86]
2.2 Many surgeons3774Risk Ratio (M-H, Random, 95% CI)0.13 [0.01, 1.16]
3 UTI71154Risk Ratio (M-H, Random, 95% CI)1.49 [1.04, 2.14]
4 UTI incidence by diagnostic criteria6 Risk Ratio (M-H, Random, 95% CI)Subtotals only
4.1 Culture only3402Risk Ratio (M-H, Random, 95% CI)1.44 [0.85, 2.43]
4.2 Culture plus symptoms/ signs3680Risk Ratio (M-H, Random, 95% CI)1.23 [0.80, 1.90]
5 UTI incidence by antibiotic regime6 Risk Ratio (M-H, Random, 95% CI)Subtotals only
5.1 Co-trimoxazole 480mg od (960 mg alt. days)3594Risk Ratio (M-H, Random, 95% CI)0.97 [0.71, 1.33]
5.2 Other regime3488Risk Ratio (M-H, Random, 95% CI)1.78 [1.44, 2.21]
6 Haematuria61046Risk Ratio (M-H, Random, 95% CI)0.74 [0.37, 1.48]
Analysis 1.1.

Comparison 1 Stent versus no stent, Outcome 1 Urine leak and obstruction.

Analysis 1.2.

Comparison 1 Stent versus no stent, Outcome 2 Surgeon number MUC subgroup analysis.

Analysis 1.3.

Comparison 1 Stent versus no stent, Outcome 3 UTI.

Analysis 1.4.

Comparison 1 Stent versus no stent, Outcome 4 UTI incidence by diagnostic criteria.

Analysis 1.5.

Comparison 1 Stent versus no stent, Outcome 5 UTI incidence by antibiotic regime.

Analysis 1.6.

Comparison 1 Stent versus no stent, Outcome 6 Haematuria.

Appendices

Appendix 1. Electronic search strategies

Database searchedSearch terms
CENTRAL
  1. MeSH descriptor: [Kidney Transplantation] this term only

  2. kidney transplant*:ti,ab,kw (Word variations have been searched)

  3. renal transplant*:ti,ab,kw (Word variations have been searched)

  4. 1 or 2 or 3

  5. MeSH descriptor: [Stents] explode all trees

  6. stent*:ti,ab,kw in Trials (Word variations have been searched)

  7. 5 or 6

  8. 4 and 7

MEDLINE
  1. Kidney Transplantation/

  2. exp Stents/

  3. stent$.tw.

  4. or/2-3

  5. and/1,4

EMBASE
  1. exp kidney transplantation/

  2. exp stent/

  3. exp urologic stent/

  4. stent$.tw.

  5. or/2-4

  6. and/1,5

What's new

DateEventDescription
9 April 2013New citation required but conclusions have not changedNew search performed
27 March 2013New search has been performedRepeat literature search performed, 14 abstracts evaluated. All excluded, no further changes to review.

History

Protocol first published: Issue 3, 2004
Review first published: Issue 4, 2005

DateEventDescription
8 January 2013AmendedSearch strategies updated
19 January 2010AmendedContact details updated.
8 May 2008New search has been performedSix potential studies identified and excluded
8 May 2008AmendedConverted to new review format.
24 August 2005New citation required and conclusions have changedSubstantive amendment

Contributions of authors

Writing of review - CHW, AAB, DMM
Screening of titles and abstracts - CHW, AAB
Quality assessment - CHW, AAB, DAR
Data extraction - CHW, AAB
Data analysis - CHW, AAB, DMM
Resolution of discrepancies/disagreements - DMM, DAR

Declarations of interest

None known

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Bassiri 1995

MethodsStudy: RCT/ quasi-RCT
Blinding: No
Intention-to-treat: No
Complete follow-up: No
Follow-up: 2-10 months
Participants

84 consecutive transplants

Treatment group
Number of patients: 35

Control group
Number of patients: 37
Excluded: "previous pelvic operations and bladder problems".

Interventions Treatment group
Stent calibre: NR
Stent length, type: 16 cm, double J
Stent duration: 6-8 weeks
Antibiotic regimen: NR
Anastomosis: L-G
Surgeon: same team
Outcomes
  1. MUCs: Haematuria: unclear (no definitions given - "frank haematuria")

  2. Graft loss

  3. Death

  4. Encrustation

  5. Expulsion

NotesDeaths and rejection excluded
Donor source: NR
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskB - Unclear

Benoit 1996

MethodsStudy: RCT/ quasi-RCT
Blinding: No
Intention-to-treat: Yes
Complete follow-up: Yes
Follow-up: up to 3 years
Participants

194 consecutive cadaveric, live, kidney-liver-pancreas

Treatment group
Number of patients: 97

Control group
Number of patients: 97

No exclusions.

Interventions

Treatment group
Stent calibre: 7 Fr
Stent length, type: 16 cm, double J
Stent duration: 1 month
Antibiotic regimen: cotrimoxazole 480 mg od
Anastomosis: L-G and L-P
Surgeon: many surgeons

Prophylactic antibiotics for 48 hrs followed by cotrimoxazole.

Outcomes
  1. MUCs: UTI: positive culture > 105

  2. MUCs: Haematuria, no definition

  3. Death

  4. Breakage

  5. Migration/malpositioning

  6. Encrustation

  7. Expulsion

Notes2 graft losses to stents.
Donor source: cadaveric, live, multiorgan
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskB - Unclear

Dominguez 2000

Methodsquasi-RCT
Blinding: No
Intention-to-treat: Yes
Complete follow-up: Yes
Follow-up: 3 months
Participants

331 consecutive patients

Treatment group
Number of patients: 143

Control group
Number of patients: 137

Excluded: "abnormal urinary tract, small calibre ureter, multiorgan, paediatric".

Interventions Treatment group
Stent calibre: 6 Fr
Stent length, type: 12 cm, double J
Stent duration: 7-10 days
Antibiotic regimen: Cotrimoxazole 480 mg, 3 doses/week
Anastomosis: L-G
Surgeon: Many surgeons
Outcomes
  1. MUCs: Urine culture > 105 bacteria plus fever/symptoms

  2. MUCs: Haematuria, no definition

  3. Irritative symptoms

  4. Breakage

  5. Migration/malpositioning

  6. Encrustation

  7. Expulsion

NotesDonor source: Cadaveric and live
Used an intraoperative stent for all anastomoses
Attending surgeon altered treatment designation
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskC - Inadequate

Guleria 1998

MethodsStudy: RCT
Blinding: No
Intention-to-treat: Yes
Complete follow-up: One patient lost
Follow-up: 6 months
Participants

108 consecutive live-related

Treatment group
Number of patients: 54

Control group
Number of patients: 54

Interventions Treatment group
Stent calibre: NR
Stent length, type: 24 cm, double J
Stent duration: 14-21 days
Antibiotic regimen: Oral cephalexin 5 days
Anastomosis: L-G and L-P
Surgeon: Same team
Outcomes
  1. MUCs: UTI: on culture. Weekly urine culture

  2. Graft loss

  3. Death

  4. Irritative symptoms

  5. Breakage

  6. Migration/malpositioning

  7. Encrustation

  8. Expulsion

NotesDonor source: live only
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskA - Adequate

Kumar 1998

MethodsStudy: RCT
Blinding: No
Intention-to-treat: Yes
Complete follow-up: Yes
Follow-up: 16 to 32 months
Participants

100 consecutive transplants

Treatment group
Number of patients: 57

Control group
Number of patients: 43

No exclusions.

Interventions Treatment group
Stent calibre: 6 Fr
Stent length, type: 16 cm, double J
Stent duration: 4 weeks
Antibiotic regimen: Cotrimoxazole 960 mg alternate days
Anastomosis: L-G
Surgeon: Same team
Outcomes
  1. MUCs: UTI: "positive culture". Urine culture reported separate to UTI

  2. MUCs: Haematuria, no definition

  3. Graft loss

  4. Death

  5. Irritative symptoms

  6. Breakage

  7. Migration/malpositioning

  8. Encrustation

  9. Forgotten

  10. Expulsion

NotesDonor source: live only
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskA - Adequate

Osman 2004

MethodsStudy: RCT
Blinding: No
Intention-to-treat: No
Complete follow-up: Yes
Follow-up: 7 to 16 months
Participants

Treatment group
Number of patients: 50

Control group
Number of patients: 50

Exclusions: "intra-operative technical difficulties", "abnormal urinary tracts", aged less than 10 years; No laparoscopic

Interventions Treatment group
Stent calibre: 5 Fr
Stent length, type: 20 cm, multilength
Stent duration: 14 days
Antibiotic regimen: IV amoxicillin 5 days
Anastomosis: L-G
Surgeon: Same team
Outcomes
  1. MUCs: UTI: positive urine culture bacteria > 105 (every other day)

  2. MUCs: Haematuria (definition - change in heparin dose required to control)

  3. Graft loss

  4. Death

  5. Breakage

  6. Migration/malpositioning

  7. Encrustation

  8. Forgotten

  9. Expulsion

NotesDonor source: Live only
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskA - Adequate

Pleass 1995

  1. a

    MUCs - major urological complications; NR - not reported

MethodsStudy: RCT
Allocation concealment: Opaque envelopes pre-randomised
Blinding: No
Intention-to-treat: Yes
Complete follow-up: Yes
Follow-up: 3 months
Participants

Treatment group
Number of patients: 150

Control group
Number of patients: 150

No exclusions

Interventions Treatment group
Stent calibre: 7 Fr
Stent length, type: 12 cm, double J
Stent duration: 3 months
Antibiotic regimen: Cotrimoxazole 960 mg alternate days
Anastomosis: L-G
Surgeon: Many surgeons
Outcomes
  1. MUCs: UTI diagnosed clinically (fever/symptoms) and confirmed on microscopy

  2. MUCs: Haematuria (definition - catheter clot obstruction requiring washout)

  3. Breakage

  4. Migration/malpositioning

  5. Encrustation

  6. Expulsion

NotesDonor source: live and cadaveric, multiorgan, no paediatric
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskA - Adequate

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Anil 2012Prospective RCT, both arms received stents- no control group without stents.
Asadpour 2011Prospective RCT comparing length of ureteric spatulation.
Battaglia 2005RCT, but compared patients receiving different types of stent.
Dadkhah 2010Comparison of anterior and posterolateral ureteroneocystostomy techniques.
Gunawansa 2011RCT, early versus late stent removal.
Huang 2012Early versus late stent removal.
Moray 2005"RCT" however on contacting author used a historical cohort of patients "randomly chosen" as controls for the treatment group.
Parapiboon 2012Early versus late stent removal
Simpson 2006Not RCT
Tavakoli 2007Prospective RCT. However, intention-to-treat analysis and randomisation flawed. "Clerical error" in randomisation process led to significantly different numbers from protocol in each group. 11/112 (c.10%) of patients in No Stent group removed from analysis. Contacted author team and asked for details of these patient outcomes; unfortunately data not available - therefore the study had to excluded.
TrUST Study 2011Early versus late stent removal
Valentini 2004Not RCT
Zargar 2005RCT, compared two different surgical techniques (Taguchi versus, modified Lich-Gregoir) rather than stents.

Ancillary