Objectives: In this systematic review and meta-analysis, our aim was to explore the optimal timing of ureteric stent removal after kidney transplant.
Materials and Methods: For our analyses, we searched the Cochrane Central Register of Controlled Trials, PubMed, and Embase databases for all randomized clinical trials that evaluated the timing of stent removal after kidney transplant. Patients with early versus late stent removal were compared.
Results: Seven eligible studies published from 2012 to 2018, which included 1277 patients, were found to be within the scope of our study. Significant differences were shown between early versus late stent removal groups with regard to development of urinary tract infections (relative risk of 0.42; 95% CI, 0.26-0.685; P < .001). In a further subgroup analysis of incidence of urinary tract infection with consideration of heterogeneity, early stent removal was also favored (relative risk at 2 and 3 weeks of 0.36 and 0.35, respectively; P < .001 for both). However, with regard to incidence of major urologic complications, there were no significant differences between early and late stent removal (odds ratio at 2 and 3 weeks of 2.79 and 1.97, respectively; P = .18 and P = .26, respectively). There were also no significant differences between groups in risk of development of urinary leakage (odds ratio at 2 weeks of 3.02, P = .18; and relative risk at 3 weeks of 2.00, P = .27). With regard to ureteral stenosis, only 3 cases were reported in the late stent removal group.
Conclusions: Our study demonstrated that early ureteral stent removal (that is, not later than 3 weeks) could significantly decrease the incidence of urinary tract infections without affecting incidence of major urological complications. We suggest that the appropriate timing of stent removal should be within 14 to 21 days.
Key words : Ureteral stenosis, Urinary leakage, Urologic complications
Over the decades, most surgical techniques involved in kidney transplant (KTx) have been standardized. The double J stent (JJ stent)1,2 has been mostly used in draining after ureteroneocystostomy of KTx, and previous studies have demonstrated that it can decrease the incidence of major urologic complications (MUCs), that is, both ureteric obstruction and ureteric leakage, from between 7% and 9% to 1.5%. However, according to the KTx transplant guidelines from the European Association of Urology,3 JJ stents can also increase the risk of urinary tract infections (UTIs) from 6% to 40% if left in place for longer than 30 days. The guidelines also advise centers to remove stents earlier than 6 weeks after transplant rather than later. Thus, the ureteric stent is similar to a double-edged sword for KTx recipients: it is helpful in the prevention of MUCs4 but is a high-risk factor in the development of UTIs5 and idiosyncratic complications such as hematuria and irritative bladder symptoms.6 Appropriate application of the ureteric stent is important in KTx.
There are different opinions among surgeons with regard to timing for stent removal. Some researchers7,8 have asserted that KTx recipients could only benefit from stents placed for 1 or 2 weeks; however, other researchers9,10 have suggested that indwelling stents can only prevent complications if left for longer periods of time, with too early removal of stents associated with UTIs as well as ureteric leakage. So far, no consensus on the appropriate time of stent removal has been reached.
In this meta-analysis and systematic review, we aimed to identify the optimal “early” timing of ureteric stent removal after KTx, which could be helpful for clinical decisions among transplant centers.
Materials and Methods
All studies included in our analyses were published in English and conformed to the following criteria: (1) studies on KTx patients, but not those on stenting of ileal conduits or continent urinary diversions, who had urinary stent removal posttransplant; (2) studies designed as randomized controlled trials (RCTs); and (3) studies that included at least 1 outcome. Duplicated results in different articles, reviews, and animal research studies were excluded.
With use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and above selection criteria, we searched PubMed, Embase, and the Cochrane Library databases for studies published from February 2011 to October 2019. Potentially relevant RCTs from references of relative studies were also searched by hand to ensure that no articles were missed. The followed medical subject headings (MeSH) or non-MeSH terms were used in our search: “kidney graft” OR “kidney transplantation” OR “renal transplant” OR “kidney transplant” AND “stent” and “urinary stent.” These search strategies were used to search each database.
The outcome measure in this meta-analysis was the timing of stent removal and the incidence of UTIs and MUCs (urinary leakage and ureteral stenosis).11 Urinary tract infections were defined as a positive urine culture with a bacterial colony count of more than 105 colony-forming units/mL.12
Two reviewers independently assessed all eligible publications, and any disagreements were discussed with a third reviewer and solved by all reviewers. With selection criteria, each reviewer used a standardized extraction form to extract the data from all full-text studies, which included details on author names, the year of publication, country, general patient data, follow-up duration, donor type, type of stent, stent removal methods, immunosuppressive therapies, and outcomes.
Review Manager Software (RevMan 5.3) was used for meta-analysis. Differences in outcomes were expressed as relative risk (RR) or odds ratio (OR; with 95% CIs). Heterogeneity across trials was quantified by using the I2 statistic. When I2 statistic was below 50% by chi-square test, which indicted a low level of heterogeneity, a fixed-effects model was used for estimates. When I2 statistic was over 50%, a random-effects model was chosen. Furthermore, subgroup analysis was used to explore possible sources of heterogeneity, and sensitivity analyses were performed to examine the results. P < .05 was affirmed as statistically significant.
The GRADE tool13,14 was recommended for assessing the risk of bias and evaluating the methodological quality of each RCT, which included 7 aspects: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other biases. Each reviewer assessed each study to find high, low, or unclear risk of bias. Disagreements were resolved through a third reviewer and discussion.
After careful review of the initial literature search, a total of 7 eligible studies15-21 from 2012 to 2018 and 1277 patients were found to be within the scope of our study. Figure 1 illustrates the selection strategy, and Table 1 lists the characteristics of the 7 included studies. Figure 2 illustrates the quality assessment of each RCT and provides a qualification of risk of bias. All studies except Parapiboon and colleagues18 reported the age of the recipients. Five of the 7 articles reported the use of the Lich-Gregoir technique, which was not reported in the remaining 2 studies. Regarding stent removal, cystoscopy was mostly used in the studies. Six studies recorded the use of antibiotic prophylaxis, such as ceftriaxone and sulfamethoxazole/trimethoprim, to protect or to prevent UTIs. Five studies reported the immunosuppressive therapies that patients received. With regard to outcomes, all articles described the incidence of UTIs and 4 articles reported MUCs. Table 2 presents the outcomes for the included studies.
Urinary tract infections
All included studies recorded UTI events with regard to various timing of stent removal. Significant differences were shown between groups with early versus late stent removal in the development of UTIs, with early removal shown to have better outcomes for UTI incidence (RR of 0.42; 95% CI, 0.26-0.685; P < .001) (Figure 3A). With the consideration of high heterogeneity (I2 = 56%), sensitivity analysis and subgroup analysis were conducted. To explore appropriate timing, we investigated 2 timelines: 2 weeks and 3 weeks. To avoid low quality and high risk of bias, we excluded Gunawansa and associates21 (the full article was not assessable). This article was also excluded for our continuous analysis of MUC. Our analysis was consistent with the previous conclusion without heterogeneity, which favored early stent removal. At the 2-week timeline, relative risk was 0.36 (95% CI, 0.26-0.52; P< .001; Figure 3B); at the 3-week timeline, relative risk was 0.35 (95% CI, 0.25-0.49; P < .001; Figure 3C).
Major urological complications
Four studies described the incidence of MUCs with a total of 718 patient. As shown in Figure 4, with regard to MUCs, there were no significant differences among the studies between early and late stent removal. The OR for 2-week timeline was 2.79 (95% CI, 0.62-12.52; P = .18), and the OR for 3-week timeline was 1.97 (95% CI, 0.61-6.33; P = .26). As shown in Figure 5, we also observed no significant differences between early and late stent removal groups in risk of developing urinary leakage, with OR for 2-week timeline of 3.02 (95% CI, 0.59-15.51; P = .18) and RR for 3-week timeline of 2.00 (95% CI, 0.59-6.80; P = .27). For ureteral stenosis, only Gunawansa and colleagues21 (2 cases) and Patel and colleagues19 (1 case) reported ureteral stenosis, all at late stent removal. Therefore, because of the low incidence among our findings, this factor was not suitable for the meta-analysis.
The universal use of ureteric stents is a good minimally invasive option for urinary drainage after KTx; however, there are still questions on indwelling time. Previous research5 has shown that the implanted stent can be accompanied by various complications, including hematuresis, stent migration, and dis-comfort. In addition, it may lead to UTIs, which could result in prolonged hospitalizations, increased costs, and even recurrent surgical interventions. However, the benefits of stents have also been shown, with KTx recipients having a lower incidence of MUCs. A number of studies22-24 have explored timing of stent removal after KTx, with ureteral stent removal usually occurring from 1 to 6 weeks after the surgery. Because, so far, no consensus has been reached with regard to timing, we explored this aspect with a systematic review and meta-analysis.
In our analysis, we found that early removal of the stent after KTx (that is, not later than 3 weeks) had a significant effect on decreasing the incidence of UTIs. We found that timing at both 2 weeks and 3 weeks had good results; therefore, we suggest 14 to 21 days as a preferred timing. In their study, Yuksel and colleagues10 reviewed 818 KTx patients and divided them into 4 groups according to the timing of stent removal (5-7 days, 8-14 days, 15-21 days, >22 days). They found that only 0.1% of UTIs were observed at 15 to 21 days versus 1.2% at 8 to 14 days and 3.2% at >22 days, with obvious lower incidence among those who had JJ stent removal before day 14 (10.6% in the combined group of 5-7 days and 8-14 days). Dadkhah and colleagues9 also showed a lower rate of UTIs in patients who had stent removal at about 20 days versus those who had removal at about 30 days after KTx (7.2% vs 12.4%, respectively). These results imply that long-duration indwelling stents could lead to high risk of UTIs.
In contrast to the results for UTIs, our analysis showed that development of MUCs was not associated with indwelling time of stents. We also found no significant differences between groups with short and long duration of stent placement with regard to risk of developing urinary leakage, with negligible rate of ureteral stenosis (0.6%). As reported previously,25-28 the incidence of urinary leakage can range from 1.5% to 6.0%, with most leakages occurring at the site of the ureteroneocystostomy during the early stage due to distal ureteral ischemia. In a meta-analysis from Alberts and colleagues,29 several factors, including graft arterial reconstruction, recipient diabetes, and multiple renal arteries, were concluded to contribute to ureteral leakage after KTx, with the Lich-Gregoir technique suggested to significantly reduce the rate of leakage. Furthermore, Yuksel and colleagues10 reported that early stent removal (<14 days) led to a higher rate of leakage and stenosis than in the unstented population. Thus, we suggest that more than 2 weeks of the implanted stent could help to prevent leakage, but longer indwelling time may have no effect on the incidence of ureteral leakages after KTx. With these considerations, we recommend removal of the ureteral stent after 2 weeks.
This meta-analysis also carries some limitations that must be considered. First, only 7 RCTs were included in our study, and 1 of the studies carried a high risk of bias, resulting in our minimization or exclusion of those results for some analyses. Second, each RCT contained a small numbers of patients; therefore, larger RCTs may be needed to confirm these results. In addition, only studies written in English were searched in this meta-analysis, which resulted in potential publication bias. Finally, various recipient and donor characteristics of included studies could also have affected our results. Because of these limitations, more trials may be needed to confirm these results.
Our study demonstrated that the early removal of ureteral stent, not later than 3 weeks, significantly decreased the incidence of UTI but did not affect the development of MUCs. We recommend that stent placement of 14 to 21 days is a preferred duration and the appropriate timing of stent removal.
Volume : 20
Issue : 1
Pages : 28 - 34
DOI : 10.6002/ect.2021.0183
From the Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Yue Yang, Urological Department, The Affiliated Hospital of Chengdu University, North Road 46, Chengdu, Sichuan, China
Phone: +86 035 88623287
Table 1. Characteristics of 7 Included Randomized Controlled Trials
Figure 1. Flowchart of Included Studies in the Meta-Analysis
Figure 2. Qualification of Risk of Bias
Table 2. Outcomes Shown in the 7 Included Randomized Controlled Trials
Figure 3. Meta-Analysis of Urinary Tract Infection
Figure 4. Meta-Analysis of Major Urologic Complications
Figure 5. Meta-Analysis of Ureteric Leakage