Key words : Major urologic complications, Renal transplant, Ureter leakage, Ureter obstruction

Introduction

Hydronephrosis is a common finding on radiologic images after kidney transplant (KT), but its pre-valence is not well known. There are 2 types of hydronephrosis: obstructive and nonobstructive.^1-3 Obstructive hydronephrosis is described as ureter obstruction; if obstructive hydronephrosis is accom-panied by renal dysfunction, invasive treatment such as percutaneous ureteral intervention (PUI) is required.^1,4 Nonobstructive hydronephrosis is caused by a decreased ureter tone secondary to vesicoureteral reflux and chronic rejection, and its treatment is different from that of obstructive hydronephrosis.^1,2 Differentiation between these 2 types of hydro-nephrosis is important to avoid unnecessary invasive procedures after KT, but doing so remains difficult.

Major urologic complications (MUCs), such as ureter obstruction and ureter leakage, are the most common urologic complications after KT.^5-7 Routine ureteral stenting (RUS) is a well-known method to successfully prevent MUCs in KT procedures.^7-13 However, theoretical disadvantages exist, including an increased incidence of urinary tract infections (UTIs) and the development of certain stent-related complications (SRCs).^7,10,14,15 In addition, invasive procedures for stent removal after KT have an extra cost and risk.^9,10 The role of ureteral stents in KT has remained controversial in both randomized trials and systematic reviews.^7,14

Many centers are presently basing decisions on whether to use a ureteral stent in KT on their own policies, without consensus or guidelines. To our knowledge, no studies have investigated the effects of RUS on postoperative hydronephrosis and PUI in KT patients. This study aimed to evaluate the effects of RUS on hydronephrosis and PUI and to share a single-center experience in terms of MUCs and UTIs after transplant in the application of RUS. Additionally, a cost-benefit analysis of RUS was conducted.

Materials and Methods

Study design and patients
We retrospectively reviewed the records of patients who underwent KT between January 2005 and December 2021 at our tertiary institution. Our institution performed 542 KTs; we analyzed 539 of these patients, with 1 patient who received en bloc KT and 2 patients with data loss who were excluded. We classified the patients into 2 groups: stent and no-stent ureteroneocystostomy groups.

Data collection
The following clinical data were collected: patient demographics and characteristics (recipient age, recipient sex, recipient body mass index [BMI], donor status, donor age, donor sex, donor BMI, ABO status, human leukocyte antigen [HLA] status, transplant type, kidney weight, and immunosuppressive agent), operative data (American Society of Anesthesiologists score, operation time, and ureter-bladder anastomosis time), surgical outcomes (1-year glomerular filtration rate [GFR], stent duration, hospital stay, urologic complications, UTIs, rejection, and in-hospital mortality), and healthcare costs. Living donors included related donors (first-degree relatives) and unrelated donors (spouse).

Routine ureteral stenting protocol
Our center has adopted the RUS protocol for KT since July 2017 and consecutively used this protocol for the purpose of excluding urinary tract-related causes of postoperative creatinine elevation and reducing urologic complications. Before the RUS protocol was used, ureteral stents were only used selectively in situations where ureterovesical viability could be compromised or anastomosis was difficult.16

Surgical technique (ureteroneocystostomy)
Ureterovesical anastomosis for all patients was performed using the standard extravesical Lich-Gregoir technique. The ureter was measured and cut to the appropriate length for nonredundant and tension-free anastomosis. Ureter-bladder mucosa anastomosis was performed with a continuous running suture of 6-0 PDS (Ethicon), and the bladder muscle was closed with an interrupted suture of 4-0 Vicryl (Ethicon). In the stent group, depending on the length of the ureter, a 14- to 21-cm 4F double-J catheter was inserted after anastomosis of 1 side was completed.

Postoperative care and follow-up
A Foley catheter was routinely inserted intraope-ratively and removed on postoperative day 5. Routine kidney ultrasonography was performed to evaluate the transplanted kidneys on postoperative day 7. If there were no postoperative complications, the patient was discharged on postoperative day 8. After 4 postoperative weeks, the ureteral stent was removed at a urology outpatient clinic through cystoscopy with the patient under local anesthesia. Regular follow-up was performed in the outpatient clinics, and the patient was instructed to visit the emergency room at any time if there were any abnormal findings or events. Ultrasonography or computed tomography (CT) was performed if imaging tests were required, depending on the situation.

Urologic complications
Urologic complications were classified as Clavien-Dindo classification grade 3 or higher MUCs and SRCs. All events that occurred during postoperative hospitalization or outpatient follow-up were included.

Hydronephrosis was defined as >7 mm by measuring the anterior-posterior diameter of the renal pelvis based on the radiology grading system.¹⁷ Hydronephrosis was assessed by routine kidney ultrasonography on postoperative day 7. In addition, hydronephrosis results found on imaging workup (ultrasonography, CT, and pyelography) performed during any patient follow-up or events were included.

Percutaneous ureteral antegrade and retrograde treatment options included nephrostomy, nephrourete-al catheter, and double-J catheter insertion for patients with most types of ureteral pathologic conditions.^18,19

Major urologic complications
Ureter leakage was defined as drainage or periureteric/perirenal fluid collection with charac-teristics of urine (ie, creatinine level was 3 times higher than the serum concentration). Ureter obstruction was defined as inadequate kidney drainage (eg, hydronephrosis) accompanied by renal dysfunction confirmed by radiologic modalities (ultrasonography, CT, and pyelography).

Stent-related complications
Stent malfunction was defined as stent-induced impairment of kidney drainage with renal dysfunction, confirmed by radiologic modalities (ultrasonography, CT, and pyelography). Stent removal failure was defined as inability to remove stent by cystoscopy with the patient under local anesthesia; removal required radiological interven-tion or ureteroscopy with the patient under general anaesthesia. Delayed stent removal was defined as surgeons forgetting to remove the stent 4 weeks after transplant and the stent was discovered incidentally and later removed.

Urinary tract infection
Bacteria were confirmed in urine cultures (≥105 colonies/mL), with infections associated with fever and urinary symptoms. Patients with cystitis, ureteritis, and acute pyelonephritis were also included in this category.

Healthcare cost
All medical expenses, including the cost of the hospital stay related to KT and costs related to the management of postoperative complications, were investigated. Expenses included the cost of stent insertion and removal, evaluation, and treatment of MUCs and SRCs. If a patient was readmitted because of urological complications, the cost of readmission was also included. The cost of readmission related to UTIs was not included.

Stent-related cost
The sum of the double-J catheter price and stent removal cost in the urology outpatient clinics was a fixed cost required for ureteral stenting.

Outcomes
For both groups (stent and no-stent), the primary outcome was the incidence of postoperative hydronephrosis and PUI. Secondary outcomes were MUCs, UTIs, the ureterovesical anastomosis time, 1-year graft function, and healthcare costs.

Ethical statements
Patients were not required to give informed consent to the study because the analysis used anonymous clinical data; this study was approved by the Institutional Review Board of our institution (B-2207-769-104). All procedures adhered to the ethical standards of the responsible committee on human experimentation (institutional and national) and were conducted in accordance with the Helsinki Declaration of 1964 and its subsequent versions.

Statistical analyses
Continuous variables are presented as mean ± SD; we compared continuous variables between the 2 groups by using t tests. We compared categorical variables by using the Fisher exact test or chi-square test. Inverse probability of treatment weighting (IPTW) analyses were performed to adjust for baseline differences between the 2 groups (stent and no-stent). We estimated the propensity of the 2 groups by using a logistic regression model based on patient age, patient sex, patient BMI, donor age, donor sex, donor BMI, pretransplant dialysis, ABO status, HLA status, transplant type, and status per the American Society of Anesthesiologists score. We assessed the weighted balance between the groups by using standardized mean differences (a standar-dized mean difference of <0.2 was considered excellent balance). We performed logistic regression analysis to obtain the odds ratios (ORs) for urological surgical outcomes between the 2 groups before and after IPTW. We compared healthcare costs between groups as averages per patient by using t tests after IPTW. Healthcare costs included management costs for postoperative complications (eg, bleeding, lymphoceles, fluid collection, wound problems) that are not urologic complications. We thus also conducted a sensitivity (subgroup) analysis after excluding postoperative complications other than urological complications to compare the healthcare costs between the 2 groups.

For statistical analyses, we used R statistical software (version 4.0.0, R Foundation for Statistical Computing). Statistical significance was defined as a 2-tailed P < .05.

Results

Patient demographics and operative findings
Among the 539 KTs included in our study, 271 (50.29%) were in the stent group and 268 (49.71%) in the no-stent group. Before adjustment, recipient age, donor age, recipient BMI, and donor BMI were slightly higher in the stent group than in the no-stent group. The stent group had more ABO-incompatible transplants and total HLA mismatch counts than the no-stent group. After IPTW adjustment, all baseline characteristics between the 2 groups were well balanced, as indicated by a standardized mean difference of 0.2. Table 1 pre-sents the baseline characteristics before and after IPTW.

The operation times (251.18 and 249.04 min, respectively; P = .980) and hospital stay (14.51 and 14.88 days, respectively; P = .658) were not signi-ficantly different between the stent and no-stent groups. Postoperative complications were reported in 9.6% and 12.3% of cases in the stent and no-stent groups, respectively, with no significant difference between the groups (P = .466). However, pos-toperative bleeding was higher in the no-stent group than in the stent group (12 [4.5%] vs 3 [1.1%]; P = .003). No significant differences in 1-year graft survival (97% and 97.8%, respectively; P = .803), in-hospital mortality (0.7% and 0.4%, respectively; P > .999), and graft rejection (17.7% and 11.9%, respectively; P = .333) were shown between the stent and no-stent groups. The postoperative outcomes are shown in Table 2. In the stent group, 9 cases (3.32%) of SRCs were reported, and the mean stent removal time was 70.28 ± 76.31 days. The stent-related cost was $112.23 (Table 3).

Primary outcomes
The primary outcomes are summarized in Figure 1. Hydronephrosis was detected in 16 patients (5.9%) and 30 patients (11.2%) in the no-stent and stent groups, respectively (P = .041). Among patients with hydronephrosis, the number of patients who underwent PUI was significantly lower in the stent group than in the no-stent group (1 [6.25%] vs 10 [33.33%]; P = .014). After IPTW adjustment, the risk of hydronephrosis was significantly lower in the stent group than in the no-stent group (OR of 0.552; 95% CI, 0.335-0.893; P = .017). The risk of requiring PUI was significantly lower in the stent group than in the no-stent group (OR of 0.150; 95% CI, 0.029-0.492; P = .006) (Figure 2).

Secondary outcomes
Twenty patients (3.71%) experienced MUCs (19 [7.1%] in the no-stent group and 1 [0.4%] in the stent group; P = .001). After IPTW adjustment, the risk of MUCs was significantly lower in the stent group than in the no-stent group (OR of 0.071; 95% CI, 0.014-0.215; P < .001). In detail, the risks of ureter leakage (OR of 0.026; 95% CI, 0.000-0.194; P < .001) and ureter obstruction (OR of 0.15; 95% CI, 0.029-0.492; P = .006) were significantly lower in the stent group than in the no-stent group. The incidence of UTIs within the 3 months after transplant was not significantly different between the stent and no-stent groups (8.9% and 8.2%, respectively; OR of 0.957; 95% CI, 0.611-1.497; P = .846) (Figure 2). The ureterovesical anastomosis time was not significantly different between the stent and no-stent groups (24.4 and 24.03 min, respectively; P = .547). Figure 3 shows the healthcare costs incurred to discharge patients after transplant. After IPTW, healthcare costs were $15 653.52 in the stent group; this value was $1374.43 less than that in the no-stent group (P < .001).

In the subgroup analysis excluding postoperative complications other than urological complications, the healthcare cost was significantly lower in the stent group than in the no-stent group by $1702.05 ($15 000.89 vs $16 702.95; P < .001). Figure 4 shows the change in the GFR (mL/min) over 1 year; no significant difference in GFR was shown between the 2 groups.

Discussion

We conducted a cohort-based study using large-volume data to describe the effects of RUS on overall urologic surgical outcomes after KT. To our knowledge, this is the first report to address the association of ureteral stenting with postoperative hydronephrosis and PUI. We confirmed that RUS significantly reduced the incidence of postoperative hydronephrosis requiring unnecessary PUI and MUCs, but it did not increase the incidence of UTIs within 3 months after KT. Moreover, RUS was cost-effective in terms of the overall medical expenses related to KT.

Hydronephrosis after KT is a common finding, and its clinical significance should be considered based on renal function and clinical data.^2,20 During the postoperative management process, we often encounter various clinical situations that lead to renal dysfunction, for example, delayed graft function, graft rejection, and surgical complications. In this situation, if hydronephrosis is detected on radiological images, PUI is often performed for diagnostic and therapeutic purposes because the cause of renal dysfunction is unclear. If obstructive hydronephrosis can be excluded, this information is of great help in deciding whether to proceed with an invasive procedure. Therefore, RUS can play a pivotal role in reducing postoperative hydronephrosis and MUCs.

The incidence of MUCs after KT has decreased because of advances in surgical techniques. However, some patients (2.5% to 17.3%) still undergo surgical revision or endourologic management because of MUCs, which leads to increased hospital stay duration and increased medical expenses.^7,21,22 Randomized controlled trials and systematic reviews have investigated whether a ureteral stent reduces MUCs after KT, but the results have been controversial.^7,14,23 In a recently published systematic review and meta-analysis, RUS was reported to have a limited role in reducing MUCs in KT.14 However, the randomized studies included in this systematic review were small in size and were conducted before the 2000s; therefore, the influence of this systematic review has limitations. In contrast, our study results could be considered as reliable because, since 2017, RUS has been performed consecutively in all KT patients, the study population was not limited to specific patients and situations, and we had a large sample size.

Concerns remain that ureteral stents could increase the risk of UTIs after KT, and a recent meta-analysis confirmed a significant increase in UTIs associated with ureteral stents.⁷ We also investigated the association between RUS and UTIs within 3 months of KT in our study patients. However, the incidence of UTIs did not increase. The reason for this was presumed to be the use of sulfamethoxazole/trimethoprim. We used a universal prophylactic protocol for Pneumocystis carinii pneumonia in all KT patients. A meta-analysis also reported that long-term use of sulfamethox-azole/trimethoprim for prevention of Pneumocystis carinii pneumonia significantly reduced the incidence of UTIs.⁷ Other studies have reported that early ureteral stent removal compared with late stent removal reduced UTIs.^7,21,24,25 Therefore, RUS can be used without the risk of increasing the incidence of UTIs through the use of prophylactic antibiotics for Pneumocystis carinii pneumonia prevention and early stent removal.

We observed a higher healthcare cost in the no-stent group compared with the stent group (by $1702.05). This amount is considered to be the cost reduction for unnecessary invasive procedures in the stent group and the difference in management cost between MUCs in the no-stent group and SRCs in the stent group, as management of MUCs has a higher cost of readmission and surgical or radiologic intervention than management of SRCs.⁹ The use of ureteral stents in KT requires fixed medical expenses, defined as stent-related costs in this study, such as the cost of a double-J catheter and stent removal. The stent-related cost was $112.23. By preventing MUCs and unnecessary invasive procedures with an investment of $112.23, we still observed a cost reduction of $1702.05. Therefore, the application of RUS is cost-effective in terms of medical expenses for KT.

This study had some limitations. First, it was a retrospective study. Therefore, the baseline characteristics and follow-up periods of all patients were heterogeneous. To address these limitations, IPTW analysis was used to ensure as much homogeneity as possible. Second, management costs for urologic complications (eg, antibiotic therapy, surgical intervention, radiological evaluation or intervention) could not be investigated in detail when calculating healthcare costs. Therefore, to compensate for this, we compared healthcare costs between the 2 groups through a sensitivity analysis of patients with urologic complications.

Conclusions

Routine ureteral stenting in KT can effectively prevent postoperative hydronephrosis, MUCs, and unnecessary PUI. In addition, RUS can be safely used without increasing the risk of UTIs and is cost-effective in terms of overall urological surgical outcomes.

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