Impact of Ureteral Stenting on Urological Complications After Kidney Transplantation Surgery: A Single-Center Experience M. Harzaa, C. Bastona,*, A. Predaa, V. Olarua, G. Ismailb, L. Domnisora, D. Daiaa, I. Mitroia, M.O. Bastonc, and I. Sinescua a Center for Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania; bCenter of Internal MedicineeNephrology, Fundeni Clinical Institute, Bucharest, Romania; and cClinical Center of Radiology, Medical Imaging and Nuclear Medicine, Central Clinical Military Emergency Hospital, Bucharest, Romania
ABSTRACT Background. Urological complications such as ureteral strictures and ureteral leakage can affect the outcome of kidney transplantation by increasing morbidity and mortality, including graft loss. Controversy still exists regarding the role of stents in renal transplantation. The aim of this study was to evaluate the role of ureteral stenting in kidney transplantation. Methods. We performed a retrospective study on a series of 798 consecutive renal transplants performed in our center between January 1, 2004, and December 31, 2011. Ureteral stents were used in 152 cases (19.1%) of the total (stent group) and were removed 2 weeks postoperatively. Donor and recipient age, sex, type of ureteroneocystostomy, stent and nonstent patients, cold and warm ischemia time, and urological complications were analyzed. Results. The overall incidence of urological complications was 7.8% (62 cases). Ureteral stenosis (3.1%) and ureteral leakage (2.4%) were the most common complications; 39.7% (25 cases) of complications were recorded in the first month after transplantation. Major urological complication rate was 3.3% in the stent group compared with 8.8% in the nonstent group (P ¼ .04). However, stent use was associated with the increase of urinary tract infections rate in the stent group (51.3%) compared with the non-stent group (17.9%) (P ¼ .03). Conclusions. In our study, the use of ureteral stents significantly decreased urological complications in kidney transplant recipients but increased the risk for development of urinary tract infections.
P
ATIENTS with renal transplant have an increased 5-year survival rate compared with patients on dialysis, and costs are significantly lower [1]. Ureteral obstruction and/or urinary leak represent the most frequent urological complications after renal transplantation. The urological complication rate in renal transplant varies widely from 6.5% to 14.1% [2e5]. Ureteral obstruction occurring after renal transplantation can reach a prevalence of 4.5%, whereas urinary leaks are recorded in up to 8.9% of cases [6e8]. There is still an active debate whether ureteral stenting can lower the urologic complication rate in these patients. The aim of this study was to evaluate and assess the outcomes and results of ureteral stenting in a series of 798 consecutive renal transplants that were performed in the
Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, between January 2004 and December 2011. METHODS Between January 2004 and December 2011, 798 renal transplants were performed in the Center of Uronephrology and Renal Transplantation Fundeni Clinical Institute, Bucharest. We performed a retrospective analysis of our center’s database. Donor and *Address correspondence to Catalin Baston, MD, PhD, Center for Uronephrology and Renal Transplantation, Fundeni Clinical Institute, 258 Fundeni Street, District 2, Bucharest, Romania 022328. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.08.051
Transplantation Proceedings, 46, 3459e3462 (2014)
3459
3460 recipient age, sex, type of ureteroneocystostomy (UCNS), stent and non-stent patients, cold and warm ischemia time, and urological complications were analyzed. All our patients were assessed preoperatively by a multidisciplinary team consisting of a transplant surgeon, nephrologist, and anesthesiologist and at times were examined by other physicians when necessary (cardiologist, gastroenterologist, infectious disease specialist). We diagnosed urinary tract infections (UTIs) by means of urine culture when more than 105 bacterial colony-forming units per milliliter were found. Urine analysis and urine culture were assessed routinely before kidney transplantation and after removal of urinary catheters in renal transplant recipients. Perioperative antibiotic prophylaxis included third generation of cephalosporine before induction of anesthesia and 3 days after transplantation. UTI and asymptomatic bacteriuria in renal transplant recipients were treated with parenteral antibiotics until negative urine culture was obtained. Each patient had a minimal follow-up period of 12 months. Follow-up consisted in-clinic examination, standard blood and urine workup, and imaging studies when necessary by scan computed tomography urography (CTU), ultrasonography (US), magnetic resonance imaging. We considered ureteral stenosis and ureteral leakage as major complications after renal transplantation. The complications were assessed through the use of laboratory values and imaging tools as stated above. Our patients received kidneys from living donors as well as from deceased donors who suffered brain death. Surgery was performed by our transplant surgeons’ team, who grafted the kidneys extraperitonealy, frequently in the right iliac fossa. UCNS was performed mostly by use of the Leddbetter-Politano (L-P) technique and in smaller proportion by use of the Lich-Gregoire (L-G) technique. The L-P technique was achieved by performing sub-mucosal bladder tunnel and then anastomosing the transplanted ureter directly to the bladder mucosa with separate absorbable sutures. The L-G technique was performed after carefully incising the detrusor muscle and afterward conducting the anastomosis directly to the bladder mucosa. In our retrospective analysis, transvesical L-P technique for UCNS was used from 2004 to 2007. Even though proportions are different regarding group case numbers, we divided our patients into stent and non-stent groups. In the stent group, we used Cook Medical ureteral pigtail stents, varying from 6F to 8F (Cook Ireland, National Technological Park, Limerick, Ireland). Ureteral stents were normally kept in place for a period of 2 weeks and removed by means of cystoscopy. In our patients, ureteral stenosis causing hydronephrosis was diagnosed by use of CTU scans and US in routine follow-up or when we detected increased levels of serum creatinine. This was treated by an open or endoscopic approach, depending on the length and location of ureteral strictures. We suspected ureteral leakage when graft function was altered or when we observed increased drainage. Diagnosis was also made by use of CTU and US, and treatment was accomplished in most cases by means of double-J placement or percutaneous nephrostomy drainage when renal function was compromised or the patient was instable. When ureteral necrosis was present, we performed open surgery, excising the damaged area and afterward reconstructing the UCNS. The study was approved by the ethics committee of our hospital.
Statistical Analysis Normally distributed variables are expressed as mean standard deviation. Nonparametric variables are described as median (lower quartile and upper quartile). For continuous variables, differences between groups were assessed with the use of the Student t test or Mann-Whitney U test, depending on the normality of the data. Categorical variables were compared with use of the c2 test. All P
HARZA, BASTON, PREDA ET AL values are 2-tailed, with a value of P < .05 considered statistically significant. Statistical analysis was performed with the use of SPSS for Windows, version 17.0 (SPSS, Inc, Chicago, Ill, United States). A multivariable Cox regression analysis was performed to determine the factors associated with lower major urological complication rate. Results are expressed as hazard ratios [Exp(B)] with 95% confidence intervals. Hazard ratios are expressed per unit of age and dichotomized for sex, donor type, and use of ureteral stents.
RESULTS
Between January 2004 and December 2011, we performed 798 consecutive renal transplants. Renal grafts were obtained from deceased donors in 224 cases (28.1%) and from living related donors in 574 cases (71.9%). Donor mean age was 45.7 14.8 years, and male-to-female ratio was 0.96:1. Recipient mean age was 34.2 12.4 years, and male-to-female ratio was 1.72:1. Preferred graft location was in the right iliac fossa in 81.9% of cases (n ¼ 654). Mean cold ischemia time was 6.8 hours for both living and deceased donors, with a minimum of 14 minutes and a maximum of 25 hours. Urinary tract continuity was obtained in 64.9% of cases by use of the L-P technique (n ¼ 518) and in 35.1% of cases by use of the L-G technique (n ¼ 280). Ureteral stents were used in 152 cases (19.1% of all subjects) (102 cases with L-P technique representing 20.2% and 50 cases with L-G technique representing 17.1%) and were removed 2 weeks after surgery. Characteristics of the 2 groups are shown in Table 1. Urological complications after kidney transplantation occurred in 62 cases, representing 7.8% of all patients; 57 patients were in the non-stented group (8.8%) and 5 were in the stent group (3.3%), the difference presenting statistical significance (P ¼ .04) (Table 2). In the L-P group, the overall incidence of urological complications was 8.5% (n ¼ 42 cases), with significant differences between the stented group (4 patients, representing 3.9%) and the non-stented group (38 patients, representing 9.4%) (P ¼ .04) (Table 2). In the L-G group, the overall incidence was 6.8% (n ¼ 20 cases), with a significant difference between the stented group (only 1 case representing 2%) and the nonstented group (19 cases, representing 7.8%) (P ¼ .03). The most common complications were ureteral stenosis in 39.6% of cases and ureteral fistulas appearing in 30.1% of patients. Of the total number of complications, 38.7% (24 cases) occurred within the first month after transplant (early complications), whereas 61.3% developed after 1 month (late complications). In our study, ureteral leakage was the most common major complication during the early postoperative period, being encountered in 2.4% of cases. Ureteral stenosis occurred within 3 months after surgery in 3.1% of cases. In our opinion, the main causes of ureteral leakage were ischemia and technical errors, and ureteral stenosis was associated with late events such as ischemia, inflammation, or UTI. Double-J stents appeared to protect against the development of 2 major urological complications: ureteral stenosis and fistulas, having statistically significant differences (P ¼ .04).
URETERAL STENTS IN RENAL TRANSPLANTATION
3461
Table 1. Patient Characteristics
Donor age (years) Donor sex (M:F) Donor type (live:deceased) Recipient age (years) Recipient sex (M:F) Type of UCNS (L-P:L-G) Cold ischemia time Live donors Deceased donors Warm ischemia time General
Donors
Total n ¼ 798
Non-Stent Group n ¼ 646
Stent Group n ¼ 152
P Value
45.7 14.8 0.96:1 2.56:1 34.2 12.4 1.72:1 1.72:1
46.4 15.4 0.98:1 2.89:1 33.7 11.7 1.8:1 1.66:1
44.3 14.2 0.87:1 1.62:1 36.5 11.3 1.45:1 2.04:1
.81 .56 .18 .57 .19 .47
e e
27.4 6.274 min 825.35 261.62 min
30.1 9.972 min 792.28 244.82 min
e e
28.75 4.51 min minimum 20 min maximum 45 min e
e
e
e
27.48 3.75 min (mean, 28 min)
32.48 6.87 (mean, 29.40 min)
Causes of Chronic Renal Failure
Unidentified Chronic glomerulonephritis, different types Polycystic kidney-liver disease Kidney stones Diabetes
No. of Patients
Percent (%)
261 216 96 64 56
32.7% 27.1% 12.1% 8% 7%
Abbreviations: UCNS, ureteroneocystostomy; L-P, Leddbetter-Politano technique; L-G, Lich-Gregoire technique.
Statistical analysis showed no statistical differences between major urological complications in the stented group and sex or donor type. However, stent use was associated with an increased rate of UTI (78 cases with UTI, representing 51.3%) compared with the non-stent group (115 cases, representing 17.8%) (P ¼ .03). During the first month after renal transplant (early phase), 70 patients (89.7%) were diagnosed with UTI in the stented group compared with 84 patients (73%) in the non-stent group. The causative microorganism was isolated in 92.2% of cases (142 patients). UTI was caused frequently by Gramnegative bacteria; 24 patients (80%) from the stent group had development of complicated UTI with reflux-associated pyelonephritis compared with 6 patients (20%) in the nonstent group. This was successfully treated promptly with parenteral antibiotics until the urine culture was negative. By Cox multivariate analysis adjusted for age, sex (both the donor and the recipient), and donor type, stent use Table 2. Outcomes in Non-Stent and Stent Group Non-Stent Group Characteristic
Stent Group
No. Percentage No. Percentage
Overall major 57 urological complications Rate of UTI 115 Complications 38 in L-P Complications 19 in L-G
8.8%
5
3.3%
Total
P Value
62 (7.8%)
.04
17.8% 9.4%
78 4
51.3% 3.9%
193 (24.2%) 42 (8.5%)
.03 .04
7.8%
1
2%
20 (6.8%)
.03
Abbreviations: UTI, urinary tract infection; L-P, Leddbetter-Politano technique; L-G, Lich-Gregoire technique.
remained independently associated with lower major urological complication rate [hazard ratio, 0.681 (0.462e0.910), P ¼ .042] (data presented in Table 3). DISCUSSION
Despite relatively low rates, major urological complications in kidney transplant represent an important cause of morbidity, leading to graft dysfunction and even graft loss. In our study, the rate of major urological complications after renal transplant was 7.8% (n ¼ 62), comparable with the literature [9]. As reported in the literature, particular care should be given to surgical techniques of organ recovery and ureterocystoneostomy [10]. The use of ureteral stents in renal transplantation to prevent major complications is still controversial. In theory, ureteral stents reduce anastomotic tension and kinking, preventing postoperative luminal obstruction caused by edema, blood clots, or external compression. In the absence of a stent, small amounts of urine leaked into the Table 3. Multivariate Cox Proportional Hazard Model 95% CI for Exp(B)
Donor age Donor sex Donor type Recipient age Recipient sex Use of ureteral stents (yes)
Significance (P)
Exp(B)
Lower
Upper
.163 .114 .754 .123 .778 .042
1.543 4.019 .530 .552 .599 .681
.839 .715 .010 .259 .017 .462
2.838 22.581 27.989 1.175 21.068 .910
Abbreviations: Exp(B), hazard ratios; CI, confidence intervals.
3462
peri-ureteral tissues, resulting in subsequent inflammation, fibrosis, and stricture formation. The decision to insert a ureteral stent depended mostly on our surgeons’ experience and intraoperative assessment (bladder characteristics, ureteral blood supply, difficult ureterovesical anastomosis, etc). The stent group had significantly lower rates of complications compared with the non-stented group. We also found an overall incidence of major urological complications of 7.8%, with differences between the stent and non-stent groups with the use of the extravesical L-G procedure. As a conclusion, the L-G technique of UCNS decreases urological rate compared with the transvesical L-P procedure, without statistical significance, and had a positive impact in the stented group. Some studies advocate the preventive role of ureteral stenting against major complications in renal transplantation, although others have shown no reduction in complication rates [11,12]. The protective role of ureteral stenting shown in our study concurs with other studies [13]. A Cochrane review of a large meta-analysis of prospective, randomized trials performed by several authors (Osman et al [11] and Wilson et al [14]) showed that stenting of renal transplant recipients results in lower major complication rates compared with that in non-stent groups. Similarly, multivariate analysis showed that insertion of a stent was the only factor associated with decreased urological complications in living related transplant recipients [11,13]. We usually expect higher complication rates in recipients with grafts from deceased donors, probably as the result of prolonged cold ischemia time and handling. Our observation of similar complication rates between recipients with grafts from living versus deceased donors are probably explained by the more frequent use of stents in deceased transplant recipients and/or short cold ischemia time in these patients. In contrast, studies by Kumar et al [13], Fayek et al [14], and others revealed decreased rates of major urological complications in deceased related recipients and not in living related recipients. There are also studies that report no reductions in ureteral leakage or stenosis rates after prophylactic use of ureteral stents for UCNS [11]. However, all authors have raised concerns regarding potential stent-related complications [14,15]. Osman et al [11] reported a significant association of urinary tract infection in an already immune-compromised patient and concluded that stents should be used in selective cases with pathologic or de-functionalized bladders. Additionally, Tavakoli et al [16] proved that there was a significantly increased risk of UTIs in patients with stents that stayed in place longer than 30 days. Dominguez et al [17] also supported this finding but showed no increase in this risk if stents were removed after 7 to 10 days. Similarly, in our cohort, stent use was associated with an increase of the UTI rate in the stent group (51.3%) compared with that in the non-stent group (17.9%) (P ¼ .03). In summary, in this single-center cohort study with a mix of living and deceased donors, we observed that the use of ureteral stenting significantly decreased urological
HARZA, BASTON, PREDA ET AL
complications after kidney transplantation but increased the rate of UTIs. This was observed in all patients. We can conclude that routine ureteral stenting in renal transplant should balance the benefits of reduced urological complications with a certain risk of developing a UTI, raising the need for more robust results from large, prospective, randomized trials without multiple variables (different surgeons and type of UCNS, mixed cohort of patients) accompanied by a cost-benefit analysis.
REFERENCES [1] National Kidney and Urologic Diseases Information Clearinghouse. Kidney Disease Statistics for the United States. Publication No. 12-3895. Washington, DC: National Institutes of Health; 2012. Available at http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/ #14 and http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/#18. [2] Streeter EH, Little DM, Cranston DW, et al. The urological complications of renal transplantation: a series of 1,535 patients. BJU Int 2002;90:627. [3] Rigg KM, Proud G, Taylor RMR. Urological complications following renal transplantation. Transpl Int 1994;7:120. [4] Hakim NS, Benedetti E, Pirenne J, et al. Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience. Clin Transplant 1994;8:504. [5] Burmeister D, Noster M, Kram W, et al. Urological complications after kidney transplantation. Urologe A 2006; 45:25. [6] Duty BD, Conlin MJ, Fuchs EF, et al. The current role of endourologic management of renal transplantation complications. Adv Urol 2013;2013:246. [7] Nie ZL, Zhang KQ, Li QS, et al. Treatment of urinary fistula after kidney transplantation. Transplant Proc 2009;41:1624. [8] Mano R, Golan S, Holland R, et al. Retrograde endoureterotomy for persistent ureterovesical anastomotic strictures in renal transplant kidneys after failed antegrade balloon dilation. Urology 2012;80:255. [9] Davari HR, Yarmohammadi H, Malekhosseini SA, et al. Urological complications in 980 consecutive patients with renal transplantation. Int J Urol 2006;13:1271. [10] Shapiro R, Simmons RL, Starzl TE, editors. The transplant procedure. In: Renal Transplantation. Stamford, CT: Appleton and Lange; 1999. p. 103e40. [11] Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation: is it worthwhile? Urology 2005;65:867. [12] Mongha R, Kumar A. Transplant ureter should be stented routinely. Indian J Urol 2010;26:450. [13] Kumar A, Verma BS, Srivastava A, et al. Evaluation of the urological complications of living related renal transplantation at a single center during the last 10 years: impact of the Double-J* stent. J Urol 2000;164:657. [14] Wilson CH, Bhatti AA, Rix DA, et al. Routine intraoperative ureteric stenting for kidney transplant recipients. Cochrane Database Syst Rev 2005;4:CD004925. [15] Fayek SA, Keenan J, Haririan A, et al. Ureteral stents are associated with reduced risk of ureteral complications after kidney transplantation: a large single center experience. Transplantation 2012;93:304. [16] Tavakoli A, Surange RS, Pearson RC, et al. Impact of stents on urological complications and health care expenditure in renal transplant recipients: results of a prospective, randomized clinical trial. J Urol 2007;177:2260. [17] Dominguez J, Clase CM, Mahalati K, et al. Is routine ureteric stenting needed in kidney transplantation? A randomized trial. Transplantation 2000;70:597.
ABSTRACT Background. Urological complications such as ureteral strictures and ureteral leakage can affect the outcome of kidney transplantation by increasing morbidity and mortality, including graft loss. Controversy still exists regarding the role of stents in renal transplantation. The aim of this study was to evaluate the role of ureteral stenting in kidney transplantation. Methods. We performed a retrospective study on a series of 798 consecutive renal transplants performed in our center between January 1, 2004, and December 31, 2011. Ureteral stents were used in 152 cases (19.1%) of the total (stent group) and were removed 2 weeks postoperatively. Donor and recipient age, sex, type of ureteroneocystostomy, stent and nonstent patients, cold and warm ischemia time, and urological complications were analyzed. Results. The overall incidence of urological complications was 7.8% (62 cases). Ureteral stenosis (3.1%) and ureteral leakage (2.4%) were the most common complications; 39.7% (25 cases) of complications were recorded in the first month after transplantation. Major urological complication rate was 3.3% in the stent group compared with 8.8% in the nonstent group (P ¼ .04). However, stent use was associated with the increase of urinary tract infections rate in the stent group (51.3%) compared with the non-stent group (17.9%) (P ¼ .03). Conclusions. In our study, the use of ureteral stents significantly decreased urological complications in kidney transplant recipients but increased the risk for development of urinary tract infections.
P
ATIENTS with renal transplant have an increased 5-year survival rate compared with patients on dialysis, and costs are significantly lower [1]. Ureteral obstruction and/or urinary leak represent the most frequent urological complications after renal transplantation. The urological complication rate in renal transplant varies widely from 6.5% to 14.1% [2e5]. Ureteral obstruction occurring after renal transplantation can reach a prevalence of 4.5%, whereas urinary leaks are recorded in up to 8.9% of cases [6e8]. There is still an active debate whether ureteral stenting can lower the urologic complication rate in these patients. The aim of this study was to evaluate and assess the outcomes and results of ureteral stenting in a series of 798 consecutive renal transplants that were performed in the
Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, between January 2004 and December 2011. METHODS Between January 2004 and December 2011, 798 renal transplants were performed in the Center of Uronephrology and Renal Transplantation Fundeni Clinical Institute, Bucharest. We performed a retrospective analysis of our center’s database. Donor and *Address correspondence to Catalin Baston, MD, PhD, Center for Uronephrology and Renal Transplantation, Fundeni Clinical Institute, 258 Fundeni Street, District 2, Bucharest, Romania 022328. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.08.051
Transplantation Proceedings, 46, 3459e3462 (2014)
3459
3460 recipient age, sex, type of ureteroneocystostomy (UCNS), stent and non-stent patients, cold and warm ischemia time, and urological complications were analyzed. All our patients were assessed preoperatively by a multidisciplinary team consisting of a transplant surgeon, nephrologist, and anesthesiologist and at times were examined by other physicians when necessary (cardiologist, gastroenterologist, infectious disease specialist). We diagnosed urinary tract infections (UTIs) by means of urine culture when more than 105 bacterial colony-forming units per milliliter were found. Urine analysis and urine culture were assessed routinely before kidney transplantation and after removal of urinary catheters in renal transplant recipients. Perioperative antibiotic prophylaxis included third generation of cephalosporine before induction of anesthesia and 3 days after transplantation. UTI and asymptomatic bacteriuria in renal transplant recipients were treated with parenteral antibiotics until negative urine culture was obtained. Each patient had a minimal follow-up period of 12 months. Follow-up consisted in-clinic examination, standard blood and urine workup, and imaging studies when necessary by scan computed tomography urography (CTU), ultrasonography (US), magnetic resonance imaging. We considered ureteral stenosis and ureteral leakage as major complications after renal transplantation. The complications were assessed through the use of laboratory values and imaging tools as stated above. Our patients received kidneys from living donors as well as from deceased donors who suffered brain death. Surgery was performed by our transplant surgeons’ team, who grafted the kidneys extraperitonealy, frequently in the right iliac fossa. UCNS was performed mostly by use of the Leddbetter-Politano (L-P) technique and in smaller proportion by use of the Lich-Gregoire (L-G) technique. The L-P technique was achieved by performing sub-mucosal bladder tunnel and then anastomosing the transplanted ureter directly to the bladder mucosa with separate absorbable sutures. The L-G technique was performed after carefully incising the detrusor muscle and afterward conducting the anastomosis directly to the bladder mucosa. In our retrospective analysis, transvesical L-P technique for UCNS was used from 2004 to 2007. Even though proportions are different regarding group case numbers, we divided our patients into stent and non-stent groups. In the stent group, we used Cook Medical ureteral pigtail stents, varying from 6F to 8F (Cook Ireland, National Technological Park, Limerick, Ireland). Ureteral stents were normally kept in place for a period of 2 weeks and removed by means of cystoscopy. In our patients, ureteral stenosis causing hydronephrosis was diagnosed by use of CTU scans and US in routine follow-up or when we detected increased levels of serum creatinine. This was treated by an open or endoscopic approach, depending on the length and location of ureteral strictures. We suspected ureteral leakage when graft function was altered or when we observed increased drainage. Diagnosis was also made by use of CTU and US, and treatment was accomplished in most cases by means of double-J placement or percutaneous nephrostomy drainage when renal function was compromised or the patient was instable. When ureteral necrosis was present, we performed open surgery, excising the damaged area and afterward reconstructing the UCNS. The study was approved by the ethics committee of our hospital.
Statistical Analysis Normally distributed variables are expressed as mean standard deviation. Nonparametric variables are described as median (lower quartile and upper quartile). For continuous variables, differences between groups were assessed with the use of the Student t test or Mann-Whitney U test, depending on the normality of the data. Categorical variables were compared with use of the c2 test. All P
HARZA, BASTON, PREDA ET AL values are 2-tailed, with a value of P < .05 considered statistically significant. Statistical analysis was performed with the use of SPSS for Windows, version 17.0 (SPSS, Inc, Chicago, Ill, United States). A multivariable Cox regression analysis was performed to determine the factors associated with lower major urological complication rate. Results are expressed as hazard ratios [Exp(B)] with 95% confidence intervals. Hazard ratios are expressed per unit of age and dichotomized for sex, donor type, and use of ureteral stents.
RESULTS
Between January 2004 and December 2011, we performed 798 consecutive renal transplants. Renal grafts were obtained from deceased donors in 224 cases (28.1%) and from living related donors in 574 cases (71.9%). Donor mean age was 45.7 14.8 years, and male-to-female ratio was 0.96:1. Recipient mean age was 34.2 12.4 years, and male-to-female ratio was 1.72:1. Preferred graft location was in the right iliac fossa in 81.9% of cases (n ¼ 654). Mean cold ischemia time was 6.8 hours for both living and deceased donors, with a minimum of 14 minutes and a maximum of 25 hours. Urinary tract continuity was obtained in 64.9% of cases by use of the L-P technique (n ¼ 518) and in 35.1% of cases by use of the L-G technique (n ¼ 280). Ureteral stents were used in 152 cases (19.1% of all subjects) (102 cases with L-P technique representing 20.2% and 50 cases with L-G technique representing 17.1%) and were removed 2 weeks after surgery. Characteristics of the 2 groups are shown in Table 1. Urological complications after kidney transplantation occurred in 62 cases, representing 7.8% of all patients; 57 patients were in the non-stented group (8.8%) and 5 were in the stent group (3.3%), the difference presenting statistical significance (P ¼ .04) (Table 2). In the L-P group, the overall incidence of urological complications was 8.5% (n ¼ 42 cases), with significant differences between the stented group (4 patients, representing 3.9%) and the non-stented group (38 patients, representing 9.4%) (P ¼ .04) (Table 2). In the L-G group, the overall incidence was 6.8% (n ¼ 20 cases), with a significant difference between the stented group (only 1 case representing 2%) and the nonstented group (19 cases, representing 7.8%) (P ¼ .03). The most common complications were ureteral stenosis in 39.6% of cases and ureteral fistulas appearing in 30.1% of patients. Of the total number of complications, 38.7% (24 cases) occurred within the first month after transplant (early complications), whereas 61.3% developed after 1 month (late complications). In our study, ureteral leakage was the most common major complication during the early postoperative period, being encountered in 2.4% of cases. Ureteral stenosis occurred within 3 months after surgery in 3.1% of cases. In our opinion, the main causes of ureteral leakage were ischemia and technical errors, and ureteral stenosis was associated with late events such as ischemia, inflammation, or UTI. Double-J stents appeared to protect against the development of 2 major urological complications: ureteral stenosis and fistulas, having statistically significant differences (P ¼ .04).
URETERAL STENTS IN RENAL TRANSPLANTATION
3461
Table 1. Patient Characteristics
Donor age (years) Donor sex (M:F) Donor type (live:deceased) Recipient age (years) Recipient sex (M:F) Type of UCNS (L-P:L-G) Cold ischemia time Live donors Deceased donors Warm ischemia time General
Donors
Total n ¼ 798
Non-Stent Group n ¼ 646
Stent Group n ¼ 152
P Value
45.7 14.8 0.96:1 2.56:1 34.2 12.4 1.72:1 1.72:1
46.4 15.4 0.98:1 2.89:1 33.7 11.7 1.8:1 1.66:1
44.3 14.2 0.87:1 1.62:1 36.5 11.3 1.45:1 2.04:1
.81 .56 .18 .57 .19 .47
e e
27.4 6.274 min 825.35 261.62 min
30.1 9.972 min 792.28 244.82 min
e e
28.75 4.51 min minimum 20 min maximum 45 min e
e
e
e
27.48 3.75 min (mean, 28 min)
32.48 6.87 (mean, 29.40 min)
Causes of Chronic Renal Failure
Unidentified Chronic glomerulonephritis, different types Polycystic kidney-liver disease Kidney stones Diabetes
No. of Patients
Percent (%)
261 216 96 64 56
32.7% 27.1% 12.1% 8% 7%
Abbreviations: UCNS, ureteroneocystostomy; L-P, Leddbetter-Politano technique; L-G, Lich-Gregoire technique.
Statistical analysis showed no statistical differences between major urological complications in the stented group and sex or donor type. However, stent use was associated with an increased rate of UTI (78 cases with UTI, representing 51.3%) compared with the non-stent group (115 cases, representing 17.8%) (P ¼ .03). During the first month after renal transplant (early phase), 70 patients (89.7%) were diagnosed with UTI in the stented group compared with 84 patients (73%) in the non-stent group. The causative microorganism was isolated in 92.2% of cases (142 patients). UTI was caused frequently by Gramnegative bacteria; 24 patients (80%) from the stent group had development of complicated UTI with reflux-associated pyelonephritis compared with 6 patients (20%) in the nonstent group. This was successfully treated promptly with parenteral antibiotics until the urine culture was negative. By Cox multivariate analysis adjusted for age, sex (both the donor and the recipient), and donor type, stent use Table 2. Outcomes in Non-Stent and Stent Group Non-Stent Group Characteristic
Stent Group
No. Percentage No. Percentage
Overall major 57 urological complications Rate of UTI 115 Complications 38 in L-P Complications 19 in L-G
8.8%
5
3.3%
Total
P Value
62 (7.8%)
.04
17.8% 9.4%
78 4
51.3% 3.9%
193 (24.2%) 42 (8.5%)
.03 .04
7.8%
1
2%
20 (6.8%)
.03
Abbreviations: UTI, urinary tract infection; L-P, Leddbetter-Politano technique; L-G, Lich-Gregoire technique.
remained independently associated with lower major urological complication rate [hazard ratio, 0.681 (0.462e0.910), P ¼ .042] (data presented in Table 3). DISCUSSION
Despite relatively low rates, major urological complications in kidney transplant represent an important cause of morbidity, leading to graft dysfunction and even graft loss. In our study, the rate of major urological complications after renal transplant was 7.8% (n ¼ 62), comparable with the literature [9]. As reported in the literature, particular care should be given to surgical techniques of organ recovery and ureterocystoneostomy [10]. The use of ureteral stents in renal transplantation to prevent major complications is still controversial. In theory, ureteral stents reduce anastomotic tension and kinking, preventing postoperative luminal obstruction caused by edema, blood clots, or external compression. In the absence of a stent, small amounts of urine leaked into the Table 3. Multivariate Cox Proportional Hazard Model 95% CI for Exp(B)
Donor age Donor sex Donor type Recipient age Recipient sex Use of ureteral stents (yes)
Significance (P)
Exp(B)
Lower
Upper
.163 .114 .754 .123 .778 .042
1.543 4.019 .530 .552 .599 .681
.839 .715 .010 .259 .017 .462
2.838 22.581 27.989 1.175 21.068 .910
Abbreviations: Exp(B), hazard ratios; CI, confidence intervals.
3462
peri-ureteral tissues, resulting in subsequent inflammation, fibrosis, and stricture formation. The decision to insert a ureteral stent depended mostly on our surgeons’ experience and intraoperative assessment (bladder characteristics, ureteral blood supply, difficult ureterovesical anastomosis, etc). The stent group had significantly lower rates of complications compared with the non-stented group. We also found an overall incidence of major urological complications of 7.8%, with differences between the stent and non-stent groups with the use of the extravesical L-G procedure. As a conclusion, the L-G technique of UCNS decreases urological rate compared with the transvesical L-P procedure, without statistical significance, and had a positive impact in the stented group. Some studies advocate the preventive role of ureteral stenting against major complications in renal transplantation, although others have shown no reduction in complication rates [11,12]. The protective role of ureteral stenting shown in our study concurs with other studies [13]. A Cochrane review of a large meta-analysis of prospective, randomized trials performed by several authors (Osman et al [11] and Wilson et al [14]) showed that stenting of renal transplant recipients results in lower major complication rates compared with that in non-stent groups. Similarly, multivariate analysis showed that insertion of a stent was the only factor associated with decreased urological complications in living related transplant recipients [11,13]. We usually expect higher complication rates in recipients with grafts from deceased donors, probably as the result of prolonged cold ischemia time and handling. Our observation of similar complication rates between recipients with grafts from living versus deceased donors are probably explained by the more frequent use of stents in deceased transplant recipients and/or short cold ischemia time in these patients. In contrast, studies by Kumar et al [13], Fayek et al [14], and others revealed decreased rates of major urological complications in deceased related recipients and not in living related recipients. There are also studies that report no reductions in ureteral leakage or stenosis rates after prophylactic use of ureteral stents for UCNS [11]. However, all authors have raised concerns regarding potential stent-related complications [14,15]. Osman et al [11] reported a significant association of urinary tract infection in an already immune-compromised patient and concluded that stents should be used in selective cases with pathologic or de-functionalized bladders. Additionally, Tavakoli et al [16] proved that there was a significantly increased risk of UTIs in patients with stents that stayed in place longer than 30 days. Dominguez et al [17] also supported this finding but showed no increase in this risk if stents were removed after 7 to 10 days. Similarly, in our cohort, stent use was associated with an increase of the UTI rate in the stent group (51.3%) compared with that in the non-stent group (17.9%) (P ¼ .03). In summary, in this single-center cohort study with a mix of living and deceased donors, we observed that the use of ureteral stenting significantly decreased urological
HARZA, BASTON, PREDA ET AL
complications after kidney transplantation but increased the rate of UTIs. This was observed in all patients. We can conclude that routine ureteral stenting in renal transplant should balance the benefits of reduced urological complications with a certain risk of developing a UTI, raising the need for more robust results from large, prospective, randomized trials without multiple variables (different surgeons and type of UCNS, mixed cohort of patients) accompanied by a cost-benefit analysis.
REFERENCES [1] National Kidney and Urologic Diseases Information Clearinghouse. Kidney Disease Statistics for the United States. Publication No. 12-3895. Washington, DC: National Institutes of Health; 2012. Available at http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/ #14 and http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/#18. [2] Streeter EH, Little DM, Cranston DW, et al. The urological complications of renal transplantation: a series of 1,535 patients. BJU Int 2002;90:627. [3] Rigg KM, Proud G, Taylor RMR. Urological complications following renal transplantation. Transpl Int 1994;7:120. [4] Hakim NS, Benedetti E, Pirenne J, et al. Complications of ureterovesical anastomosis in kidney transplant patients: the Minnesota experience. Clin Transplant 1994;8:504. [5] Burmeister D, Noster M, Kram W, et al. Urological complications after kidney transplantation. Urologe A 2006; 45:25. [6] Duty BD, Conlin MJ, Fuchs EF, et al. The current role of endourologic management of renal transplantation complications. Adv Urol 2013;2013:246. [7] Nie ZL, Zhang KQ, Li QS, et al. Treatment of urinary fistula after kidney transplantation. Transplant Proc 2009;41:1624. [8] Mano R, Golan S, Holland R, et al. Retrograde endoureterotomy for persistent ureterovesical anastomotic strictures in renal transplant kidneys after failed antegrade balloon dilation. Urology 2012;80:255. [9] Davari HR, Yarmohammadi H, Malekhosseini SA, et al. Urological complications in 980 consecutive patients with renal transplantation. Int J Urol 2006;13:1271. [10] Shapiro R, Simmons RL, Starzl TE, editors. The transplant procedure. In: Renal Transplantation. Stamford, CT: Appleton and Lange; 1999. p. 103e40. [11] Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation: is it worthwhile? Urology 2005;65:867. [12] Mongha R, Kumar A. Transplant ureter should be stented routinely. Indian J Urol 2010;26:450. [13] Kumar A, Verma BS, Srivastava A, et al. Evaluation of the urological complications of living related renal transplantation at a single center during the last 10 years: impact of the Double-J* stent. J Urol 2000;164:657. [14] Wilson CH, Bhatti AA, Rix DA, et al. Routine intraoperative ureteric stenting for kidney transplant recipients. Cochrane Database Syst Rev 2005;4:CD004925. [15] Fayek SA, Keenan J, Haririan A, et al. Ureteral stents are associated with reduced risk of ureteral complications after kidney transplantation: a large single center experience. Transplantation 2012;93:304. [16] Tavakoli A, Surange RS, Pearson RC, et al. Impact of stents on urological complications and health care expenditure in renal transplant recipients: results of a prospective, randomized clinical trial. J Urol 2007;177:2260. [17] Dominguez J, Clase CM, Mahalati K, et al. Is routine ureteric stenting needed in kidney transplantation? A randomized trial. Transplantation 2000;70:597.
