- Email: [email protected]
Does Pre-Transplantation Antireflux Surgery Eliminate Post-Renal Transplantation Pyelonephritis in Children?
Does Pre-Transplantation Antireflux Surgery Eliminate Post-Renal Transplantation Pyelonephritis in Children? A. Basiri,* H. Otookesh, N. Simforoosh, R. Hosseini, S. M. M. Hosseini-Moghaddam and M. Sharifian From the Urology and Nephrology Research Center, Labbafi Nejad Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
Purpose: Antireflux surgery for VUR before renal transplantation decreases the risk of post-kidney transplant UTI in pediatric patients with primary vesicoureteral reflux. We studied the risk of post-kidney transplant UTI in patients with or without surgical correction of VUR before transplantation compared to patients without VUR. Materials and Methods: We compared 12 patients who had VUR corrected before transplantation (group 1) to 17 patients with VUR who did not undergo antireflux surgery before transplantation (group 2) and 36 patients undergoing renal transplantation without VUR (group 3). A total of 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. Results: Eight patients in group 1 (66.7%), 6 in group 2 (35.3%) and 33 in group 3 (91.7%) remained free of febrile UTI during followup (p ⫽ 0.00). Among patients with high grade VUR 6 in group 1 and 1 in group 2 remained UTI-free (p ⫽ 0.02). A total of 33 patients in the control group (91.7%) remained free of febrile UTI, an incidence that was significantly lower compared to group 1 (p ⫽ 0.03) and group 2 (p ⫽ 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p ⫽ 0.64). Conclusions: Even after surgical correction of VUR before transplantation the frequency of febrile UTI remained higher than that in kidney transplant recipients without VUR. In cases of high grade VUR reimplantation before renal transplantation decreased the rate of febrile UTI but it was still higher than the level of risk in the control group. Key Words: pediatrics, kidney transplantation, vesico-ureteral reflux
atients with a history of VUR may have a high incidence of urinary tract infections following transplantation. In these patients symptomatic urinary tract infections are common in the first 3 months after transplantation.1 Although the incidence of febrile urinary tract infections is lower than that of lower urinary tract infection, it appears to be a major risk factor for graft failure. The occurrence of VUR related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.2 We assessed kidney transplant recipients with a history of vesicoureteral reflux to determine whether pre-transplant antireflux surgery had an impact on post-transplant graft survival and incidence of febrile urinary tract infection. Additionally, we analyzed our data in terms of VUR grade before transplantation.
P
MATERIALS AND METHODS A total of 207 pediatric kidney transplants were performed at our institution between 1984 and 2003. Of the treated patients 29 (14%) had a history of vesicoureteral reflux. A total of 36 pediatric patients without VUR undergoing kidney transplantation were selected as controls. All patients suffering from voiding dysfunction, urinary incontinence, urgency and enuresis were excluded, and we included only Submitted for publication July 13, 2005. * Correspondence: Urology and Nephrology Research Center, No. 44, Boostan 9th-Shaheed Djaafari St., Pasdaran Ave., Tehran, Iran (telephone: 98-21-2567222; FAX: 98-21-2567282; e-mail: [email protected]).
0022-5347/06/1754-1490/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
patients who did not need bladder rehabilitation postoperatively. These cases were matched with VUR cases regarding age, gender, time of transplantation, immunosuppression, donor age and HLA. Pre-transplantation dimercapto-succinic acid radionuclide scan of patients in groups 1 and 2 demonstrated renal scarring and global shrinkage, and a significant decrease in size. We routinely performed voiding cystourethrograms as a part of the pre-transplant evaluations. All patients received kidneys from living unrelated donors who underwent extensive medical and psychological evaluation, and signed an informed consent. All kidney recipients received an immunosuppressive protocol consisting of cyclosporine, prednisolone and azathioprine. After 1990 mycophenolate mofetil was used as a substitute for azathioprine. Donors were interested in the issue of organ donation for altruistic reasons. The technique for transplant ureteral implantation was the same in all patient groups. We defined 3 groups in our study. Group 1 consisted of 12 patients (8 males and 4 females, mean age 14 ⫾ 1.8 years) who had vesicoureteral reflux corrected before transplantation. Surgical correction of VUR in group 1 patients was performed elsewhere. Group 2 was composed of 17 patients (10 males and 7 females, mean age 11.6 ⫾ 2.9 years) with VUR who did not undergo antireflux surgery before transplantation. Six patients in group 1 (50%) and 9 in group 2 (53%) had bilateral VUR (p ⫽ 0.80). Group 3, which included 36 children (23 males and 13 females, mean age 10.9 ⫾ 3.8 years) without VUR undergoing kidney transplantation, served as controls.
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Vol. 175, 1490-1492, April 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00670-1
POST-TRANSPLANTATION PYELONEPHRITIS TABLE 1. Background variables in 3 patient groups Variable
Group 1
Male-to-female donor ratio 10:2 Mean donor age ⫾ SD (yrs) 26.7⫾6.8 No. previous renal 1 transplantation No. congenital renal disorders: Hypodysplasia of kidney 1 Congenital nephrotic 0 syndrome Medullary kidney disease 0 Cystinosis 0 Polycystic kidney disease 0 Median yrs hemodialysis 7 (0–32) (range) Mean days followup 1,078
Group 2
Group 3
14:3 24:12 29.3⫾5.3 27.8⫾4.6 0 1
p Value 0.4 0.5
1491
total of 33 patients in the control group (91.7%) remained free of febrile UTI, compared to 66.7% in group 1 (p ⫽ 0.03) and 35.3% in group 2 (p ⫽ 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p ⫽ 0.64). DISCUSSION
0 0
4 1
0 0 0 4.5 (0–36)
2 1 2 1 (0–30)
0.04
1,604
1,465
0.5
Surgeon and time of transplantation were identical between the 3 groups. All patients in groups 1 and 2 had a history of UTI at the time of VUR diagnosis, while only 2 patients in group 3 had a history of cystitis. In addition, we analyzed our data in terms of reflux grade, with category A including cases of grade I to II reflux, and category B including cases of grade III or higher (high grade). Mean followup was 58.8 months (range 4 months to 19 years). All febrile urinary tract infections were classified in the outcomes. All patients received trimethoprim/sulfamethoxazole for prevention of post-transplantation UTI. We considered 2 or more episodes of febrile urinary tract infection as recurrent febrile UTIs. Statistical analysis was performed using the chi-square test, Fisher’s exact test and Kaplan-Meier survival analysis as appropriate, with significance considered at p ⬍0.05. The end point for survival analysis was defined as death, need for re-transplantation or return to hemodialysis. RESULTS Table 1 outlines the background variables in the 3 groups. There was no case of hyperacute rejection. Seven patients (58.3%) in group 1, 8 (47.1%) in group 2 and 26 (72.2%) in group 3 experienced acute rejection (p ⫽ 0.18). Chronic rejection was diagnosed in 6 patients (50%) in group 1, 8 (47.1%) in group 2 and 10 (27.8%) in group 3 (p ⫽ 0.23). One patient in group 1 died during followup due to nonrenal disorders. Four patients (33.3%) in group 1, 4 (23.5%) in group 2 and 6 (16.7%) in group 3 returned to hemodialysis (p ⫽ 0.46). The graft survival rate was 92% at 1 year, 71% at 3 years, 68% at 5 years and 40% at 7 years following transplantation in patients with primary reflux, compared to 88% at 1 year, 78% at 3 years, 59% at 5 years and 48% at 7 years after transplantation in patients without VUR (p ⫽ 0.90). Table 2 shows our findings regarding the frequency of febrile UTI in different groups and categories. Eight patients (66.7%) in group 1, 6 (35.3%) in group 2 and 33 (91.7%) in group 3 remained free of febrile UTI during followup (p ⫽ 0.00). Although the differences between groups 1 and 3 (p ⫽ 0.009) and groups 2 and 3 (p ⫽ 0.00) were significant, the difference between groups 1 and 2 was negligible (p ⫽ 0.1). Using voiding cystourethrogram classification, 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. Among these patients 6 in group 1 and 1 in group 2 remained UTI-free during followup (p ⫽ 0.02). A
The incidence of urinary tract infection in patients undergoing renal transplantation remains high. The first episode of UTI is usually observed soon after transplantation and the rate gradually decreases thereafter.3 Risk factors for posttransplantation UTI are female gender due to gender related urine cytokine patterns,4 end stage renal disease due to urological disorders such as VUR and posterior urethral valves,5 diabetes 6 and urinary catheterization.7 Among these factors VUR seems to be a significant contributor. UTI is considered a major risk factor for renal allograft failure. However, in a study of 363 adult renal transplant recipients operated on between 1990 and 1996 Takai et al reported that UTI had no effect on the number of rejections, or on graft or patient survival in living donor transplant recipients.8 They found no significant difference in graft and patient survival rates at 3 years between patients with and without UTI. Despite these results, a retrospective cohort study by Abbott et al of 28,942 renal transplant recipients in the United States from 1996 through 2000 revealed that the association of UTI with death persisted even after adjusting for cardiac problems, inpatient or outpatient treatment, and other infectious complications.9 In this series late UTI was significantly associated with an increased risk of death in Cox regression analysis (p ⬍0.001, adjusted hazard ratio 2.93, 95% CI 2.22 to 3.85), and adjusted hazard ratio for graft loss was 1.85 (95% CI 1.29 to 2.64). However, UTI in the first 6 months after renal transplantation was not associated with significant mortality. The discrepancy between our results and those of Abbott et al 9 regarding the association between UTI and survival may be explained by considering the infrequency of some mortality associated etiologies such as diabetic nephropathy, atherosclerosis and other prolonged diseases in pediatric cases. Although they adjusted for cardiac complications as a direct cause of death, the effect of these complications in their study may have influenced the findings as indirect or predisposing factors, specifically in elderly patients. In our study regardless of groups and categories, there was no association between febrile UTI and acute rejection. In the same way graft survival in our patients with and without febrile UTI was similar. Approximately 20 years ago Pontin and Jacobson recommended that ureteral reimplantation be performed at the time of transplantation.10 Six years later Bouchot et al re-
TABLE 2. UTI episodes by category and grade
Grade I to II: Group 1 Group 2 Grade III or higher: Group 1 Group 2
No. UTI-Free
No. 1 Episode
No. 2 Episodes or More
Total No.
2 5
0 1
0 1
2 7
6 1
1 5
3 4
10 10
1492
POST-TRANSPLANTATION PYELONEPHRITIS
ported a lower rate of post-transplantation urinary tract infection in reimplanted cases.11 They stressed a higher rate of febrile and complicated UTI in patients with grades III to IV VUR, and recommended surgical correction of VUR before transplantation. In our study the discrepancy in UTIfree status between groups 1 and 2 was not significant. In other words, regardless of grade of reflux, surgical correction of VUR before transplantation does not seem to decrease the risk of febrile UTI. In the 1980s there were 2 reports on this topic that demonstrated favorable results and a low rate of urinary tract infection without pre-transplant reimplantation.12,13 These authors recommended pre-transplant surgery solely in those patients with poorly controlled febrile UTI or severe VUR. Erturk et al conducted a study of 36 patients with documented VUR.14 They compared 10 patients undergoing ureteral reimplantation before transplantation, 8 undergoing bilateral nephrectomy before transplantation and 18 with persistent reflux at the time of transplantation. They reported that the occurrence of symptomatic or asymptomatic UTI did not change significantly regardless of whether patients underwent pre-transplant surgery or had persistent vesicoureteral reflux. Patients who underwent ureteral reimplantation had fewer episodes of complicated and uncomplicated urinary tract infection. However, this difference was not significant. The main advantage of the report by Erturk et al is the comparison between 2 surgical approaches—reimplantation and bilateral nephrectomy—in patients with VUR at the time of transplantation.14 However, the main shortcoming is the lack of data on reflux grade. Additionally, the authors did not mention whether the VUR was primary or secondary. However, as a whole, their results were similar to our findings regarding frequency of UTI in patients undergoing pre-transplant ureteral reimplantation and those with persistent reflux at the time of transplantation. In our study the incidence of febrile UTI was significantly higher in patients with VUR (with or without surgical correction) compared to controls. Not surprisingly, among patients with VUR the incidence of febrile urinary tract infection was lower in those who underwent pre-transplant ureteral reimplantation. However, the difference was not statistically significant. Interestingly, the frequency of febrile UTI even after surgical correction of VUR was still significantly higher than in controls. In other words, regardless of VUR grade, there was no significant difference in the incidence of febrile urinary tract infections between patients who underwent pre-transplant antireflux surgery and those who did not. CONCLUSIONS Although there was no significant difference between patients with VUR with or without reimplantation before transplantation, the differences between these 2 groups and kidney recipients without VUR was significant. If we consider only patients with high grade VUR, reimplantation before renal transplantation significantly decreases the rate of febrile UTI. However, it is still significantly higher than in kidney transplant recipients with no history of VUR. Interestingly, with respect to recurrent febrile UTIs there was no significant difference between corrected and noncorrected
VUR groups. Consequently, we suggest that antireflux surgery before transplantation seems helpful in patients with high grade VUR, and we believe that even after surgical correction of VUR before transplantation the risk of febrile UTI remains high.
Abbreviations and Acronyms UTI ⫽ urinary tract infection VUR ⫽ vesicoureteral reflux REFERENCES 1. Crowe, A., Cairns, H. S., Wood, S., Rudge, C. J., Woodhouse, C. R. and Neild, G. H.: Renal transplantation following renal failure due to urological disorders. Nephrol Dial Transplant, 13: 2065, 1998 2. Ohba, K., Matsuo, M., Noguchi, M., Nishikido, M., Koga, S., Kanetake, H. et al: Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation. Clin Transplant, 18: 34, 2004 3. Mastrosimone, S., Pignata, G., Maresca, M. C., Calconi, G., Rabassini, A., Butini, R. et al: Clinical significance of vesicoureteral reflux after kidney transplantation. Clin Nephrol, 40: 38, 1993 4. Sadeghi, M., Daniel, V., Naujokat, C., Wiesel, M., Hergesell, O. and Opelz, G.: Strong inflammatory cytokine response in male and strong anti-inflammatory response in female kidney transplant recipients with urinary tract infection. Transpl Int, 18: 177, 2005 5. Mochon, M., Kaiser, B. A., Dunn, S., Palmer, J., Polinsky, M. S., Schulman, S. L. et al: Urinary tract infections in children with posterior urethral valves after kidney transplantation. J Urol, 148: 1874, 1992 6. Goya, N., Tanabe, K., Iguchi, Y., Oshima, T., Yagisawa, T., Toma, H. et al: Prevalence of urinary tract infection during outpatient follow-up after renal transplantation. Infection, 25: 101, 1997 7. de Oliveira, L. C., Lucon, A. M., Nahas, W. C., Ianhez, L. E. and Arap, S.: Catheter-associated urinary infection in kidney post-transplant patients. Sao Paulo Med J, 119: 165, 2001 8. Takai, K., Tollemar, J., Wilczek, H. E. and Groth, C. G.: Urinary tract infections following renal transplantation. Clin Transplant, 12: 19, 1998 9. Abbott, K. C., Swanson, S. J., Richter, E. R., Bohen, E. M., Agodoa, L. Y., Peters, T. G. et al: Late urinary tract infection after renal transplantation in the United States. Am J Kidney Dis, 44: 353, 2004 10. Pontin, A. R. and Jacobson, J. E.: Renal transplantation in primary reflux nephropathy without nephro-ureterectomy. A report of 4 cases. S Afr Med J, 68: 593, 1985 11. Bouchot, O., Guillonneau, B., Cantarovich, D., Hourmant, M., Le Normand, L., Soulillou, J. P. et al: Vesicoureteral reflux in the renal transplantation candidate. Eur Urol, 20: 26, 1991 12. Le Guillou, M., Ferriere, J. M., Potaux, L., Aparicio, M. and Pourquie, J.: Surgical indications for primary vesico-ureteral reflux in adult candidates for renal transplantation. Ann Urol (Paris), 18: 124, 1984 13. Morales, J. M., Andres, A., Prieto, C., Prage, M., Alcazar, J. M., Diaz-Gonzales, R. et al: Urinary morbidity of vesicoureteral reflux patients without surgical correction prior to renal transplantation. Nephron, 51: 571, 1989 14. Erturk, E., Burzon, D. T., Orloff, M. and Rabinowitz, R.: Outcome of patients with vesicoureteral reflux after renal transplantation: the effect of pretransplantation surgery on posttransplant urinary tract infections. Urology, 51: 27, 1998
Purpose: Antireflux surgery for VUR before renal transplantation decreases the risk of post-kidney transplant UTI in pediatric patients with primary vesicoureteral reflux. We studied the risk of post-kidney transplant UTI in patients with or without surgical correction of VUR before transplantation compared to patients without VUR. Materials and Methods: We compared 12 patients who had VUR corrected before transplantation (group 1) to 17 patients with VUR who did not undergo antireflux surgery before transplantation (group 2) and 36 patients undergoing renal transplantation without VUR (group 3). A total of 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. Results: Eight patients in group 1 (66.7%), 6 in group 2 (35.3%) and 33 in group 3 (91.7%) remained free of febrile UTI during followup (p ⫽ 0.00). Among patients with high grade VUR 6 in group 1 and 1 in group 2 remained UTI-free (p ⫽ 0.02). A total of 33 patients in the control group (91.7%) remained free of febrile UTI, an incidence that was significantly lower compared to group 1 (p ⫽ 0.03) and group 2 (p ⫽ 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p ⫽ 0.64). Conclusions: Even after surgical correction of VUR before transplantation the frequency of febrile UTI remained higher than that in kidney transplant recipients without VUR. In cases of high grade VUR reimplantation before renal transplantation decreased the rate of febrile UTI but it was still higher than the level of risk in the control group. Key Words: pediatrics, kidney transplantation, vesico-ureteral reflux
atients with a history of VUR may have a high incidence of urinary tract infections following transplantation. In these patients symptomatic urinary tract infections are common in the first 3 months after transplantation.1 Although the incidence of febrile urinary tract infections is lower than that of lower urinary tract infection, it appears to be a major risk factor for graft failure. The occurrence of VUR related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.2 We assessed kidney transplant recipients with a history of vesicoureteral reflux to determine whether pre-transplant antireflux surgery had an impact on post-transplant graft survival and incidence of febrile urinary tract infection. Additionally, we analyzed our data in terms of VUR grade before transplantation.
P
MATERIALS AND METHODS A total of 207 pediatric kidney transplants were performed at our institution between 1984 and 2003. Of the treated patients 29 (14%) had a history of vesicoureteral reflux. A total of 36 pediatric patients without VUR undergoing kidney transplantation were selected as controls. All patients suffering from voiding dysfunction, urinary incontinence, urgency and enuresis were excluded, and we included only Submitted for publication July 13, 2005. * Correspondence: Urology and Nephrology Research Center, No. 44, Boostan 9th-Shaheed Djaafari St., Pasdaran Ave., Tehran, Iran (telephone: 98-21-2567222; FAX: 98-21-2567282; e-mail: [email protected]).
0022-5347/06/1754-1490/0 THE JOURNAL OF UROLOGY® Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION
patients who did not need bladder rehabilitation postoperatively. These cases were matched with VUR cases regarding age, gender, time of transplantation, immunosuppression, donor age and HLA. Pre-transplantation dimercapto-succinic acid radionuclide scan of patients in groups 1 and 2 demonstrated renal scarring and global shrinkage, and a significant decrease in size. We routinely performed voiding cystourethrograms as a part of the pre-transplant evaluations. All patients received kidneys from living unrelated donors who underwent extensive medical and psychological evaluation, and signed an informed consent. All kidney recipients received an immunosuppressive protocol consisting of cyclosporine, prednisolone and azathioprine. After 1990 mycophenolate mofetil was used as a substitute for azathioprine. Donors were interested in the issue of organ donation for altruistic reasons. The technique for transplant ureteral implantation was the same in all patient groups. We defined 3 groups in our study. Group 1 consisted of 12 patients (8 males and 4 females, mean age 14 ⫾ 1.8 years) who had vesicoureteral reflux corrected before transplantation. Surgical correction of VUR in group 1 patients was performed elsewhere. Group 2 was composed of 17 patients (10 males and 7 females, mean age 11.6 ⫾ 2.9 years) with VUR who did not undergo antireflux surgery before transplantation. Six patients in group 1 (50%) and 9 in group 2 (53%) had bilateral VUR (p ⫽ 0.80). Group 3, which included 36 children (23 males and 13 females, mean age 10.9 ⫾ 3.8 years) without VUR undergoing kidney transplantation, served as controls.
1490
Vol. 175, 1490-1492, April 2006 Printed in U.S.A. DOI:10.1016/S0022-5347(05)00670-1
POST-TRANSPLANTATION PYELONEPHRITIS TABLE 1. Background variables in 3 patient groups Variable
Group 1
Male-to-female donor ratio 10:2 Mean donor age ⫾ SD (yrs) 26.7⫾6.8 No. previous renal 1 transplantation No. congenital renal disorders: Hypodysplasia of kidney 1 Congenital nephrotic 0 syndrome Medullary kidney disease 0 Cystinosis 0 Polycystic kidney disease 0 Median yrs hemodialysis 7 (0–32) (range) Mean days followup 1,078
Group 2
Group 3
14:3 24:12 29.3⫾5.3 27.8⫾4.6 0 1
p Value 0.4 0.5
1491
total of 33 patients in the control group (91.7%) remained free of febrile UTI, compared to 66.7% in group 1 (p ⫽ 0.03) and 35.3% in group 2 (p ⫽ 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p ⫽ 0.64). DISCUSSION
0 0
4 1
0 0 0 4.5 (0–36)
2 1 2 1 (0–30)
0.04
1,604
1,465
0.5
Surgeon and time of transplantation were identical between the 3 groups. All patients in groups 1 and 2 had a history of UTI at the time of VUR diagnosis, while only 2 patients in group 3 had a history of cystitis. In addition, we analyzed our data in terms of reflux grade, with category A including cases of grade I to II reflux, and category B including cases of grade III or higher (high grade). Mean followup was 58.8 months (range 4 months to 19 years). All febrile urinary tract infections were classified in the outcomes. All patients received trimethoprim/sulfamethoxazole for prevention of post-transplantation UTI. We considered 2 or more episodes of febrile urinary tract infection as recurrent febrile UTIs. Statistical analysis was performed using the chi-square test, Fisher’s exact test and Kaplan-Meier survival analysis as appropriate, with significance considered at p ⬍0.05. The end point for survival analysis was defined as death, need for re-transplantation or return to hemodialysis. RESULTS Table 1 outlines the background variables in the 3 groups. There was no case of hyperacute rejection. Seven patients (58.3%) in group 1, 8 (47.1%) in group 2 and 26 (72.2%) in group 3 experienced acute rejection (p ⫽ 0.18). Chronic rejection was diagnosed in 6 patients (50%) in group 1, 8 (47.1%) in group 2 and 10 (27.8%) in group 3 (p ⫽ 0.23). One patient in group 1 died during followup due to nonrenal disorders. Four patients (33.3%) in group 1, 4 (23.5%) in group 2 and 6 (16.7%) in group 3 returned to hemodialysis (p ⫽ 0.46). The graft survival rate was 92% at 1 year, 71% at 3 years, 68% at 5 years and 40% at 7 years following transplantation in patients with primary reflux, compared to 88% at 1 year, 78% at 3 years, 59% at 5 years and 48% at 7 years after transplantation in patients without VUR (p ⫽ 0.90). Table 2 shows our findings regarding the frequency of febrile UTI in different groups and categories. Eight patients (66.7%) in group 1, 6 (35.3%) in group 2 and 33 (91.7%) in group 3 remained free of febrile UTI during followup (p ⫽ 0.00). Although the differences between groups 1 and 3 (p ⫽ 0.009) and groups 2 and 3 (p ⫽ 0.00) were significant, the difference between groups 1 and 2 was negligible (p ⫽ 0.1). Using voiding cystourethrogram classification, 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. Among these patients 6 in group 1 and 1 in group 2 remained UTI-free during followup (p ⫽ 0.02). A
The incidence of urinary tract infection in patients undergoing renal transplantation remains high. The first episode of UTI is usually observed soon after transplantation and the rate gradually decreases thereafter.3 Risk factors for posttransplantation UTI are female gender due to gender related urine cytokine patterns,4 end stage renal disease due to urological disorders such as VUR and posterior urethral valves,5 diabetes 6 and urinary catheterization.7 Among these factors VUR seems to be a significant contributor. UTI is considered a major risk factor for renal allograft failure. However, in a study of 363 adult renal transplant recipients operated on between 1990 and 1996 Takai et al reported that UTI had no effect on the number of rejections, or on graft or patient survival in living donor transplant recipients.8 They found no significant difference in graft and patient survival rates at 3 years between patients with and without UTI. Despite these results, a retrospective cohort study by Abbott et al of 28,942 renal transplant recipients in the United States from 1996 through 2000 revealed that the association of UTI with death persisted even after adjusting for cardiac problems, inpatient or outpatient treatment, and other infectious complications.9 In this series late UTI was significantly associated with an increased risk of death in Cox regression analysis (p ⬍0.001, adjusted hazard ratio 2.93, 95% CI 2.22 to 3.85), and adjusted hazard ratio for graft loss was 1.85 (95% CI 1.29 to 2.64). However, UTI in the first 6 months after renal transplantation was not associated with significant mortality. The discrepancy between our results and those of Abbott et al 9 regarding the association between UTI and survival may be explained by considering the infrequency of some mortality associated etiologies such as diabetic nephropathy, atherosclerosis and other prolonged diseases in pediatric cases. Although they adjusted for cardiac complications as a direct cause of death, the effect of these complications in their study may have influenced the findings as indirect or predisposing factors, specifically in elderly patients. In our study regardless of groups and categories, there was no association between febrile UTI and acute rejection. In the same way graft survival in our patients with and without febrile UTI was similar. Approximately 20 years ago Pontin and Jacobson recommended that ureteral reimplantation be performed at the time of transplantation.10 Six years later Bouchot et al re-
TABLE 2. UTI episodes by category and grade
Grade I to II: Group 1 Group 2 Grade III or higher: Group 1 Group 2
No. UTI-Free
No. 1 Episode
No. 2 Episodes or More
Total No.
2 5
0 1
0 1
2 7
6 1
1 5
3 4
10 10
1492
POST-TRANSPLANTATION PYELONEPHRITIS
ported a lower rate of post-transplantation urinary tract infection in reimplanted cases.11 They stressed a higher rate of febrile and complicated UTI in patients with grades III to IV VUR, and recommended surgical correction of VUR before transplantation. In our study the discrepancy in UTIfree status between groups 1 and 2 was not significant. In other words, regardless of grade of reflux, surgical correction of VUR before transplantation does not seem to decrease the risk of febrile UTI. In the 1980s there were 2 reports on this topic that demonstrated favorable results and a low rate of urinary tract infection without pre-transplant reimplantation.12,13 These authors recommended pre-transplant surgery solely in those patients with poorly controlled febrile UTI or severe VUR. Erturk et al conducted a study of 36 patients with documented VUR.14 They compared 10 patients undergoing ureteral reimplantation before transplantation, 8 undergoing bilateral nephrectomy before transplantation and 18 with persistent reflux at the time of transplantation. They reported that the occurrence of symptomatic or asymptomatic UTI did not change significantly regardless of whether patients underwent pre-transplant surgery or had persistent vesicoureteral reflux. Patients who underwent ureteral reimplantation had fewer episodes of complicated and uncomplicated urinary tract infection. However, this difference was not significant. The main advantage of the report by Erturk et al is the comparison between 2 surgical approaches—reimplantation and bilateral nephrectomy—in patients with VUR at the time of transplantation.14 However, the main shortcoming is the lack of data on reflux grade. Additionally, the authors did not mention whether the VUR was primary or secondary. However, as a whole, their results were similar to our findings regarding frequency of UTI in patients undergoing pre-transplant ureteral reimplantation and those with persistent reflux at the time of transplantation. In our study the incidence of febrile UTI was significantly higher in patients with VUR (with or without surgical correction) compared to controls. Not surprisingly, among patients with VUR the incidence of febrile urinary tract infection was lower in those who underwent pre-transplant ureteral reimplantation. However, the difference was not statistically significant. Interestingly, the frequency of febrile UTI even after surgical correction of VUR was still significantly higher than in controls. In other words, regardless of VUR grade, there was no significant difference in the incidence of febrile urinary tract infections between patients who underwent pre-transplant antireflux surgery and those who did not. CONCLUSIONS Although there was no significant difference between patients with VUR with or without reimplantation before transplantation, the differences between these 2 groups and kidney recipients without VUR was significant. If we consider only patients with high grade VUR, reimplantation before renal transplantation significantly decreases the rate of febrile UTI. However, it is still significantly higher than in kidney transplant recipients with no history of VUR. Interestingly, with respect to recurrent febrile UTIs there was no significant difference between corrected and noncorrected
VUR groups. Consequently, we suggest that antireflux surgery before transplantation seems helpful in patients with high grade VUR, and we believe that even after surgical correction of VUR before transplantation the risk of febrile UTI remains high.
Abbreviations and Acronyms UTI ⫽ urinary tract infection VUR ⫽ vesicoureteral reflux REFERENCES 1. Crowe, A., Cairns, H. S., Wood, S., Rudge, C. J., Woodhouse, C. R. and Neild, G. H.: Renal transplantation following renal failure due to urological disorders. Nephrol Dial Transplant, 13: 2065, 1998 2. Ohba, K., Matsuo, M., Noguchi, M., Nishikido, M., Koga, S., Kanetake, H. et al: Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation. Clin Transplant, 18: 34, 2004 3. Mastrosimone, S., Pignata, G., Maresca, M. C., Calconi, G., Rabassini, A., Butini, R. et al: Clinical significance of vesicoureteral reflux after kidney transplantation. Clin Nephrol, 40: 38, 1993 4. Sadeghi, M., Daniel, V., Naujokat, C., Wiesel, M., Hergesell, O. and Opelz, G.: Strong inflammatory cytokine response in male and strong anti-inflammatory response in female kidney transplant recipients with urinary tract infection. Transpl Int, 18: 177, 2005 5. Mochon, M., Kaiser, B. A., Dunn, S., Palmer, J., Polinsky, M. S., Schulman, S. L. et al: Urinary tract infections in children with posterior urethral valves after kidney transplantation. J Urol, 148: 1874, 1992 6. Goya, N., Tanabe, K., Iguchi, Y., Oshima, T., Yagisawa, T., Toma, H. et al: Prevalence of urinary tract infection during outpatient follow-up after renal transplantation. Infection, 25: 101, 1997 7. de Oliveira, L. C., Lucon, A. M., Nahas, W. C., Ianhez, L. E. and Arap, S.: Catheter-associated urinary infection in kidney post-transplant patients. Sao Paulo Med J, 119: 165, 2001 8. Takai, K., Tollemar, J., Wilczek, H. E. and Groth, C. G.: Urinary tract infections following renal transplantation. Clin Transplant, 12: 19, 1998 9. Abbott, K. C., Swanson, S. J., Richter, E. R., Bohen, E. M., Agodoa, L. Y., Peters, T. G. et al: Late urinary tract infection after renal transplantation in the United States. Am J Kidney Dis, 44: 353, 2004 10. Pontin, A. R. and Jacobson, J. E.: Renal transplantation in primary reflux nephropathy without nephro-ureterectomy. A report of 4 cases. S Afr Med J, 68: 593, 1985 11. Bouchot, O., Guillonneau, B., Cantarovich, D., Hourmant, M., Le Normand, L., Soulillou, J. P. et al: Vesicoureteral reflux in the renal transplantation candidate. Eur Urol, 20: 26, 1991 12. Le Guillou, M., Ferriere, J. M., Potaux, L., Aparicio, M. and Pourquie, J.: Surgical indications for primary vesico-ureteral reflux in adult candidates for renal transplantation. Ann Urol (Paris), 18: 124, 1984 13. Morales, J. M., Andres, A., Prieto, C., Prage, M., Alcazar, J. M., Diaz-Gonzales, R. et al: Urinary morbidity of vesicoureteral reflux patients without surgical correction prior to renal transplantation. Nephron, 51: 571, 1989 14. Erturk, E., Burzon, D. T., Orloff, M. and Rabinowitz, R.: Outcome of patients with vesicoureteral reflux after renal transplantation: the effect of pretransplantation surgery on posttransplant urinary tract infections. Urology, 51: 27, 1998