Successful Salvage of Kidney Allografts Threatened by Ureteral Stricture Using Pyelovesical Bypass

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1 American Journal of Transplantation 2010; 10: Wiley Periodicals Inc. C 2010 The Authors Journal compilation C 2010 The American Society of Transplantation and the American Society of Transplant Surgeons doi: /j x Successful Salvage of Kidney Allografts Threatened by Ureteral Stricture Using Pyelovesical Bypass R. A. Azhar a,, M. Hassanain b,d,, M. AlJiffry b, S. Aldousari a,t.cabrera c, S. Andonian a, P. Metrakos b,d, M. Anidjar a, *, and S. Paraskevas 2, *, a Department of Urology, b Section Hepatopancreatobiliary and Transplant Surgery, Department of Surgery, c Department of Radiology, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada and d Department of Surgery, King Saud University, Riyadh, Saudi Arabia *Corresponding authors: Steven Paraskevas, steven.paraskevas@muhc.mcgill.ca and Maurice Anidjar, maurice.anidjar@muhc.mcgill.ca Contributed equally as the first author. Contributed equally as senior authors. Study Type: Retrospective analysis. Nothingtodisclose. Ureteral stricture is the most common urologic complication after renal transplantation. When endourologic management fails, open ureteral reconstruction remains the standard treatment. The complexity of some of these procedures makes it necessary to explore other means of repair. This study evaluated the intermediate-term outcome of subcutaneous pyelovesical bypass graft (SPBG) on renal transplant recipients. We reviewed 8 patients (6 male and 2 female; mean age 52 years) with refractory ureteral strictures postrenal transplantation, who received SPBG as salvage therapy. All patients failed endourologic management and half failed open management of their strictures. After a mean follow-up of 19.4 months, 7 out of 8 renal grafts have good function with mean GFR of 58.5 ml/min/1.73 m 2, without evidence of obstruction or infection. One patient lost his graft due to persistent infection of the SPBG and one patient developed a recurrent urinary tract infection managed with long-term antibiotics. SPBG offers a last resort in the treatment of ureteral stricture after renal transplantation refractory to conventional therapy. Key words: Artificial grafts, kidney transplantation, renal bypass grafts, ureteral stenosis/strictures Received 16 November 2009, revised 11 February 2010 and accepted for publication 20 February 2010 Introduction Ureteral stricture is the most common urologic complication after renal transplantation, occurring at a rate of 2% to 5% (1,2). Of all ureteral strictures, 73% occur at the distal third of the ureter including the ureteroneocystostomy, 12% at the mid-ureter level and 15% at the proximal third of the ureter (3). The major etiological factor responsible for ureteral strictures is ischemia, which may be caused by faulty preparation of the ureter during donor nephrectomy (i.e. division of a lower pole artery or stripping of the ureter with failure to preserve the periureteral tissue). Furthermore, anastomotic technical complications, variations in vascular anatomy, allograft rejection episodes, BK viral infection and medications are other risk factors for the development of ureteral strictures (4 6). Primarily, symptomatic strictures are treated with percutaneous nephrostomy followed by antegrade dilatation and stenting. Ureteral stenting is not always technically feasible or definitive, and in these cases, open ureteral reconstruction remains the standard treatment (2). Open surgical reconstruction consist of either ureteroneocystostomy or pyeloureteral anastomosis of the graft to the native ureter. In addition, uncommonly performed bladder reconstructive techniques may be necessary when no ureter exists. Nevertheless, such procedures are not always successful, technically demanding and may expose the patient to major complications (7,8). The subcutaneous pyelovesical bypass graft (SPBG) using an artificial ureter has been shown to be safe and effective in patients with irreversible malignant ureteral obstruction (9,10). The SPBG consists of an internal silicone tube covered by an outer polyester sheath (Figure 1). Our center has previously reported the short-term success of using the newer SPBG (Detour Coloplast, Denmark) as salvage therapy to prevent renal graft loss (11). In that report, we described two renal transplant recipients with refractory ureteral strictures. These two patients failed all treatment options including surgery, but were treated successfully with the use of SPBG. They experienced no urinary tract infections, and had stable renal function, 12 and 15 months after treatment, respectively (11). Similarly, another group reported three patients managed with SPBG, with a mean follow-up of 30 months without evidence of encrustations or obstruction (12). The aim of this study is to report and evaluate a larger series of patients with SPBG repairs with a longer follow-up interval. 1414

2 Artificial Ureters in Renal Transplantation Figure 1: Drawing of the SPBG (Reproduced with permission from Coloplast, Inc.). Patients and Methods We retrospectively reviewed eight patients who had SPBG implantation for refractory ureteral strictures following kidney transplantation. Between January 2002 and September 2009, we performed 585 adult kidney transplants. Twenty-one (3.6%) patients were diagnosed with ureteral strictures. Eight patients could not be repaired with the standard approaches and were repaired with the use of SPBG to salvage their grafts. There were 6 men and 2 women with a mean age of 52 years (range 39 to 68). Seven patients presented with ureteral stricture early after renal transplantation, with a mean time of diagnosis of 10.5 weeks (range 2 to 20). One patient presented 10 years posttransplantation. GFR is calculated using the six variables MDRD formula. The clinical characteristics of these patients are summarized in Table 1. Clinical course All patients presented with rising serum creatinine and hydronephrosis on imaging. Patients were initially managed by placement of percutaneous nephrostomy tube. Ureteral strictures were confirmed and further characterized by nephrostogram at the time of nephrostomy tube insertion. The site of ureteral stricture was found to be at the ureterovesical junction in two patients, at the distal ureter in three patients, and at mid-ureter in two patients. Furthermore, one patient had two strictures, one at the ureteropelvic junction and one at the ureterovesical junction. All patients had multiple Table 1: Clinical features of the patients treated with pyelovesical bypass graft Primary Kidney DJS at Side of transplant Pt Age Etiology type transplantation transplantation function 1 40 IgA nephropathy DD No CL DGF 2 46 IgA nephropathy DD No N/A DGF 3 43 Glomerulosclerosis LD No CL SGF 4 52 DM type I DD No IL SGF 5 68 ADPKD DD No CL DGF 6 39 DM type II DD No IL SGF 7 68 Obstructive Uropathy LD No CL SGF 8 59 FSGS DD Yes IL SGF DM = diabetes mellitus; PCKD = autosomal dominant polycystic kidney disease; FSCS = focal segmental glomerulosclerosis; DD = deceased donor; LD = living donor; DJS = double J stent; IL = ipsilateral side; CL = contralateral; DGF = delayed graft function; SGF = slow graft function; N/A = not available. American Journal of Transplantation 2010; 10:

3 Azhar et al. Figure 2: Dilatation (Reproduced with permission from Coloplast, Inc.). attempts at antegrade balloon dilatation and/or indwelling stent insertion with a mean of 6.25 (range 2 23). Operative intervention was attempted in four patients; three failed pyeloureterostomy using the native ureter, and one failed uretereral reimplantation. Open surgical management was avoided in the other four patients because of either high stricture location or high surgical risk. All eight patients had SPBG placed as a salvage procedure. Placement of the SPBG has been previously described in detail (11,12). To summarize; all patients received an intravenous first-generation cephalosporin 30 min prior to skin incision. The nephrostomy tube site was Figure 4: Tunneling (Reproduced with permission from Coloplast, Inc.). dilated to insert a 30-F Amplatz sheath (Figure 2). This is important to ease the insertion of the SPBG given the reaction around the nephrostomy tube insertion site. The SPBG was then advanced through the Amplatz sheath to the renal collecting system under fluoroscopic guidance. Next, a 3-cm suprapubic incision was made and carried down to the anterior bladder wall (Figure 3). A tunneling device was used to create a subcutaneous tunnel between the suprapubic incision and the nephrostomy tube site (Figure 4). The SPBG was tunneled subcutaneously to the suprapubic site and cut to the appropriate length. The polyester sheath was removed from the distal 3 cm of the SPBG. The SPBG was introduced through a cystotomy and the edge of the polyester sheath was sutured to the muscular layers of the bladder wall using two interrupted 3 0 braided, absorbable sutures (Figure 3). Care was taken to leave only the 3 cm of exposed silicone inside the bladder lumen (Figure 5). An intraoperative cystoscopy is then performed to confirm the location of the SPBG before closing. Minimal blood loss was noted in every case. A cystogram was performed 1 2 weeks postoperatively to rule out urinary leak before removal of the Foley catheter (Figure 6). Patients Figure 3: Bladder exposure and SPBG insertion (Reproduced with permission from Coloplast, Inc.). Figure 5: Bladder insertion, the Silicone end cut leaving only 3 cm in bladder (Reproduced with permission from Coloplast, Inc.) American Journal of Transplantation 2010; 10:

4 Artificial Ureters in Renal Transplantation were then followed periodically at 1, 3, 6 and 12 months, and annually thereafter with serial serum creatinine, urine culture and ultrasonography. Results Postoperatively, two patients had dislodgment of their SPBG, one patient at the nephrostomy site and the other at the bladder entry site. These were diagnosed and easily repaired within 3 days postoperatively. The diagnosis was made by bedside physical examination of the wound and groin areas. One patient developed recurrent (n = 8) urinary tract infections secondary to E.coli (6/8) and Pseudomonas aeruginosa (2/8). This was managed by intravenous Ticarcillin/Clavulanate followed by long-term oral antibiotic therapy using both Cefixime and Ciprofloxacin for a total of 3 months. The patient responded favorably with sterile urine cultures for 12 months of follow-up. Treatment failure occurred in one individual, who developed a resistant infection in the SPBG several weeks after discharge with Enterococcus species, Pseudomonas aeruginosa, Candida Albicans and eventually Methicillin-resistant Staphylococcus aureus. This led to graft nephrectomy including the removal of the SPBG to control the infection. However, that patient subsequently had a successful living donor kidney transplant. One patient died of metastatic lung cancer after 15 months of follow-up with an intact and functioning SPBG. After a mean follow-up of 19.4 months (range 2 to 58), six patients with SPBG are alive without any evidence of encrustation, obstruction or erosion and with stable renal function (Table 2). Mean GFR was 51.5 and 58.5 ml/min/1.73 m 2 at 1-year and at last follow-up, respectively (Table 3). Discussion Figure 6: (A) A cystogram postoperatively demonstrated reflux to the transplanted kidney. (B) A cystogram with good drainage. Ureteral stricture in renal transplant patients poses a unique challenge because of difficult retrograde access. Ureteral stenosis is typically managed with percutaneous nephrostomy, balloon dilatation and indwelling stent placement. The reported success rates of percutaneous stenting is 71% 86% in patients presenting with strictures within the first 3 months of transplantation, and 29% with strictures that develop after 3 months (1,7). When these endoscopic manipulations fail, open ureteral reconstruction is the standard management option (2). Open surgical management options include ureteroneocystostomy and pyeloureteral anastomosis to the native ureter (1). Vesicopyelostomy, vesicocalycostomy and interposition of an intestinal conduit have also been described (13). However, reoperation on the transplanted kidney is associated with technical challenges especially when hilar dissection is needed and exposes the patient to potentially serious complications, with a reported graft loss rate of 7% to 13% (7,8). In this report, we describe the use of a SPBG (Detour Coloplast, Denmark) composed of an inner American Journal of Transplantation 2010; 10:

5 Azhar et al. Table 2: Uretral strictures management summary Pyeloureterostomy using the native ureter None None None None None Pyeloureterostomy using the native ureter None None None None None Pyeloureterostomy using the native ureter Urine leak (dislodged SPBG) Recurrent UTIs None Urine leak (dislodged SPBG) None Reimplantation of the ureter None None None None Infected artificial ureter Mean SPBG = subcutaneous pyelovesical bypass graft; UTI = urinary tract infection; Cr = creatinine. Table 3: Renal function prior to and at last follow up after SPBG therapy Follow-up Cr pre-spbg Cr post-spbg egfr post-spbg Pt (months) (lmol/l) (lmol/l) ml/min/1.73 m Mean SPBG = subcutaneous pyelovesical bypass graft; Cr = creatinine; egfr = estimated glomerular filtration rate using the sex variables MDRD method. silicone tube with an outer polyester sheath. This SPBG has been used successfully for palliative treatment of malignant ureteral obstruction (9,10). Jabbour et al., described a series of 35 SPBG that were implanted in 27 patients (19 unilateral and 8 bilateral) to bypass extrinsic ureteral obstructions. Long-term follow-up (mean 47 months) of the surviving patients showed that these grafts do not encrust or become infected (10). However, there was one case of skin erosion and two patients required percutaneous nephrostomy tubes due to bladder tumor obstruction distal to the grafts (10). The use of SPBG has also been described in France in three renal transplant recipients with ureteral necrosis. After a mean follow-up of 32 months, there was no encrustation or obstruction (12). However, one of the three patients had asymptomatic Staphylococcus epidermidis urinary tract infection (12). In the present series of eight patients, after a mean follow-up of 19.4 months, one graft was lost due to infection (6 months) and the second was lost due to death of the patients from lung cancer (26 months). The other six implanted SPBG devices are functional without encrustation or obstruction. Long-term follow-up of these patients is necessary to assess the risk of late encrustation. The risk of encrustation and obstruction is theoretically low in SPBG as it has a large caliber (17F) and a large dead space. The large dead space prevents reflux of urine into the renal pelvis. Although reflux has been observed radiologically, it has no clinical significance evidenced by painless micturition and the absence of pyleonephritis. Desgrandchamps et al. caution the risk of late encrustation and advised maintaining a high fluid intake and correction of secondary hyperparathyroidism and distal renal tubular acidosis (12). The risk of infection remains high in the immunosuppressed patient population. The infection rate with the Detour SPBG in immunocompetent patients is 30% (14). Half of such infections are recurrent bacteriuria especially in patients with preexisting percutaneous nephrostomy tubes (14). The risk of infection in immunocompromised patients with chronic nephrostomy tube is theoretically higher. In our series, two patients had postoperative infections. One patient had an SPBG infection that was resistant to continuous antimicrobial treatment and resulted in graft loss. The other patient developed eight recurrent febrile UTIs without graft infection, which was successfully managed with long-term antibiotics. Using this therapy the patient remained infection free for 12 months of follow-up from the last UTI. This procedure is associated with a learning curve, albeit a rather shallow one. In our experience, we added the performance of an intraoperative flexible cystoscopy prior to complete closure, to confirm the accurate placement of the graft within the urinary bladder. SPBG offers the advantage of avoiding dissection around the renal hilum with the potential harm that can cause to the graft and the recipient. This is a particularly hazardous in patients with proximal strictures, strictures in ipsilateraly implanted grafts (vessels anterior to renal pelvis), and in 1418 American Journal of Transplantation 2010; 10:

6 Artificial Ureters in Renal Transplantation Table 4: Suggested indication for the use of SPBG in ureteral strictures Proximal strictures Strictures in ipsilateral implanted grafts High-risk surgical patients Strictures resistant to conventional approaches high-risk surgical patients. SPBG can be also used as a salvage therapy in renal grafts with ureter strictures that are refractory to conventional approaches (Table 4). Conclusion Artificial ureters have intermediate-term safety profiles that make them an attractive, minimally invasive management option in patients with difficult ureteral strictures after renal transplantation. Suppressive antibiotic therapy might be needed for patients with recurrent urinary tract infections. Long-term follow-up is planned to assess their long-term encrustation and obstruction. Although the use of foreign bodies is usually not encouraged in immunosuppressed patients, our experience with this prosthesis showed an acceptable risk of infection. The caveat however, is that the recipient should be free of infection at the time of placement, and long-term nephrostomy drainage prior to SPBG placement may not be ideal. If refractory SPBG infection occurs, this is more likely to lead to loss of the graft, as separation of the proximal SPBG from the renal parenchyma and pelvis is difficult. The use of SPBG, however, provided another treatment option for recipients who had failed conventional therapy, and the ability to salvage many years of graft function in this small case series is illustrative of the potential utility of this technique in the management of the complicated renal transplant recipient. Acknowledgments The authors would like to acknowledge the work done by Ms. Myriam Fernadez for her great efforts in data collection from the McGill Transplant Database. References 1. Whang M, Geffner S, Baimeedi S, Bonomini L, Mulgaonkar S. Urologic complications in over 1000 kidney transplants performed at the Saint Barnabas healthcare system. Transplant Proc 2003; 35: Shoskes DA, Hanbury D, Cranston D, Morris PJ. Urological complications in 1000 consecutive renal transplant recipients. J Urol 1995; 153: Jaskowski A, Jones RM, Murie JA, Morris PJ. Urological complications in 600 consecutive renal transplants. Br J Surg 1987; 74: Karam G, Maillet F, Parant S, Soulillou JP, Giral-Classe M. Ureteral necrosis after kidney transplantation: Risk factors and impact on graft and patient survival. Transplantation 2004; 78: Keller H, Noldge G, Wilms H, Kirste G. Incidence, diagnosis, and treatment of ureteric stenosis in 1298 renal transplant patients. Transpl Int 1994; 7: Coleman DV, Mackenzie EF, Gardner SD, Poulding JM, Amer B, Russell WJ. Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. J Clin Pathol 1978; 31: Lojanapiwat B, Mital D, Fallon L et al. Management of ureteral stenosis after renal transplantation. J Am Coll Surg 1994; 179: Kashi SH, Lodge JP, Giles GR, Irving HC. Ureteric complications of renal transplantation. Br J Urol 1992; 70: Desgrandchamps F, Cussenot O, Meria P, Cortesse A, Teillac P, Le Duc A. Subcutaneous urinary diversions for palliative treatment of pelvic malignancies. J Urol 1995; 154(2 Pt 1): Jabbour ME, Desgrandchamps F, Angelescu E, Teillac P, Le Duc A. Percutaneous implantation of subcutaneous prosthetic ureters: Long-term outcome. J Endourol 2001; 15: Andonian S, Zorn KC, Paraskevas S, Anidjar M. Artificial ureters in renal transplantation. Urology 2005; 66: Desgrandchamps F, Duboust A, Teillac P, Idatte JM, Le Duc A. Total ureteral replacement by subcutaneous pyelovesical bypass in ureteral necrosis after renal transplantation. Transpl Int 1998; 11(Suppl 1): S150 S Shokeir AA, Shamaa MA, Bakr MA, Eraky I, Ghoneim MA. Ileal ureter in renal transplant recipients. Transplant Proc 1993; 25: Schmidbauer J, Kratzik C, Klingler HC, Remzi M, Lackner J, Marberger M. Nephrovesical subcutaneous ureteric bypass: Longterm results in patients with advanced metastatic diseaseimprovement of renal function and quality of life. Eur Urol 2006; 50: ; discussion 8. American Journal of Transplantation 2010; 10: