EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Since its inception in 1954, kidney transplantation (KT) has substantially evolved, becoming the sole curative option for end-stage renal disease.¹ In 2021 alone, 92 532 KTs were performed worldwide.² Notably, advancements in surgery and immunology have led to a remarkable 5-year patient survival rate of 97.3% and a graft survival rate of 84.6%³ Kidney transplant offers substantial benefits, rescuing patients from dialysis and enhancing their quality of life. However, postsurgical complications may lead to significant mortality and morbidity. Urological complications are particularly prevalent in both the early and late stages after KT, with an incidence ranging from 2.9% to 30%.^4-6 Most urological complications are ureteral complications and usually occur at the junction of the distal part of the ureter and the ureterovesical anastomosis. These complications involve urinary leakage from the ureteral anastomosis, stenosis, and obstruction of the ureteral anastomosis.^7,8 Ureteral complications can now be successfully treated with interventional methods instead of surgical revisions.⁹ In this study, we aimed to assess the effectiveness of the interventional methods for treatment of ureteral complications after KT and their long term outcomes. If our study demonstrates comparable success to surgical revisions, validating interventional methods, patients will be protected from unnecessary surgical stress and morbidity while receiving cost-effective treatment.

Materials and Methods

Our team performed the first living-related KT in Turkey in November 1975, the first deceased donor KT in Turkey in October 1978, and the first local deceased donor KT in Turkey in July 1979. In May 1992, our team performed a combined liver-kidney transplant procedure from a living related donor, which was the first operation of its kind anywhere in the world. Since 1975, our center at Baskent University has performed 3463 KT procedures.¹⁰ The Polytano-Leadbetter technique was used for ureteroneocystostomy anastomoses in 300 KTs performed in our center from 1975 to 1983. After 1983, the Lich-Gregoir technique was used, and 1141 KTs have been performed with this technique. Since September 2003, the corner-saving technique has been used.¹¹ In cases where this technique has been used, a double J stent was not routinely used after anastomosis. We conducted a retrospective analysis of KT recipients seen between January 1, 2000, and May 1, 2020. Among the 2223 KT recipients, we included 70 patients who experienced ureteral leakage or ureteral obstruction in the early or late posttransplant period in our study. Demographic information, types of complications, time between transplant and occurrence of complications, interventional procedures, and long-term outcomes were obtained. Complications within the first 2 months post-transplant were classified as early complications, whereas those occurring after 2 months were considered late complications. At out center, after KT, patients with elevated serum creatinine, reduced urine output, kidney pain, sensitivity, or wound discharge receive a Doppler ultrasonography scan. If hydronephrosis is present on ultrasonography, ureteral stricture or obstruction is considered. Perirenal collections or discharge from surgical incisions will raise suspicion of ureteral leakage, and fluid samples are examined for creatinine levels to confirm the presence of urinary leakage. All percutaneous treatment procedures were performed in the Baskent University Interventional Radiology unit. All percutaneous procedures were carried out while the patient was sedated intravenously. During the procedure, all patients, including their blood pressure, oxygen saturation, and electrocardiograms, were continuously moni-tored. The area to be treated was wiped with povidone iodine for sterilization, and the surrounding area was completely covered with sterile drapes. At our center, the initial step for all ureteral complications is antegrade pyelography. We frequently use the upper pole calyx for antegrade access because it is simpler to insert a guidewire into the ureter. Patients receive color Doppler ultrasonography during percutaneous puncture to limit the risk of vascular injury ((Figure 1), a and b). Antegrade pyelography is conducted after the percutaneous ultrasonography-guided puncture into the calyx with a 21-gauge needle (AccuStick Introducer System) to confirm the diagnosis ((Figure 1)c). Over a 0.018-inch guidewire, a coaxial introducer is inserted; if needed, additional antegrade pyelograms are taken. A 5F Kumpe catheter (Cook) over a 0.035-inch glide wire (Terumo) is used to pass through the problematic ureter through the antegrade route. Microcatheters (fast tracker or Direxion; Boston Scientific) and 0.014-inch guidewires are also used in certain cases with severe stenosis. Depending on the patient’s clinical status, a nephrostomy or nephrocatheter (Flexima drainage catheter; Boston Scientific) insertion, further procedures such as balloon dilatation, and double J stent placement are performed during the same session or within 1 month. Patients with a leak have perirenal urine collec-tions percutaneously drained using drainage catheters before or simultaneously with nephrostomy or nephroureterostomy. To treat ureteral stricture, we use balloon dilatation (Blue Max 20 or Mustang balloon catheter; Boston Scientific), 5 to 8 mm in diameter, at a pressure of 8 to 15 atmospheres while the patient is deeply sedated with propofol (1 mg/kg) ((Figure 1), d-f). For sufficient dilatation in cases with resistant stenosis, repeated balloon dilatation sessions are performed at 1- or 4-week intervals. A nephroureterostomy catheter with its distal end in the bladder is left in the transplant urinary system after dilatation if a repeat balloon dilatation is needed. A Flexima catheter is prepared as a nephroureterostomy catheter by making new holes with a scalpel according to the length of the graft collecting system ((Figure 2), a and b). This process is checked by antegrade pyelography to confirm that the proximal holes of the prepared catheter are in the renal pelvis ((Figure 2)c). Patients with ureteral occlusion caused by an intraluminal blood clot are treated by placement of a nephroureterostomy catheter and irrigation with saline. A patient with urolithiasis is treated with basket extraction. One or side-by-side double J stents are placed in the urinary system of all patients with ureteral stenosis, and a control nephrostomy catheter is clamped for 24 hours ((Figure 2)e). The next day, antegrade pyelography is performed as a final check, and the nephrostomy catheter is removed. In cases with ureteral leak, a 10F to 12F nephroureterostomy catheter is inserted in the transplant ureter to facilitate closing the ureteral defect. The leak in the graft ureter is checked by periodic antegrade pyelograms. After the leak is closed, the nephroureterostomy catheter is withdrawn and a 7F to 10F double J stent is inserted (Figure 1). In all patients until 2008, after 3 to 6 months, percutaneously placed double J stents were removed cystoscopically. After 2008, double J stents were removed by transurethral route, under fluoroscopy guidance in the interventional radiology unit. Patients are followed for recurrent ureteral complications until surgical treatment, graft loss, or death. Ultrasonography is routinely performed at 3-month intervals in the first year of follow-up and twice every year afterward.

Among patients in our study, there were 22 patients in the early obstruction group, 22 patients in the late obstruction group, and 26 patients with ureteral anastomosis leakage. In the 22 patients in the early obstruction group (18 male, 4 female; mean age of 39.2 years; range, 8-53 years), the time between KT and diagnosis of obstruction averaged 24.9 days (range, 1-65 days). The main causes of early obstruction were distal ureteral stricture (14 cases) due to ureteroneocystos-tomy anastomosis, intraluminal blood clots (2 cases), diffuse ureteral dilatation (2 cases), with both patients diagnosed with cytomegalovirus infection by immunohistochemical methods, midureteral stricture (2 cases), and proximal ureteral stricture (2 cases). Both patients with proximal stricture experienced recurrent acute rejection episodes in the early posttransplant period, leading to graft nephrectomy at 1 and 11.5 months, respectively. In the 2 patients with midureteral stricture, 1 patient developed recurring rejection episodes from the early stages, resulting in graft nephrectomy after 71 months. The cause of the stricture in the other patient remained unidentified, but no recurrences or long-term complications were encountered after percutaneous treatments. All patients with early ureteral obstruction were successfully treated using percutaneous methods. The average follow-up duration for these patients was 46.9 months (range, 1-141 months). Two patients underwent a second balloon dilatation procedure at 5 and 7 months, respectively. Three patients underwent intraluminal metallic stent placement due to recurrence at 5, 9, and 15 months after the initial procedure. Two patients required repeat nephroure-terostomy and double J stent placement 1 month after the initial procedure due to recurrence (Table 1). Among the 22 patients in the late ureteral obstruction group, we observed that 1 patient had obstruction due to ureteral stones, whereas the remainder had ureteral strictures (Table 1). The average time from KT to diagnosis for these patients was 13.1 months (range, 2.5-25 months). Among the 22 patients with late-onset obstruction, 15 had obstruction localized in the distal ureter region, at the ureteroneocystostomy anastomosis site. Four patients had obstruction due to diffuse ureteral strictures, 1 patient had a proximal stricture, 1 patient had a midureteral stricture, and 1 patient had obstruction caused by a ureteral stone. In addition, 2 patients with distal ureteral strictures also had ureteral leaks. Histologic evaluation of renal biopsies revealed pathological results in 13 patients: 7 had acute rejection, 2 had cyclosporine toxicity, 2 had chronic nephropathy, and 2 had tubulointerstitial nephritis. All patients with late-onset obstruction were successfully treated using percutaneous methods. The average follow-up duration for this group was 48.3 months (range, 3.5-141 months). Among these patients, 5 experienced recurrent obstruction. Three patients underwent balloon dilatation for recurrence, and 2 patients received intraluminal metallic stents due to persistent stricture despite repeated dilatations. Surgical treatment was required for 1 patient who showed no response to balloon dilatations because of excessive fibrosis. During follow-up of the late obstruction group, 4 patients developed chronic rejection because of recurrent acute rejection episodes, and 1 patient underwent graft nephrectomy after repeated rejection episodes. The remaining 17 patients showed normal graft functions during follow-up. Twenty-six patients with ureteral leakage were diagnosed an average of 30.9 days (range, 4-108 days) after KT. Among these, leakage was found in the distal ureter without involvement of the anastomosis in 12 patients, at the anastomosis site in 9 patients, and in the proximal ureter in 5 patients. Among those with distal leakage, 3 developed obstructions at the same location in the late period. In 1 patient with leakage at the anastomosis site, early obstruction occurred due to stricture. In addition, 5 patients diagnosed with leakage also showed rejection findings in the kidney biopsy. Among these patients, 18 underwent nephroureterostomy with double J stent placement, 7 had nephroureterostomy alone, and 1 required balloon dilatation in addition to nephroureterostomy and double J stent because of coexisting early stricture. Drainage catheters were inserted in patients with urinomas. For 2 patients with ureteral leakage, surgical treatment was necessary because of persistent leakage despite percutaneous treatment methods. The average time for the disappearance of ureteral leakage in the other patients was 46 days (range, 15-67 days). The average follow-up for this group was 44 months (range, 2-121 months). During follow-up, 5 patients developed chronic rejection, and 4 patients died as a result of reasons unrelated to ureteral complications. The graft functions remained within normal limits for the remaining patients throughout their follow-up.

In our study group, rejection was one of the primary reasons for the development of ureteral strictures and leaks after KT. However, almost all of these complications were successfully treated using percutaneous methods. Studies in the literature have shown that the incidence of ureteral complications after KT ranges from 2% to 15%.^12-14 These complications can be categorized as strictures, obstructions, and leaks. Ureteral obstructions and strictures typically develop as a result of surgical techniques, rejection, and ischemic fibrosis, whereas leaks occur as a result of surgical technique errors during anastomosis and ischemic damage.^15,16 Strictures resulting from surgical errors usually occur in the early postoperative period, whereas those secondary to rejection or ischemia develop in the late period. The use of surgical methods for stricture treatment may lead to complications, even resulting in graft loss.¹⁷ Develop-ments in percutaneous interventional treatment methods have made it possible to successfully treat such complications without the need for surgery, with success rates reaching up to 98%.^18-20 However, some sources suggest that the treatment of late-onset strictures secondary to ischemia may be unsatisfactory.^21,22 In our study, all 20 patients with early-onset strictures (100%) and 20 of 21 patients with late-onset strictures (95.2%) were successfully treated using percutaneous methods, with only 1 patient requiring surgical treatment due to the failure of percutaneous methods. Percutaneous treatment of ureteral strictures involves temporary stent placement with or without balloon dilatation. For persistent strictures, repeat balloon dilatation or cutting balloons are also utilized.²³ Some studies recommend temporary double J stent placement after ureteral balloon dilation. If repeated balloon dilatations are unsuccessful, another option is to insert a metallic stent in the strictured area. Metallic stents are typically coated with a titanium and nickel alloy, and they are thermo-expandable with a shape-memory feature, preventing epithelial growth and providing long-term success in treatment. They can be removed if needed through cystoscopy.²⁴ In our cases, we used metallic stents in the treatment of 5 patients. After KT, aside from early and late ureteral strictures, intraluminal obstacles and external compressions may also cause urinary obstruction. Examples of intraluminal obstacles include stones, blood clots, and debris, whereas lymphocele, urinoma, and hematoma are examples of fluid collections causing external compression. Fluid collections causing external compression can be easily treated with percutaneous drainage methods, and intraluminal obstacles can also be effectively treated with percutaneous methods. In our study, intraluminal blood clots and ureteral stones developed in a total of 3 patients, and they were successfully treated using percutaneous methods. Ureteral leaks commonly occur as early comp-lications because of ischemic damage in the distal ureter or surgical technique errors during ureteroneocystostomy anastomosis.¹⁵ In particular, ligation of the accessory arteries supplying the lower part of the graft kidney can lead to ischemic damage and necrosis in the ureter, resulting in ureteral leaks.²⁵ Although surgical revisions are often used for treatment of ureteral leaks according to the literature, successful treatment can also be achieved using percutaneous methods.^21,22 In percutaneous treatment, it is essential to direct urine flow toward the bladder to prevent outflow from the defect area.^26,27 In our study, 24 of 26 patients (96.1%) were successfully treated with percutaneous methods, with only 2 patient requiring surgical treatment. Among the 24 patients treated percutaneously, 5 patients (20%) developed strictures in the follow-up period.

After KT in the presence of ureteral complications, rejection should be considered as a potential etiology; if suspected, patients should undergo pathological examination. In addition, interventional treatment methods for ureteral obstructions should be priori-tized as the first-line treatment due to their high success rates. Successful interventional treatments performed in experienced centers will not only ensure long-term graft survival but also protect the patient from complications associated with unnecessary surgical procedures.

Volume: 21 Issue: 8 August 2023

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