EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: To assess the safety and efficacy of minimally invasive procedures for urolithiasis in transplanted kidneys.

Materials and Methods: A retrospective study was done on kidney transplant patients who had urolithiasis treated with minimally invasive procedures between January 1989 and September 2011. We evaluated patient characteristics, predisposing factors, clinical presentation, minimally invasive procedures used, frequency of success, and complications.

Results: In 1800 kidney transplants, 21 recipients developed urolithiasis (mean age, 31 y; 13 men and 8 women) and were treated with minimally invasive procedures. Predisposing factors included hyperparathyroidism (6 patients), hyperuricemia (5 patients), recurrent urinary tract infection (4 patients), ureteral stricture or obstruction (2 patients), and unknown factors (4 patients). Clinical presentation included hematuria (5 patients), azotemia (4 patients), anuria (3 patients), urinary tract infection (3 patients), and hydronephrosis (2 patients). The stones were located in the kidney (11 patients) or ureter (10 patients). Mean stone size was 11 ± 3 mm (range, 6-18 mm). Depending on the size and location of stones, treatment included extracorporeal shock wave lithotripsy in 10 patients, transurethral lithotripsy in 9 patients, and percutaneous nephrolithotomy in 2 patients. Stone-free status was achieved in 7 of 10 patients who were treated with shock wave lithotripsy (70%), 8 of 9 patients who were treated with transurethral lithotripsy (89%), and 2 of 2 patients who were treated with percutaneous nephrolithotomy (100%). All 4 patients who did not become stone-free after initial treatment (3 patients after shock wave lithotripsy and 1 patient after transurethral lithotripsy) became stone-free after secondary treatment with percutaneous nephrolithotomy (100%). No intraoperative complications occurred.

Conclusions: Minimally invasive procedures (mono-therapy or combination therapy) for urolithiasis in transplanted kidneys are safe and effective, and high overall stone-free results may be achieved.

Key words : Percutaneous nephrolithotomy, Shock wave lithotripsy, Transurethral lithotripsy, Ureter

Urolithiasis is observed rarely in renal allografts and has an incidence of 0.2% to 3%.^1-5 Many factors can predispose transplant recipients to urolithiasis, such as recurrent urinary tract infection in an immuno-suppressed patient, metabolic and endocrine disorders, and ureteral stricture.^6-8 Treatment of urolithiasis in transplant recipients depends on factors related to the patient and stones including location and size of the stones. Minimally invasive procedures are used alone or in combination including shock wave lithotripsy (SWL), transurethral lithotripsy (TUL), and percutaneous nephrolithotomy (PCNL), and each procedure has specific indications and limitations. Important challenging technical factors include the proximity of the bony pelvis, iliac vessels, and peritoneum, orientation of the calyces and transplanted kidneys, and location of the ureteral orifice.^6,8,9 In this article, we reviewed our experience with SWL, TUL, PCNL, and combination therapy for treatment of urolithiasis in transplanted kidneys.

Materials and Methods

We retrospectively reviewed the records of all patients who had kidney graft urolithiasis between January 1989 and September 2011 and who were treated with minimally invasive procedures. We analyzed their clinical and demographic findings including age, sex, type of transplant (living-related or deceased-donor transplant), clinical presentation, location and size of stones, method of intervention, complications, and postoperative residual or recurrent stones. Success was defined as complete stone-free status or a residual stone < 3 mm. In all patients, preoperative plain radiography was performed and diagnosis was confirmed by ultrasonography. Noncontrast computed tomography scan was performed in some patients. Patients who presented with anuria or azotemia were treated initially with percutaneous nephrostomy, and definitive therapy was done after the creatinine level became normal. The study was approved by the Ethical Review Committee of the Institute. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration. Informed consent was obtained from all subjects.

We classified the patients according to the treatment received: SWL monotherapy, TUL monotherapy, PCNL monotherapy, and combination therapy. The SWL was performed with an electrohydraulic machine (Dornier MPL 9000; Dornier Medizintechnik GmbH, Munich, Germany). Patients were placed in the supine position and the stones were located by ultra-sonography. Low-voltage and low-frequency SWL was performed (voltage, 4-6 kV; impulse frequency, 2000-2500 SWs/min [normal range, 60-80 SWs/min]). Each patient had 1 treatment with SWL, and if the patient did not have a response, definitive therapy was done with PCNL (combination therapy).

For TUL, patients were placed in the lithotomy position, and ureteroscopy (8-Fr Wolf rigid ureter-oscope) was performed under general anesthesia. Ureteral reimplantation was performed with the modified Lich-Gregoir method. When access to the ureteral orifice was difficult because of its position, a safety wire and hydrodilation were used during endoscopy. After access to the stone, pneumatic lithotripsy was performed and stone fragments were removed using a grasper or basket.

The PCNL was performed with the patient in the supine position under general anesthesia. In a sterile field, the graft calyx was punctured with a radiopaque 18-gauge needle that was guided by fluoroscopy. After placement of a guide wire and 28-Fr Amplatz sheath, tract dilation was performed with a radiopaque Amplatz dilator. Pneumatic lithotripsy was performed and fragments were removed with forceps. After the procedure, a nephrostomy tube was left in place. When ultrasonography and plain radiography were clear at 2 days after the procedure, the tube was removed.

In patients who received combination therapy, the first intervention was SWL or TUL. When the stone was not fragmented or removed completely, PCNL was performed as the secondary procedure.

All patients received antibiotics, antispasmodic drugs, and appropriate medical therapy for predisposing factors. Immunosuppressive regimens were continued. All patients had follow-up with regular ultrasonography and renal function tests.

In 1800 kidney transplants, 21 patients (1.2%) underwent minimally invasive procedures for treatment of urolithiasis. None of the stones were present in the donor organ at transplant. The mean age of recipients was 31 ± 17 years, and there were 13 men and 8 women.

Predisposing factors for urolithiasis included hyperparathyroidism (6 patients), hyperuricemia (5 patients), recurrent urinary tract infection (4 patients), ureteral stricture or obstruction (2 patients), and unknown factors (4 patients). The clinical presentation included hematuria (5 patients), azotemia (4 patients), anuria (3 patients), urinary tract infection (3 patients), and hydronephrosis (2 patients). There were 15 patients who had living-related donor transplant and 6 patients who had deceased-donor transplant. The stones were located in the kidney (11 patients: pelvis, 8 patients; lower calyx, 2 patients; ureteropelvic junction, 1 patient) or ureter (10 patients). The stones had mean size 11 ± 3 mm (range, 6 to 18 mm). According to size and location of calculi, we used different treatment types.

Monotherapy with SWL was used in 10 patients (mean age, 37 ± 16 y; range, 8-55 y). Mean size of stones was 14 mm (range, 10-18 mm) (Table 1). There were 7 patients who became stone-free after SWL (70%). The other 3 patients had residual stones after SWL and were treated with PCNL, so they also were analyzed in the combination therapy group.

Monotherapy with TUL was used in 9 patients (mean age, 27 ± 19 y; range, 9 -55 y). The stones were located in the ureter in all 9 patients (100%). Mean size of stones was 9 ± 2 mm (range, 6-12 mm) (Table 2). There were 8 patients who became stone-free after TUL (89%). In 1 patient, the stone was pushed back to the lower calyx, and additional treatment was given with PCNL.

There were 2 patients who received PCNL monotherapy, and both had successful outcome (Table 3). There were 4 patients who had combination therapy (mean age, 34 years). Mean size of stones was 14 mm (range,12-18 mm) (Table 4). The first intervention received was SWL (3 patients) or TUL (1 patient), and the stones were fragmented in all 4 patients but the system did not become stone-free; after PCNL, all 4 patients became stone-free (Table 4). In all patients, there were no intraoperative complications such as major bleeding, stone expulsion, or ureteral avulsion.

Urolithiasis is an uncommon but challenging complication of transplanted kidneys. It affects 0.2% to 3% kidney transplants, and the incidence is increasing.^1-5 This increase is related to the increasing number of kidney transplants and improvements in long-term survival after transplant.⁸ Several factors may predispose the transplanted patient to urolithiasis. Anatomic factors include secondary vesicoureteral reflux, partial ureteral obstruction, and retained suture material. Physiologic factors include renal tubular acidosis and tertiary hyperparathyroidism that are common in kidney transplant recipients and may cause hypercalciuria and hypocitraturia. Hyperuricosuria also may occur because of calcineurin inhibitors such as cyclosporine and tacrolimus. In addition, immunosuppression may increase the risk of developing urinary tract infection that may cause urolithiasis.^10-13

The most common clinical findings of urolithiasis in kidney transplant recipients include unexplained fever, increased creatinine level, decreased urine output, and hematuria. Renal colic usually is absent because the innervation of the kidney is impaired, but lower abdominal discomfort may occur from peritoneal irritation caused by a hydronephrotic collecting system. The diagnosis is made from ultrasonography. When hydronephrosis is present, a noncontrast computed tomography scan may show the anatomy more clearly.^8,11

Treatment options for stones include observation, dietary and medical therapy, extracorporeal SWL, endourologic procedures including TUL and PCNL, and open procedures. Small stones (< 4-5 mm) with little or no deterioration in renal function can be monitored. Open approaches are difficult after kidney transplant because of fibrosis. Immuno-suppressive therapy may affect wound healing and predispose the patient to infection. Therefore, open surgery usually is reserved for selected patients. Minimally invasive procedures have been reported in different studies.^14-18 However, no level 1 data are available for transplant patients that may help guide treatment decisions.¹¹ Nevertheless, SWL or TUL are reasonable options for stones < 1.5 cm, and PCNL is used for larger calculi.^16,17

The SWL may be used as an initial approach for nonobstructive stones (< 15 mm), but the pelvic location of the transplanted kidney can be problematic during SWL. In addition, close follow-up is mandatory in unstented patients because of the risk of ureteral obstruction during fragment passage.^18,19 Patients may require multiple sessions to become stone-free; in a study of 13 patients who were treated with SWL, 8 patients required multiple sessions.¹⁴

Treatment with SWL has been confirmed as an appropriate option in several small studies. In patients who had kidney transplant lithiasis, SWL had high effectiveness (87%), and the best results were noted for solitary stones located at the ureteral anastomosis.²⁰ In another study, success was 100% in 3 patients.²¹ Another study reported 100% success after SWL in 7 patients, but size of the stones was not noted.⁸ In the present study, 10 patients (mean stone size, 14 mm) had SWL and frequency of success was 70%; 3 patients needed secondary PCNL because of residual stones. Placement of a double J catheter before SWL may increase the success of stone excretion, especially for larger stones.

The TUL is a good approach for ureteral stones and has the advantage of enabling removal of stone fragments. Although the position and orientation of the transplanted ureter can be problematic, TUL is a good option for obstructive ureteral stones when an experienced surgeon and good equipment are available. In a previous study of 12 patients who had TUL, all patients were stone-free on postoperative imaging except 1 patient who had a 2-mm fragment observed; 2 recipients had complications including nephrocutaneous fistula and ureteral stent encrustation.²² In another study, ureteroscopy was successful in 13 of 18 patients (72%), 4 ureteral calculi (67%) were removed with the ureteroscope, and 7 of 9 migrated stents (78%) were retrieved; in this study, 2 complications (1 urinary leakage and 1 symptomatic urinary tract infection) occurred and were treated nonoperatively.²³ In the present study, 8 of 9 patients treated with TUL became stone-free; all patients had stone size < 15 mm. Ureteral stones usually can be treated successfully with TUL.

The PCNL has been described in kidney transplant recipients in several studies and is the most common treatment for stones > 1.5 cm. However, complications after PCNL may include bowel perforation, excessive bleeding, urinary fistula, and urinoma.²⁴ In 13 patients who had PCNL after kidney transplant (mean stone size, 1.4 mm), nephrostogram at 24 hours after the procedure showed no residual fragments in 10 patients (77%); repeat endoscopy was required in 3 patients to achieve subsequent stone-free status.²⁵ In that study, postoperative complications developed in 3 patients including sepsis, gastrointestinal bleeding, and herpes esophagitis.²⁵ In another study, PCNL was successfully performed at 1 to 2 months after transplant in 3 patients who had donor-derived allograft urolithiasis.¹⁸ Furthermore, another study showed stone-free status in 6 of 7 patients (86%) with no intraoperative complications (mean stone size, 32.8 mm).²⁶ In the present study, PCNL alone or in combination was a safe and effective treatment method for large pelvicaliceal stones or unfragmented stones after SWL or TUL; all patients who were treated with PCNL as a primary or secondary procedure became stone-free without any complications.

In summary, minimally invasive and endourologic procedures are safe and effective in the treatment of transplant urolithiasis, and a combination of different techniques can increase the frequency of successful treatment.

Volume: 12 Issue: 3 June 2014

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