306 Central European Journal of Urology

O R I G I N A L P A P E R TRANSPLANTOLOGY Urological complications after renal transplantation – a single centre experience Wojciech Krajewski1, Janusz Dembowski1, Anna Kołodziej1, Bartosz Małkiewicz1, Krzysztof Tupikowski1, Michał Matuszewski1, Paweł Chudoba2, Maria Boratyńska3, Marian Klinger4, Romuald Zdrojowy1

1Urology and Oncological Urology Department, Wrocław Medical University, Wrocław, Poland 2Department of Vascular, General and Transplant , Wrocław Medical University, Wrocław, Poland 3Department of Nephrology and Transplantation Medicine, Wrocław Medical University, Wrocław, Poland 4Department of Nephrology and Transplantation Medicine, Wrocław Medical University, Wrocław, Poland Citation: Krajewski W, Dembowski J, Kołodziej A, et al. Urological complications after renal transplantation – a single centre experience. Cent European J Urol. 2016; 69: 306-311.

Article history IntroductionUrological complications after renal transplantation occur in between 2.5% and 30% Submitted: March 22, 2016 of all graft recipients. The aim of the study was to present 7 years of experience in urological treatment Accepted: June 13, 2016 of patients with a transplanted . We aimed to identify retrospectively late urological complications Published online: July 11, 2016 in renal transplant recipients at a single center and analyze the treatment modalities and their outcome. Material and methods Between January 2008 and December 2014, a total of 58 patients after KTX were treated in the Department of Urology because of post-transplant urological complications that occurred during follow-up at the Transplant Outpatient Department. Retrieved data were analysed in retrospectively. Results In the group of 38 patients with ureteral stenosis (Clavien grade III), 29 patients underwent , 8 open surgical procedures and one both endoscopic and open operation. Ten patients were admitted with symptomatic lymphocoele (Clavien III), of which 9 were successfully treated with drainage and one with surgical marsupialization. Because of urolithiasis in the grafted kidney (Clavien grade III), Corresponding author Wojciech Krajewski 4 patients were treated with ureterorenoscopic (URSL) and one only with the extracorporeal Wrocław Medical shock wave lithotripsy (ESWL) procedure. Five urethral strictures plasties and one graftectomy because University of purulent pyelonephritis were also conducted. The average age in the group of recipients who experi- Department of Urology enced urologic complications was similar (46.1vs. 47.8) to those without complications. There was and Oncological Urology no vesicoureteral reflux or ureteral necrosis requiring surgical intervention, no graft loss and death re- 213, Borowska Street 50-556 Wrocław lated to urological complication and treatment. phone: +48 71 733 10 10 Conclusions Most complications could be successfully treated with endourological procedures. The kidney [email protected] function improved in the majority of patients.

Key Words: complications ‹› renal transplantation

INTRODUCTION Many factors influence treatment outcome. Im- provements in surgical techniques and upgrades (KTX) is the optimal treat- in pharmacotherapy protocols, such as the reduction ment for dialysed patients with end-stage chronic of steroid dosage and the introduction of multi-drug kidney disease. It significantly reduces the risk immunosuppression, have significantly decreased the of death (by over 60% compared to ), doubles incidence of surgical/urological complications dur- the expected survival time and greatly improves ing the last decades. However, urological complica- quality of life [1]. In addition, KTX is cost-efficient tions in renal transplant recipients are still common compared to dialysis [2]. and their occurrence is associated with significant

Cent European J Urol. 2016; 69: 306-311 doi: 10.5173/ceju.2016.833 307 Central European Journal of Urology morbidity, impairment of graft function and, in some RESULTS cases, graft loss and even recipient death. Urological complications can be divided into early Between January 2008 and December 2014, of the (occurring during first 90 days after the procedure) total of 22 patients after KTX underwent various and late (occurring after 90 days post-procedure). oncological procedures and 5 were treated due to be- We aimed to identify retrospectively late urological nign prostatic hyperplasia (BPH) in our Department complications in renal transplant recipients at a sin- of Urology. Fifty-eight patients (19 women, 39 men) gle center and analyze the treatment modalities and were treated as a result of post-transplant urologi- their outcome. cal complications. They received their kidney from deceased donors. The mean age in the group of re- MATERIAL AND METHODS cipients who had experienced urologic complications was similar to those without complications (46.1 Between January 2008 and December 2014, a total vs. 47.8 years). The mean donor age was 42.7 years. of 58 patients after KTX were treated in the Depart- Thirty-eight patients (14 females, 24 males) were ment of Urology as a result of post-transplant uro- admitted with ureteral stenosis (Clavien grade III). logical complications that occurred during follow-up Diagnosis was confirmed mainly by ultrasound, (19–22 months) at the Transplant Outpatient De- and in some cases by percutaneous transplant neph- partment. Retrieved data were analysed retrospec- rostomy followed by antegrade ureterogram, re- tively. vealing pyelocaliectasis or ureteropyelocaliectasis. A total of 460 kidneys were transplanted between Thirty-five patients had stenosis located at the ure- 2008 and 2014 in the Department of Vascular Sur- terovesical junction (92.2%). Initially, in 10 patients gery of Wrocław University Hospital. All kidneys percutaneous was performed and were harvested in the classic manner as per accepted in 15 patients a double J was reinserted standards concerning the removal of organs of the to decompress the collecting system and to ensure abdominal cavity. All were anastomosed the patency of the kidney prior to further treatment. by the Lich-Gregoire procedure. In the Lich-Gre- Single endoscopic orifice incision was success- goire technique, the bladder mucosa is reached via fully performed in 29 patients. A total of nine open a single cystotomy, and the distal ureter is sutured operations were carried out: in one patient because to the mucosa with an absorbable monofilament of a failed endoscopic approach and recurrent steno- 5-0 suture. Subsequently, a tunnel is created to sis; in a patient with ureteropelvic junction obstruc- prevent reflux [3]. Routinely, in every recipient tion, a Hynes-Anderson operation was performed; a double J (DJ) stent was inserted into the anas- in a case of stenosis in the central ureter, resection tomosed ureter during transplantation and was of short stenosis and end-to-end anastomosis was removed after 6 weeks in the majority of cases. carried out; one instance of ureter dissection from The was removed 5–7 days post-pro- massive adhesions; in 2 patients with ureterovesical cedure. According to standard protocol, patients re- junction stenosis, reimplantation of the ureter, and ceived 1.5 g cefuroxime once perioperatively as anti- 2 Y-V plasties were performed. In all patients a dou- microbial prophylaxis. Suction drains were removed ble-J catheter was left in place after the procedure usually at 4 to 5 days after surgery. Patients received for 6 weeks. Patients’ mean kidney function, esti- calcineurin inhibitors (cyclosporine or tacrolimus), mated by GFR, improved from 30 to 48 ml/min after mycophenolate mofetil and steroids as immunosup- urological treatment. pressive therapy. In high-risk patients, anti-CD25 Ten patients (3 females, 7 males) presented with antibodies were introduced additionally. symptomatic lymphocoele (Clavien grade III). Nine At our centre, the role of the urology department patients were successfully treated with ultrasonog- is centered on patient qualification for transplanta- raphy-guided percutaneous drainage performed tion, assistance during the procedure in complicated in the operating theatre. In 6 patients, the procedure cases and complication management. was performed only once, whereas three patients re- Urological complications were diagnosed according quired 2–3 drainages, and one, with recurrent lym- to clinical symptoms and kidney function markers, phocoele (more than 3 drainages), required open sur- and the use of ultrasound, CT scan, renal scintigra- gical drainage with marsupialization. phy and antegrade or retrograde pyeloureterogra- Five patients (1 female, 4 males) were admitted phy. All urological complications were categorized with stones in the ureters of the transplanted kid- according to the Clavien-Dindo classification [4]. neys (Clavien grade III). Three patients underwent The choice of treatment modality depended on the single, successful ureterorenoscopic lithotripsy severity of symptoms and complication type. (URSL). Two patients required DJ catheter inser- 308 Central European Journal of Urology tion. One patient had 3 consecutive extracorporeal urology department, we also perform laparoscopic shock wave lithotripsies (ESWL) performed and ex- LDN procedures without postoperative complica- pulsed the fragments of stone quickly. The second tions. Finally, urological evaluation and intervention unerwent 2 ESWL sessions, but these proved unsuc- is often necessary in patients after KTX to save the cessful; URSL with holmium laser was subsequently transplanted kidney and patient. performed. Complications such as urine leakage, ureteral ste- Five patients (1 female, 4 males) with urethral stric- nosis, lymphocoele, lithiasis, and tures were treated in our department. Three of them vesicoureteral reflux are reported to occur in be- had a single successful with optic ure- tween 2.5% and 30% of all recipients, depending throtome performed. One patient underwent 2 con- on the criteria [6]. The majority of these are ureteral secutive with a good final result. One complications arising from anastomosis defects. patient required open because of long- The majority of urological complications were man- standing stenosis resulting from iatrogenic injury aged by endourological approach (82.5%) instead during catheterization. of open surgery. Since 2002, routine insertion There was no vesicoureteral reflux or ureteral necro- of a ureteral stent resulted in a substantial reduc- sis requiring surgical intervention, no graft loss or tion of urinary leakage or fistula. Ureteral stenting, death related to urological complication and treat- despite lowering the frequency of urinary leaks and ment (Table 1). early obstruction due to anastomotic edema, can cause urinary tract or urethral injury DISCUSSION with bleeding. In our centre, the ureteral stent was generally maintained for 6 weeks (but now reduced The first successful renal transplantation was- car to 3–4 weeks) and then removed during . ried out on 23 December 1954 by Dr Joseph Mur- Yet, some authors advocate the early removal of the ray, a plastic surgeon, and Dr Hartwell Harrison, stent at the end of 2 weeks after renal transplantation an urologist [5]. For years, urologists were the pri- to decrease the rate of urinary tract infections [7, 8]. mary surgeons to perform renal transplantations. At present, the surgical role of the urologist in re- Ureteral stenosis nal transplantation has become less important be- cause of, among others, reduced training in vascu- Ureteral stenosis, with urine flow obstruction, was lar surgery for specializing urologists. However, due the most frequently observed complication, hav- to specific problems related to the genitourinary ing occurred in 38 patients. In the literature, ure- tract, urological input in renal transplantation is still teral stenosis has been reported as the major long- vital and the urologist’s familiarity with operations term urological complication, at a rate of 3–8% [9, on the genitourinary tract is frequently invaluable. 10], but accounted for about 50% of all urologi- Moreover, in many centres urologists perform lapa- cal complications. Almost all of our patients (92%) roscopic living donor (LDN). In our had stenosis located at the ureterovesical junction

Table 1. Urological complications in kidney transplant patients

Kidney function Treatment modalities (eGFR ml/min/1.73 m2) No. Mean Mean time Donor Mean of patients Mean recipient age from KTX Endouro- Open Complication gender donor (female/ BMI at the time to treatment before after logical surgery (f/m) age male) of KTX (months) urological urological treatment treatment treatment treatment (number (no. of of patients) patients) Ureteral 29 endoure- 38 (14/24) 27.1 10/28 40.7 44 17.1 30 48 9* stenosis terotomy 9 percutane- 1 marsupiali- Lymphocoele 10 (3/7) 23.1 6/4 46.3 53.8 12.2 54.2 56.7 ous drainage zation USRL – 4 Lithiasis 5 (1/4) 26.7 2/3 45.3 52 75.9 75 76.7 0 ESWL – 1 Urethral 3 urethro- 1 open 5 (1/4) 22.8 4/1 42.5 41.2 9.4 47.3 41 stenosis tomy urethroplasty

KTX – kidney transplantation; USRL – ureterorenoscopic lithotripsy; ESWL- extracorporeal shock wave lithotripsy ; *see ‚Results‘ 309 Central European Journal of Urology as a consequence of development of fibrosis at anasto- symptomatic lymphocoele was ultrasonography- mosis site. Previous reports indicate that anastomotic guided percutaneous drainage without sclerotic stenosis occurred in 60–95% of patients with stenosis. agent administration, performed in the operation In our department, ureteral stenosis was observed theatre. Some patients required multiple drainages. late after transplantion (mean time 17 months). One patient with recurrent lymphocoele underwent Some authors have described an average time open drainage with marsupialisation. Percutaneous to ureteral stenosis of 5.4 months, but the 10-year drainage and fenestration (both open and laparo- risk post-transplantation is estimated to be 9%. Our scopic) are commonly applied in the management group observed increased frequency of ureteral ste- of lymphocoele. It has been shown that laparoscopic nosis in male patients whose donors were men. fenestration is a safe treatment for symptomatic It is believed that ureteral strictures and their sub- lymphocoele and is associated with the lowest risk sequent obstructions are caused by surgical errors of lymphocoele recurrence. Yet, it seems that small in anastomosis, ureter ischemia, immunological fac- and benign lymphocoeles should be treated with per- tors and acute or chronic rejection episodes, infec- cutaneous drainage [16, 17]. tions, and immunosuppressive drugs. It has been The cause of lymphocoele is not entirely clear. proven that dissection of periureteral connective It is believed to result from accumulating lymph, tissue and excessive manipulation of the so-called originating from lymphatic vessels surrounding the ‘golden triangle’ (the site confined by the ureter, kid- iliac vessels damaged during the operation or from ney and renal artery) should be avoided [9]. These lymph vessels of the transplanted kidney itself. Cau- actions can damage the blood vessels supplying tious and limited dissection, with careful ligation the ureter, causing restriction. Necrosis of the distal of damaged lymphatic vessels, is recommended ureter was reported in up to 70% of patients with to decrease the incidence of this complication. damage to this site [11]. Ureteral spatulation length It is also important to run proper post-operative is also an important factor in reducing distal ureteral drainage. stenosis incidence. It has been shown that ureteral spatulation of more than 10 mm is effective in de- Urolithiasis creasing this complication [12]. Another proven risk factor of late ureteral stenosis is Polyomavirus BK In our department, ureteral calculi were diagnosed (BKV) [13]. in 5 recipients. Transplant urolithiasis occurred The therapy of ureteral obstruction must be in- 6 years after transplantion. Though the incidence troduced as early as possible to avoid loss of graft of urinary stones following renal transplantation function. A wide range of therapeutic methods is is low (0.17–1.8%), it is not negligible. Urolithiasis available, depending on stricture location and ae- is a dangerous complication due to the risk of ob- tiology. In our department, of the 38 patients with struction, sepsis, and potential loss of allograft func- ureteral obstruction, 25 were initially treated with tion [18–21]. Symptoms include anuria, renal fail- nephrostomy or ureteral stent insertion to restore ure, hematuria and urinary infection. Typical colic renal function. Twenty-nine patients with anasto- pain is rare in patients after KTX because of graft motic stricture underwent single endoscopic ure- denervation [22]. Urolithiasis following renal trans- ter orifice incision and double-J stent placement plantation can be both formed de novo or donor-gift- to good effect. The remaining 9 patients (24%) under- ed. Factors predisposing to stone formation include went open surgical procedures, including a Hynes- amongst others hyperparathyroidism, recurrent uri- Anderson operation, resection of central ureter ste- nary tract infection, hypercalciuria, and hypocitratu- nosis and end-to-end anastomosis, reimplantation ria [20, 22, 23] of a ureter and 2 Y-V plasties. In patients with mul- Treatment options for urolithiasis in renal trans- tiple or long ureteral stenosis, ureteropyelostomy plant recipients include all methods used in the gen- or can be employed and in cas- eral population [24]. However, because of altered es with an unusable ureter, the ‘Boari flap’ proce- anatomy and the patient’s immunocompromised dure may be considered [12, 14, 15] condition, therapy can be difficult and may be associ- In the majority of the patients, kidney function sig- ated with a higher risk of complications. In our de- nificantly improved following urological treatment. partment, 4 patients were successfully treated with URSL and 1 patient with 3 consecutive repeated Lymphocoele ESWL procedures. Other authors reported less ef- fective treatment of transplant calculi with URSL. Lymphocoele occurred in 10 renal transplant recipi- On the other hand, Del Pizzo et al. reported a 100% ents. The first-line treatment in every patient with success rate using endoscopic removal of ureteral 310 Central European Journal of Urology calculi. In our study, no complications were observed with neither graft loss nor patient death. Over with the above-mentioned procedures. the last decade, the ratio of endoscopic to open surgical procedures in the treatment of urologi- Urethral strictures cal complications has more than doubled, with about 76% of complications treated endoscopi- In addition to the above, 5 patients with urethral cally. In our previously published paper concern- strictures were treated in our department. The suc- ing the period 1983–1999, we reported a rate cessful urethrotomy with optic urethrotome was of only 43% [26]. performed in 4 patients, with the remaining patient requiring open urethroplasty because of long-stand- CONCLUSIONS ing stenosis, resulting from iatrogenic injury during catheterization. Urethral strictures following KTX The improvement of transplant surgery techniques are rare, yet serious complications, possibly leading has subsequently decreased the incidence of severe to hydronephrosis and graft function deterioration. urological complications in renal transplant recipi- Urethrography is very useful in revealing the precise ents. Most of these complications can now be suc- location and length of the urethral stenosis. Urethral cessfully treated with endourological procedures. strictures may be associated with iatrogenic urethral Open surgical procedures were employed mainly injury, prolonged catheterization time and urinary in patients with severe ureteral strictures. Kidney tract infection. Therapeutic options include urethral function improved in the patients being treated and dilation, endoscopic urethrotomy or recon- there was no graft loss. struction [25]. The urological treatment was successful in all CONFLICTS OF INTEREST patients: renal transplant function improved, The authors declare no conflicts of interest.

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