EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Benign prostate hyperplasia is frequently diagnosed in elderly chronic renal failure patients. Although it is asymptomatic because urine flow declines in those with chronic renal failure, it may become symptomatic when urine flow increases after renal transplant. Untreated benign prostate hyperplasia may lead to several complications that adversely affect the kidney allograft.

Materials and Methods: Our retrospective study investigated data from 286 male transplant patients. Data obtained included medical history, clinical examination, prostate-specific antigen, prostate volume, and residual urine volume results. Patients had completed an International Prostate Symptom Score questionnaire to assess the low urinary symptoms. Creatinine level, residual urine volume, International Prostate Symptom Score, and uroflow-metry results were reviewed.

Results: The average age of patients in our group was 54.8 years. Seven patients were diagnosed with benign prostate hyperplasia, and transurethral resection of the prostate was performed. The average creatinine levels before and after transurethral resection were 2.53 ± 0.76 mg/dL and 1.66 ± 1.12 mg/dL, respectively. Creatinine levels measured 6 months after transurethral resection versus before resection were statistically significant (P < .018). Furthermore, there was a statistically significant difference (P < .017) in the postmicturition residual urine volume between the preoperative and postoperative values, which were 132.14 ± 19.33 and 47.6 ± 18.6 mL, respectively. Maximum urine flow rates before and after transurethral resection were also significantly different (P < .017).

Conclusions: Although the main reasons for graft function loss after renal transplant are rejection and infections, obstructive pathologies should also be considered. Especially for elderly patients, anamnesis, uroflowmetry, and digital rectal examination play critical roles in the evaluation of benign prostate hyperplasia before and after transplant.

Key words : Chronic renal failure, Obstructive uropathy, Renal transplantation

Renal transplant is the best treatment for kidney failure, and new advances in surgical techniques have increased the lifetime of grafts in elderly patients, particularly in those who are under immunosuppressive treatment.¹ The incidence of chronic kidney disease has increased faster among people over 65 years old, and transplant procedures have been done safely for these patients.²

However, the early diagnosis and treatment of complications observed in the lower urinary system are also important for the continuation of graft function. Illnesses, particularly benign prostatic hyperplasia (BPH), which can occur due to aging and which can be noted for elderly patients requiring transplant, have been gaining attention regarding their adverse effects in transplant patients. The prevalence of BPH and lower urinary system symptoms was 2.7% for patients who were between 45 and 49 years old. Benign prostatic hyperplasia has been observed among half of male patients > 60 years old, and it increases and reaches its peak value of incidence for patients over 80 years old, which is 24%.^3,4 Benign prostatic hyperplasia can be identified for most elderly patients with chronic renal failure, but it remains asymptomatic in those without urine production. Benign prostatic hyperplasia, which is symptomatic with urine flow, can be a risk factor after renal transplant for patients who have not been previously treated for this disease and can lead to many complications. The pressure inside the bladder increases over time, and this pressure can cause hydronephrosis, initiating a negative effect on graft function.⁵ As a result, these developments can lead to acute urinary retention, bringing on urinary tract infections and allograft failure.

In this study, we evaluated the effects of transurethral resection of the prostate (TURP) and BPH on renal function in transplant patients.

Materials and Methods

From 2005 to 2015 at our center, 477 living-donor and deceased-donor kidney transplant procedures were conducted. Patients with occasional visits and missing data were not included in the study (n = 32). Data of 286 male patients who were included in this study were investigated retrospectively. In all patients, urinary cultures were negative before transplant, and all had been using antibiotic prophylaxis. Data evaluated included medical history, clinical examination, prostate-specific antigen, prostate volume, and postmicturation residual urine volume (PMR) results. Living and deceased donor grafts were placed in the location and prepared in the left or right inguinal region of the recipient. Renal artery internal iliac or common iliac arteries to renal external iliac veins were anastomosed. Extravesical ureteroneocystostomy was conducted between the ureter and bladder through the Lich-Gregoire technique. All patients received double J catheters (4F). Urethral catheters were removed after 4 to 7 days, and double J catheters were removed along with cystoscopy. Patients received triple immunosuppression treatment (cyclosporine/tacrolimus, mycophenolate mofetil, and steroids).

All patients were followed on a weekly basis, and acute rejection, posttransplant urinary infection, and graft function were evaluated. Patients completed an International Prostate Symptom Score (IPSS) questionnaire to assess lower urinary symptoms (for example, urinary calibration decrease, dysuria, pollakiuria). Ultrasonography was used to measure prostate volume and postvoid residual urine amount. We evaluated maximum urine flow rate (Qmax) and average urine flow rate trends with uroflowmetry tests on patients, and residual urine amount after voiding was found to be over 100 cm3. Alpha-adrenergic blocker treatment and placement of urethral catheters were initiated in patients diagnosed with bladder outlet obstruction with high urinary tension or high residual volume. After 7 days, urethral catheters were removed. We used the TURP procedure in patients under anesthesia who were receiving alpha-receptor blocker treatment, still showing no improvement, and still having high creatinine values and residual urine volume. This procedure allowed a full bladder neck opening. During follow-up after TURP, creatinine level, PMR, IPSS, and uroflowmetry results were again evaluated in patients.

Wilcoxon test was used due to abnormal results of the difference distribution between preoperative and postoperative creatinine values. The difference distribution between preoperative and postoperative Qmax values was as expected. Therefore, paired simple test was used, and P < .05 was accepted as being significant.

Among 286 transplant patients, 38 patients had lower urinary tract symptoms (LUTS), and alpha-adrenergic antagonist drug therapy was started as part of the medical treatment. The average age of these patients was 54.8 years. Seven patients received cystoscopy under anesthesia because of increased creatinine values and Qmax values lower than 15 mL/s. Seven of 38 patients were diagnosed with BPH, and TURP was carried out. All 7 patients obtained a full opening with TURP, allowing complete resection, with no observed complications. The period between transplant and TURP was between 2 months and 13 years.

Average preoperative and postoperative creatinine values were 2.53 ± 0.76 mg/dL (range, 0.83-3.03 mg/dL) and 1.66 ± 1.12 mg/dL (range, 0.9-2.24 mg/dL), respectively. There was an apparent improvement in IPSS values before versus after the TURP procedure. We observed a significant difference between preoperative and postoperative creatinine values at month 6 (P < .018). We also observed statistically significant differences (P < .05) for the PMR values before and after the procedure (132.14 ± 19.33 vs 47.6 ± 18.6 mL) (Table 1). The Qmax values were also significantly different before versus after TURP (P < .017) (Table 1).

Obstructive pathologies belonging to the lower urinary system stay asymptomatic because most patients have anuria and oliguria before renal transplant. These pathologies start to be symptomatic as urine production begins after transplant. Pathologies that cause obstruction in the lower urinary system are BPH and urethra strictures. The symptoms of such pathologies bear some resemblance to each other, with the most common symptoms being frequency and nocturia. Benign prostatic hyperplasia occurs in older ages, whereas urethral strictures can be observed at every age. Both BPH and urethral strictures can occur secondary to the transurethral attempts and traumatic urethral catheterization.⁶

Reports have suggested conducting TURP after renal transplant because of better operation results. In 1 study, TURP and transurethral incision of the prostate were conducted in 20 patients 10 to 30 days after renal transplant, with an average of 15.2 days. The study reported that Qmax of 22.1 (18-33) mL/s and the PMR results were not significantly different before versus after the procedure.⁷ In a similar study, 8 patients had TURP operation 10 days after renal transplant.⁵

Severe urinary tension has been observed among half of patients during the early postoperative period after the removal of the urethral catheter. In our patients, even with medical treatment, creatinine levels did not fall. Therefore, it was decided that graft functions might get worse while waiting for a better response to medical treatment, and patients underwent TURP operations. Creatinine values rapidly fell to normal levels, and Qmax increased. Creatinine values remained at normal levels after 3 to 6 months.

Severe complications leading to death can occur after TURP. In a study conducted in 1992, Reinberg and associates observed the functional results of 8 patients who had TURP 10 days after renal transplant. Rate of major postoperative complications was 25%, and 1 patient died.5 Since then, surgical techniques and technologies and surgical instruments used in TURP have greatly improved. Operation time has also become shorter, the amount of bleeding during the operation has decreased, and complications are lower. In recent years, studies have shown that TURP can be accomplished safely and without complications. Koziolek and associates conducted TURP in 11 patients and reported no complications. Symptoms disappeared after the procedure, and uroflowmetry values on day 8 after TURP increased to 12.3 ± 4.8 mL/second.8 In this study, complete resection was done without any complications among the patients. Three days after the removal of the urethral catheter, patients were able to urinate easily, and low urinary system symptoms disappeared. Maximum urine flow rate increased from 10.14 to 21.57 mL/second.

Because symptom severity is independent of prostate volume, a BPH diagnosis may not be observed among patients with low prostate volume. However, patients with high prostate volume may have low LUTS or no LUTS at all. Applying TURP to patients who have anuria or oliguria depending on the prostate volume may increase the risk of urethral stricture. In our study of the same cohort of 286 male patients, 19 patients diagnosed with urethral stricture received internal urethrotomy and urethroplasty operations.⁹ Among most of these patients, prostate volume was lower than 50 cm³. Because of the high obstruction level, maximum flow rate did not increase despite medical treatment, and creatinine values did not fall. After the TURP procedure, creatinine levels started to decrease.

In a recent study, the possibility of occurrence of LUTS after renal transplant was investigated. The study of 111 patients included features such as patient age, causes of end-stage renal disease, time on dialysis until transplant, symptom surveys, and urine amount produced before transplant. Among these, the study found that urine production before renal transplant and approved questionnaires could aid in predicting severe LUTS continuing for about 1 year.¹⁰

In our patient group, the average age was 55.14 years, thus relatively younger. We will have the opportunity to apply new techniques to patients in this age group and show that renal transplant can be safely performed in these patients.

Low-pressure urine deposition and removal of urine from bladder without any residual is necessary for the long-term healthy functioning of renal grafts. Discharge of the urine with low pressure and without leaving any residue is essential for graft function after renal transplant. Urinary retention that is a result of high PMR causes urinary infections, adversely affecting graft function. Urinary tract infections in renal transplant patients are considered to be an independent risk factor for graft loss.¹ For our patients, medical treatment was limited to 1 week and the TURP surgical procedure was conducted without loss of time in patients who showed no improvements. The decision to perform TURP prevents PMR from further increasing, and accompanying risks of complications are eliminated.

Although the primary reasons for functional loss of graft after renal transplant are rejection and infections, obstructive pathologies should also be considered. Particularly for elderly patients, anamnesis, uroflow-metry, and digital rectal examination play critical roles in the evaluation of BPH before and after renal transplant.

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