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The mean age of patients undergoing renal transplantation (RT) has been increasing in recent years [1, 2]. According to the 2006 United States Renal Data System Annual Report, the proportion of RT recipients >60 years old increased from 10.4% in 1994 to 20.7% in 2004 . This reflects the increasing age of the overall population and of patients on renal replacement therapy [1, 2].
Functional outcomes of transplanted kidneys in elderly patients are satisfactory overall [4, 5] and recent studies on series of older RT recipients reported similar graft survival rates compared with those observed for younger recipients [6-9]; however, the widespread use of extended-criteria donors in this setting (‘old-for-old’ allocation) makes these grafts prone to developing chronic interstitial fibrosis owing to calcineurin-inhibitor nephrotoxicity or chronic urinary tract obstruction [10, 11].
Benign prostatic hyperplasia is a common disease in elderly men. It is estimated that in the USA >70% of men aged 60–69 years are affected by BPH . The incidence of bladder outlet obstruction (BOO) attributable to benign prostatic hyperplasia (BPH) among RT recipients is often underestimated as patients undergoing dialysis are oliguric or anuric. Nevertheless, after RT and restoration of diuresis, urinary obstruction and related lower urinary tract symptoms (LUTS) become evident , being responsible for patient bother and risk for graft function.
Today, TURP is considered to be the ‘gold standard’ treatment for LUTS attributable to BPH and its safety and efficacy have been confirmed in large series [14, 15]. Studies in the literature have reported that TURP after RT is a safe procedure, but these studies were focused only on urological outcomes and had a short mean follow-up. Furthermore, to our knowledge, no information is available about the effects of TURP on renal functional outcomes after RT.
The aim of the present prospective study was to evaluate the long-term safety and efficacy of TURP performed after RT and to assess the impact of this procedure on graft function.
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A total of 32 patients who underwent TURP after RT at our centre with a minimum follow-up of 48 months were included in the study. The median (IQR) time between RT and TURP was 6 (3–14) months. Patient characteristics are shown in Table 1. Overall, five patients had an indwelling urethral catheter placed before TURP and four patients underwent urodynamic tests without evidence of neurogenic voiding disorders. No patient had significant hydronephrosis of the transplanted kidney before TURP.
Table 1. Preoperative characteristics of the 32 patients in the study
|Age, years||58 (48–64)|
|Time on dialysis before RT, months||54 (22–81)|
|Residual diuresis before RT, mL||100 (50–200)|
|Preoperative Qmax, mL/s||9 (4.3–10)|
|Preoperative IPSS||15 (12–19)|
|Preoperative PVR, mL||140 (80–200)|
|Preoperative PSA, ng/mL||1.24 (0.5–1.45)|
|Volume of adenoma at TRUS, mL||26 (16–36)|
|Preoperative sCr, mg/dL||2.4 (1.8–2.7)|
|Preoperative proteinuria, g||0.2 (0.1–0.4)|
|Preoperative Hb level, g/dL||11.8 (9.9–13.2)|
Thirteen patients (40.6%) underwent a biopsy of the transplanted kidney before TURP because of persistently impaired renal function and proteinuria. Immunological lesions were seen in five patients (three cases of chronic transplant glomerulopathy and two cases of acute cell-mediated rejection) and required treatment before TURP. Nephrotoxicity lesions were observed in five patients and aspecific lesions in the remaining ones. At the time of intervention all patients were receiving steroids with a median (IQR) prednisone dose of 5 (2.5–10) mg/day. Thirty out of 32 (93.8%) patients were on a calcineurin inhibitor-based regimen (tacrolimus in all patients except one, who was on cyclosporine A) and 7/32 (21.9%) were taking an mTOR-inhibitor (rapamycin). Furthermore, 9/32 (28.1%) patients were under treatment with antiplatelet agents which were withdrawn 1 week before TURP and replaced with low-molecular-weight heparin until 2 weeks after TURP. No patient was on anticoagulant therapy.
In 21 (65.6%) and 11 cases (34.4%), TURP was performed with a monopolar and bipolar resectoscope, respectively. The median (IQR) operating time was 41 (33–56) min and the median (IQR) volume of tissue resected was 28 (22–34) g. The median (IQR) catheterization time and hospital stay were 1 (1–2) and 3 (3–4) days, respectively. Pathology confirmed BPH in all cases and no incidental carcinoma was detected.
No intraoperative complications were observed. Postoperative complications were observed in seven patients (21.9% [Table 2]). Early complications occurred in two patients (6.3%). A patient with history of beta-thalassemia developed fever >38 °C on the first postoperative day. The antibiotic therapy was changed with resolution of hyperthermia. Another patient experienced persistent haematuria with a decrease in Hb levels (7 g/dL) and underwent blood transfusions. No transurethral resection syndrome occurred in the postoperative period. Delayed complications occurred in five patients (15.6%). Three patients developed acute urinary retention at catheter removal. In all patients, a 16-F Foley urethral catheter was placed and maintained for 48 h with no further episodes of retention. Two patients developed a bulbar urethral stricture 6 months after the procedure. In both cases the stricture was successfully treated with laser visual internal urethrotomy. No patient required repeat endoscopic procedures during follow-up. All early complications were Clavien grade II and all delayed complications were Clavien grade IIIa.
Table 2. Early (<24 h after TURP) and delayed (>24 h after TURP) complications (n = 32)
|Complication||n (%)||Treatment||Clavien grade|
|Early|| || || |
|Anaemia||1 (3.1)||Blood transfusion||II|
|Hypertermia (>38 °C)||1 (3.1)||Antibiotic therapy||II|
|Delayed|| || || |
|Acute urinary retention||3 (9.4)||Bladder catheterization||IIIa|
|Bulbar urethral stricture||2 (6.2)||Visual internal urethrotomy||IIIa|
The median (IQR) follow-up was 64 (48–125) months. Preoperative and postoperative variables at the different follow-up points are shown in Table 3. Postoperative Qmax was significantly higher (P < 0.001), and IPSS and PVR were significantly lower than preoperative values (P < 0.001). Qmax, IPSS and PVR values remained stable until 48 months (Fig. 1). No significant Hb reduction was observed after TURP, while Hb level was significantly higher at 24 and 48 months follow-up compared with the preoperative value (P < 0.001).
Table 3. Urological and renal functional outcomes during follow-up of TURP
| ||Preoperative||1 Month||6 Months||24 Months||48 Months|
|Median (IQR; min–max) IPSS||15 (12–19; 11–20)||4* (0–5; 0–6)||3* (0-4; 0–5)||4* (0–6; 0–6)||3* (0–6; 0–6)|
|Median (IQR; min–max) Qmax, mL/s||9.5 (7.0–10.0; 4.3–27.0)||21.0* (18–24; 16–32)||20.5* (18-24; 16–32)||19.5* (17–24.7; 17–33)||20* (16.5–22; 15–44)|
|Median (IQR; min–max) PVR, mL||100 (100–150, 70–400)||0* (0–0; 0–40)||0* (0–0; 0–0)||0* (0–0; 0–50)||0* (0–0; 0–50)|
|Median (IQR; min–max) Hb, g/dL||11.8 (9.9–13.2, 8.9–16.6)||11.5 (10.1–13.4, 8.3–14.8)||12.0 (11.5–14.2, 9.9–16.0)||12.8*† (11.7–14.5; 9.5–16)||13.0*† (12.0–14.0, 11.0–16.6)|
|Median (IQR; min–max) SCr, mg/dL||2.4 (1.85–2.77; 1.2–8.8)||1.9* (1.5–2.35, 1.0–3.1)||1.7* (1.2–2.1, 1.0–3.0)||2* (1.4–2.3; 1.0–2.8)||2* (1.5–2.3, 0.8–2.4)|
Patients' sCr levels were significantly lower 1 and 6 months after TURP (P < 0.001) and were slightly higher at 24 and 48 months (Fig. 2); however, sCr at 48 months after TURP was still significantly lower compared with preoperative values and not significantly different compared with sCr values recorded at 6- and 24-month follow-ups. It is noteworthy that 52 and 79% of patients had a reduction in sCr levels beyond the critical difference after 1 and 6 months, respectively.
A comparative analysis with a control group of age-matched transplanted patients who did not undergo TURP showed that sCr was significantly higher in patients awaiting TURP compared with control patients 6 months after RT (2.63 vs 1.69 mg/dL, P < 0.001). Conversely, there was no significant difference between the sCr levels of patients who underwent TURP and those of control patients at 48-month follow-up (sCr = 1.9 vs 1.69 mg/dL, P = 0.13).
Five patients (15.6%) underwent a renal biopsy for clinical reasons after TURP; immunological lesions (chronic transplant glomerulopathy) were detected in one patient, while aspecific chronic vasculopathy without signs of chronic rejection was the predominant finding in the remaining patients.
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The incidence of end-stage renal disease increases with advancing age. Owing to low survival rates and the comparatively poor quality of life of patients in dialysis, RT has been increasingly performed in older patients over the past decade [1, 2].
Although transplantation has been shown to be a good option for renal replacement therapy also in this category of patients [5-7], with graft survival outcomes that are similar to those of younger recipients, older RT recipients are more likely to have comorbidities that can affect graft survival and patient quality of life. BPH is a chronic condition that is associated with progressive LUTS attributable to BOO in aging men. These symptoms affect ∼75% of patients in the seventh decade of life . It is therefore not surprising that Tsaur et al.  reported a high incidence of voiding dysfunctions largely attributable to urinary obstruction caused by BPH in male RT recipients aged ≥60 years. LUTS are frequently experienced in this category of patients after RT while their presence is generally underestimated in patients with uraemia of the same age in dialysis owing to the decreased or absent diuresis . The presence of severe BOO is worrisome in transplanted patients since this condition can lead to urinary retention with high PVR levels, recurrent UTIs and progressive deterioration of renal function. The median sCr level of patients in our series before TURP was found to be significantly higher than the median sCr level of an age-matched population without signs of chronic urinary obstruction 6 months after transplantation. Chronic urinary obstruction can affect graft function, either by increasing urethral resistances to urinary flow or by affecting glomerular filtration rate (GFR) .
The current gold standard treatment for BPH and related symptoms is TURP . This is based on consistent data in the literature supporting the safety and efficacy of this procedure . Although transurethral incision of the prostate is performed by some authors to relieve BOO after RT , at our centre TURP is the preferred option for the treatment of LUTS attributable to BPH in transplanted patients.
Only few, retrospective series of TURP in RT recipients have been reported in the literature. In 1992, Reinberg et al.  retrospectively compared the functional outcomes of eight patients who underwent TURP within 10 days of RT with those of another group of patients who did not undergo prostate surgery, and observed no significant difference between the groups in terms of graft and patient survival; however, there was a 25% incidence of major postoperative complications after TURP (including one mortality). With the improvement in TURP technique, other authors subsequently reported the efficacy of TURP in the treatment of BOO after RT without significant risk of complications in the presence of preoperative and postoperative sterile urinary cultures [22, 23]. Although these studies were based on a low number of cases, a single institutional study very recently reported 70 patients who underwent TURP for urinary retention after RT. The authors identified patient age >60 years and duration of dialysis >120 months as significant predictors of urinary retention requiring TURP in this category of patients . Finally, in a retrospective chart review of a large cohort of 23 622 recipients, Hurst et al.  observed that 7.3% of patients underwent TURP after RT. At multivariate analysis, BPH was independently associated with the incidence of acute urinary retention episodes, UTIs and graft loss.
All these studies were retrospective, focused mainly on the assessment of urological outcomes and have a relatively short follow-up. The present study represents, to our knowledge, the first prospective assessment of long-term urological and functional results of TURP after RT.
In the present series, 32.8% of male recipients aged >40 years developed LUTS after RT, which is consistent with the observations of Tsaur et al.  and emphasizes the clinical importance of chronic urinary obstruction management in transplanted patients.
Most patients with LUTS attributable to BPH can be initially treated with medical therapy, either with α-blockers, 5-ARIs or a combination of both . At our centre, patients are scheduled for TURP only after clinical evidence of failure of a trial of medical treatment. This represents our policy both in the general population and in transplant recipients with LUTS. We believe this is appropriate to avoid surgical overtreatment of patients with moderate urinary obstruction and at the same time to select patients that are most likely to benefit from endoscopic resection.
In the present series, TURP was confirmed as a safe procedure. No cases of transurethral resection syndrome occurred. This can be explained by the relatively low median size of the adenomas resected and by the employment of continuous flow resectoscopes and bipolar technology for TURP of larger prostates. Minor (Clavien grade II) early complications were observed only in two patients, including one case of bleeding requiring blood transfusion and one of fever requiring modification of the antibiotic regimen.
According to major urological guidelines the duration of perioperative prophylaxis for a TURP should be ideally minimized to a single preoperative dose ; however, because of the higher risk of infections in the transplanted, immunocompromised population, we preferred to extend the administration of i.v. antibiotics to the entire first postoperative day. Our policy seemed to be effective as only one case of UTI (3.1%) was observed postoperatively in the present series.
Delayed postoperative complications were observed in 15.6% of cases, including three urinary retentions after catheter removal and two urethral strictures. All these complications required an invasive treatment (re-insertion of a urethral catheter or visual internal urethrotomy under regional anaesthesia) and are therefore classified as Clavien grade IIIa; however, all cases of postoperative urinary retention were attributable to oedema or clots and resolved spontaneously after a few days of further catheterization. No re-TURP was needed during follow-up, confirming the success of the procedure. The higher incidence of postoperative strictures compared with other series of TURP in the general population may be simply attributable to the small number of patients in the present study .
Regarding urological outcomes, the present study clearly confirms the clinical efficacy of TURP in RT recipients. Urinary flow, bladder emptying and related urinary symptoms improved significantly after TURP and this improvement was maintained at long-term follow-up. In particular, median Qmax at uroflowmetry increased from 9.5 mL/s preoperatively to 21 mL/s postoperatively (P < 0.001), and median IPSS score decreased from 15 preoperatively to 4 postoperatively (P < 0.001). No significant decrease in Qmax or increase in IPSS score was observed at 24- or 48-month follow-up (Table 3; Fig. 2). Five out of 32 (15.6%) patients continued chronic treatment with α-blockers (doxazosin) for hypertension after TURP, potentially biasing the results, but as these men were taking the same drug before TURP, this was unlikely to have had a significant influence on the degree of improvement of the urological outcomes.
Until now, no prospective and thorough assessment of the efficacy of TURP on renal function at short- and long-term follow-up has been available in the literature. The present study shows that renal function of transplanted patients who underwent TURP for LUTS attributable to BPH improves at short-term follow-up. In fact, median sCr levels showed a significant and progressive decline in the first 6 months after TURP (2.4 mg/dL preoperatively; 1.9 mg/dL 1 month after TURP; and 1.7 mg/dL 6 months after TURP; P < 0.001). The median sCr level subsequently slightly increased (2 mg/dL at 24–48 months), but remained comparable with that observed in the postoperative period confirming a satisfactory long-term graft function. Since urological outcomes were stable over time confirming the absence of recurrent urinary obstruction, the relative increase in sCr levels 24–48 months after RT is probably explained by the onset of new conditions affecting renal function. Furthermore, no significant difference in sCr levels at long-term follow-up was observed between patients who underwent TURP after RT in the present series and an age-matched population of transplanted patients without signs of chronic urinary obstruction. Although the two groups were not matched for immunological parameters, immunosuppressive protocol and comorbidities such as diabetes and cardiovascular disease, this also suggests that the beneficial effects of TURP on renal function are maintained over time.
In summary, the present study confirms the safety and long-term efficacy of TURP in the treatment of BPH after RT. TURP relieves BOO and significantly decreases related LUTS in the postoperative period. The benefits for urological outcomes are maintained until 48 months. Furthermore, the study shows a significant improvement of sCr levels in the postoperative months, with no significant worsening at long-term follow-up. Larger series of TURP in RT recipients with urodynamic confirmation of the presence and degree of urinary obstruction are needed to confirm our findings.