Renal Transplantation Does Not Improve Erectile Function in Hemodialysed Patients

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1 EUROPEAN UROLOGY 56 (2009) available at journal homepage: Sexual Medicine Renal Transplantation Does Not Improve Erectile Function in Hemodialysed Patients Vincenzo Mirone a, Nicola Longo a, Ferdinando Fusco a, Paolo Verze a, Massimiliano Creta a, *, Fabio Parazzini b, Ciro Imbimbo a a Department of Urology, University Federico II of Naples, Naples, Italy b Department of Obstetric and Gynaecology, University of Milan, Milan, Italy Article info Article history: Accepted September 16, 2008 Published online ahead of print on September 24, 2008 Keywords: Erectile dysfunction Hemodialysis Renal transplantation Abstract Background: Effects of renal transplantation (RT) on erectile dysfunction (ED) is a controversial issue. Objective: To verify the efficacy of RT in restoring erectile function (EF) in hemodialysed patients. Design, setting, and participants: We conducted a prospective, interventional, nonrandomised study from September 2001 to September 2005 on 78 hemodialysed male patients undergoing RT. EF was evaluated during the baseline visit and 1 yr after RT, using the International Index of Erectile Function (IIEF) questionnaire. A subanalysis was performed by splitting the total cohort into two age groups: <45 yr and 45 yr. Intervention: RT was performed. Measurements: EF was evaluated using the IIEF scoring system. Results and limitations: Before RT, 68 patients with a mean total IIEF score of complained about ED. One year after RT, 71 patients reported ED, and the mean total IIEF score had decreased to The mean pre-rt IIEF EF domain score was 18.48, and it decreased to after RT. Patients aged 45 yr reported no significant variations in any IIEF domain, while patients aged <45 yr reported a significant decrease in mean total IIEF score due to variations in domain scores for erectile function, sexual desire, and overall satisfaction. In the younger age group, we found significant differences between baseline and post-rt IIEF scores in dyslipidaemic patients and in those patients using immunosuppressive (methylprednisolone and cyclosporin) or antihypertensive (ACE-inhibitors, b-blockers, and Ca-antagonists) drugs. The main limitations were the absence of any aetiological characterisation of ED and the small number of patients. Conclusions: After RT, EF worsens in patients <45 yr but is not modified in patients 45 yr. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University Federico II of Naples, Via S. Pansini, Naples, Italy. Tel ; Fax: address: mxx79@inwind.it (M. Creta) /$ see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1048 EUROPEAN UROLOGY 56 (2009) Introduction Erectile dysfunction (ED) is the persistent inability to achieve and/or to maintain an erection for satisfactory sexual intercourse [1]. Although it is a benign disorder, ED is related to physical and psychosocial health, and it has a significant impact on the quality of life (QoL) of both sufferers and their partners [2]. End-stage renal disease (ESRD) is a chronic illness frequently associated with ED; the prevalence of ED is high in patients undergoing both chronic hemodialysis (HD) and renal transplantation (RT) [3 5]. Higher age, longer time on HD prior to RT, higher comorbidity, diabetes mellitus, medications, and a prior RT are variables associated with ED in renal transplant recipients (RTRs) [6]. RT appears to have very variable effects on ED. After RT, EF has been reported to improve in 75% of patients, but ED may persist in 20% to 50% of patients [4]. The aetiology of ED in patients with ESRD and in RTRs is multifactorial; factors include uraemia, hypertension, endocrine factors, and nonorganic factors like depression [5]. Some causes of ED in hemodialysed patients are partially corrected by RT, but other factors can subsequently be involved, such as drugs or vascular conditions [3 5]. The International Index of Erectile Function (IIEF) has been shown to be a valid diagnostic tool in determining men with and without ED, and it is a current gold-standard for measurement of male sexual function and is used in the majority of clinical trials regarding ED [7]. The main purpose of this study was to investigate the effects of a successful RT on EF in male hemodialysed patients. Additionally, we evaluated the presence of significant differences between pre-rt and post-rt mean total IIEF scores and mean IIEF EF domain scores in relation to the following aspects: patient age, HD duration, drugs used, comorbidities, alcohol intake, smoking habit, previous renal graft. 2. Methods The study design consisted of a prospective, interventional, nonrandomised clinical investigation conducted from September 2001 to September The only inclusion criterion was that patients be adult males with ESRD on HD included in a waiting list only for RT. Exclusion criteria were penile abnormalities, psychological disorders, alcohol dependence, and diseases that preclude sexual intercourse. Our institutional ethics committee reviewed and approved the study protocol. All patients gave informed written consent. At the baseline visit, patients were evaluated by means of detailed medical and sexual histories, clinical examinations, and laboratory renal function assessments (recent serum creatinine level and glomerular filtration rate [GFR]). Patients did not explicitly request an office visit for ED. All of the patients were asked to complete the IIEF questionnaire both at the baseline visit and 1 yr after RT. The IIEF domain scores were calculated, and ED grading was determined using EF domain scoring according to Cappelleri et al [7]: absent ED (EF score 26 30), mild ED (EF score 17 25), moderate ED (EF score 11 16), and severe ED (EF score <10). The questionnaires were submitted in the setting of a nephrologist s office after a nephrologic evaluation; they reflected the sexual activity relative to the previous 4 wk. We evaluated the presence of significant differences between pre-rt and post-rt IIEF scores in relation to specific comorbidities, drugs used, and voluptuous habits. Comorbidities were scored according to the Charlson Comorbidity Index (CCI) [8]. Statistical analysis was performed using the student t test to compare mean IIEF total scores and mean IIEF EF scores before and after RT. A subanalysis was further performed by splitting the total cohort into two age groups: <45 yr and 45 yr. The cut-off of 45 yr was established according to the median age within the entire cohort. Differences resulting in p < 0.05 were considered statistically significant. Linear regression analyses were performed to correlate age and IIEF total score in each age group both pre-rt and post-rt. A multivariate logistic regression analysis was further performed to evaluate the association between potential predictors of EF changes after RT and subsequent outcomes in patients aged <45 yr. 3. Results 3.1. Baseline data A total of 78 male patients, aged between 19 yr and 71 yr (mean: yr), were included in the study. Thirty-two patients (41.02%) were aged <45 yr, while 46 patients (58.97%) were aged 45 yr. Mean body weight was kg (range: kg). Mean values of serum creatinine level and GFR were 1.70 mg/dl (range: mg/dl) and ml/min (range: ml/min), respectively, with no significant differences between the two age groups. Aetiologies of chronic renal failure (CRF) are reported in Table 1. The mean duration of ESRD (time on dialysis) was 53.9 mo (range: mo). There was a high prevalence of both hypertension and dyslipidemia in both age groups (Table 2). Patients did not suffer from other urological disorders. The prevalence of risk factors for ED in the overall cohort as well as in the two age groups is reported in Table 2. The mean CCI score was 2.55 in the overall cohort and did not differ significantly between the patient age groups (mean CCI score for the <45-yr-old group: 2.25; mean CCI score for the 45-yr-old group: 2.76). A detailed description of CCI category frequencies and CCI scores is reported in Table 3. Sixty-nine patients (88.46%) used antihypertensive drugs, while 32 patients (41.02%) used antilipidaemics (atorvastatin). Antihypertensive regimens included the following drug classes administered as single agents or in combination: a-blockers (28 patients), diuretics Table 1 Aetiologies of chronic renal failure in the overall cohort Disease Patients n (%) Chronic glomerulonephritis 40 (51.28) Unknown disease 10 (12.82) Polycystic kidney disease 10 (12.82) IgA nephropathy (Berger s disease) 7 (8.97) Focal glomerular sclerosis 3 (3.84) Vesicoureteral reflux 2 (2.56) Hereditary nephropathy 1 (1.28) Trauma in a solitary kidney 1 (1.28) Bilateral staghorn calculus 1 (1.28) Malignant hypertension 1 (1.28) Diabetes mellitus 1 (1.28) Postinfectious glomerulonephritis 1 (1.28) IgA = immunoglobulin A.

3 EUROPEAN UROLOGY 56 (2009) Table 2 Prevalence of erectile dysfunction risk factors in overall cohort and in two age groups Risk factor Total (78 patients) n (%) <45 yr (32 patients) n (%) 45 yr (46 patients) n (%) Hypertension 69 (88.46) 29 (90.62) 40 (86.95) Heart disease 13 (16.66) 1 (3.12) 12 (26.08) Diabetes 7 (8.97) 2 (6.25) 5 (10.86) Dyslipidaemia 46 (58.97) 20 (62.5) 26 (56.52) Smoking habit 16 (20.51) 9 (28.12) 7 (15.21) Neuropathy 0 (0.00) 0 (0.00) 0 (0.00) Previous renal transplantation 5 (6.41) 1 (3.12) 4 (8.69) Alcohol intake 12 (15.38) 3 (9.37) 9 (19.56) (5 patients), b-blockers (34 patients), Ca-antagonists (38 patients), and ACE-inhibitors (38 patients). All patients entirely completed the IIEF questionnaire both at the baseline visit and 1 yr after RT. Mean total IIEF scores and single domain scores in the overall cohort as well as in the age groups are reported in Table 4. Sixty-eight patients (87.17%) complained about ED of any degree. The prevalence of mild, moderate, and severe cases in the overall cohort as well as in both age groups is reported in Table 5. Mean ages of patients with absent, mild, moderate, and severe ED were 48.6 yr, (range: yr), yr (range: yr), yr (range: yr), and 35 yr, respectively. The prevalence of ED for patients <45 yr and 45 yr were 90.62% (29/32) and 82.60% (38/46), respectively Renal transplantation All patients underwent successful RT and received an immunosuppressive regimen. All grafts were revascularised with end-to-lateral anastomosis to the right internal iliac artery. All kidneys were from deceased donors; 73 patients received their first RT, and 5 patients had received a prior RT. Immunosuppressive regimens included the following drugs variously combined: azathioprine (8 patients), mycophenolate (18 patients), Ly antigen (3 patients), methylprednisolone (30 patients), prednisone (31 patients), everolimus (5 patients), rapamycin (2 patients), sirolimus (5 patients), tacrolimus (10 patients), and cyclosporin (57 patients) One-year follow-up data One year after RT, 71 patients (91.02%) complained about ED. The prevalence of mild, moderate, and severe cases is reported in Table 5. Mean total IIEF scores and scores relative to single IIEF domains are reported in Table 4. Shifts in ED class after RT are reported in Table 6. The mean ages of RTRs declaring ameliorated, stable, and worsened ED were 51.6 yr, 45.5 yr, and 42.8 yr, respectively. Patients aged 45 yr showed no significant variation in their mean total IIEF scores. On the contrary, patients aged <45 yr reported a Table 3 Frequency of Charlson Comorbidity Index (CCI) categories and CCI scores in two age groups Condition Weight <45 yr n (%) 45 yr n (%) Myocardial infarction 1 0 (0.00) 4 (8.69) Congestive heart failure 1 1 (3.12) 8 (17.39) Peripheral vascular disease 1 0 (0.00) 1 (2.17) Cerebrovascular accident 1 0 (0.00) 0 (0.00) Dementia 1 0 (0.00) 0 (0.00) Chronic pulmonary disease 1 0 (0.00) 1 (2.17) Connective tissue disease 1 0 (0.00) 1 (2.17) Gastrointestinal ulcer disease 1 1 (3.12) 2 (4.34) Mild liver disease 1 0 (0.00) 3 (6.52) Diabetes mellitus 1 2 (6.25) 5 (10.86) Haemiplegia 2 0 (0.00) 0 (0.00) Moderate to severe renal disease 2 32 (100.00) 46 (100.00) Diabetes with end-organ damage 2 0 (0.00) 0 (0.00) Any tumour 2 1 (3.12) 3 (6.52) Leukaemia 2 0 (0.00) 0 (0.00) Lymphoma 2 0 (0.00) 0 (0.00) Moderate or severe liver disease 3 0 (0.00) 0 (0.00) Autoimmune deficiency syndrome 6 0 (0.00) 0 (0.00) Metastatic solid tumour 6 0 (0.00) 0 (0.00) CCI score 2 25 (78.12) 26 (56.52) 3 6 (18.75) 12 (26.08) 4 1 (3.12) 4 (8.69) 5 0 (0.00) 2 (4.34) 6 0 (0.00) 1 (2.17) 7 0 (0.00) 1 (2.17)

4 1050 EUROPEAN UROLOGY 56 (2009) Table 4 Mean values of International Index of Erectile Function (IIEF) domain scores in the overall cohort and in two age groups at baseline and at one year after renal transplant (RT) IIEF domains Total patients <45 yr 45 yr Baseline Post-RT Diff. Baseline Post-RT Diff. p Baseline Post-RT Diff. p Erectile function (EF) Intercourse satisfaction (IS) Orgasmic function (OF) Sexual desire (SD) Overall satisfaction (OS) Total IIEF score Table 5 Severity of erectile dysfunction (ED) at baseline and at one year after renal transplant (RT) in two age groups ED severity <45 yr 45 yr Baseline n (%) Post-RT n (%) p Baseline n (%) Post-RT n (%) p Absent 3 (9.37) 0 (0.00) (15.21) 7 (15.21) Mild 12 (37.50) 3 (9.37) (36.95) 15 (32.60) Moderate 16 (50.00) 25 (78.12) (47.82) 22 (47.82) Severe 1 (3.12) 4 (12.50) (0.00) 2 (4.34) significant decrease in mean total IIEF score: the subanalysis of single IIEF domains revealed a significant decrease in EF, sexual desire, and overall satisfaction (Table 4). In the subgroup aged <45 yr, RT was associated with a significant worsening in patients reporting a mild ED and a significant improvement in those reporting a moderate ED (Table 5). Linear regression analysis confirmed the decrease in the total IIEF score in patients aged <45 yr after RT and the stability in those aged 45 yr (Fig. 1). We evaluated the presence of significant differences between pre-rt and post-rt mean total IIEF and IIEF EF domain scores in relation to concomitant medical conditions, drugs used, and voluptuous habits in patients aged <45 yr. As reported in Table 3, a large percentage of patients had a low CCI, so it was not possible to find significant differences in IIEF scores in relation to CCI scores. We observed a significant decrease in both mean total IIEF score (40.85 vs 34.55, p = ) and mean IIEF EF domain score (17.25 vs 14.40, p = 0.008) in dyslipidaemic patients. Hypertension was highly prevalent in patients aged <45 yr (Table 2), so it was not possible to find differences between patients with or without hypertension. In patients with hypertension, a significant decrease in mean IIEF EF domain score was observed in those using b-blockers (18.26 vs 14.53, p = ), Ca-antagonists (16.76 vs 14.64, p = ), and ACE-inhibitors (17.33 vs 14.6, p = 0.045). Patients using ACE-inhibitors also had a significant decrease in mean total IIEF score (41.46 vs 34.46, p = ). In patients using immunosuppressive drugs methylprednisolone and cyclosporine, we found a significant decrease in both mean total Table 6 Post renal transplant erectile dysfunction (ED) severity shifts in total cohort and in two age groups ED severity shifts Total cohort n (%) <45 yr n (%) 45 yr n (%) Ameliorated 14 (17.94) 2 (6.25) 12 (26.08) Severe to moderate 1 (1.28) 1 (3.12) 0 (0.00) Severe to mild 0 (0.00) 0 (0.00) 0 (0.00) Severe to absent 0 (0.00) 0 (0.00) 0 (0.00) Moderate to mild 7 (8.97) 1 (3.12) 6 (13.04) Moderate to absent 3 (3.84) 0 (0.00) 3 (6.52) Mild to absent 3 (3.84) 0 (0.00) 3 (6.52) Stable 33 (42.30) 13 (40.62) 20 (43.47) Absent 1 (1.28) 0 (0.00) 1 (2.17) Mild 9 (11.53) 1 (3.12) 8 (17.39) Moderate 24 (30.76) 13 (40.62) 11 (23.91) Severe 0 (0.00) 0 (0.00) 0 (0.00) Worsened 31 (39.74) 17 (53.12) 14 (30.43) Absent to mild 2 (2.56) 1 (3.12) 1 (2.17) Absent to moderate 7 (8.97) 2 (6.25) 5 (10.86) Absent to severe 0 (0.00) 0 (0.00) 0 (0.00) Mild to moderate 15 (19.23) 9 (28.12) 6 (13.04) Mild to severe 2 (2.56) 2 (6.25) 0 (0) Moderate to severe 4 (5.12) 2 (6.25) 2 (4.34)

5 EUROPEAN UROLOGY 56 (2009) Fig. 1 Relationship between age and total International Index of Erectile Function (IIEF) score in patients aged <45 yr (a,b) and I45 yr (c,d), both pre-rt (a,c) and one year after RT (b,d). IIEF score (40.40 vs 34.16, p = for methylprednisolone; vs 35.64, p = for cyclosporin) and mean IIEF EF domain score (17.40 vs 14.93, p = for methylprednisolone; vs 14.92, p = for cyclosporin). In relation to voluptuous habits, we found that at the baseline visit smokers reported lower mean scores compared with nonsmokers (mean total IIEF score: vs 42.39, p = 0.037; mean IIEF EF domain score: vs 17.87, p = 0.081). Post-RT data revealed that nonsmokers had a significant decrease in both mean total IIEF score (42.39 vs 34.91, p = ) and mean IIEF EF domain score (17.87 vs 14.69, p = ), while smokers reported nonsignificant variations (mean total IIEF score: vs 34.77; mean IIEF EF domain score: vs 14.22). Because of the low prevalence of the reported conditions in the analysed subgroup, significant differences were not observed in diabetics, in patients suffering from cardiovascular diseases, in those with a previous RT, or in patients declaring alcohol consumption. Moreover, HD duration did not affect IIEF score changes (Table 7). According to multivariate regression analysis, hypertension was the only potential predictive factor for ED worsening in patients aged <45 yr ( p = , odds ratio [OR]: 18). However, a very large confidence interval (CI, ) impaired the statistical significance of this result. 4. Discussion An ED prevalence of 52% has been reported in the general population of men aged yr [9]. It is a distressing problem in uraemic men and adversely affects their QoL: an association has been reported since 1975 [10]. Progresses in the fields of HD and RT have considerably improved survival and QoL in patients with CRF but this improvement does not always include a patient s sex life [5]. Studies in men with uraemia undergoing HD showed varying degrees of erectile Table 7 Relationship between differences in mean total International Index of Erectile Function (IIEF) scores and hemodialysis (HD) duration in patients younger than age 45 HD duration <24 mo (n = 15) HD duration 24 mo (n = 17) Baseline Post-RT p Baseline Post-RT p RT = renal transplant.

6 1052 EUROPEAN UROLOGY 56 (2009) impairment (41 93%) depending on disease stage [11,12]. Several organic and psychological factors have been reported to affect the pathophysiology of this condition. Arslan [13] reported the prevalence of ED of any degree in hemodialysed men to be 80.07% with a percentage of mild, mild to moderate, moderate, and severe cases being 18.1%, 17.1%, 14.9%, and 30.4% respectively; in the same study, higher age was significantly associated with a higher prevalence and severity of the disorder. Our study confirmed the increased prevalence of ED among hemodialysed men (Table 5). The effects of RT on ED in hemodialysed patients are controversial. Although several studies showed significant improvement in EF after RT, neuroendocrine, metabolic, and other abnormalities present in HD patients may persist after a successful RT [14 18]. Other studies reported minimal benefits of RT on EF [4,19,20]. About 20 50% of RTRs continue to complain about ED [4]. In a study by El-Bahnasawy [19], the prevalence of ED in male hemodialysed patients was 28% pre-rt and 26% post-rt; significant variations were reported only in the IIEF sexual desire domain. In the same study post-rt EF was improved, deteriorated, or remained static in 40%, 18%, and 42% of RTRs, respectively. The aetiology of ED in RTRs is not clear but is possibly multifactorial. Both organic and psychological factors could be involved in determining the disorder. The role of penile haemodynamics is controversial [21,22]. In patients affected by CRF, different molecular and ultrastructural abnormalities are responsible for cavernous tissue damage [23]. Endothelial dysfunction is a systemic processthatisrecognisedasplayingacentralroleinthe pathogenesis of ED [24]. Hypertension, diabetes mellitus, hyperlipidaemia, smoking habit, and uraemic toxins are well-recognised causative agents of this disorder [25]. Although it may be improved, endothelial dysfunction persists after RT [26,27]. Cyclosporin exerts a wellrecognised negative effect on endothelial function. Tacrolimus may not have the same disruptive effects, but its endothelial activity is still being established [28]. According to Rebollo [6], variables associated with ED in RTRs were the following: higher age, longer time on HD, higher comorbidity, diabetes mellitus, prostate surgery, some antihypertensive drugs, and peripheral artheriopathy. A second or subsequent transplant was also related to ED [4]. In other studies, younger age was significantly associated with a greater chance of improvement of EF, while previous HD duration had no effect on the probability of improvement of EF [29]. In our study, RT did not correlate with improvement in any IIEF domain score. On the contrary, while older patients remained substantially stable, we reported a significant decrease in sexual function in patients aged <45 yr. As reported in Table 6, 53.12% of patients aged <45 yr reported worsened ED, and a great percentage of them shifted from mild to moderate ED. Linear regression analysis confirmed these results (Fig. 1). We found significant differences between pre-rt and post- RT mean total IIEF scores and/or mean IIEF EF domain scores in relation to some comorbidities, medications, or voluptuous habits, but the study of a larger cohort of patientsisadvisableinordertofindapredictivevaluein terms of EF changes after RT. Unexpectedly, a significant decrease in EF was reported in the nonsmoking subgroup after RT compared with the smoking subgroup. However, the detrimental effects of smoking on EF was confirmed by the significantly lower mean total IIEF score and the lower mean IIEF EF domain score reported in the smoking subgroup compared with the nonsmoking subgroup in the pre-rt evaluation. ED in hemodialysed patients recognises a multifactorial aetiology in which organic and psychological agents are closely related. Many organic causes share a progressive and irreversible trends that are unresponsive to RT and may explain the persistence or the worsening of ED after this substitutive approach. Although not directly demonstrated, an organic component in ED is commonly expected in ESRD patients. However, an even more relevant psychogenic component could be involved, especially in younger patients, and this could explain the worsening of ED observed in the present study cohort. The IIEF questionnaire provides a self-estimation of sexual function, so it is widely influenced by psychological aspects concerning ESRD and RT. In our opinion,thesignificant decrease in EF reported by patients aged <45 yr is probably due to both higher sexual expectations and the major negative psychological impact of ESRD and subsequent RT. Older men can easily accept a reduction of sexual performance in the context of a long-term, stable couple relationship, while younger, less mature men do not yet have strong self-confidence in sexual ability. Moreover, younger men are already affected with the disease responsible for ESRD at the time of first sexual experience. The significant decrease in sexual desire observed in younger patients after RT could be a consequence of psychological factors that might further explain worsening EF in this age group. ED in hemodialysed patients and RTRs is a challenging issue, and, to date, diagnostic and therapeutic approaches to the problem are poorly defined by European Association of Urology (EAU) guidelines on ED [2]. In our opinion, these patients, particularly the younger ones, need psychological counselling and, when feasible, a prudent modulation of drug administration in order to avoid both false expectations and drug-related worsening of ED. Phosphodiesterases-5 inhibitors are considered to be safe, effective, and well-tolerated agents for the treatment of ED in RTRs [30]. The main limitations of the present study are the absence of any aetiologic characterisation of ED and the small number of patients. 5. Conclusions ED is prevalent in hemodialysed men. Although RT is the elective treatment of ESRD, it should be not regarded as a restorative treatment in terms of sexual function. Unexpectedly, EF worsens after RT in younger patients. In the light of the present data, patients should be informed that RT unpredictably affects sexual function, in order to lower patient expectations of restoration of sexual life.

7 EUROPEAN UROLOGY 56 (2009) Author contributions: Massimiliano Creta had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Fusco. Acquisition of data: Verze. Analysis and interpretation of data: Creta. Drafting of the manuscript: Imbimbo. Critical revision of the manuscript for important intellectual content: Mirone. Statistical analysis: Parazzini. Obtaining funding: None. Administrative, technical, or material support: Longo. Supervision: Longo. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. 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8 1054 EUROPEAN UROLOGY 56 (2009) Editorial Comment on: Renal Transplantation Does Not Improve Erectile Function in Hemodialysed Patients Gerald Brock University of Western Ontario, London, Ontario, Canada The field of sexual medicine is undergoing a paradigm shift in its approach toward erectile dysfunction (ED). Whereas just a decade ago the idea of symptomatic treatment for erectile concerns was felt to be state of the art, several recent reports have introduced the possibility of disease modification and/or cure through chronic phosphodiesterase type 5 inhibitor (PDE5-I) therapy or other means. Although undoubtedly an enviable goal, is a cure for ED really a possibility for many of our patients [1,2]? In this report [3], the authors address the important issue of whether reversibility or improvement of ED can be achieved in a population of men with end-stage renal disease (ESRD) who are undergoing cadaveric transplantation. Their population size and methodology is appropriate, and their results are clear. At least in this population of men, with multiple comorbid conditions and established ED, it is unlikely that significant erectile improvement can be achieved through normalization of renal function with transplantation. In fact, among the subpopulation of men <45 yr of age who are studied, decreased erectile function was experienced postoperatively. Although not definitive from this report, potential causative factors include reduced penile arterial flow owing to vascularization of the graft, and increased endothelial dysfunction through use of cyclosporin or psychologic factors may be etiologic. Perhaps the most important take-home message of this manuscript for the readers of European Urology is the understanding that ED is truly a systemic disease for most men, and particularly for men with ESRD. The key causative elements underlying ED in these men are hypertension, hypercholesterolemia, endothelial dysfunction, uremic toxins, antirejection drugs, and smoking. Although this cohort of men represents an extreme example of potential comorbid factors responsible for ED, it highlights the challenge clinicians face in pursuing curative approaches for ED. References [1] Hellstrom WJG, Kendirci M. Type 5 phosphodiesterase inhibitors: curing erectile dysfunction. Eur Urol 2006;49: [2] Uckert S, Mayer ME, Stief CG, Jonas U. The future of the oral pharmacotherapy of male erectile dysfunction: things to come. Expert Opin Emerg Drugs 2007;12: [3] Mirone V, Longo N, Fusco F, et al. Renal transplantation does not improve erectile function in hemodialysed patients. Eur Urol 2009;56: DOI: /j.eururo DOI of original article: /j.eururo