Treatment of Erectile Dysfunction With Sildenafil Citrate in Renal Allograft Recipients: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial
2006; Elsevier BV; Volume: 48; Issue: 1 Linguagem: Inglês
10.1053/j.ajkd.2006.04.061
ISSN1523-6838
AutoresRaj Kumar Sharma, Narayan Prasad, Amit Gupta, Rakesh Kapoor,
Tópico(s)Marriage and Sexual Relationships
ResumoBackground: Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. Methods: The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Results: Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post–placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Conclusion: Treatment with sildenafil in renal transplant recipients is a valid option with an effective response. Background: Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. Methods: The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Results: Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post–placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Conclusion: Treatment with sildenafil in renal transplant recipients is a valid option with an effective response. ERECTILE DYSFUNCTION (ED) is the persistent inability to achieve a sustained erection sufficient for satisfactory sexual performance. The mental stress resulting from ED affects patients' interactions with family and others.1National Institutes of Health Consensus Development Panel on ImpotenceImpotence.JAMA. 1993; 270: 83-90Crossref PubMed Scopus (1172) Google Scholar ED is observed frequently in patients with end-stage renal disease and patients on hemodialysis therapy, and the estimated prevalence is between 71% and 82% in these patients.2Turk S. Karalezli G. Tonbul H.Z. et al.Erectile dysfunction and the effects of sildenafil treatment in patients on haemodialysis and continuous ambulatory peritoneal dialysis.Nephrol Dial Transplant. 2001; 16: 1818-1822Crossref PubMed Scopus (81) Google Scholar, 3Rosas S.E. Joffe M. Franklin E. et al.Prevalence and determinants of erectile dysfunction in hemodialysis patients.Kidney Int. 2001; 59: 2259-2266PubMed Google Scholar Only up to 75% of these patients recover from ED after renal transplantation.4Salvatierra J.R. Fortman J.L. Belzar F.O. Sex function of males before and after renal transplantation.Urology. 1975; 5: 64-66Abstract Full Text PDF PubMed Scopus (64) Google Scholar ED also may occur in up to a third of patients receiving a double transplant with vascular anastomosis to the hypogastric artery because of reduced arterial flow to the penis.5Gittes R.F. Waters W.B. Sexual impotence The overlooked complication of a second renal transplant.J Urol. 1979; 121: 719-720Abstract Full Text PDF PubMed Scopus (39) Google Scholar Treatment options for men with ED include psychosexual therapy, drug therapy, transurethral or intracavernosal therapy, treatment with vacuum constriction devices, and surgical treatment.6Lue T.F. Erectile dysfunction.N Engl J Med. 2000; 342: 1802-1813Crossref PubMed Scopus (1245) Google Scholar Sildenafil citrate is a selective inhibitor of phosphodiesterase type 5, which is the predominant isozyme interacting with cyclic guanosine monophosphate in corpus cavernosum and results in increased smooth muscle relaxation and improved erection. Recently, sildenafil was shown to be an effective, safe, and well-tolerated drug for men with ED7Goldstein I. Lue T.F. Padma-Nathan H. Rosen R.C. Steers W.D. Wicker P.A. Sildenafil Study GroupOral sildenafil in the treatment of erectile dysfunction.N Engl J Med. 1998; 338: 1397-1404Crossref PubMed Scopus (2078) Google Scholar and end-stage renal disease and maintenance hemodialysis patients with ED.8Paul H.R. McLeish D. Rao T.K.S. Friedman E.A. Initial experience with sildenafil for erectile dysfunction in maintenance hemodialysis (MD) patients.J Am Soc Nephrol. 1999; 11 (abstr): 222AGoogle Scholar, 9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar, 10Rosas S.E. Wasserstein A. Kobrin S. Feldman H.I. Preliminary observation of sildenafil treatment for erectile dysfunction in dialysis patients.Am J Kidney Dis. 2001; 37: 134-137Abstract Full Text PDF PubMed Scopus (46) Google Scholar, 11Chen J. Mabjeesh N.J. Greenstein A. Nadu A. Matzkin H. Clinical efficacy of sildenafil in patients on chronic dialysis.J Urol. 2001; 165: 819-821Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar There are few either nonrandomized or uncontrolled studies on the use of sildenafil in renal allograft recipients.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar There have been no double-blind placebo-controlled studies with sildenafil in renal allograft recipients. The area under the curve (AUC) of cyclosporine before and after sildenafil therapy was not compared in any of these studies.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Therefore, we conducted a randomized, double-blind, placebo-controlled, crossover study to establish the safety and efficacy of sildenafil in renal transplant recipients with ED. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Inclusion criteria for patients were renal transplant recipients who: (1) had stable graft function in the last 6 months, (2) were 18 years and older, (3) had medically documented ED as defined by the National Institute of Health Consensus Panel,1National Institutes of Health Consensus Development Panel on ImpotenceImpotence.JAMA. 1993; 270: 83-90Crossref PubMed Scopus (1172) Google Scholar and (4) were in a stable relationship with a female partner in the last 6 months. All patients were subjected to a detailed medical history and physical examination that included blood pressure, pulse rate, 12-lead electrocardiogram, cyclosporine A level by means of enzyme multiplied immunoassay method, and standard biochemistry (blood urea nitrogen, serum creatinine) and hematologic tests (hemoglobin, total and differential leukocyte count, and platelet count) at baseline and after each crossover. Exclusion criteria included the following: (1) penile anatomic deformities, (2) history of recent stroke, (3) myocardial infarction in the previous 6 months, (4) proliferative diabetic retinopathy, (5) severe autonomic neuropathy, (6) regular treatment with nitrates and androgens, and (7) spinal cord injury. At week 0, each eligible patient was given a randomization number that followed a randomization table generated by the method of random permuted blocks. The system generating the randomization assignment was operationally independent from study investigators who executed the randomization assignment and conducted the study. Renal allograft recipients with ED were divided into 2 groups, the placebo group and sildenafil group, by randomization and then crossed over to another group after 8 weeks in a double-blind manner. The washout period of 2 weeks was ensured in each patient during crossover from 1 group to the other by the investigator. Patients were instructed to take a single dose of study medication in a day, not more than once daily. The initial dose was 50 mg of sildenafil citrate or placebo of identical appearance. Based on the investigator's judgment of efficacy and tolerability, the dose could be increased to 100 mg or decreased to 25 mg of sildenafil or placebo. The initial dose of the drug was taken 1 hour before sexual intercourse, avoiding heavy meals or excessive alcohol intake. All patients completed the International Index of Erectile Function (IIEF) and a diary card to record response to the drug and the occurrence of side effects. Efficacy was assessed by using the self-administered IIEF, a 15-question validated measure of ED,17Rosen R.C. Riley A. Wagner G. Osterloh I.H. Kirkpatrick J. Mishra A. The International Index of Erectile Function (IIEF) A multidimensional scale for assessment of erectile dysfunction.Urology. 1997; 49: 822-830Abstract Full Text PDF PubMed Scopus (4547) Google Scholar, 18Cappelleri J.C. Rosen R.C. Smith M.D. Mishra A. Osterloh I.H. Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.Urology. 1999; 54: 346-351Abstract Full Text Full Text PDF PubMed Scopus (865) Google Scholar and a global efficacy question (Did the treatment improve your erection?).19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar The IIEF system is used for clinical assessment of ED and treatment outcome in clinical studies. It evaluates several aspects of sexual performance, rating each answer from 0 to 5, with 0 meaning no sexual activity/no attempt at sexual intercourse, 1 meaning the worst response (almost never/never), and 5 meaning the best response (almost always/always). Total score ranges from 5 to 75. Treatment efficacy was assessed through the answer to questions 3 (penetration ability) and 4 (maintenance frequency). Efficacy also was evaluated through the score for the 5 separate response domains of male sexual function of the IIEF: erectile function (questions 1 to 5 and 15; total score, 1 to 30), intercourse satisfaction (questions 6 to 8; total score, 0 to 15), orgasmic function (questions 9 and 10; total score, 0 to 10), sexual desire (questions 11 and 12; total score, 2 to 10), and overall satisfaction (questions 13 and 14; total score, 2 to 10). The final score of each domain is the sum of scores for individual questions in that domain. Patients with a score of 26 or higher on the erectile function domain were considered to have no ED and were excluded from analysis. In a selected group of 5 patients with normal graft function, cyclosporine level was estimated at 0-, 0.5-, 1-, 2-, 3-, 4-, and 6-hour intervals with and without sildenafil, and the AUC of cyclosporine level was estimated to see the effect of sildenafil on cyclosporine level. AUC was estimated by using a linear trapezoid rule. The study was conducted at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, a tertiary-care academic institute. Informed consent was obtained from all patients included in the study. Both sildenafil and placebo of identical aspect were provided by Zydus Cadila (Ahmedabad, India) free of charge. The authors received no other support from the drug and placebo provider to avoid any conflict of interest. Mean ± SD was calculated for each IIEF question or domain. Results of the placebo and sildenafil groups were compared by using t-test and Mann-Whitney U test for parametric and nonparametric data, respectively. Comparison of basal and final results in each group was performed by using paired t-test and Wilcoxon test for parametric and nonparametric data, respectively. Thirty-two eligible renal transplant recipients were included in this study. Mean age was 40 ± 8 years. Mean duration of the transplant was 4.7 ± 3 years, duration of ED was 17 ± 22 months, and duration of dialysis therapy was 3.5 ± 2 months. All patients had undergone living-related transplantations. No patient in our study had a vascular anastomosis to both the internal iliac artery and hypogastric artery. Of these patients, 14 patients had chronic glomerulonephritis, 8 patients had chronic interstitial nephritis, 7 patients had diabetic nephropathy, and 3 patients had other basic diseases. No patient had autonomic neuropathy at time of enrollment into this study. At baseline, mean hemoglobin level was 12.3 ± 1.5 g/dL (123 ± 15 g/L), mean blood urea nitrogen level was 18.3 ± 7.6 mg/dL (6.53 ± 2.71 mmol/L), and creatinine level was 1.48 ± 0.3 mg/dL (131 ± 27 μmol/L). In total, 32 tablets of sildenafil or placebo were offered to patients during the study period. At end of the study, mean numbers of tablets of sildenafil and placebo taken by patients were 24.3 ± 3.3 and 23.8 ± 2.6, respectively (P = 0.49). Table 1 lists scores for each of the 15 IIEF questions. After treatment with sildenafil, patients administered sildenafil had highly significantly better scores in 13 of 15 questions. The only questions for which differences were not significant were questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. Data show no significant differences between baseline and post–placebo treatment scores, except for question 13 (relationship satisfaction), which was significantly better after placebo treatment.Table 1IIEF Scores in Patients at Baseline and After Placebo and Sildenafil TreatmentIIEF QuestionBaselinePost–Placebo TreatmentPost–Sildenafil TreatmentP, Baseline v PlaceboP, Baseline v SildenafilErection frequency2.31 ± 0.692.32 ± 0.73.7 ± 0.701.0<0.001Erection firmness1.87 ± 0.701.90 ± 0.733.53 ± 0.640.86<0.001Penetration ability2.28 ± 0.722.28 ± 0.733.90 ± 0.851.0<0.001Maintenance frequency2.09 ± 0.922.15 ± 0.983.80 ± 0.660.79<0.001Maintenance ability1.71 ± 0.811.75 ± 0.843.75 ± 0.910.88<0.001Intercourse frequency1.31 ± 0.591.31 ± 0.63.00 ± 1.01.0<0.001Intercourse satisfaction1.90 ± 0.641.96 ± 0.63.62 ± 0.791.0<0.001Intercourse enjoyment2.21 ± 0.972.2 ± 0.973.75 ± 0.761.0<0.001Ejaculation frequency2.84 ± 1.163.18 ± 1.14.03 ± 0.890.23<0.001Orgasm frequency2.25 ± 1.192.25 ± 1.193.71 ± 0.771.0<0.001Desire frequency3.28 ± 1.273.84 ± 1.163.50 ± 0.670.150.39Desire level3.06 ± 0.613.09 ± 0.533.15 ± 0.840.530.61Overall satisfaction2.71 ± 0.812.78 ± 0.713.56 ± 0.660.16<0.001Relationship satisfaction2.06 ± 0.562.40 ± 0.713.75 ± 0.510.03<0.001Erection confidence2.69 ± 0.922.68 ± 0.893.66 ± 0.651.0<0.001NOTE. Data expressed as mean ± SD. Open table in a new tab NOTE. Data expressed as mean ± SD. The 5 IIEF domains are listed in Table 2. No significant differences between placebo and baseline scores were detected in any domain. Patients treated with sildenafil had better scores in 4 domains in comparison to the baseline score, but no difference was observed in the sexual desire domain (P = 0.32).Table 2IIEF Domain Scores at Baseline and After Placebo and Sildenafil TreatmentIIEF DomainBaselinePlaceboSildenafilP, Baseline v PlaceboP, Baseline v SildenafilErectile function13 ± 3.313.3 ± 3.4322.3 ± 3.30.910.001Orgasmic function5.4 ± 1.85.4 ± 1.7710.4 ± 2.01.00.001Sexual desire6.3 ± 1.45.9 ± 1.996.65 ± 1.00.280.32Intercourse satisfaction5.1 ± 1.65.4 ± 1.997.7 ± 1.40.450.001Overall satisfaction4.8 ± 0.975.1 ± 1.317.31 ± 0.90.230.001NOTE. Data expressed as mean ± SD. Open table in a new tab NOTE. Data expressed as mean ± SD. On analyzing the outcome of efficacy of sildenafil on the global efficacy question (whether treatment showed an improvement), 26 of 32 patients (81.3%) showed improvement in the sildenafil group, whereas only 6 patients (18.7%) showed improvement with placebo (P ≤ 0.01). On analyzing AUC and maximum concentration (Cmax) of cyclosporine in 5 selected patients, mean AUC and Cmax were not different with and without sildenafil. Mean AUC of cyclosporine was 7,454 ± 1,483 ng/h/mL with sildenafil compared with 7,460 ± 1,480 ng/h/mL without sildenafil. Mean Cmax also was similar: 1,605 ng/mL with sildenafil compared with 1,604 ng/mL without sildenafil. As listed in Table 3, there were no significant differences between biochemical parameters pre– and post–sildenafil treatment. Serum creatinine and blood urea nitrogen levels were not significantly different in the pre–and post–sildenafil treatment period.Table 3Biochemical Parameters Pre– and Post–Sildenafil TreatmentPre–Sildenafil TreatmentPost–Sildenafil TreatmentPBlood urea nitrogen (mg/dL)18.3 ± 7.617.9 ± 51Not significantCreatinine (mg/dL)1.48 ± 0.361.40 ± 0.39Not significantHemoglobin (g/dL)12.3 ± 1.513.2 ± 1.4Not significantCyclosporine trough level (ng/mL)90 ± 9.991 ± 10.5Not significantNOTE. Data expressed as mean ± SD. To convert hemoglobin in g/dL to g/L, multiply by 10; blood urea nitrogen in mg/dL to mmol/L, multiply by 0.357; creatinine in mg/dL to μmol/L, multiply by 88.4. Open table in a new tab NOTE. Data expressed as mean ± SD. To convert hemoglobin in g/dL to g/L, multiply by 10; blood urea nitrogen in mg/dL to mmol/L, multiply by 0.357; creatinine in mg/dL to μmol/L, multiply by 88.4. Five patients developed headache, 2 patients developed rhinorrhea and flushing, and 1 patient each developed generalized body ache and typical bluish visual hallucination with sildenafil, whereas only 2 patients developed headache with placebo. No patient discontinued the drug, except for the 1 patient with visual hallucination. This study shows that sildenafil is safe and effective for the treatment of ED in renal allograft recipients. This is the first randomized, placebo-controlled, crossover study to show the efficacy of sildenafil in renal transplant recipients. sildenafil has an efficacy similar to that in other nontransplantation patients with ED.9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar, 10Rosas S.E. Wasserstein A. Kobrin S. Feldman H.I. Preliminary observation of sildenafil treatment for erectile dysfunction in dialysis patients.Am J Kidney Dis. 2001; 37: 134-137Abstract Full Text PDF PubMed Scopus (46) Google Scholar, 11Chen J. Mabjeesh N.J. Greenstein A. Nadu A. Matzkin H. Clinical efficacy of sildenafil in patients on chronic dialysis.J Urol. 2001; 165: 819-821Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar sildenafil significantly improved erectile function score, although it did not improve desire level and sexual frequency as expected (Table 1) and also reported in other studies.9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar, 19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar These results are similar to previous results in patients with diabetes,19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar hemodialysis patients,8Paul H.R. McLeish D. Rao T.K.S. Friedman E.A. Initial experience with sildenafil for erectile dysfunction in maintenance hemodialysis (MD) patients.J Am Soc Nephrol. 1999; 11 (abstr): 222AGoogle Scholar, 9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar, 10Rosas S.E. Wasserstein A. Kobrin S. Feldman H.I. Preliminary observation of sildenafil treatment for erectile dysfunction in dialysis patients.Am J Kidney Dis. 2001; 37: 134-137Abstract Full Text PDF PubMed Scopus (46) Google Scholar, 11Chen J. Mabjeesh N.J. Greenstein A. Nadu A. Matzkin H. Clinical efficacy of sildenafil in patients on chronic dialysis.J Urol. 2001; 165: 819-821Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar and renal transplant recipients12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar with ED. Treatment efficacy assessed through questions 3 (penetration ability) and 4 (maintenance frequency) was significantly better in these renal transplant recipients (P < 0.001), similar to other patients with ED in another study.19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar In this study, all IIEF domain scores improved significantly after sildenafil, except for the sexual desire domain, whereas IIEF domain score did not improve after placebo (Table 2). Similar results were reported in patients with ED with diabetes19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar and hemodialysis patients.9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar Studies focusing on the use of sildenafil in renal transplant recipients showed a satisfactory response in 60% to 81% of transplant patients with ED.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 20Sklar G.N. Sildenafil citrate in the transplant recipient with erectile dysfunction.Int J Impotence Res. 1999; 11: S70AGoogle Scholar However, in our study, the response rate was 81.3%, on the higher side of the range. Recently, Zhang et al13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar also showed a response in 81.5% of patients, similar to our study. This higher response rate may be caused by a shorter duration of dialysis therapy (mean, 3 months; range, 1 to 5.5 months) before transplantation in our patients. Prieto Castro et al12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar showed a satisfactory response in 60% of transplant recipients, with a mean time on dialysis therapy of 23 months in patients with a satisfactory response, compared with 43 months in patients for whom the drug was not effective. We do not have a maintenance hemodialysis program, and only patients with a renal transplantation prospect are accepted for hemodialysis therapy. The drug is more effective in patients who have less time on dialysis therapy before transplantation because penile vascular disease is less advanced.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar A greater prevalence of ED usually is seen in patients with a longer duration of maintenance hemodialysis.2Turk S. Karalezli G. Tonbul H.Z. et al.Erectile dysfunction and the effects of sildenafil treatment in patients on haemodialysis and continuous ambulatory peritoneal dialysis.Nephrol Dial Transplant. 2001; 16: 1818-1822Crossref PubMed Scopus (81) Google Scholar, 3Rosas S.E. Joffe M. Franklin E. et al.Prevalence and determinants of erectile dysfunction in hemodialysis patients.Kidney Int. 2001; 59: 2259-2266PubMed Google Scholar In a large experience of 22 years of ED in renal transplant recipients, Lasaponara et al16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar reported that ED is an important problem in male renal transplant recipients, and cultural resistance to treatment is common. However, sildenafil is an accepted mode of treatment. They also showed that more renal transplant patients are reporting ED (78%) after 1998, after the invention of sildenafil, compared with 45% before 1998.16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Russo et al14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar showed improvement in IIEF domain scores in 20 renal transplant recipients with ED with the use of sildenafil. This study was designed more to show the effect of renal transplantation on ED, rather than the effect of sildenafil.14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar Chatterjee et al21Chatterjee R. Wood S. McGarrigle H.H. Lees W.R. Ralph D.J. Neild G.H. A novel therapy with testosterone and sildenafil for erectile dysfunction in patients on renal dialysis or after renal transplantation.J Fam Plann Reprod Health Care. 2004; 30: 88-90Crossref PubMed Scopus (46) Google Scholar also showed a good response to combined testosterone and sildenafil therapy in all patients, but only 8 of 12 patients were renal transplant recipients and 4 patients were on hemodialysis therapy in this pilot study with a different design. Therefore, the response rate to combined sildenafil and testosterone therapy cannot be compared with the response rate of sildenafil alone in our renal transplant recipients. Sildenafil and cyclosporine are metabolized through cytochrome P-450 isoform 3A4, and there is concern of a drug interaction between the 2 drugs. However, AUC and Cmax were not changed after use of sildenafil, and this may have been caused by highly selective action on phosphodiesterase type 5 and the short half-life (60 to 90 minutes) of sildenafil. No change in drug dosing of cyclosporine is required, which was shown in other studies.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 16Lasaponara F. Paradiso M. Milan M.G. et al.Erectile dysfunction after kidney transplantation Our 22 years of experience.Transplant Proc. 2004; 36: 502-504Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 20Sklar G.N. Sildenafil citrate in the transplant recipient with erectile dysfunction.Int J Impotence Res. 1999; 11: S70AGoogle Scholar, 22Cuellar D.C. Hamilton J.P. Sklar G.N. Sildenafil citrate in the transplant recipient with erectile dysfunction.J Urol. 2000; 163: 200-201Google Scholar However, only the trough level of cyclosporine was compared in these studies. We are the first to compare the AUC of cyclosporine before and after sildenafil therapy. Blood urea nitrogen and serum creatinine levels were not changed significantly after the use of sildenafil in our study. Similar observations were seen in other studies.12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 13Zhang Y. Guan D.L. Ou T.W. et al.Sildenafil citrate treatment for erectile dysfunction after kidney transplantation.Transplant Proc. 2005; 37: 2100-2103Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 14Russo D. Musone D. Alteri V. et al.Erectile dysfunction in kidney transplanted patients Efficacy of sildenafil.J Nephrol. 2004; 17: 291-295PubMed Google Scholar An increase in glomerular filtration rate was seen in kidney transplant recipients after use of sildenafil.23Rostaing L. Tran Van T. Alder J.L. Increased glomerular filtration rate in kidney transplant recipients who take sildenafil.N Engl J Med. 2000; 342 (letter): 1679Crossref PubMed Scopus (18) Google Scholar, 24Malavaud B. Rostaing L. Tran-Van T. Tack I. Ader J.L. Transient renal effects of sildenafil in male kidney transplant recipients.Transplantation. 2001; 15: 1331-1333Crossref Scopus (13) Google Scholar However, a slight increase in serum creatinine levels between the inclusion visit and study end was observed in a study, but there was no evidence of a causal relationship between this increase and sildenafil administration in this study.15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar In the present study, side effects were reported in both the placebo and sildenafil groups. Headache was the most common side effect. No patient, except for the 1 patient with bluish visual hallucination, discontinued the drug. Similar side-effect profiles were reported in other studies.9Seibel I. Eduardo Poli De Figueiredo C. Teloken C. Feliz Moraes J. Efficacy of oral sildenafil in hemodialysis patients with erectile dysfunction.J Am Soc Nephrol. 2002; 13: 2770-2775Crossref PubMed Scopus (69) Google Scholar, 12Prieto Castro R.M. Anglada Curado F.J. Regueiro Lopez J.C. et al.Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction.Br J Urol Int. 2001; 88: 241-243Crossref PubMed Google Scholar, 15Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (38) Google Scholar, 19Rendell M.S. Rajfer J. Wicker P.A. Smith M.D. Sildenafil for treatment of erectile dysfunction in men with diabetes A randomized controlled trial.JAMA. 1999; 281: 421-426Crossref PubMed Scopus (580) Google Scholar However, such visual changes similar to those of our patient also are reported in the literature of patients administered sildenafil.25Vobig M.A. Klotz T. Saak M. Bartz Schmidt K.V. Engelmann U. Walter P. Retinal side-effects of sildenafil.Lancet. 1999; 353: 375Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar In conclusion, treatment with sildenafil citrate in selected renal transplant recipients with ED is a valid option with an effective response. Although the same metabolic degradation pathway is used for sildenafil as for cyclosporine, no change is required in the initial dose of immunosuppression.
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