title: Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus.
abstract: This prospective, randomized, double-blind, placebo-controlled study evaluated the effects of ramipril on urinary protein excretion in renal transplant patients treated with sirolimus following conversion from a calcineurin inhibitor. Patients received ramipril or placebo for up to 6 weeks before conversion and 52 weeks thereafter. Doses were increased if patients developed proteinuria (urinary protein/creatinine ratio ≥0.5); losartan was given as rescue therapy for persistent proteinuria. The primary end point was time to losartan initiation. Of 295 patients randomized, 264 met the criteria for sirolimus conversion (ramipril, 138; placebo, 126). At 52 weeks, the cumulative rate of losartan initiation was significantly lower with ramipril (6.2%) versus placebo (23.2%) (p < 0.001). No significant differences were observed between ramipril and placebo for change in glomerular filtration rate from baseline (p = 0.148) or in the number of patients with biopsy-confirmed acute rejection (13 vs. 5, respectively; p = 0.073). One patient in the placebo group died due to cerebrovascular accident. Treatment-emergent adverse events were consistent with the known safety profile of sirolimus and were not potentiated by ramipril co-administration. Ramipril was effective in reducing the incidence of proteinuria for up to 1 year following conversion to sirolimus in maintenance renal transplant patients.
authors.affiliation: Department of Medicine, University of Wisconsin Hospital, Madison, WI.
authors.forename: D A
authors.initials: DA
authors.lastname: Mandelbrot
authors.affiliation: Transplantation Department, Instituto Nacional de Ciencias Médicas y Nutrición SZ, Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Alberú
authors.affiliation: Department of Surgery, University of Montréal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Barama
authors.affiliation: Internal Medicine/Nephrology, Presbyterian/St Luke's Medical Center, Denver, CO.
authors.forename: B A
authors.initials: BA
authors.lastname: Marder
authors.affiliation: Nephrology Division, Hospital do Rim-Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: H T
authors.initials: HT
authors.lastname: Silva
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH.
authors.forename: S M
authors.initials: SM
authors.lastname: Flechner
authors.affiliation: Global Innovative Pharma, Pfizer, Collegeville, PA.
authors.forename: A
authors.initials: A
authors.lastname: Flynn
authors.affiliation: Global Innovative Pharma, Pfizer, Collegeville, PA.
authors.forename: C
authors.initials: C
authors.lastname: Healy
authors.affiliation: Global Innovative Pharma, Pfizer, Collegeville, PA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Global Innovative Pharma, Pfizer, Collegeville, PA.
authors.forename: M A
authors.initials: MA
authors.lastname: Tortorici
authors.affiliation: Global Innovative Pharma, Pfizer, Collegeville, PA.
authors.forename: S L
authors.initials: SL
authors.lastname: Schulman
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy*; D017257:Ramipril / Q000494:pharmacology*; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D000959:Antihypertensive Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D017257:Ramipril; D020123:Sirolimus; D016559:Tacrolimus
keywords: Calcineurin inhibitor (CNI); clinical research/practice; glomerular filtration rate (GFR); immunosuppressant; immunosuppression/immune modulation; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; mechanistic target of rapamycin: sirolimus; rejection: acute, immunosuppressant