Effect of ramipril on urinary protein excretion in maintenance renal transplant patients converted to sirolimus

PURPOSE: Evaluate the effect of ramipril on urinary protein excretion in maintenance renal transplant pts converted to sirolimus (SRL). METHODS: This placebo (pbo)‐controlled, double‐blind, multicenter study randomized pts to ramipril or pbo for up to 6 wks preconversion from calcineurin inhibitors to SRL. Pts then received assigned treatment plus SRL for 52 wks. Pts who developed proteinuria (urinary protein:creatinine ratio [U p/c] >=0.5) were treated with increased doses of assigned treatment; losartan was initiated if proteinuria persisted. Primary endpoint was time to losartan initiation after SRL conversion, presented by Kaplan‐ Meier curves and analyzed using the log‐rank test. Secondary endpoints included change in estimated glomerular filtration rate (eGFR) from baseline to 12, 24, and 52 wks and % of pts with U p/c <0.5 at 24 and 52 wks. RESULTS: 295 pts (mean age 47y; 67% male; 64% white) were randomized and received >=1 dose of study drug; 264 met criteria for SRL conversion (mITT population; ramipril 138; pbo 126). Cumulative rate of losartan initiation for 52 wks was significantly lower with ramipril vs pbo (6.2% vs 23.2%; HR=0.228; 95% CI: 0.099‐0.528; P=.0002). Percentage of pts with U p/c <0.5 was significantly higher with ramipril vs pbo at 24 wks (92% vs 78%; P=.002) and remained numerically higher at 52 wks (83% vs 73%, P=.07). No significant differences in ramipril vs pbo pts in eGFR were observed from baseline to 12, 24, or 52 wks. The 5 most common treatment‐emergent AEs included diarrhea, peripheral edema, upper respiratory infection, acne and cough. Biopsy‐confirmed acute rejection occurred in 13 ramipril pts and 5 pbo pts (P=.07). No pts experienced graft loss. One pt (pbo group) died due to cerebrovascular accident. One pt in each group experienced angioedema; neither case was considered serious by investigators. CONCLUSIONS: This study demonstrated the efficacy of ramipril in preventing proteinuria after SRL conversion. The AEs observed were consistent with the known safety profile of SRL and were not potentiated with the coadministration of ramipril.