Sirolimus Produced S-Shaped Effect on Adult Polycystic Kidneys After 2-Year Treatment

This double-blind trial followed 16 patients with autosomal dominant polycystic kidney disease (ADPKD) who received telmisartan or sirolimus plus telmisartan for 24 months. The 6-month pilot study showed a promising effect of sirolimus. The primary metric of this 2-year study was the change in total kidney volume at 12 and 24 months, as measured on magnetic resonance imaging. Secondary outcome was changes in renal function from the baseline at months 12 and 24. Among patients receiving sirolimus, the mean total kidney volume increased from 2845 mL to 3381 mL at 1 year and to 3901 mL at 2 years versus placebo values increasing from 2667 mL to 3680 mL and 3776 mL, respectively. The posttreatment mean total kidney volume increased less on sirolimus (P = .07) versus control therapy (P = .05) after 1 year, but there was no difference at 24 months. Kidney volume was stable on sirolimus to 12 months, increasing steadily to 24 months. In contrast, kidney volume increased steadily among patients on telmisartan alone both at 12 and 24 months. In conclusion, sirolimus appeared to retard kidney growth among patients with ADPKD during the first 6 months of therapy but not to halt growth thereafter, thus eliciting S-shaped effect. The dose of sirolimus (1 mg per day) was associated with a low rate of side effects similar those observed in kidney transplantation.