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Published on: June 23, 2015
Sirolimus produced S-shaped effect on adult polycystic kidneys after 2-year treatment
Abstract:
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.
Insights
Sirolimus showed potential in slowing kidney growth in autosomal dominant polycystic kidney disease (ADPKD) patients for the first six months. However, this effect diminished over 24 months, indicating a limited long-term impact on total kidney volume.
Area of Science:
- Nephrology
- Pharmacology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic disorder characterized by kidney cyst formation and enlargement.
- Current treatments for ADPKD primarily focus on managing symptoms and slowing disease progression, with limited options for directly targeting cyst growth.
Purpose of the Study:
- To evaluate the efficacy of sirolimus in combination with telmisartan for reducing total kidney volume (TKV) in ADPKD patients over 24 months.
- To assess the impact of sirolimus on renal function and identify potential side effects.
Main Methods:
- A 24-month, double-blind, randomized controlled trial involving 16 ADPKD patients.
- Patients received either telmisartan alone or telmisartan plus sirolimus (1 mg/day).
- Total kidney volume was measured using magnetic resonance imaging (MRI) at baseline, 12 months, and 24 months.
Main Results:
- Sirolimus demonstrated a trend towards reduced TKV increase at 12 months (P = .07) compared to telmisartan alone (P = .05).
- Kidney volume remained relatively stable in the sirolimus group for the first 6 months, showing an 'S-shaped' growth pattern.
- No significant difference in TKV change was observed between groups at 24 months. Side effects were minimal and comparable to those in kidney transplant patients.
Conclusions:
- Sirolimus may transiently retard kidney growth in ADPKD patients during the initial phase of therapy.
- The effect of sirolimus on kidney volume appears to be limited beyond the first six months of treatment.
- Further research is needed to explore optimal dosing and long-term efficacy of sirolimus in ADPKD management.
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