Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease
Z Novalic, AM van der Wal, WN Leonhard… - Journal of the …, 2012 - journals.lww.com
Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal
models of polycystic kidney disease (PKD); however, two clinical trials in patients with
autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or
progressive stages of disease. The stage of disease during treatment and the dose of mTOR
inhibitors may account for these differing results. Here, we studied the effects of a
conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30–60 …
models of polycystic kidney disease (PKD); however, two clinical trials in patients with
autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or
progressive stages of disease. The stage of disease during treatment and the dose of mTOR
inhibitors may account for these differing results. Here, we studied the effects of a
conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30–60 …