Mammalian target of rapamycin and autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of innumerable cysts in both kidneys, which distort the normal kidney architecture, leading to a loss of renal function that may necessitate renal replacement therapy and/or kidney transplantation. In experimental animal models for dominant and recessive forms of polycystic kidney disease, mammalian target of rapamycin (mTOR)-inhibitors such as rapamycin effectively reduced cyst growth and loss of renal function. Furthermore, an analysis of sirolimus-treated renal transplant ADPKD patients showed that cystic kidney volumes regressed. An interventional study has been initiated to investigate whether sirolimus retards cyst growth and slows renal functional deterioration in patients with ADPKD. This prospective study is an 18-month, controlled, open label clinical trial with 2 parallel groups of patients with ADPKD. The aim of the study is to investigate whether sirolimus used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. It is anticipated that the inhibition of mTOR with sirolimus can slow disease progression and delay the need for chronic renal replacement therapy. Preliminary study results are expected in 2010.