title: Impact of mammalian target of rapamycin inhibition on autosomal-dominant polycystic kidney disease.
abstract: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of countless cysts in both kidneys, which compress the cyst-free renal parenchyma, leading to a loss of renal function and the need for renal replacement therapy and/or kidney transplantation in ∼50% of affected patients. In animal models of experimental polycystic kidney disease, the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus effectively reduce cyst growth and loss of renal function. Furthermore, an analysis of renal transplant patients with ADPKD has shown that cystic kidney and liver volumes regress more on a sirolimus-based regimen than on a calcineurin inhibitor-based immunosuppressive regimen. Several prospective controlled clinical trials have been initiated to investigate whether mTOR inhibitors retard cyst growth and slow renal functional deterioration in patients with ADPKD. Study results are expected in 2010.
authors.affiliation: Division of Nephrology, University Hospital, Zürich, Switzerland. rudolf.wuethrich@usz.ch
authors.forename: R P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: A D
authors.initials: AD
authors.lastname: Kistler
authors.forename: A L
authors.initials: AL
authors.lastname: Serra
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000068338:Everolimus; D006801:Humans; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus