title: Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study.
abstract: BACKGROUND
  Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD.
  
  
  METHODS
  This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus.
  
  
  CONCLUSIONS
  The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD.
authors.affiliation: Clinic for Nephrology, University Hospital, CH-8091 Zürich, Switzerland. andreas.serra@usz.ch
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Kistler
authors.forename: Diane
authors.initials: D
authors.lastname: Poster
authors.forename: Marian
authors.initials: M
authors.lastname: Struker
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Dominik
authors.initials: D
authors.lastname: Weishaupt
authors.forename: Frank
authors.initials: F
authors.lastname: Tschirch
mesh_terms: D000293:Adolescent; D000328:Adult; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D010865:Pilot Projects; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis* / Q000188:drug therapy*; D020123:Sirolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus