Rapamycin for treatment of type I autosomal dominant polycystic kidney disease (RAPYD-study): a randomized, controlled study

Nephrol Dial Transplant. 2012 Sep;27(9):3560-7. doi: 10.1093/ndt/gfs264. Epub 2012 Jul 10.


Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. An inappropriate stimulation of mammalian target of rapamycin may represent the converging point in the molecular pathways leading to renal cyst growth.

Methods: The primary objectives of this prospective, open-label, randomized clinical trial were to assess whether rapamycin may reduce the progressive increase in single cyst and total kidney volume in type I ADPKD and the decline in renal function and to identify the optimal rapamycin dose. Fifty-five patients with type I ADPKD were enrolled and randomized to receive ramipril (Group A), ramipril + high-dose rapamycin (Group B, trough level 6-8 ng/mL) and ramipril + low-dose rapamycin (Group C, trough levels 2-4 ng/mL). Rapamycin efficacy was monitored measuring p70 phosphorylation in peripheral blood mononuclear cells.

Results: Both rapamycin doses significantly reduced p70 phosphorylation. Nevertheless, total kidney volume increased in all groups after 24 months, although only in Groups A and B, was the final volume significantly higher compared with the baseline. Single cyst final volume was not significantly different in the three groups, although it was increased in Group A compared with the baseline, whereas in Groups B and C, it was significantly reduced. We did not observe any difference in renal function at 24 months among the three study groups. Group A presented a significant worsening of renal function that remained stable in both Groups B and C.

Conclusions: Our study would suggest that rapamycin does not influence the progression of type I ADPKD, although the higher drug dose tested prevented both the increase in kidney volume and the worsening of renal function (RAPYD-study, EUDRACT No. 2007-006557-25).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Diseases, Cystic / drug therapy*
  • Kidney Diseases, Cystic / etiology
  • Kidney Diseases, Cystic / metabolism
  • Male
  • Middle Aged
  • Phosphorylation
  • Polycystic Kidney, Autosomal Dominant / complications
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Prognosis
  • Prospective Studies
  • Ramipril / therapeutic use
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Sirolimus / therapeutic use*
  • Young Adult


  • Antihypertensive Agents
  • Immunosuppressive Agents
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Ramipril
  • Sirolimus