Abstract | BACKGROUND: 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).
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Authors | Giovanni Stallone, Barbara Infante, Giuseppe Grandaliano, Christos Bristogiannis, Luca Macarini, Daniela Mezzopane, Francesca Bruno, Eustacchio Montemurno, Annalisa Schirinzi, Massimo Sabbatini, Antonio Pisani, Tiziana Tataranni, Francesco Paolo Schena, Loreto Gesualdo |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 27
Issue 9
Pg. 3560-7
(Sep 2012)
ISSN: 1460-2385 [Electronic] England |
PMID | 22785114
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antihypertensive Agents
- Immunosuppressive Agents
- Ribosomal Protein S6 Kinases, 70-kDa
- Ramipril
- Sirolimus
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Topics |
- 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, etiology, metabolism)
- Male
- Middle Aged
- Phosphorylation
- Polycystic Kidney, Autosomal Dominant
(complications, drug therapy, metabolism)
- Prognosis
- Prospective Studies
- Ramipril
(therapeutic use)
- Ribosomal Protein S6 Kinases, 70-kDa
(metabolism)
- Sirolimus
(therapeutic use)
- Young Adult
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