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Sirolimus therapy to halt the progression of ADPKD

Norberto Perico1, Luca Antiga, Anna Caroli

  • 1Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.

Journal of the American Society of Nephrology : JASN
|May 15, 2010
PubMed

Insights

Sirolimus, an mTOR inhibitor, halted cyst growth and increased kidney parenchymal volume in autosomal dominant polycystic kidney disease (ADPKD) patients. Further studies are needed to confirm long-term benefits.

Area of Science:

  • Nephrology
  • Pharmacology
  • Genetics

Background:

  • Mammalian target of rapamycin (mTOR) pathway activation is implicated in autosomal dominant polycystic kidney disease (ADPKD) pathogenesis, potentially driving cell proliferation and cyst growth.
  • Understanding the role of mTOR in ADPKD progression is crucial for developing targeted therapies.

Purpose of the Study:

  • To evaluate the efficacy of mTOR inhibition using sirolimus in managing kidney volume and its components in patients with ADPKD.
  • To compare the effects of sirolimus versus conventional therapy on cyst and parenchymal volume changes over a 6-month period.

Main Methods:

  • A randomized, crossover study (The SIRENA Study) involving 21 ADPKD patients with GFR ≥ 40 ml/min/1.73 m².
  • Patients received either 6 months of sirolimus or conventional therapy, followed by a crossover to the alternative treatment.
  • Kidney volume, cyst volume, parenchymal volume, GFR, albuminuria, and proteinuria were monitored.

Main Results:

  • Sirolimus treatment resulted in stable cyst volume and a significant increase in parenchymal volume.
  • Conventional therapy led to an increase in both cyst and parenchymal volumes.
  • While total kidney volume increased less with sirolimus compared to conventional therapy, the difference was not statistically significant between treatments.
  • Aphthous stomatitis occurred in 10 of 15 patients completing the study but was manageable with topical treatment.

Conclusions:

  • Sirolimus demonstrated the ability to halt cyst growth and promote parenchymal volume expansion in ADPKD patients.
  • The long-term clinical significance of these findings requires further investigation.
  • Sirolimus did not significantly impact GFR but caused a marginal increase in albuminuria and proteinuria.

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