• DOI:10.1056/NEJMoa1003491
• Corpus ID: 205092156

Everolimus in patients with autosomal dominant polycystic kidney disease.

@article{Walz2010EverolimusIP,
  title={Everolimus in patients with autosomal dominant polycystic kidney disease.},
  author={Gerd Walz and Klemens Budde and Marwan Mannaa and Jens N{\"u}rnberger and Christoph Wanner and Claudia Sommerer and Ulrich Kunzendorf and Bernhard Banas and Walter Hermann H{\"o}rl and Nicholas Obermüller and Wolfgang W Arns and Hermann Pavenst{\"a}dt and Jens Gaedeke and M B{\"u}chert and Christoph May and Harald Gschaidmeier and Stefanie Kramer and Kai-Uwe Eckardt},
  journal={The New England journal of medicine},
  year={2010},
  volume={363 9},
  pages={
          830-40
        }
}

• G. Walz, K. Budde, +15 authors K. Eckardt
• Published 25 August 2010
• Medicine, Biology
• The New England journal of medicine

BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a slowly progressive hereditary disorder that usually leads to end-stage renal disease. Although the underlying gene mutations were identified several years ago, efficacious therapy to curtail cyst growth and prevent renal failure is not available. Experimental and observational studies suggest that the mammalian target of rapamycin (mTOR) pathway plays a critical role in cyst growth.

METHODS
In this 2-year, double-blind trial, we randomly assigned 433 patients with ADPKD to receive either placebo or the mTOR inhibitor everolimus. The primary outcome was the change in total kidney volume, as measured on magnetic resonance imaging, at 12 and 24 months.

RESULTS
Total kidney volume increased between baseline and 1 year by 102 ml in the everolimus group, versus 157 ml in the placebo group (P=0.02) and between baseline and 2 years by 230 ml and 301 ml, respectively (P=0.06). Cyst volume increased by 76 ml in the everolimus group and 98 ml in the placebo group after 1 year (P=0.27) and by 181 ml and 215 ml, respectively, after 2 years (P=0.28). Parenchymal volume increased by 26 ml in the everolimus group and 62 ml in the placebo group after 1 year (P=0.003) and by 56 ml and 93 ml, respectively, after 2 years (P=0.11). The mean decrement in the estimated glomerular filtration rate after 24 months was 8.9 ml per minute per 1.73 m2 of body-surface area in the everolimus group versus 7.7 ml per minute in the placebo group (P=0.15). Drug-specific adverse events were more common in the everolimus group; the rate of infection was similar in the two groups.

CONCLUSIONS
Within the 2-year study period,as compared with placebo, everolimus slowed the increase in total kidney volume of patients with ADPKD but did not slow the progression of renal impairment [corrected]. (Funded by Novartis; EudraCT number, 2006-001485-16; ClinicalTrials.gov number, NCT00414440.)