Walz, Gerd and Budde, Klemens and Mannaa, Marwan and Nuernberger, Jens and Wanner, Christoph and Sommerer, Claudia and Kunzendorf, Ulrich and Banas, Bernhard and Hoerl, Walter H. and Obermueller, Nicholas and Arns, Wolfgang and Pavenstaedt, Hermann and Gaedeke, Jens and Buechert, Martin and May, Christoph and Gschaidmeier, Harald and Kramer, Stefan and Eckardt, Kai-Uwe (2010) Everolimus in Patients with Autosomal Dominant Polycystic Kidney Disease. NEW ENGLAND JOURNAL OF MEDICINE, 363 (9). pp. 830-840. ISSN 0028-4793,
Full text not available from this repository. (Request a copy)Abstract
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 m(2) 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. (Funded by Novartis; EudraCT number, 2006001485-16; ClinicalTrials.gov number, NCT00414440.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PRIMARY CILIUM; ADPKD; PROGRESSION; CYSTOGENESIS; INHIBITION; PATHWAY; VOLUME; MODEL; MTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2020 09:35 |
| Last Modified: | 15 Jul 2020 09:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24308 |
Actions (login required)
 |
View Item |
