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Kidney

Going with the flow

A phase 3 clinical trial published in the New England Journal of Medicine (doi:10.1056/NEJMoa1205511) shows mixed results in the treatment of autosomal dominant polycystic kidney disease (ADPKD).

Credit: BSIP / Science Source

ADPKD is marked by renal fluid-filled cysts that eventually lead to kidney failure. Preclinical studies have suggested that the antidiuretic hormone vasopressin contributes to pathogenesis, and a previous 3-year open-label clinical trial showed that tolvaptan, a vasopressin receptor antagonist, reduces the rate of increase in kidney volume and the decline in glomerular filtration rate in 63 patients with ADPKD.

In the new study, Vincente E. Torres et al. report in a 3-year multicenter double-blind, placebo-controlled phase 3 clinical trial that tolvaptan had similar beneficial effects on 740 patients. But they also found that the tolvaptan-treated patients had more adverse events, such as increased thirst, increased urine production and hepatic injury. Overall approximately threefold more patients in the treated group discontinued the trial versus those in the placebo group.

Tolvaptan could eventually be approved to treat ADPKD, but clearly other treatment modalities are needed. Fortunately, basic research in this area has been proceeding well, and other targets are in the works.

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Levinson, R. Going with the flow. Nat Med 18, 1753 (2012). https://doi.org/10.1038/nm.3034

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