Urine osmolality, response to tolvaptan, and outcome in autosomal dominant polycystic kidney disease: Results from the TEMPO 3:4 trial

Olivier Devuyst, Arlene B. Chapman, Ron T. Gansevoort, Eiji Higashihara, Ronald D. Perrone, Vicente E. Torres, Jaime D. Blais, Wen Zhou, John Ouyang, Frank S. Czerwiec

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31 Scopus citations

Abstract

The vasopressin-cAMP-osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, andwhether change inUosmassociated with key trial end points.At baseline, lowerUosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200-300 mOsm/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renalbenefitoccurred in subjects achieving greater suppression of Uosm, that is, thosewithbetter eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.

Original languageEnglish (US)
Pages (from-to)1592-1602
Number of pages11
JournalJournal of the American Society of Nephrology
Volume28
Issue number5
DOIs
StatePublished - May 2017

ASJC Scopus subject areas

  • Nephrology

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    Devuyst, O., Chapman, A. B., Gansevoort, R. T., Higashihara, E., Perrone, R. D., Torres, V. E., Blais, J. D., Zhou, W., Ouyang, J., & Czerwiec, F. S. (2017). Urine osmolality, response to tolvaptan, and outcome in autosomal dominant polycystic kidney disease: Results from the TEMPO 3:4 trial. Journal of the American Society of Nephrology, 28(5), 1592-1602. https://doi.org/10.1681/ASN.2016040448