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Novel criteria of urine osmolality effectively predict response to tolvaptan in decompensated heart failure patients--association between non-responders and chronic kidney disease
University of Tokyo, Japan .
University of Tokyo, Japan .
University of Tokyo, Japan .
University of Tokyo, Japan .
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2013 (English)In: Circulation Journal, ISSN 1346-9843, E-ISSN 1347-4820, Vol. 77, no 2, 397-404 p.Article in journal (Refereed) Published
Abstract [en]


A newly-developed vasopressin type 2 receptor antagonist, tolvaptan (TLV), has a unique feature of diuresis, but the response to this drug can be unpredictable.


Data were collected from hospitalized patients with decompensated congestive heart failure who were administered TLV at 3.75-15 mg/day (n=61). A responder/non-responder to TLV was determined as having any increase/decrease in urine volume (UV) during the next 24h after TLV treatment on the first day. Logistic regression analyses for increases in UV were performed, and independent predictors of the responder were the following: C1, baseline urine osmolality (U-OSM) >352 mOsm/L; and C2, %decrease in U-OSM >26% at 4-6h after TLV administration. Criteria consisting of C1 and C2 had a good predictability for responders by receiver-operating characteristic analysis (area under the curve=0.960). Kidneys of the non-responders no longer had diluting ability (%decrease of U-OSM at 4-6h=2.7 ± 14.6%*), but also barely kept concentrating ability (baseline U-OSM=296.4 ± 68.7*mOsm/L) with markedly reduced estimated glomerular filtration ratio (35.5 ± 29.4 m l · min(-1) · 1.73 m(-2)*) (*P<0.05 vs. patients who had at least 1 positive condition [n=42]).


More than 26% decrease in U-OSM from a baseline >352 mOsm/L for the first 4-6h predicts responders to TLV. Unresponsiveness to TLV is attributable to nephrogenic diabetes insipidus complicated by chronic renal disease.

Place, publisher, year, edition, pages
Japanese Circulation Society , 2013. Vol. 77, no 2, 397-404 p.
Keyword [en]
Nephrogenic diabetes insipidus; Renal dysfunction; Vasopressin
National Category
Health Sciences
URN: urn:nbn:se:liu:diva-111188DOI: 10.1253/circj.CJ-12-0971ISI: 000314263000022PubMedID: 23131721OAI: diva2:754510

Funding Agencies|FUGAKU trust for medicinal research; Japan Society for the Promotion of Science [224943]; Japan Society for the Promotion of Science (JSPS) through its Funding Program for World-Leading Innovative RandD on Science and Technology (FIRST Program)

Available from: 2014-10-10 Created: 2014-10-10 Last updated: 2014-10-20Bibliographically approved

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Kato, Naoko
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