Novel Criteria of Urine Osmolality Effectively Predict Response to Tolvaptan in Decompensated Heart Failure Patients

Abstract

Background: A newly-developed vasopressin type 2 receptor antagonist,tolvaptan (TLV), has a unique feature of diuresis, but the response tothis drug can be unpredictable.Methods and Results: Data were collected from hospitalized patients withdecompensated congestive heart failure who were administered TLV at3.75-15 mg/day (n=61). A responder/non-responder to TLV was determinedas having any increase/decrease in urine volume (UV) during the next 24h after TLV treatment on the first day. Logistic regression analyses forincreases in UV were performed, and independent predictors of theresponder were the following: C1, baseline urine osmolality (U-OSM) >352mOsm/L; and C2, %decrease in U-OSM >26% at 4-6 h after TLVadministration. Criteria consisting of Cl and C2 had a goodpredictability for responders by receiver-operating characteristicanalysis (area under the curve=0.960). Kidneys of the non-responders nolonger had diluting ability (%decrease of U-OSM at 4-6 h=2.7 +/-14.6\%{*}), but also barely kept concentrating ability (baselineU-OSM=296.4 +/- 68.7{*} mOsm/L) with markedly reduced estimatedglomerular filtration ratio (35.5 +/- 29.4 ml.min(-1).1.73 m(-2){*})({*}P<0.05 vs. patients who had at least 1 positive condition {[}n=42]).Conclusions: More than 26% decrease in U-OSM from a baseline >352mOsm/L for the first 4-6 h predicts responders to TLV. Unresponsivenessto TLV is attributable to nephrogenic diabetes insipidus complicated bychronic renal disease. (Circ J 2013; 77: 397-404)