Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure

Abstract

Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V₂receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×10³clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×10³. Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).Conclusions:U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment. (Circ J 2014; 78: 2240–2249)