Imamura Teruhiko, Kinugawa Koichiro, Fujino Takeo, Inaba Toshiro, Maki Hisataka, Hatano Masaru, Yao Atsushi, Komuro Issei
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo.
Circ J. 2014;78(9):2240-9. doi: 10.1253/circj.cj-14-0244. Epub 2014 Jun 20.
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 ≥0.5×10(3)clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×10(3). 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).
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.
肾集合管功能的保留可能是对加压素V2受体拮抗剂托伐普坦（TLV）产生反应的关键，但对TLV反应的预测因素尚不清楚。方法与结果：回顾性纳入60例初治接受TLV治疗的D期失代偿性心力衰竭（HF）患者（TLV(+)组）。其中，41例患者根据TLV开始治疗后尿量（UV）增加被定义为反应者。在UV定义的反应者中，血浆精氨酸加压素（P-AVP）与尿水通道蛋白-2（U-AQP2；5.42±3.54 ng/ml；r=0.843，P<0.001）密切相关。相比之下，19例为UV定义的无反应者，无论P-AVP水平如何，他们的U-AQP2极低（0.76±0.59 ng/ml，与反应者相比P<0.001）。在受试者工作特征分析中，U-AQP2/P-AVP≥0.5×10(3)能清晰区分UV定义的反应者与无反应者。然后我们将U-AQP2/P-AVP≥0.5×10(3)的患者定义为AQP定义的反应者。检查了60例倾向评分匹配的未接受TLV治疗的HF患者，并选择了与AQP定义的反应者数量完全相同的患者（n=41）。在2年观察期内，这些未接受TLV治疗的患者的生存率低于接受TLV治疗的反应者（73.8%对94.8%，P=0.034）。结论：U-AQP2/P-AVP是失代偿性HF患者对TLV反应的新预测指标。AQP定义的反应者接受TLV治疗可能有更好的预后。
