Tolvaptan Prolongs Blockage of the Vasopressin Type II Receptor Over 24 Hours in Responders With Stage D Heart Failure
Tolvaptan Prolongs Blockage of the Vasopressin Type II Receptor Over 24 Hours in Responders With Stage D Heart Failure
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DOI：
10.1536/ihj.15-297
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发表时间：
2016-01-01
影响因子：
1.5
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Imamura, Teruhiko;Kinugawa, Koichiro;Komuro, Issei
尿水通道蛋白-2（U-AQP 2）水平相对于血浆精氨酸加压素（P-AVP）水平是对加压素2型受体（V2 R）拮抗剂托伐普坦（TLV）反应性的新预测因子。然而，很少有关于TLV处理后U-AQP 2的浓度-时间曲线的报道。我们评估了24例失代偿性D期心力衰竭（HF）患者，这些患者接受了3.75 mg/d TLV治疗，持续> 7天，以治疗传统利尿剂难治性充血。17例患者为TLV应答者，其24小时尿量（UV）在TLV开始后增加;其他7例患者为TLV无应答者。TLV应答者的U-AQP 2（经尿肌酐浓度校正）在TLV给药后4小时显著降低，但在第7天早晨未恢复至第1天早晨水平。即使在TLV治疗之前，TLY-非应答者U-AQP 2水平仍然较低。在第7天早晨，TLV应答者的U-AQP 2/P-AVP比值与TLV无应答者的U-AQP 2/P-AVP比值相当。在18例患者（11例应答者和7例无应答者）中，第7天TLV谷浓度为64 +/- 62 ng/mL，与估计的肾小球滤过率（eGFR）呈负相关。在患有晚期心力衰竭和慢性肾病的TLV应答者中，TLV在24小时内对V2 R具有拮抗作用，可能是由于血液TLV浓度持续升高。TLV无应答者对TLV的无应答并非吸收不良所致。
The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV). However, little has been reported about the concentration-time profile of U-AQP2 after TLV treatment. We evaluated 24 patients with decompensated stage D heart failure (HF) who had received 3.75 mg/day of TLV on a de novo basis for > 7 days to treat congestion refractory to conventional diuretics. Seventeen patients were TLV-responders, whose 24-hour urine volume (UV) increased after TLV initiation; the other 7 patients were TLV-non-responders. The U-AQP2 of the TLV-responders, corrected for the urine creatinine concentration, decreased significantly at 4 hours after TLV administration without returning to the day-1 morning level on the morning of day-7. The TLY-non-responder U-AQP2 levels remained low even before the TLV treatment. On the morning of day-7, the TLV-responder U-AQP2/P-AVP ratio was comparable to that of the TLV-non-responders. Among 18 patients (11 responders and 7 non-responders), the day-7 TLV trough concentration was 64 +/- 62 ng/mL and was negatively correlated with the estimated glomerular filtration rate (eGFR). TLV has antagonistic effects on the V2R over 24 hours in TLV-responders with advanced heart failure and chronic kidney disease, probably due to persistently elevated blood TLV concentration. The unresponsiveness to TLV in the TLV-non-responders is not attributable to malabsorption.