托伐普坦与肾水通道蛋白-2丰度在慢性肾脏病患者容量超负荷管理中的作用
Tolvaptan and the role of kidney aquaporin-2 abundance in managing volume overload in patients with CKD.
作者信息
Yan Yu, Li Xiao-Min, Yang Yan, Wang Feng-Mei, Liu Hong, Tang Ri-Ning, Zhang Xiao-Liang, Liu Bi-Cheng, Wang Bin
机构信息
Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, China.
Department of Pharmacy, Zhongda Hospital, Southeast University, Nanjing, China.
出版信息
Clin Kidney J. 2024 Oct 4;17(10):sfae303. doi: 10.1093/ckj/sfae303. eCollection 2024 Oct.
OBJECTIVE
This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients.
METHODS
CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc., were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan.
RESULTS
Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output ( < .001) and weight reduction ( < .001). At day 7, Group T maintained more significant diuretic effects ( < .001). More Group C patients required ultrafiltration therapy ( = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy.
CONCLUSION
Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy.This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html).
目的
本回顾性研究评估了托伐普坦在治疗慢性肾脏病（CKD）患者容量超负荷方面的疗效、安全性及预测指标。
方法
纳入2022年3月1日至2023年12月31日在东南大学附属中大医院接受治疗的单纯使用襻利尿剂或联合托伐普坦治疗的容量超负荷CKD患者。患者分为襻利尿剂组（C组）和襻利尿剂联合托伐普坦组（T组）。主要结局包括用药后1周内的容量控制、体重变化、尿量及实验室参数变化。记录高钠血症、高钾血症等不良事件。我们进一步对肾活检组织进行免疫组化染色，以研究集合管中水通道蛋白2（AQP2）和血浆白蛋白在预测托伐普坦疗效中的作用。
结果
174例容量超负荷的CKD患者中，男性108例（67.07%）。C组和T组各87例。基线时，尿量和体重无显著差异。至第3天，T组尿量增加更多（<0.001），体重减轻更多（<0.001）。至第7天，T组维持更显著的利尿效果（<0.001）。更多C组患者需要超滤治疗（P = 0.040）。不良事件发生率无显著差异。值得注意的是，集合管中AQP2的表达可能预测托伐普坦的反应性，而血浆白蛋白不影响疗效。
结论
托伐普坦在治疗CKD患者容量超负荷方面显示出疗效和安全性。集合管中AQP2的表达可预测托伐普坦的疗效。本研究方案已获得东南大学附属中大医院伦理委员会批准（批准号：2023ZDSYLL180-P01，临床试验注册号：ChiCTR2300075274，试验注册链接：https://www.chictr.org.cn/guide.html）。
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