Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease
Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease
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DOI：
10.1007/s10157-022-02192-2
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发表时间：
2022-02-14
影响因子：
2.3
通讯作者：
Nitta, Kosaku
中科院分区：
文献类型：
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作者：
Akihisa, Taro;Kataoka, Hiroshi;Nitta, Kosaku
托伐普坦是一种抗利尿激素V2受体拮抗剂，用于治疗常染色体显性多囊肾病（ADPKD）。虽然托伐普坦可以抑制疾病进展，但一些报告研究了与治疗反应相关的因素。估计肾小球滤过率（eGFR）降低后不久托伐普坦开始。我们研究了初始eGFR下降是否会影响患者的肾脏预后。方法采用单中心、回顾性观察队列研究。83例开始使用托伐普坦的ADPKD患者被选中。我们分析了初始eGFR变化与临床参数的关系，并利用单变量和多变量线性回归分析了eGFR年度变化对肾脏预后的价值。结果初始eGFR变化为- 4.6 +/- 8.0%/月。多变量分析中，初始eGFR变化与年度eGFR变化呈显著相关，提示初始eGFR变化下降幅度越大，肾脏预后越好。此外，游离水（FEH2O）分数排泄（FE）的变化与初始eGFR变化呈正相关。FEH2O和尿素氮FE （FEUN）显著升高；而FE钠（fea）水平保持不变。在大约一半的患者中，fea出乎意料地下降。结论最初的eGFR下降可能是由于托伐普坦的药理作用抑制肾小球高滤过和/或由于潜在的体积耗损而减少肾血浆流量引起的。初始eGFR变化反映了托伐普坦的作用，在临床实践中易于评估，可作为预测托伐普坦治疗患者肾脏预后的临床指标之一。
Background Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. Methods This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. Results The initial eGFR change was - 4.6 +/- 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. Conclusions The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.