Higashihara Eiji, Matsukawa Miyuki, Jiang Huan
Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Medical Affairs, Otsuka Pharmaceutical Co., Ltd., Osaka, Japan.
Clin Exp Nephrol. 2025 May;29(5):638-649. doi: 10.1007/s10157-024-02589-1. Epub 2025 Jan 2.
Despite of long-lasting tolvaptan treatment, individual renal outcomes are unclear in autosomal dominant polycystic kidney disease (ADPKD). This post-hoc analysis of the TEMPO 3:4 trial aimed to evaluate the predictability of estimated height-adjusted total kidney volume growth rate (eHTKV-α) on renal outcomes.
In TEMPO 3:4, 1445 patients with ADPKD were randomised to tolvaptan or placebo for 3 years. The present analysis included patients with total kidney volume (TKV) data available at baseline and month 12 (tolvaptan, n = 812; placebo, n = 453); tolvaptan-assigned patients were grouped into quartiles based on percent change in eHTKV-α from baseline at 1 year. Clinical parameters were compared between quartiles, and regression analyses evaluated the predictive value of 1-year percent change in eHTKV-α and other factors on annual changes in TKV and estimated GFR (eGFR) over 3 years.
Trend tests identified significant differences between quartiles for several baseline parameters. Multivariate regression models confirmed that 1-year percent change in eHTKV-α was a significant predictor of annual changes in both TKV and eGFR over 3 years. Other significant predictors of annual changes in TKV and eGFR over 3 years were sex, age and body mass index, and first-year change in eGFR, race and baseline eGFR, respectively. Predicting factors using urine osmolality and plasma copeptin levels were not significant by backward stepwise selection analysis.
1-year percent change in eHTKV-α is useful biomarker to identify treatment good responders and may be utilized for early estimate of trial outcomes of new drugs in ADPKD.
尽管托伐普坦进行了长期治疗，但常染色体显性遗传性多囊肾病（ADPKD）患者的个体肾脏预后仍不明确。本项对TEMPO 3:4试验的事后分析旨在评估估计的身高校正后总肾体积增长率（eHTKV-α）对肾脏预后的预测能力。
在TEMPO 3:4试验中，1445例ADPKD患者被随机分为托伐普坦组或安慰剂组，治疗3年。本分析纳入了基线和第12个月有总肾体积（TKV）数据的患者（托伐普坦组，n = 812；安慰剂组，n = 453）；根据1年时eHTKV-α相对于基线的变化百分比，将接受托伐普坦治疗的患者分为四分位数组。对四分位数组之间的临床参数进行比较，并通过回归分析评估1年时eHTKV-α的变化百分比及其他因素对3年期间TKV和估计肾小球滤过率（eGFR）年度变化的预测价值。
趋势检验确定了几个基线参数在四分位数组之间存在显著差异。多变量回归模型证实，1年时eHTKV-α的变化百分比是3年期间TKV和eGFR年度变化的显著预测指标。3年期间TKV和eGFR年度变化的其他显著预测指标分别为性别、年龄和体重指数，以及eGFR的第一年变化、种族和基线eGFR。通过向后逐步选择分析，使用尿渗透压和血浆 copeptin 水平的预测因素不显著。
1年时eHTKV-α的变化百分比是识别治疗有效应答者的有用生物标志物，可用于早期评估ADPKD新药的试验结果。
