Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Clin J Am Soc Nephrol. 2011 Oct;6(10):2499-507. doi: 10.2215/CJN.03530411. Epub 2011 Sep 8.
Autosomal dominant polycystic kidney disease (ADPKD), a frequent cause of end-stage renal disease, has no cure. V2-specific vasopressin receptor antagonists delay disease progression in animal models.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a prospectively designed analysis of annual total kidney volume (TKV) and thrice annual estimated GFR (eGFR) measurements, from two 3-year studies of tolvaptan in 63 ADPKD subjects randomly matched 1:2 to historical controls by gender, hypertension, age, and baseline TKV or eGFR. Prespecified end points were group differences in log-TKV (primary) and eGFR (secondary) slopes for month 36 completers, using linear mixed model (LMM) analysis. Sensitivity analyses of primary and secondary end points included LMM using all subject data and mixed model repeated measures (MMRM) of change from baseline at each year. Pearson correlation tested the association between log-TKV and eGFR changes.
Fifty-one subjects (81%) completed 3 years of tolvaptan therapy; all experienced adverse events (AEs), with AEs accounting for six of 12 withdrawals. Baseline TKV (controls 1422, tolvaptan 1635 ml) and eGFR (both 62 ml/min per 1.73 m(2)) were similar. Control TKV increased 5.8% versus 1.7%/yr for tolvaptan (P < 0.001, estimated ratio of geometric mean 0.96 [95% confidence interval 0.95 to 0.97]). Corresponding annualized eGFR declined: -2.1 versus -0.71 ml/min per 1.73 m(2)/yr (P = 0.01, LMM group difference 1.1 ml/min per 1.73 m(2)/yr [95% confidence interval 0.24 to 1.9]). Sensitivity analyses including withdrawn subjects were similar, whereas MMRM analyses were significant at each year for TKV and nonsignificant for eGFR. Increasing TKV correlated with decreasing eGFR (r = -0.21, P < 0.01).
ADPKD cyst growth progresses more slowly with tolvaptan than in historical controls, but AEs are common.
常导致终末期肾病的常染色体显性多囊肾病（ADPKD）尚无治愈方法。V2 特异性加压素受体拮抗剂可延缓动物模型中的疾病进展。
设计、地点、参与者和测量方法：这是对托伐普坦两项 3 年研究中 63 例 ADPKD 患者的年度总肾体积（TKV）和每 3 次年度估计肾小球滤过率（eGFR）测量值进行的前瞻性分析，这些患者按性别、高血压、年龄和基线 TKV 或 eGFR 1:2 随机匹配至历史对照。使用线性混合模型（LMM）分析，规定了 36 个月完成者的 log-TKV（主要终点）和 eGFR（次要终点）斜率的组间差异。对主要和次要终点的敏感性分析包括使用所有受试者数据的 LMM 和每年基线变化的混合模型重复测量（MMRM）。Pearson 相关性检验了 log-TKV 和 eGFR 变化之间的关联。
51 例患者（81%）完成了 3 年托伐普坦治疗；所有患者均出现不良事件（AE），其中 6 例因 AE 退出。基线 TKV（对照组 1422ml，托伐普坦组 1635ml）和 eGFR（均为 62ml/min/1.73m2）相似。对照组 TKV 增加 5.8%，而托伐普坦组增加 1.7%/年（P<0.001，几何均数比估计值为 0.96[95%置信区间 0.95-0.97]）。相应的年度 eGFR 下降：-2.1 与-0.71ml/min/1.73m2/yr（P=0.01，LMM 组间差异 1.1ml/min/1.73m2/yr[95%置信区间 0.24-1.9]）。包括退出患者的敏感性分析相似，而每年的 MMRM 分析对 TKV 有统计学意义，对 eGFR 无统计学意义。TKV 增加与 eGFR 下降相关（r=-0.21，P<0.01）。
与历史对照相比，ADPKD 囊肿生长在托伐普坦治疗下进展更慢，但 AE 很常见。
