Perrone Ronald D, Mouksassi Mohamad-Samer, Romero Klaus, Czerwiec Frank S, Chapman Arlene B, Gitomer Berenice Y, Torres Vicente E, Miskulin Dana C, Broadbent Steve, Marier Jean F
Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA.
Pharsight, Montreal, Quebec, Canada.
Kidney Int Rep. 2017 Jan 16;2(3):442-450. doi: 10.1016/j.ekir.2017.01.003. eCollection 2017 May.
Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. TKV is a promising imaging biomarker for tracking and predicting the natural history of autosomal dominant polycystic kidney disease. The prognostic value of TKV was evaluated, in combination with age and eGFR, for the outcomes of 30% decline in eGFR and progression to ESRD. Observational data including 2355 patients with TKV measurements were available.
Multivariable Cox models were developed to assess the prognostic value of age, TKV, height-adjusted TKV, eGFR, sex, race, and genotype for the probability of a 30% decline in eGFR or ESRD.
TKV was the most important prognostic term for 30% decline in eGFR in autosomal dominant polycystic kidney disease patients with and without preserved baseline eGFR. For a 40-year-old subject with preserved eGFR (70 ml/min per 1.73 m), the adjusted hazard ratios for a 30% decline in eGFR were 1.86 (95% CI, 1.65-2.10) for a 2-fold larger TKV (600 vs. 1200 ml) and 2.68 (95% CI, 2.22-3.24) for a 3-fold larger TKV (600 vs. 1800 ml), respectively. Hazard ratios for progression to ESRD for 2- and 3-fold larger TKV were 1.72 (95% CI, 1.49-1.99) and 2.36 (95% CI, 1.88-2.97), respectively.
The capability to predict 30% decline in eGFR is a novel aspect of this study. TKV was formally qualified, both by FDA and EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline in renal function for inclusion in interventional clinical trials.
常染色体显性遗传性多囊肾病是最常见的遗传性肾病。肾总体积（TKV）是用于追踪和预测常染色体显性遗传性多囊肾病自然病程的一种很有前景的影像学生物标志物。结合年龄和估算肾小球滤过率（eGFR），评估了TKV对eGFR下降30%及进展至终末期肾病（ESRD）结局的预后价值。可获得包括2355例有TKV测量值患者的观察性数据。
建立多变量Cox模型，以评估年龄、TKV、身高校正的TKV、eGFR、性别、种族和基因型对eGFR下降30%或ESRD发生概率的预后价值。
在基线eGFR正常和不正常的常染色体显性遗传性多囊肾病患者中，TKV是eGFR下降30%最重要的预后指标。对于一名40岁且eGFR正常（70 ml/min/1.73 m²）的受试者，TKV增大2倍（600 vs. 1200 ml）时，eGFR下降30%的校正风险比为1.86（95%CI，1.65 - 2.10）；TKV增大3倍（600 vs. 1800 ml）时，校正风险比为2.68（95%CI, 2.22 - 3.24）。TKV增大2倍和3倍时进展至ESRD的风险比分别为1.72（95%CI，1.49 - 1.99）和2.36（95%CI，1.88 - 2.97）。
预测eGFR下降30%的能力是本研究的一个新方面。TKV已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的正式认可，作为一种预后富集生物标志物，用于选择肾功能进行性下降高危患者纳入干预性临床试验。
