rogates in APOL1 kidney disease. Background Surrogate end points for the clinical outcome of kidney failure have been accepted by the US Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 (APOL1)-associated kidney disease. Methods This random-effects meta-analysis included Black participants in the Atherosclerosis Risk in Communities study (N=3071), Chronic Renal Insufficiency Cohort (N=998), and African American Study of Kidney Disease and Hypertension (N=609). Surrogate end points included a 3-year 30% and 40% decline in GFR, doubling of urine protein–creatinine ratio, and >3 ml/min per 1.73 m2 per year decline in GFR. Clinical outcomes included kidney failure requiring KRT, heart failure, cardiovascular disease, and death after 3 years. Results 22% in the African American Study of Kidney Disease and Hypertension, 18% in the Chronic Renal Insufficiency Cohort, and 13% in the Atherosclerosis Risk in Communities study had the APOL1 high-risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all 3-year GFR outcomes but not doubling of urine protein–creatinine ratio, as well as kidney failure after 3 years. The 3-year outcomes were strongly associated with kidney failure with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status. Conclusions Individuals with the APOL1 high-risk genotype were more susceptible to 3-year GFR-related end points and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1-associated kidney disease....

中文翻译：

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载脂蛋白 L1 相关肾病的替代终点：三个队列的评估


在 APOL1 肾病中 rogates。背景 肾功能衰竭临床结果的替代终点已被美国食品和药物管理局接受。然而，它们尚未在载脂蛋白 L1 （APOL1） 相关肾病中进行特异性评估。方法 该随机效应荟萃分析包括社区动脉粥样硬化风险研究 （N=3071）、慢性肾功能不全队列 （N=998） 和非裔美国人肾脏疾病和高血压研究 （N=609） 的黑人参与者。替代终点包括 GFR 的 3 年下降 30% 和 40%，尿蛋白-肌酐比值翻倍，以及 GFR 每年每 1.73 m2 下降 >3 ml/min。临床结局包括需要 KRT 的肾衰竭、心力衰竭、心血管疾病和 3 年后死亡。结果 在非裔美国人肾脏病和高血压研究中，22% 的人、慢性肾功能不全队列中 18% 的人和社区动脉粥样硬化风险研究中 13% 的人具有 APOL1 高危基因型。具有 APOL1 高危基因型的参与者发生所有 3 年 GFR 结局的风险较高，但尿蛋白-肌酐比值没有翻倍，3 年后肾功能衰竭的风险更高。3 年结局与肾衰竭密切相关，与心力衰竭、心血管疾病和死亡率的发生相关性较弱但具有统计学意义。APOL1 风险状态的短期和长期临床结局之间的关联没有差异。结论 与 APOL1 低风险基因型个体相比，具有 APOL1 高危基因型的个体更容易出现 3 年 GFR 相关终点和长期肾功能衰竭。 APOL1 基因型的短期临床结果关联没有一致的差异，支持在 APOL1 相关肾病中使用替代物。