Rosenberg Alix T, Flaherty Carina, Anderson Amanda H, Appel Lawrence J, Coresh Josef, He Jiang, Lash James P, Liu Celina, Rao Panduranga S, Taliercio Jonathan, Surapaneni Aditya, Grams Morgan E
Division of Precision Medicine, Department of Medicine, New York University, New York, New York.
Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Alabama, Birmingham, Alabama.
Clin J Am Soc Nephrol. 2025 Jan 1;20(1):23-30. doi: 10.2215/CJN.0000000000000575. Epub 2024 Nov 5.
Apolipoprotein L1 (APOL1) high-risk genotype had higher risk of 3-year GFR-related surrogate end points and long-term kidney failure than those with the low-risk genotype. No consistent difference in surrogate–clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1 kidney disease.
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 ()-associated kidney disease.
This random-effects meta-analysis included Black participants in the Atherosclerosis Risk in Communities study (=3071), Chronic Renal Insufficiency Cohort (=998), and African American Study of Kidney Disease and Hypertension (=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 m per year decline in GFR. Clinical outcomes included kidney failure requiring KRT, heart failure, cardiovascular disease, and death after 3 years.
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 high-risk genotype. Participants with the 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 risk status.
Individuals with the 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 genotype, supporting the use of surrogates in -associated kidney disease.
与载脂蛋白L1（APOL1）低风险基因型相比，APOL1高风险基因型发生3年肾小球滤过率（GFR）相关替代终点和长期肾衰竭的风险更高。APOL1基因型在替代终点与临床结局的关联方面无一致差异，这支持在APOL1肾病中使用替代终点。
肾衰竭临床结局的替代终点已获美国食品药品监督管理局认可。然而，它们尚未在载脂蛋白L1（APOL1）相关肾病中得到专门评估。
这项随机效应荟萃分析纳入了社区动脉粥样硬化风险研究（n = 3071）、慢性肾功能不全队列研究（n = 998）和非裔美国人肾病与高血压研究（n = 609）中的黑人参与者。替代终点包括3年内GFR下降30%和40%、尿蛋白肌酐比翻倍以及GFR每年下降超过3 ml/min/1.73 m²。临床结局包括需要肾脏替代治疗（KRT）的肾衰竭、心力衰竭、心血管疾病以及3年后的死亡。
非裔美国人肾病与高血压研究中22%、慢性肾功能不全队列研究中18%以及社区动脉粥样硬化风险研究中13%的参与者具有APOL1高风险基因型。具有APOL1高风险基因型的参与者发生所有3年GFR结局的风险更高，但尿蛋白肌酐比未翻倍，且3年后发生肾衰竭的风险更高。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也有较弱但具有统计学意义的关联。APOL1风险状态在短期和长期临床结局的关联方面无差异。
与APOL1低风险基因型个体相比，APOL1高风险基因型个体更易发生3年GFR相关终点和长期肾衰竭。APOL1基因型在短期临床结局关联方面无一致差异，这支持在APOL1相关肾病中使用替代终点。
