Peralta Carmen A, Bibbins-Domingo Kirsten, Vittinghoff Eric, Lin Feng, Fornage Myriam, Kopp Jeffrey B, Winkler Cheryl A
Department of Medicine, University of California, San Francisco, California; San Francisco VA Medical Center, San Francisco, California;
Department of Medicine, University of California, San Francisco, California;
J Am Soc Nephrol. 2016 Mar;27(3):887-93. doi: 10.1681/ASN.2015020124. Epub 2015 Jul 15.
Variants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m(2), and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6-22.1) for high-risk blacks, 7.8 (6.4-9.4) for low-risk blacks, and 3.9 (3.1-4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64-8.94) for high-risk blacks and 2.32 (1.73-3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86-1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors.
APOL1基因变异与黑人肾病相关。在年轻人冠状动脉风险发展研究(CARDIA研究)中,我们对3030名肾小球滤过率(GFR)正常的年轻人进行了研究,以探讨APOL1基因与蛋白尿发病及肾功能下降之间的关联。在定期检查时测量了基于胱抑素C的估算肾小球滤过率(eGFRcys)和白蛋白与肌酐比值。参与者包括白人(n = 1700)、高危黑人(两个APOL1风险等位基因,n = 176)和低危黑人(零/一个风险等位基因,n = 1154)。平均年龄为35岁,平均eGFRcys为每1.73平方米107毫升/分钟,13.2%的黑人有两个APOL1等位基因。15年间每1000人年蛋白尿的发病率(95%置信区间),高危黑人是15.6(10.6 - 22.1),低危黑人是7.8(6.4 - 9.4),白人为3.9(3.1 - 4.8)。与白人相比,高危黑人发生蛋白尿的比值比(95%置信区间)为5.71(3.64 - 8.94),低危黑人为2.32(1.73 - 3.13)。对风险因素进行校正后,低危黑人与白人之间的差异有所减弱(比值比1.21,95%置信区间0.86 - 1.71)。校正后,高危黑人在9.3年期间每年eGFRcys下降速度比白人快0.45%。与白人相比,低危黑人每年eGFRcys下降速度也更快,但在校正风险因素和社会经济地位后,这种差异有所减弱。总之,有两个APOL1风险等位基因的黑人在青年期发生蛋白尿和eGFRcys下降的风险最高,而低危黑人和白人之间的差异与传统风险因素的差异有关。