种族、APOL1 风险变异体与老年人临床结局：ARIC 研究。
Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study.
机构信息
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
出版信息
J Am Geriatr Soc. 2021 Jan;69(1):155-163. doi: 10.1111/jgs.16797. Epub 2020 Sep 7.
BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and self-reported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study.
DESIGN
Observational longitudinal cohort study.
SETTING
The Atherosclerosis Risk in Communities (ARIC) study.
PARTICIPANTS
Community-dwelling older adults (mean age = 75.8 years; range = 66-90 years).
RESULTS
Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFR ) below 60 mL/min/1.73 m at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFR and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFR , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86).
CONCLUSION
Among older Black adults, APOL1 high-risk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.
背景/目的：APOL1 高危基因型增加了患肾病的风险，但它们在老年人中的临床意义尚不清楚。我们旨在确定 APOL1 基因型状况（高危=2 个风险等位基因；低危=0-1 个风险等位基因）和自我报告的种族（黑人；白人）是否与参与社区为基础的队列研究的老年人的住院次数、新发慢性肾脏病（CKD）、终末期肾病（ESRD）和死亡率有关。
设计
观察性纵向队列研究。
地点
动脉粥样硬化风险社区（ARIC）研究。
参与者
居住在社区的老年人（平均年龄=75.8 岁；范围=66-90 岁）。
结果
在 5564 名 ARIC 参与者中（78.2%为白人，19.1%为 APOL1 低危黑人，2.7%为 APOL1 高危黑人），基线时肌酐和胱抑素 C 估算肾小球滤过率（eGFR）低于 60mL/min/1.73m2 的比例分别为 40.6%、34.8%和 43.2%。在平均 5.1 年的随访中，APOL1 高危黑人患 ESRD 的风险比低危黑人高 2.67 倍（95%置信区间[CI]：1.05-6.79），在调整年龄和性别后。在进一步调整基线 eGFR 和白蛋白尿后，这种关联不再显著（风险比[HR]=1.08；95%CI=.39-2.96）。APOL1 基因型状态与住院率以及死亡率和新发 CKD 的风险无显著差异。与白人相比，黑人在调整年龄、性别、eGFR 和白蛋白尿后，新发 CKD 和 ESRD 的风险分别高出 1.85 倍和 3.45 倍。在进一步调整临床/社会经济因素和 APOL1 基因型后，这些关联仍然存在（新发 CKD：HR=1.38；95%CI=1.06-1.81；ESRD：HR=3.20；95%CI=1.16-8.86）。
结论
在老年黑人中，APOL1 高危基因型与较低的肾功能相关，因此 ESRD 的风险较高。老年时肾脏疾病的种族差异仍然存在，并且不能完全用 APOL1 来解释。
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