UNC Kidney Center, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Department of Pathology, University of North Carolina, Chapel Hill, North Carolina.
Clin J Am Soc Nephrol. 2023 Mar 1;18(3):337-343. doi: 10.2215/CJN.0000000000000070. Epub 2023 Feb 8.
Disparity in CKD progression among Black individuals persists in glomerular diseases. Genetic variants in the apolipoprotein L1 ( APOL1 ) gene in the Black population contribute to kidney disease, but the influence in membranous nephropathy remains unknown.
Longitudinally followed participants enrolled in the Glomerular Disease Collaborative Network or Cure Glomerulonephropathy Network were included if they had DNA or genotyping available for APOL1 (Black participants with membranous nephropathy) or had membranous nephropathy but were not Black. eGFR slopes were estimated using linear mixed-effects models with random effects and adjusting for covariates and interaction terms of covariates. Fisher exact test, Kruskal-Wallis test, and Kaplan-Meier curves with log-rank tests were used to compare groups.
Among 118 Black membranous nephropathy participants, 16 (14%) had high-risk APOL1 genotype (two risk alleles) and 102 (86%) had low-risk APOL1 genotype (zero or one risk alleles, n =53 and n =49, respectively). High-risk APOL1 membranous nephropathy participants were notably younger at disease onset than low-risk APOL1 and membranous nephropathy participants that were not Black ( n =572). eGFR at disease onset was not different between groups, although eGFR decline (slope) was steeper in participants with high-risk APOL1 genotype (-16±2 [±SE] ml/min per 1.73 m 2 per year) compared with low-risk APOL1 genotype (-4±0.8 ml/min per 1.73 m 2 per year) or membranous nephropathy participants that did not identify themselves as Black (-2.0±0.4 ml/min per 1.73 m 2 per year) ( P <0.0001). Time to kidney failure was faster in the high-risk APOL1 genotype than low-risk APOL1 genotype or membranous nephropathy participants that were not Black.
The prevalence of high-risk APOL1 variant among Black membranous nephropathy participants is comparable with the general Black population (10%-15%), yet the high-risk genotype was associated with worse eGFR decline and faster time to kidney failure compared with low-risk genotype and participants that were not Black.
在肾小球疾病中，黑人群体的慢性肾脏病进展存在差异。载脂蛋白 L1（APOL1）基因中的遗传变异在黑人群体中导致肾脏疾病，但在膜性肾病中的影响尚不清楚。
如果参与者有 APOL1 的 DNA 或基因分型（黑人群体中的膜性肾病患者）或患有膜性肾病但不是黑人，则将参加肾小球疾病合作网络或治疗肾小球肾炎网络的纵向随访参与者纳入研究。使用带有随机效应的线性混合效应模型来估计 eGFR 斜率，并调整协变量和协变量交互项。使用 Fisher 确切检验、Kruskal-Wallis 检验和 Kaplan-Meier 曲线与对数秩检验来比较组间差异。
在 118 名黑人膜性肾病患者中，有 16 名（14%）为高风险 APOL1 基因型（两个风险等位基因），102 名（86%）为低风险 APOL1 基因型（零或一个风险等位基因，n=53 和 n=49）。与低风险 APOL1 和非黑人膜性肾病患者（n=572）相比，高风险 APOL1 膜性肾病患者的发病年龄明显更小。尽管高风险 APOL1 基因型组的 eGFR 下降（斜率）更陡峭（-16±2[±SE]ml/min/1.73m 2/年），但与低风险 APOL1 基因型组（-4±0.8ml/min/1.73m 2/年）或非黑人膜性肾病患者（-2.0±0.4ml/min/1.73m 2/年）相比，两组患者的疾病发病时 eGFR 并无差异（P<0.0001）。高风险 APOL1 基因型患者的肾功能衰竭时间快于低风险 APOL1 基因型或非黑人膜性肾病患者。
黑人膜性肾病患者中高风险 APOL1 变异的患病率与黑人总体人群（10%-15%）相当，但与低风险基因型和非黑人患者相比，高风险基因型与更严重的 eGFR 下降和更快的肾功能衰竭时间相关。
Zotero 插件