Atta Mohamed G, Estrella Michelle M, Skorecki Karl L, Kopp Jeffrey B, Winkler Cheryl A, Wasser Walter G, Shemer Revital, Racusen Lorraine C, Kuperman Michael, Foy Matthew C, Lucas Gregory M, Fine Derek M
Departments of Medicine and
Departments of Medicine and.
Clin J Am Soc Nephrol. 2016 Feb 5;11(2):262-70. doi: 10.2215/CJN.07490715. Epub 2015 Dec 14.
Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation.
The addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology.
APOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.
既往研究表明,载脂蛋白L1(APOL1)风险等位基因与HIV阳性黑人发生HIV相关性肾病和局灶节段性肾小球硬化(FSGS)的风险增加有关。我们试图确定APOL1高风险基因型是否能在传统临床因素的基础上进一步改善对这些潜在病变的预测。
设计、地点、参与者及测量方法:在一项横断面研究中,我们分析了203例HIV阳性黑人的数据,这些患者在1996年至2011年间接受了肾活检,并对APOL1 G1和G2等位基因进行了基因分型。使用受试者工作特征曲线以及带有交叉验证的自抽样分析,将包含传统临床因素的预测逻辑回归模型与同时包含APOL1基因型的模型进行比较。
在预测模型中,将APOL1基因型添加到与HIV相关的肾病风险因素中,可改善对非HIV相关性肾病FSGS的预测,具体而言,c统计量从0.65增加到0.74(P=0.04)。尽管两个风险等位基因与HIV相关性肾病的较高几率显著相关,但APOL1基因型并未在该特定组织病理学的预测中进一步增加预测价值。
在预测HIV阳性黑人潜在的FSGS谱系病变时,APOL1基因型可能为传统临床变量提供额外的诊断信息。相比之下,尽管APOL1风险基因型可预测HIV相关性肾病,但其c统计量不足以用于鉴别诊断,无法消除肾活检在HIV阳性且有肾病性蛋白尿或不明原因肾病的黑人临床治疗中的作用。