APOL1 Risk Variants Predict Histopathology and Progression to ESRD in HIV-Related Kidney Disease
APOL1 Risk Variants Predict Histopathology and Progression to ESRD in HIV-Related Kidney Disease
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DOI：
10.1681/asn.2011060562
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发表时间：
2012-02-01
影响因子：
13.6
通讯作者：
Skoreckis, Karl
中科院分区：
文献类型：
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作者：
Fine, Derek M.;Wasser, Walter G.;Skoreckis, Karl
随着抗逆转录病毒治疗的早期建立，除hiv相关肾病（HIVAN）以外的肾脏疾病在hiv感染者中占主导地位。这些疾病的结果在感染艾滋病毒的人群中通常更糟，但其原因尚不清楚。在这里，我们研究了APOL1风险变异在预测98例hiv感染非hiv肾病的非裔美国人肾脏组织病理学和进展到ESRD中的作用。我们使用生存分析来确定与APOL1基因型相关的ESRD时间。在29例有两个APOL1风险等位基因的患者中，大多数（76%）患有FSGS， 10%患有高血压性肾硬化。相比之下，在54例具有一个APOL1风险等位基因的患者中，47%的患者以免疫复合物GN为主要病变，只有23%的患者患有FSGS。在25例无APOL1风险等位基因的患者中，40%患有免疫复合物GN， 12%患有FSGS。在310人年的观察中，29名患者进展为ESRD。在校正分析中，具有两个APOL1风险等位基因的个体与具有一个或零风险等位基因的个体相比，发生ESRD的风险高出近三倍（P=0.03）。总之，这些数据证明了APOL1变异与非hiv肾病患者肾脏预后之间的关联，提示APOL1基因分型可能用于帮助指导hiv感染患者的护理。
With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.