Rednor Samuel J, Ross Michael J
Division of Nephrology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, United States.
Department of Development and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States.
Front Med (Lausanne). 2018 Jun 7;5:177. doi: 10.3389/fmed.2018.00177. eCollection 2018.
HIV-associated nephropathy (HIVAN) is an important cause of secondary focal glomerulosclerosis that occurs primarily in persons of African ancestry with advanced HIV disease. Although HIVAN is characterized by severe proteinuria and rapid progression to end stage renal disease without treatment, the phenotype is markedly attenuated by treatment with antiretroviral medications. HIV infection of glomerular and tubular epithelial cells and subsequent viral gene expression is a key contributor to HIVAN pathogenesis and the kidney can serve as reservoir for HIV strains that differ those in blood. HIV gene expression in renal epithelial cells leads to dysregulation of cellular pathways including cell cycle, inflammation, cell death, and cytoskeletal homeostasis. Polymorphisms in the APOL1 gene explain the marked predilection of HIVAN to occur in persons of African descent and HIVAN. Since HIVAN has the strongest association with APOL1 genotype of any of the APOL1-associated nephropathies, studies to determine the mechanisms by which HIV and APOL1 risk variants together promote kidney injury hold great promise to improve our understanding of the pathogenesis of APOL1-mediated kidney diseases.
人类免疫缺陷病毒相关性肾病（HIVAN）是继发性局灶性节段性肾小球硬化的重要病因，主要发生于患有晚期HIV疾病的非洲裔人群。尽管HIVAN的特征是严重蛋白尿且未经治疗会迅速进展至终末期肾病，但抗逆转录病毒药物治疗可显著减轻其表型。肾小球和肾小管上皮细胞的HIV感染及随后的病毒基因表达是HIVAN发病机制的关键因素，肾脏可作为与血液中不同的HIV毒株的储存库。肾上皮细胞中的HIV基因表达导致包括细胞周期、炎症、细胞死亡和细胞骨架稳态在内的细胞途径失调。载脂蛋白L1（APOL1）基因多态性解释了HIVAN在非洲裔人群中显著的易感性。由于在所有与APOL1相关的肾病中，HIVAN与APOL1基因型的关联最为紧密，因此确定HIV和APOL1风险变异共同促进肾损伤的机制的研究，有望极大地增进我们对APOL1介导的肾脏疾病发病机制的理解。
