Lan Xiqian, Rao T K S, Chander Praveen N, Skorecki Karl, Singhal Pravin C
Hofstra North Shore-LIJ School of Medicine Long Island, NY, USA.
Department of Medicine, State University of New York Downstate Medical Center Brooklyn, NY, USA.
Front Microbiol. 2015 Jun 9;6:571. doi: 10.3389/fmicb.2015.00571. eCollection 2015.
In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in African-Americans (AAs). In 1980s, with the surge of Acquired Immune Deficiency Syndrome (AIDS) in AAs, HAN more or less disappeared, and the incidence of Human Immunodeficiency Virus associated Nephropathy (HIVAN) markedly increased. Recent studies in AAs have identified APOL1 variants (Vs) as a major risk factor for the development and progression of non-diabetic kidney diseases including idiopathic FSGS and hypertension-attributed nephrosclerosis. These observations have also offered partial insights into the mechanisms of development, and higher rate of occurrence of both HAN and HIVAN in AAs. AAs with APOL1Vs develop idiopathic FSGS at four-fold higher rate compared to European Americans (EAs). Similarly, HIV infected AAs with APOL1Vs (if not on antiviral therapy), risk a 50% (10-fold greater) chance of developing HIVAN. It has been suggested that APOL1Vs expression may render podocytes more vulnerable to various types of injury: bacterial, viral, and others. However, in addition to genetic variants, additional factors such as persistence of a second hit may determine the nature and severity of glomerular disease. In patients with HAN, heroin or contaminants may have been the offending second insult(s) which caused renal disease in susceptible AA patients. In the 80's, since heroin-induced second hit was neither consistent nor sustained (depending on drug availability in the street), the disease was masked or replaced HIV infected patients (especially in untreated subjects), by an overwhelming second hit by the virus which was both intense as well as persistent. It appears that APOL1Vs may be one of the links between the disappearance of HAN and emergence of HIVAN in AA patients.
20世纪70年代，海洛因相关性肾病（HAN）作为局灶节段性肾小球硬化（FSGS）的一种形式，是美国非裔（AA）终末期肾病（ESKD）的主要病因。20世纪80年代，随着美国非裔中获得性免疫缺陷综合征（AIDS）的激增，HAN或多或少消失了，而人类免疫缺陷病毒相关性肾病（HIVAN）的发病率显著增加。最近对美国非裔的研究已将载脂蛋白L1（APOL1）变异体（Vs）确定为包括特发性FSGS和高血压所致肾硬化在内的非糖尿病性肾脏疾病发生和进展的主要危险因素。这些观察结果也为美国非裔中HAN和HIVAN的发病机制及较高发病率提供了部分见解。携带APOL1变异体的美国非裔发生特发性FSGS的几率是欧洲裔美国人（EA）的四倍。同样，感染HIV且携带APOL1变异体的美国非裔（若未接受抗病毒治疗）发生HIVAN的风险增加50%（高出10倍）。有人提出，APOL1变异体的表达可能使足细胞更容易受到各种类型的损伤：细菌、病毒等。然而，除了基因变异外，其他因素如二次打击的持续存在可能决定肾小球疾病的性质和严重程度。在HAN患者中，海洛因或污染物可能是导致易感美国非裔患者发生肾脏疾病的有害二次打击因素。在20世纪80年代，由于海洛因引起的二次打击既不一致也不持续（取决于街头毒品的可得性），该疾病被掩盖或被HIV感染患者（尤其是未治疗的患者）取代，因为病毒造成的压倒性二次打击既强烈又持久。看来APOL1变异体可能是美国非裔患者中HAN消失和HIVAN出现之间的联系之一。
