Wearne Nicola, Manning Kathryn, Price Brendon, Rayner Brian L, Davidson Bianca, Jones Erika Sw, Spies Ruan, Cunningham Carol, Omar Aadil, Ash Samantha, Bohmer Raphaela, Kennedy Luca, Post Frank
Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.
Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa.
Kidney Int Rep. 2023 Feb 23;8(5):1087-1096. doi: 10.1016/j.ekir.2023.02.1076. eCollection 2023 May.
Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury.
This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005-2009), tenofovir disoproxil (TDF) introduction (2010-2012), TDF-based fixed dose combination (2013-2015), and ART at HIV diagnosis (2016-2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID).
We included 671 participants (median age 36, interquartile range, 21-44 years; 49% female; median CD4 cell count 162 [interquartile range, 63-345] cells/mm). Over time, ART (31%-65%, < 0.001), rate of HIV suppression (20%-43%, < 0.001), nonelective biopsies (53%-72%, < 0.001), and creatinine at biopsy (242-449 μmol/l, < 0.001) increased. A decrease in HIVAN (45%-29% < 0.001) was accompanied by an increase in TID (13%-33%, < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89-4.73 < 0.001).
As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.
撒哈拉以南非洲地区仍然面临着人类免疫缺陷病毒(HIV)感染负担最重、结核病(TB)流行以及接受抗逆转录病毒治疗(ART)的HIV感染者(PWH)数量不断增加等挑战,所有这些都可能导致肾损伤。
这项观察性队列研究描述了2005年至2020年期间南非PWH的肾脏疾病谱。在4个时间段对肾活检进行了分析,具体如下:ART早期推广阶段(2005 - 2009年)、替诺福韦二吡呋酯(TDF)引入阶段(2010 - 2012年)、基于TDF的固定剂量复方制剂阶段(2013 - 2015年)以及HIV诊断时即开始ART阶段(2016 - 2020年)。采用逻辑回归分析来确定与HIV相关肾病或局灶节段性肾小球硬化(HIVAN/FSGS)以及肾小管间质疾病(TID)相关的因素。
我们纳入了671名参与者(中位年龄36岁,四分位间距为21 - 44岁;49%为女性;中位CD4细胞计数为162[四分位间距为63 - 345]个/mm)。随着时间推移,接受ART治疗的比例(31% - 65%,<0.001)、HIV抑制率(20% - 43%,<0.001)、非选择性活检比例(53% - 72%,<0.001)以及活检时的肌酐水平(242 - 449μmol/l,<0.001)均有所增加。HIVAN比例下降(45% - 29%,<0.001),同时TID比例上升(13% - 33%,<0.001)。肉芽肿性间质性肾炎占TID的48%,主要原因是结核病。接触TDF与TID密切相关(调整后的优势比为2.99,95%置信区间为1.89 - 4.73,<0.001)。
随着ART项目的强化以及TDF使用的增加,PWH的肾脏组织学谱从ART早期以HIVAN为主演变为近期以TID为主。TID的增加可能是由于包括结核病、败血症、TDF以及其他损伤在内的多种暴露因素所致。