Advances in the pathogenesis of HIV-associated kidney diseases

Abstract

Despite improved outcomes among persons living with HIV who are treated with antiretroviral therapy, they remain at increased risk for acute and chronic kidney diseases. Moreover, since HIV can infect renal epithelial cells, the kidney might serve as a viral reservoir that would need to be eradicated when attempting to achieve full virologic cure. In recent years, much progress has been made in elucidating the mechanism by which HIV infects renal epithelial cells and the viral and host factors that promote development of kidney disease. Polymorphisms in APOL1 confer markedly increased risk of HIV-associated nephropathy; however, the mechanism by which ApoL1 variants may promote kidney disease remains unclear. HIV-positive persons are at increased risk of acute kidney injury, which may be a result of a high burden of subclinical kidney disease and/or viral factors and frequent exposure to nephrotoxins. Despite the beneficial effect of antiretroviral therapy in preventing and treating HIVAN, and possibly other forms of kidney disease in persons living with HIV, some of these medications, including tenofovir, indinavir, and atazanavir can induce acute and/or chronic kidney injury via mitochondrial toxicity or intratubular crystallization. Further research is needed to better understand factors that contribute to acute and chronic kidney injury in HIV-positive patients and to develop more effective strategies to prevent and treat kidney disease in this vulnerable population.

HIV in the dialysis population: Current issues and future directions

“…Histologically, HIVAN was characterized by a collapsing pattern of FSGS with proliferation of glomerular epithelial cells, as well as microcystic dilation of renal tubules and interstitial inflammation. Further investigation revealed that HIVAN was secondary to direct infection of renal epithelial cells by HIV, with evidence of viral genome expression in the kidney . There is strong epidemiologic evidence that initiation of ART can improve outcomes of patients with HIVAN, reducing the progression to dialysis‐dependence .…”

Epigenetic Modulation of Human Podocyte Vitamin D Receptor in HIV Milieu

“…Environmental factors associated with diabetic nephropathy such as hyperhomocysteinemia, dyslipidemia, inflammation, and oxidative stress are known to induce DNA methylation (3-5). Several of these factors are also present in patients with HIV-associated nephropathy (HIVAN) (6, 7); however, the role of epigenetic factors in the development of HIVAN has not been studied so far (8). The renin angiotensin system (RAS) has been shown to play important roles in the development and progression of HIVAN (9-13).…”

Persistent proteinuria as an indicator of renal disease in HIV-infected children

“…Children with HIVAN who had mesangial hyperplasia showed slower progression towards ESRD, so the incidence of proteinuria was more common in teenagers. 2 Other studies showed that proteinuria occurred in a younger age group. 31 Age is not the sole cause of persistent proteinuria, as other factors, including the degree of immunological suppression and provision of ARV also affect proteinuria.…”

“…Nevertheless, patients with human immunodeficiency virus (HIV) have an increased risk of diseases that affect multiorgan systems, including kidney disease. 1,2 Renal abnormalities in HIV patients consist of chronic HIV-associated nephropathy (HIV-associated chronic nephropathy), including HIV-associated nephropathy (HIVAN), HIV-related immune complex disease (HIVICK), as well as thrombotic microangiopathy (TMA-HIV) and diseases related to opportunistic infections. HAART has been beneficial in slowing renal involvement and the rapid progression to endstage renal disease.…”