HIV-associated nephropathy: pathogenesis

Abstract

Purpose of review HIV-associated nephropathy (HIVAN) is characterized histologically by a collapsing form of FSGS, microcystic tubular dilation, interstitial inflammation and fibrosis. In this review, we provide a summary of the current state of knowledge about the mechanisms involved in the pathogenesis of HIVAN. Recent Findings Two variants in the ApoL1 gene have been identified as the susceptibility alleles that account for a majority of the increased risk of FSGS and non-diabetic ESRD in Blacks. HIVAN1 and HIVAN 2 are the other host susceptibility genes that have been identified in animal models for HIVAN. HIV infects renal tubular epithelial cells likely through direct cell-cell transmission. Both in vivo and in vitro evidence suggests that nef and vpr are the key viral genes mediating HIVAN. Nef induces podocyte dysfunction whereas Vpr induces RTEC apoptosis. Summary HIVAN results from direct infection by HIV-1 and expression of viral genes, especially nef and vpr, in renal epithelial cells in a genetically susceptible host. The infected renal epithelium acts as a separate viral compartment from the blood and facilitates evolution of strains distant from blood. Dysregulation of several host cellular pathways, including those involved in cell cycle and apoptosis, ultimately results in the unique histopathological syndrome of HIVAN.

APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults

“…This scenario is proposed for renal disease associated with sickle cell disease, with collapsing nephropathy associated with lupus or HIV and with compromised graft survival after transplantation. [4][5][6][7][8][9] APOL1 risk variants are associated with earlier age of onset and progression to renal failure of subjects with FSGS, and prospective studies in the African American Study of Kidney Disease and Chronic Renal Insufficiency cohorts show that carriage of two APOL1 risk variants is associated with more rapid progression to clinical endpoints in persons with renal insufficiency at study entry. 2,3,5,7,8 Moreover, African-American participants without renal disease on enrolment in the ARIC study were more likely to develop CKD and to progress to renal failure if they had two APOL1 risk alleles, compared with those with no alleles or one allele.…”

In-Depth Review of Human Immunodeficiency Virus-Associated Nephropathy

“…Some pieces of evidence even suggested the existence of renal tropic strains of HIV (Ray et al, 1998). HIV has been proven to be able to replicate in the kidney even though the patients had achieved serological viral suppression from the combination antiretroviral therapy (Medapalli et al, 2011).…”

“…This finding adds to the evidence that podocyte genes are regulated by a network of other genes. In the presence of host susceptibility alleles, this network can be altered by HIV infection (Medapalli et al, 2011).…”

“…Those histological characteristics of HIVAN are collapsing form of FSGS, microcystic tubular dilation and interstitial inflammation and fibrosis (Medapalli et al, 2011). (Vashistha et al, 2008;Kapasi et al, 2002;Ross et al, 2005;2006a;2006b).…”

HIV-1 Pathogenesis: The Virus

“…Kidney: HIV-associated nephropathy can play a significant role in end-stage renal disease in infected people (Medapalli et al 2011). Infection of renal epithelial cells has been frequently invoked to explain this condition.…”