Advances in the pathogenesis of HIV-associated kidney diseases Michael J. Ross  Kidney International  Volume 86, Issue 2, Pages 266-274 (August 2014) DOI: 10.1038/ki.2014.167 Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 1 HIV RNA is present in tubular epithelial cells in HIV-associated nephropathy (HIVAN) as detected by RNA in situ hybridization. Adapted from Marras et al.10 with permission. Kidney International 2014 86, 266-274DOI: (10.1038/ki.2014.167) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 2 Proposed mechanism of transfer of HIV from lymphocytes to tubular epithelial cells. HIV proviral DNA integrated in the lymphocyte genomic DNA (A) is transcribed to RNA (B) and exported to the cytoplasm where viral proteins are synthesized. Viruses then assemble and bud from the plasma membrane (C). Viruses are transferred from lymphocytes to tubular epithelial cells at sites of cell contact into endosomal compartment (D) and subsequently released into the cytosol (E) and viral genes are expressed in the recipient cell (F). It remains unclear whether this viral transfer can result in viral integration and production of infectious virions (G) and whether viral transfer occurs across apical versus basolateral membrane, or both. Kidney International 2014 86, 266-274DOI: (10.1038/ki.2014.167) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 3 Diagram depicting general mechanisms by which HIV infection of podocytes can promote glomerular injury. GFR, glomerular filtration rate. Kidney International 2014 86, 266-274DOI: (10.1038/ki.2014.167) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 4 Tenofovir-induced nephrotoxicity is characterized by proximal tubular injury, which is often accompanied by intracytoplasmic inclusions that appear reddish on hematoxylin and eosin (a) and trichrome staining (b). These inclusions correspond to accumulation of markedly enlarged mitochondria with loss of mitochondrial cristae in proximal tubular cells as visualized by transmission electron microscopy (c). Adapted from Herlitz et al.110 with permission. Kidney International 2014 86, 266-274DOI: (10.1038/ki.2014.167) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 5 In addition to glomerular filtration, tenofovir is cleared via tubular secretion, which is mediated predominantly by basolateral uptake via organic ion transporter (OAT)1 and apical efflux via multidrug resistance-associated protein4 (MRP4), which can be inhibited by probenecid113 and diclofenac,114 respectively. Some studies also suggested a role for OAT3 in basolateral tenofovir transport.108 Kidney International 2014 86, 266-274DOI: (10.1038/ki.2014.167) Copyright © 2014 International Society of Nephrology Terms and Conditions