Renal disease in HIV-infected patients has evolved over the 3 decades since the outset of the infection. Whereas HIV-associated nephropathy (HIVAN) manifesting collapsing glomerulopathy, tubular microcysts and endothelial tubuloreticular inclusions predominated early in the epidemic, the incidence of HIVAN has declined following the introduction of anti- retroviral therapy. Despite this trend, the incidence of ESRD has remained unchanged, reflecting the development of other histopathology. This proposal will explore the long-term consequences of HIV infection in the kidney beyond HIVAN. The role of Core B will be to provide technical and interpretative support in light microscopy, immunohistochemistry, immunofluorescence and electron microscopy in mouse and human kidney tissues for all projects.
For Specific Aim 1, archived kidney biopsy tissue from HIV positive patients will be selected based on histopathologic diagnosis for investigation of inflammatory pathways identified in the in vitro models using immunohistochemistry and immunofluorescence.
In Specific Aim 2, renal pathology in Tg26 mice with different intestinal microbiome will be evaluated and immunostaining performed to quantify immune cell infiltrates.
For Specific Aim 3, the hypothesis that chronic HIV infection promotes comorbid disease though enhanced pro- inflammatory response via SIRT-1-regulated NF-kB and STAT3 acetylation and mitochondrial injury will be investigated in murine kidneys and validated in human kidney tissues. Core B will collaborate with the Clinical Core to identify appropriate kidney biopsy samples from the Core C repository or from anonymized archived samples in the Columbia biopsy database as needed.
Project Relevance The proposed research has important implications for the health of individuals living with chronic HIV infection. The Histopathology Core will support research to characterize the contribution of chronic HIV infection to the increased risk of kidney disease in HIV-infected individuals. This research will be particularly relevant to African-Americans, who have a disproportionate burden of both HIV infection and chronic kidney disease.
|Gu, Xiangchen; Mallipattu, Sandeep K; Guo, Yiqing et al. (2017) The loss of Krüppel-like factor 15 in Foxd1+ stromal cells exacerbates kidney fibrosis. Kidney Int 92:1178-1193|
|Achhra, Amit C; Mocroft, Amanda; Ross, Michael et al. (2017) Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial. Int J Antimicrob Agents 50:453-460|
|Fan, Ying; Xiao, Wenzhen; Lee, Kyung et al. (2017) Inhibition of Reticulon-1A-Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development. J Am Soc Nephrol 28:2007-2021|
|Sheets, Kerry M; Atta, Mohamed G; Fine, Derek M et al. (2017) Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications. J Acquir Immune Defic Syndr 75:45-51|
|Fan, Ying; Zhang, Jing; Xiao, Wenzhen et al. (2017) Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy. Sci Rep 7:323|
|Corona-Villalobos, Celia P; Shlipak, Michael G; Tin, Adrienne et al. (2017) Predictors of Acute Renal Injury Study (PARIS) among HIV-positive individuals: design and methods. BMC Nephrol 18:289|
|Wei, Chengguo; Li, Li; Menon, Madhav C et al. (2017) Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis. J Am Soc Nephrol 28:1385-1393|
|Koech, M K; Owiti, M O G; Owino-Ong'or, W D et al. (2017) Absence of HIV-Associated Nephropathy Among Antiretroviral Naive Adults With Persistent Albuminuria in Western Kenya. Kidney Int Rep 2:159-164|
|He, Li; Fan, Ying; Xiao, Wenzhen et al. (2017) Febuxostat attenuates ER stress mediated kidney injury in a rat model of hyperuricemic nephropathy. Oncotarget 8:111295-111308|
|Fu, Jia; Wei, Chengguo; Lee, Kyung et al. (2016) Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes. J Am Soc Nephrol 27:1006-14|
Showing the most recent 10 out of 104 publications