Abstract: SA-OR030
RNA Sequencing of Microdissected Kidney Biopsies Differentiates HIV+ FSGS from HIV-Negative FSGS
Session Information
- ANCA It Is
November 09, 2019 | Location: 207, Walter E. Washington Convention Center
Abstract Time: 06:18 PM - 06:30 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Zhang, Weijia, Icahn School of Medicine at Mount Sinai, Elmhurst, New York, United States
- Wyatt, Christina M., Duke University School of Medicine, Durham, North Carolina, United States
- Estrella, Michelle M., University of California, San Francisco and San Francisco VA Medical Center, San Francisco, California, United States
- Yi, Zhengzi, Icahn School of Medicine at Mount Sinai, Elmhurst, New York, United States
- Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States
- Godfrey, Brad A., University of Michigan, Ann Arbor, Michigan, United States
- Eichinger, Felix H., University of Michigan, Ann Arbor, Michigan, United States
- Atta, Mohamed G., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Fine, Derek M., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Rosenberg, Avi Z., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Ross, Michael J., Albert Einstein College of Medicine/ Montefiore Medical Center, Bronx, New York, United States
Background
Antiretroviral therapy (ART) has reduced the incidence of “classic” HIV-associated nephropathy (HIVAN), characterized by rapidly progressive proteinuric CKD from underlying collapsing focal glomerulosclerosis and severe tubulointerstitial (TI) disease including tubular microcysts. Whether FSGS without other histologic findings of HIVAN in HIV+ persons represents a partially treated HIVAN phenotype or FSGS unrelated to HIV infection is unclear. We therefore compared gene expression in kidney biopsies from HIV+ persons with non-HIVAN FSGS to biopsies from HIV- persons with FSGS.
Methods
27 kidney biopsies from HIV+ persons with FSGS were microdissected, and glomerular and TI RNA were analyzed by RNAseq. We compared RNA expression from these samples to that of 22 HIV-negative FSGS biopsies which were matched for eGFR, demographic, and histologic variables. RNAseq data were processed and analyzed using the pipeline consisting of raw data processing, normalization, batch correlation and differential analysis based on LIMMA test. Differentially expressed genes were subjected to enrichment analysis for gene ontology function and KEGG pathways.
Results
Principal component analysis demonstrated that glomerular and TI RNA from HIV+ FSGS biopsies clustered separately from HIV- FSGS biopsies. 1081 genes were differentially expressed by 1.5 fold in glomeruli from HIV+ vs. HIV- biopsies, and 607 genes were differentially expressed in TI from HIV+ vs. HIV- biopsies. Pathway analysis revealed that the predominant cellular pathways represented by differentially expressed genes from HIV+ biopsies have roles in metabolism, solute transport, and cell cycle regulation. HIV sequences were detected in the majority of HIV+ biopsies and were detected in more glomerular than TI samples.
Conclusion
These results suggest that FSGS occurring in HIV+ persons may have a different molecular pathogenesis than FSGS occurring in HIV- persons and may reflect residual effects of HIV not fully treated by ART. Future studies are needed to determine whether new treatment strategies targeting deleterious effects of HIV can improve kidney outcomes in this population.
Funding
- NIDDK Support