# Effect of Chronic HIV Infection on Progression of Kidney Disease (MSSM)

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $410,888

## Abstract

PROJECT SUMMARY: 
With the widespread use of combination antiretroviral agents, the incidence of HIV-associated 
nephropathy (HIVAN) has dramatically decreased in the recent years. Yet, the prevalence of chronic 
kidney disease (CKD) and end-stage renal disease (ESRD) in HIV sero-positive patients remains 
high, suggesting that HIV-positive patients are at increased risk for a variety of acute and chronic 
kidney diseases. Indeed, several lines of evidence from recent epidemiological and animal model 
studies indicate that concurrent HIV infection and age-related comorbidities, such as diabetes 
mellitus, have a synergistic effect on the incidence of chronic kidney disease, thereby necessitating 
an examination of mechanisms by which HIV infection accelerates the progression of CKD such as 
diabetic kidney disease (DKD). We have recently shown that the upregulation of local inflammation 
induced by HIV aggravates the progression of DKD through increased transcriptional activities of NF- 
κB and STAT3, indicating that HIV-induced chronic inflammation may predispose and excerbate the 
course of non-HIV related CKD. We have also shown that SIRT1 histone deacetylase is a key 
modulator of the transcriptional activities of NF-κB and STAT3 in diabetic kidneys, suggesting that 
pro-inflammatory responses that drive CKD progression may share a common pathway. We 
therefore posit that SIRT1 is a central modulator of chronic HIV infection-induced inflammation 
through deacetylation of key transcription factors such as NF-κB and STAT3, and that the regulation 
of SIRT1 and NF-κB may be effective therapeutic approaches against HIV-induced CKD. Using small 
molecule agonist of SIRT1 and antagonist of NF-κB, and novel transgenic mouse models, we 
propose to determine the role of SIRT1 in regulating HIV-mediated cellular injuries in diabetic 
kidneys. Our results will provide a better understanding of the underlying molecular mechanisms by 
which chronic HIV infection accelerates the progression of CKD and a proof-of-concept for novel 
target treatment for CKD in HIV patients.

## Key facts

- **NIH application ID:** 10155095
- **Project number:** 5P01DK056492-21
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** John Cijiang He
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,888
- **Award type:** 5
- **Project period:** 1999-09-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155095

## Citation

> US National Institutes of Health, RePORTER application 10155095, Effect of Chronic HIV Infection on Progression of Kidney Disease (MSSM) (5P01DK056492-21). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10155095. Licensed CC0.

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