# Optimal Management of HIV Infected Adults at Risk for Kidney Disease in Nigeria

> **NIH NIH U01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $586,149

## Abstract

PROJECT SUMMARY: Persons of African descent have a disproportionate risk for several forms of kidney
disease including diabetic nephropathy, arterionephrosclerosis (hypertension-attributed kidney disease), focal
segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy (HIVAN), a distinct form of FSGS.
Kopp and Winkler et al have shown that variants in the apolipoprotein-1 (APOL1) gene confer sizeable odds
ratios (OR) for FSGS (OR = 17), HIVAN (OR = 29 in the US; 89 in South Africa), and hypertension-attributed
kidney disease (OR = 7). These variants are present only on African-origin chromosomes and represent an
evolutionary protective mechanism against African trypanosomiasis. The presence of these risk genotypes is
highest in West Africa, and specifically in Nigeria among persons of Hausa, Fulani, Igbo, and Asante descent.
Markers of kidney disease include microalbuminuria, proteinuria, and/or reduced estimated glomerular filtration
rate (eGFR). All three have been associated with increased mortality in HIV-infected adults. Increased urinary
albumin excretion has diagnostic and prognostic value in the initial identification and confirmation of renal
disease, and changes in albuminuria can be useful in assessing the effectiveness of therapy as well as the
progression of the disease. The renin-angiotensin aldosterone system (RAAS) is recognized as the central
player in the pathophysiology of CKD based on numerous clinical trials in diabetics. The blockade of RAAS
with angiotensin converting enzyme inhibitors (ACE-I) is a well-recognized strategy to slow down renal disease
progression in diabetic patients with CKD. Aldosterone, together with angiotensin II, has been shown to
mediate oxidative stress, inflammation and tissue fibrosis. Therefore by more aggressively blocking RAAS via
the addition of an aldosterone receptor antagonist to an ACE-I, one may be able to elicit a more potent and
durable response thereby altering their risk trajectory for the development of potentially serious kidney
complications. To evaluate this at-risk population more in-depth and to determine the optimal means to reduce
their risk for renal complications, we plan to screen 2,200 HIV-infected adults receiving suppressive ART (≥ 6
months) at the Aminu Kano Teaching Hospital; to conduct the following Specific Aims:
1) To determine the prevalence of APOL1 variants and assess whether their presence correlates with
 prevalent albuminuria, median eGFR, and/or CKD.
2) To assess whether RAAS inhibition (with the ACE-I lisinopril) compared to placebo will significantly
 reduce the risk of kidney complications; and
3) To evaluate whether more aggressively blocking the RAAS system via the addition of the
 mineralocorticoid antagonist spironolactone (in addition to lisinopril) is an even more potent means of
 sustainably reducing the risk of kidney complications in this population.

## Key facts

- **NIH application ID:** 10003837
- **Project number:** 5U01DK112271-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Muktar Hassan Aliyu
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $586,149
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003837

## Citation

> US National Institutes of Health, RePORTER application 10003837, Optimal Management of HIV Infected Adults at Risk for Kidney Disease in Nigeria (5U01DK112271-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10003837. Licensed CC0.

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