# Shared Mechanisms and Markers of Renal Injury and Neurocognitive Impairment in People with HIV

> **NIH NIH R03** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $80,500

## Abstract

PROJECT SUMMARY
 People with HIV (PWH) experience an unusually high burden of chronic, aging-related diseases, which have
major impact on functional status and quality of life. Chronic kidney disease (CKD) and neurocognitive
impairment (NCI) are two prototype disorders of aging that are frequently encountered in this population and
may be linked by a common underlying mechanism. While vascular and metabolic factors, in addition to altered
mitochondrial metabolism, chronic inflammation and oxidative stress, are implicated in CKD and NCI, the
possibility of shared mechanisms that drive development of multiple such disorders in the same individual has
not been sufficiently explored. Altered iron metabolism is a fundamental hallmark of aging that links several
important aspects of the aging process - inflammation, reduced mitochondrial function, and oxidative stress -
and our team has identified levels of a critically important iron-binding protein (ferritin) subunit as an independent
predictor of neurocognitive function in a longitudinal study of NCI in PWH on suppressive therapy. Preliminary
data link this protein also to CKD in the same individuals. The newly identified receptor in brain for this protein is
also expressed in kidney and doubles as a marker of chronic kidney injury (Kim-1), possibly playing a role in
CKD. We therefore propose that an HIV-related shift in the ratio of ferritin subunits may explain several aging
phenomena in PWH, due to the critical role of one of the subunits in antioxidant responses, immune-cell function,
and mitochondrial energy metabolism. In 324 participants from an observational HIV cohort with a wealth of
outcome data and biospecimens, we will measure ferritin subunit levels in serum and urinary Kim-1. Specifically,
we plan the following: AIM 1: Evaluate associations between ferritin subunit levels, sensitive markers of oxidative
stress, and existing plasma metabolite levels in virologically suppressed PWH; AIM 2: Assess associations
between urinary Kim-1 and ferritin subunit levels, and evaluate Kim-1 as a noninvasive marker of NCI; AIM 3:
Determine associations of ferritin subunits with prevalent and incident CKD, NCI, and frailty outcomes, which are
ascertained in this cohort of middle-aged and older PWH, adjusting for important confounders. Results from this
proof-of-concept study could significantly improve our understanding of accentuated aging in PWH, highlighting
new markers and targets for intervention.

## Key facts

- **NIH application ID:** 10013426
- **Project number:** 1R03MH123291-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** ASHA R KALLIANPUR
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $80,500
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013426

## Citation

> US National Institutes of Health, RePORTER application 10013426, Shared Mechanisms and Markers of Renal Injury and Neurocognitive Impairment in People with HIV (1R03MH123291-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10013426. Licensed CC0.

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