# Impact of Clonal Hematopoiesis on the Progression of Kidney Disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $740,540

## Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is a newly recognized disorder characterized by the
ontogenesis of a genetically distinct, proliferative clonal leukocyte population. The prevalence of CHIP increases
with older age and is associated not only with risk of hematologic cancers, but with fibrosis, systemic
inflammation, and atherosclerotic cardiovascular diseases. Recapitulation of CHIP in mice by transplantation of
clonal leukocytes results in accelerated atherosclerosis, cardiac fibrosis and direct tissue infiltration of clonal
macrophages and stimulation of interstitial fibrosis.
Age is a dominant risk factor for chronic kidney disease (CKD), which is associated with accelerated
cardiovascular disease, premature death, and progression to dialysis dependence. The biological mechanisms
conferring this age-associated risk are incompletely understood. The final common pathologic process in
progressive CKD is tubulointerstitial fibrosis, which is characterized by the accumulation of inflammatory
infiltrates and fibroblasts within the kidney interstitium and permanent loss of tubular epithelial cells.
Tubulointerstitial fibrosis also represents the central underlying lesion in the progression of acute kidney injury
(AKI) to chronic disease.
Based on mechanistic links between CHIP and atherogenesis, kidney interstitial inflammation, and fibrosis, we
hypothesize that CHIP is a novel biological risk factor for CKD progression. To test this hypothesis, we propose
to determine the associations of CHIP with kidney disease progression in established cohorts of CKD and AKI.
In parallel, we propose to delineate potential causal mechanisms using recognized animal models of chronic
and acute kidney disease.
The identification of clonal leukocytes as a novel mechanism of CKD progression would represent a new disease
pathway that could motivate future targeted interventions.

## Key facts

- **NIH application ID:** 10419907
- **Project number:** 1R01DK132155-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** RAYMOND C. HARRIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $740,540
- **Award type:** 1
- **Project period:** 2022-04-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419907

## Citation

> US National Institutes of Health, RePORTER application 10419907, Impact of Clonal Hematopoiesis on the Progression of Kidney Disease (1R01DK132155-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10419907. Licensed CC0.

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