# Mononuclear phagocytes in the pathogenesis of acute kidney injury

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $456,571

## Abstract

Acute kidney injury (AKI) is a common and serious complication of medical and surgical diseases that has
significant attributable morbidity and mortality in critically ill patients. Analysis of outcomes data reported that
patients who develop AKI during a hospitalization are at substantial risk for the development of chronic kidney
disease within 1 year. Mononuclear phagocytes (MP), which consist of macrophages and dendritic cells, have
long been known to exist within the kidney. They are actively involved in maintenance of renal homeostasis
and, more importantly, the restoration of homeostasis after injury. We propose to study the role of MP in AKI
with the guiding hypothesis that the course and outcome of AKI is a function of the involvement of specific
subpopulations of MP, delineated on the basis of their embryonic origin and expression of genes associated
with macrophage function with respect to time post-injury. Intrarenal resident MP are a unique F4/80HiCD11bInt
subpopulation that constitute 50% of renal MP in normal kidneys and are distinct from monocyte derived MP
that arrive from the peripheral circulation. They initially arise from the fetal yolk sac, colonizing the kidney
during embryonic days 8.5-11 in mice and receive little to no further input from the circulation in normal
kidneys. Other subpopulations of renal MP arise from hematopoietic stem cells in the fetal liver and bone
marrow. Very little is known about the role of these F4/80HiCD11bInt resident renal MP in kidney homeostasis
and disease. Our preliminary bulk and single cell RNAseq data, flow cytometry analyses and morphological
studies indicate that resident renal MP follow a developmental program which encompasses a developmental
switch in the resident MP, exemplified by turning on expression of major histocompatibility complex (MHC)
class II between 7-21 days after birth. Notably, there is a reversion of resident renal MP to the MHC negative
phenotype shortly after AKI and preliminary RNAseq data indicate that resident renal MP secrete Wnt
glycoproteins, which are known to be intimately involved with kidney embryonic development. These findings
suggest there is at least partial recapitulation of a developmental program after injury, which has been
previously proposed, but never proven. Our central hypothesis is that renal resident MP undergo a
developmental program that is recapitulated, at least in part, following AKI. This developmental program is a
component of the mechanism of recovery from injury and could be involved in a failure to re-establish
homeostasis (i.e. unsuccessful or deranged repair) leading to CKD. To test this hypothesis, we will execute the
following specific aims: 1) To test the hypothesis that renal resident MP are an independent, self-renewing
subpopulation that receives no input from the peripheral circulation after AKI; 2) To test the hypothesis that
renal MP recapitulate a developmental program after AKI; 3) To test the hypothesis that the tra...

## Key facts

- **NIH application ID:** 10536615
- **Project number:** 5R01DK118932-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** ANUPAM AGARWAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $456,571
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536615

## Citation

> US National Institutes of Health, RePORTER application 10536615, Mononuclear phagocytes in the pathogenesis of acute kidney injury (5R01DK118932-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10536615. Licensed CC0.

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