# Developing imaging nanoprobes to advance prognosis of kidney fibrosis

> **NIH NIH R03** · YALE UNIVERSITY · 2023 · $125,625

## Abstract

Project Summary
Chronic kidney disease (CKD) has a high global prevalence, estimated at 11-13%, and it is ranked third
highest for years of life lost due to premature mortality. Interstitial fibrosis is a chronic and progressive process
affecting kidneys during CKD progression, regardless of cause. It can disrupt kidney architecture, reduce blood
supply, disturb renal function, and ultimately cause kidney failure. Histologically, the degree of kidney interstitial
fibrosis correlates with the severity of CKD. Hence, assessment of kidney fibrosis can facilitate prognosis and
guide therapy in CKD progression. Currently, biopsy remains the gold standard for assessing kidney fibrosis,
but complications and limitations exist. Hence, novel noninvasive imaging probes or methods are in high
demand for the evaluation and follow-up of patients with CKD. Recently, we and others have shown that
macrophages play a key role in the progression of kidney fibrosis. Macrophage accumulation significantly
correlates with the degree of the extent of interstitial fibrosis and tubular atrophy in the mouse models of CKD
and in human kidney diseases and chronic allograft injury. Therefore, developing novel imaging probes to
noninvasively assess kidney interstitial profibrotic macrophages will help diagnose and quantify kidney fibrosis,
and thus be useful to prognosticate CKD progression. This proposal presents a potential shift in current
approaches to develop a novel molecular imaging probe that specifically target profibrotic macrophages in the
kidneys to sensitively and specifically report renal fibrosis in the course of CKD progression. Nanoparticles
have become increasingly attractive as a candidate tool to serve as effective diagnostic agents to reduce
undesirable systemic side effects and overcome several physical and physiological barriers following systemic
administration. Among these, dendrimers have become one of the most versatile compositionally and
structurally controlled nanoscale building blocks for use as contrast agents in the field of biomedical imaging.
To test this hypothesis, we propose to first engineer dendrimer nanoprobes that specifically target profibrotic
macrophages (Aim 1) and then to assess dendrimer nanoprobe efficacy for diagnosis and quantification of
kidney fibrosis in the mouse models of CKD (Aim 2). This application will provide us the opportunity to develop
innovative nanoprobes that can be tested preclinically to non-invasively report kidney fibrosis.

## Key facts

- **NIH application ID:** 10574964
- **Project number:** 1R03DK134791-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Leyuan Xu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $125,625
- **Award type:** 1
- **Project period:** 2023-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10574964

## Citation

> US National Institutes of Health, RePORTER application 10574964, Developing imaging nanoprobes to advance prognosis of kidney fibrosis (1R03DK134791-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10574964. Licensed CC0.

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