# Kidney Injury by Cisplatin and Renoprotective Strategies.

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $417,004

## Abstract

Project Summary
The goal of this project is to investigate the long-term sequelae of cisplatin chemotherapy in kidneys.
Cisplatin is one of the most widely used and most potent cancer therapy drugs. However, cisplatin
chemotherapy is frequently associated with adverse side-effects in kidneys, resulting in acute kidney
injury and chronic kidney problems. While the past work has focused on acute kidney injury by cisplatin,
very little is known about the chronic or long-term effect of cisplatin treatment in kidneys. A major hurdle
in studying the long-term effect of cisplatin is the lack of appropriate animal models. But we and others
have recently established the mouse model of repeated low dose cisplatin treatment that leads to renal
fibrosis and chronic kidney disease, opening the door to the research of the long-term sequelae of
cisplatin chemotherapy in kidneys. Using this model, the current application will investigate autophagy
in renal fibrosis and chronic kidney disease following cisplatin treatment. The application is supported
by critical preliminary findings: (1) Following cisplatin treatment, autophagy is induced along with the
development of chronic kidney pathologies including renal fibrosis; (2) Autophagy inhibitors given after
cisplatin treatment can prevent the development of chronic kidney problems; (3) Renal tubular cells
may produce and secret specific profibrotic factors in an autophagy-dependent manner; and (4) At the
upstream, cisplatin treatment leads to the activation of p53 and hypoxia-inducible factor-1 (HIF-1), two
potential regulators of autophagy. Based on these findings, we hypothesize that: Cisplatin treatment
leads to the activation of p53 and HIF-1, which induce persistent autophagy in renal tubular cells.
Persistent autophagy then triggers a secretory phenotype in these tubular cells for the production and
secretion of profibrotic factors, which activate interstitial fibroblasts to promote renal fibrosis and the
progression to CKD. We will test this hypothesis by three Specific Aims: (1) test the hypothesis that
blockade of autophagy may ameliorate renal fibrosis and CKD following cisplatin treatment, while
enhancing chemotherapy in tumors; (2) test the hypothesis that p53 and/or HIF-1 contribute to
autophagy activation, renal fibrosis and CKD following cisplatin treatment; and (3) test the hypothesis
that renal tubular cells produce profibrotic factors in an autophagy-dependent manner for fibroblast
activation and fibrogenesis. Completion of the research will gain significant new insights into the long-
term side-effects of cisplatin treatment in kidneys. Moreover, by targeting autophagy and HIF-1, the
work may identify novel strategies that not only protect kidneys in cisplatin treatment but also enhance
chemotherapy in tumors.

## Key facts

- **NIH application ID:** 9914632
- **Project number:** 2R01DK087843-10
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Zheng Dong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,004
- **Award type:** 2
- **Project period:** 2010-09-30 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914632

## Citation

> US National Institutes of Health, RePORTER application 9914632, Kidney Injury by Cisplatin and Renoprotective Strategies. (2R01DK087843-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9914632. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*