# Kidney Tubule Dysfunction and Future Risk of Acute Kidney Injury

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $694,270

## Abstract

PROJECT SUMMARY
 Acute kidney injury (AKI) is common in hospitalized patients, costly, and strongly associated with mortality.
It is also now widely recognized to be a driver of progressive chronic kidney disease (CKD). AKI occurs
frequently in common clinical scenarios including sepsis, heart failure, and after coronary artery bypass graft
(CABG) surgery, but it is unclear why some individuals develop AKI in these settings while others do not. We
hypothesize that abnormalities in kidney function that are not captured by creatinine or proteinuria may identify
those predisposed to AKI risk. In preliminary studies in the SPRINT trial, we have shown that abnormalities in
kidney tubule function at baseline predict future development of AKI, independent of creatinine, proteinuria, or
other AKI risk factors. If confirmed, this finding could provide a paradigm shift as it would allow identification of
apparently healthy individuals who are at risk of AKI before the event occurs, enabling strategies to minimize
AKI risk such as alterations in medications, hydration protocols, and surgical approaches. This knowledge
may also give critical new insights into potential pathological mechanisms driving AKI events. By leveraging
the large 30,239 subject Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, this
application seeks to utilize blood and urine specimens collected when REGARDS participants were clinically
stable outpatients to characterize their kidney tubule health. We will identify REGARDS participants who
subsequently experience sepsis, heart failure, or CABG, and will abstract daily in-patient hospital creatinine
data during these admissions to ascertain AKI presence and severity. We will then determine whether tubule
dysfunction at times of relative health predicts AKI in these clinical scenarios (Aim 1). Next, we will build a
parsimonious biomarker panel that will predict AKI in these settings, setting the stage for future clinical
implementation (Aim 2). Finally, we will re-examine changes in these biomarkers after 10 years of follow-up,
and determine whether tubule injury or dysfunction is differentially altered in survivors of AKI versus controls.
This biomarker signature may allow clinicians to determine whether outpatient (unwitnessed) AKI episodes
may underlie the development or progression of CKD (Aim 3). Our efforts will directly link baseline tubule
function with future AKI risk, setting the stage for innovative therapies to mitigate or prevent AKI.

## Key facts

- **NIH application ID:** 10376834
- **Project number:** 5R01DK128803-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Orlando M Gutierrez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $694,270
- **Award type:** 5
- **Project period:** 2021-08-19 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376834

## Citation

> US National Institutes of Health, RePORTER application 10376834, Kidney Tubule Dysfunction and Future Risk of Acute Kidney Injury (5R01DK128803-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10376834. Licensed CC0.

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