# Discriminating Causes of Creatinine Change in Acute Heart Failure

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2024 · —

## Abstract

This is a resubmission of a Career Development Award (CDA) application by Dr. Nicholas Wettersten,
mentored by Dr. Joachim Ix at the VA San Diego Health System (VASDHS). Through this proposal Dr.
Wettersten intends to establish himself as an independent investigator studying acute heart failure (AHF),
cardiorenal syndrome, and biomarkers.
Candidate: Dr. Wettersten’s training objectives are designed to parallel his research project and provide skills
required to lead an independent VA Merit Award upon completion of his CDA. These include: learning
biostatistics for interpretation and analysis of multiple biomarkers concurrently, develop skills for designing and
implementing clinical trials, and develop skills for scientific writing and independent lab management. Dr.
Wettersten will achieve these objectives through coursework, workshops, and mentorship. His mentorship
committee includes Dr. Joachim Ix (primary mentor), an expert in heart-kidney disease interaction, and co-
mentors Dr. Kirk Hammond, an expert in clinical trials and translational research at the VASDHS, Dr. Patrick
Murray, an expert in acute kidney injury and biomarkers at University College Dublin, and Dr. Florin Vaida, an
expert biostatistician at UCSD.
Research: AHF accounts for almost 1 million hospitalizations annually with significant morbidity and mortality.
Approximately 350,000 Veterans suffer from heart failure with an annual mortality of almost 15%. Periods of
AHF are an especially vulnerable period of heightened morbidity and mortality. Up to one-third of AHF patients
will experience a rise in serum creatinine (sCr) with diuretics. This rise in sCr could be from true kidney injury
or a benign reversible hemodynamic effect. Currently, clinicians have no means to distinguish these scenarios.
Recently, a panel of urine kidney biomarkers of injury and dysfunction has been shown to discriminate the rise
in sCr with intensive blood pressure lowering as hemodynamic vs. injury. This same process may occur in
AHF, but this panel has not been tested in AHF. This proposal will leverage the Acute Kidney Injury N-gal
Evaluation of Symptomatic Heart Failure Study (AKINESIS), a well-characterized study of 927 patients
presenting with AHF and with repeat urine specimens available during treatment, as well as conduct an
observational pilot study from admission into the post-discharge period of AHF patients admitted to the VASD
hospital, to address the following specific aims: 1) To determine if admission values of urinary kidney tubule
function and injury biomarkers associate with risk of adverse outcomes among AHF patients beyond admission
sCr, 2) to determine whether changes in urinary kidney tubule function and injury biomarkers during
hospitalization for AHF are more strongly associated with mortality and HF readmission than changes in sCr,
and 3) to assess trajectories of urine kidney tubule function and injury biomarkers with changes in patient
volume status during hospitalization ...

## Key facts

- **NIH application ID:** 10738784
- **Project number:** 5IK2CX002105-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Nicholas Wettersten
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738784

## Citation

> US National Institutes of Health, RePORTER application 10738784, Discriminating Causes of Creatinine Change in Acute Heart Failure (5IK2CX002105-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10738784. Licensed CC0.

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