# Complement Activation in Sepsis

> **NIH NIH K23** · UNIVERSITY OF COLORADO DENVER · 2024 · $190,932

## Abstract

Every year, more than 75,000 children and 750,000 adults in the United States are admitted to an
Intensive Care unit with a diagnosis of sepsis. Sepsis-associated acute kidney injury (SA-AKI) has a high
morbidity and mortality rate and unfortunately there are no methods to predict, prevent, or treat SA-AKI.
Emerging evidence implicate the role of complement activation as a key driver of SA-AKI development. We
have shown that urine complement factor Ba is associated with incident AKI in both critically ill children and
adults with sepsis. However, whether complement activation is involved in SA-AKI pathogenesis in critically ill
children and adults is unknown. We hypothesize that urine Ba elevation temporally precedes development of
SA-AKI and associates with urine cellular changes. This proposal will examine the association between urine
Ba and AKI in critically ill patients with sepsis. First, we will prospectively enroll critically ill children with sepsis
and longitudinally obtain urine Ba levels to determine the association between urine Ba levels and severe AKI
outcomes, and then validate these findings in a large multicenter trial of pediatric sepsis (Aim 1). We will
validate this association through two biorepositories from clinical trials in critically ill septic adults (Aim 2). This
will determine when urine Ba peaks and identify cutoff values and identification of an ideal window to study use
of therapeutic trials of factor B inhibition in the future. Finally, we will measure complement deposition on shed
tubular epithelial cells in the urine to determine if complement activation is occurring in the kidney (Aim 3).
 As an Assistant Professor in Pediatric Critical Care with a strong publication record, I am establishing
myself in the field of critical care nephrology. A K23 Career development award would support the following
research goals: 1) strengthen the evidence implicating the complement cascade’s role in SA-AKI development;
2) identify a potential therapeutic window to stratify patients for treatment with a complement therapeutic in
future R01 proposals; 3) obtain mechanistic insight discriminating systemic versus localized kidney
complement activation. My career development plan includes dedicated time to 1) train and gain experience in
conducting patient-oriented research and clinical trials; 2) work with a multidisciplinary team of experts in Adult
and Pediatric Nephrology, Emergency/Critical Care, and Biostatistics; 3) pursue training in biostatistics and
biomarker analytics; 4) gain skills in interpretation of complement quantification methods; 5) develop
professional skills including manuscript preparation, grant writing, presentation skills, etc.; and 6) establish the
foundation for an independent research career aimed at improving outcomes for critically ill patients with SA-
AKI. My training environment is outstanding with mentorship from Dr. Kendrick, an adult nephrologist with
clinical research expertise and a strong r...

## Key facts

- **NIH application ID:** 10949497
- **Project number:** 1K23DK140617-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Erin K Stenson
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $190,932
- **Award type:** 1
- **Project period:** 2024-07-22 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949497

## Citation

> US National Institutes of Health, RePORTER application 10949497, Complement Activation in Sepsis (1K23DK140617-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10949497. Licensed CC0.

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