Association of Fluid Volume With uNGAL as a Biomarker of Kidney Injury in Pediatric Septic Shock

Sunday, February 23, 2025

9:45am – 10:45am Eastern Time

Location: Connections Central Theater 1

Scott L. Weiss, MD, FCCM

Nemours Childrens Hospital
Sidney Kimmel Medical Center at Thomas Jefferson University

Disclosure information not submitted.
JF

Julie C. Fitzgerald, MD, PhD, MSCE

Division of Critical Care Medicine, Department of Anesthesia and Critical Care
Children’s Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania

Disclosure information not submitted.
BL

Benjamin Laskin, MD

Associate Professor
Children's Hospital of Philadelphia

Disclosure information not submitted.
RS

Ruchi Singh, PhD

Project Manager
Children's Hospital of Philadelphia

Disclosure information not submitted.
AA

Amanda Artis, MS

Biostatistician
Children's Hospital of Philadelphia

Disclosure information not submitted.
AV

Ananya Vohra, BS

Research Coordinator
Children's Hospital of Philadelphia

Disclosure information not submitted.
AC

Atzael Campos, N/A

Data Manager
Children's Hospital of Philadelphia

Disclosure information not submitted.
JH

Jing Huang, PhD

Assistant Professor
University of Pennsylvania

Disclosure information not submitted.
ME

Michelle Eckerle, MD

Assistant Professor
Cincinnati Children's Hospital

Disclosure information not submitted.
RH

Robert Hickey, MD

Professor
Childrens Hospital of Pittsburgh of UPMC

Disclosure information not submitted.
NK

Nathan Kuppermann, MD, MPH

Professor
University of California, Davis Medical Center

Disclosure information not submitted.
FB

Fran Balamuth, MD, MSCE, PhD

Associate Professor
Children's Hospital of Philadelphia

Disclosure information not submitted.

Introduction: Fluid overload is associated with adverse outcomes in sepsis, but it is not known if volume of fluid resuscitation promotes kidney injury over time. Because urine neutrophil gelatinase-associated lipocalin (uNGAL) reflects kidney tubular injury better than serum creatinine, we hypothesized that volume of fluid resuscitation would be associated with persistently elevated uNGAL in children with septic shock.

Methods: We performed a prospective cohort study of children ages >2 months to < 18 years treated for septic shock at 3 US sites from 8/2020 to 4/2024. Patients with chronic kidney disease were excluded. We collected blood and urine at enrollment (T1), day 2-3 (T2), and day 27 or at discharge/death (T3). Exposure was defined as fluid volume (bolus and maintenance) received from presentation through 11:59 PM the following day, categorized as ≤40, 40-100, and >100 mL/kg. Outcomes were persistently elevated uNGAL (defined as uNGAL ≥150 ng/mL at T1 and at T2 or T3) and persistently elevated creatinine for age at T3. We used multivariable regression to estimate propensity scores for fluid volume and applied inverse probability treatment weighting (IPTW) logistic regression to compare outcomes across exposure categories with balanced covariates.

Results: Of 478 patients, 12%, 46%, and 42% received fluid volumes of ≤40, 40-100, and >100 mL/kg, respectively. At presentation, 19%, 5%, and 7% met KDIGO stage 1, 2, and 3 AKI by serum creatinine definitions. Both creatinine and uNGAL were higher with KDIGO stage 2/3 compared to no/stage 1 AKI at T1 and T2, but only creatinine remained higher at T3. After IPTW, 14% of patients who received >100 mL/kg had persistently elevated uNGAL compared to 6% who received 40-100 mL/kg (OR 2.7, 95% CI 1.1 to 6.2). The proportion with persistently elevated creatinine did not differ between fluid volume groups. IPTW did not achieve sufficient covariate balance to include the small number who received ≤40 mL/kg in the analysis.

Conclusions: Children resuscitated with fluid volumes >100 mL/kg for septic shock had more than twice the odds of persistently elevated uNGAL over time compared to those who received 40-100 mL/kg. These data suggest that high-volume fluid resuscitation is associated with ongoing kidney tubular injury that was detected by uNGAL but not creatinine.