Association of inflammatory and endothelial cell activation biomarkers with acute kidney injury after sepsis.
OBJECTIVE
Acute kidney injury (AKI) is a sequela of sepsis associated with increased morbidity and mortality. We sought to determine if individuals with elevated baseline levels of inflammation and endothelial cell activation are at increased risk for future AKI after sepsis.


METHODS
We conducted an analysis of individuals developing sepsis in the national 30,239 subject REGARDS cohort. Biomarkers measured at the beginning of an 8-year observation period included high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), E-selectin, inter-cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and urinary Albumin-to-creatinine ratio (ACR). We defined subsequent sepsis as hospitalization for a serious infection with ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria. We excluded patients with prior dialysis or kidney transplantation, or those receiving less than two serum creatinine (sCr) measurements during hospitalization. We defined AKI as an increase in sCr ≥0.3 mg/dL from the initial sCr measurement, or the initiation of hemodialysis. Using logistic regression, we evaluated the associations between AKI and biomarker quartiles, adjusting for comorbidities.


RESULTS
We identified 212 sepsis cases encompassing 41 (19.3%) AKI. Elapsed time from biomarker measurement to sepsis episode was 3.1 years (IQR 1.6-4.5). Compared with non-AKI, AKI individuals exhibited higher TNF-α (9.4 vs. 6.2 pg/mL, p = 0.003) and ACR (504.82 vs 61.81 mg/g, p < 0.001). hsCRP, IL-6, E-selectin, ICAM-1 and VCAM-1 were similar between AKI and non-AKI. After adjustment for confounders, AKI after sepsis was more likely in those with higher E-selectin (adjusted ORs 2.91 (0.95-8.93), 1.99 (0.61-6.47), 4.01 (1.30-12.35), test of linear trend p = 0.04), and higher ACR (adjusted ORs 2.29 (0.99-5.30), 10.67 (3.46-32.90), test of linear trend p < 0.001). Baseline hsCRP, TNF-α, IL-6, VCAM-1 and ICAM-1 were not associated with AKI after sepsis.


CONCLUSIONS
Elevated baseline levels of E-selectin and ACR are associated with future AKI in the setting of sepsis. Baseline inflammatory and endothelial activation biomarkers may be useful for predicting future risk of AKI in sepsis.
Department of Emergency Medicine, University of Alabama School of Medicine, 619 19th Street South, OHB 251, Birmingham, AL 35249 USA.
T Clark
TC
Powell
Department of Emergency Medicine, University of Alabama School of Medicine, 619 19th Street South, OHB 251, Birmingham, AL 35249 USA.
Stephen L
SL
Powell
Department of Emergency Medicine, University of Alabama School of Medicine, 619 19th Street South, OHB 251, Birmingham, AL 35249 USA ; Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina USA.
Bryant K
BK
Allen
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina USA.
Russell L
RL
Griffin
Department of Emergency Medicine, University of Alabama School of Medicine, 619 19th Street South, OHB 251, Birmingham, AL 35249 USA ; Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina USA.
David G
DG
Warnock
Department of Emergency Medicine, University of Alabama School of Medicine, 619 19th Street South, OHB 251, Birmingham, AL 35249 USA.
Henry E
HE
Wang
Acute kidney injury (AKI); Biomarkers; Endothelium; Inflammation; Sepsis