Association of inflammatory and endothelial cell activation biomarkers with acute kidney injury after sepsis.

T Clark Powell,Henry E Wang,Russell L Griffin,David G Warnock,Stephen L Powell,Bryant K Allen

doi:10.1186/2193-1801-3-207

Abstract

ObjectiveAcute 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.MethodsWe 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.ResultsWe 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.ConclusionElevated 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.

Highlights

Acute Kidney Injury (AKI) is the syndrome of rapid loss of kidney function, a process that may result from decreased renal blood flow, obstruction of the outflow tract, or damage to the renal filtration system
In a cohort of 1,886 subjects hospitalized for community-acquired pneumonia, Kellum, et al observed that inflammatory cytokines were higher in individuals that developed severe sepsis or septic shock (Kellum et al 2007)
In a prior study we found that individuals with high circulating levels of inflammatory and endothelial cell activation biomarkers were prone to future episodes of sepsis (Wang et al 2013b)

Summary

Introduction

Acute Kidney Injury (AKI) is the syndrome of rapid loss of kidney function, a process that may result from decreased renal blood flow, obstruction of the outflow tract, or damage to the renal filtration system Among the many pathophysiological processes underlying sepsis, inflammation and endothelial activation play prominent roles (Aird 2003; Kellum et al 2007; Aird 2007). In a cohort of 1,886 subjects hospitalized for community-acquired pneumonia, Kellum, et al observed that inflammatory cytokines (interleukin-6, interleukin-10, tumor necrosis factor-α) were higher in individuals that developed severe sepsis or septic shock (Kellum et al 2007). Recent attention has focused on the role of endothelial activation and dysfunction in sepsis pathophysiology (Aird 2003, 2007; Shapiro et al 2010). In a prior study we found that individuals with high circulating levels of inflammatory and endothelial cell activation biomarkers were prone to future episodes of sepsis (Wang et al 2013b)

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