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

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.

Syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery

“…Our data are in accordance with a previous study that failed to demonstrate any difference regarding these adhesion molecules in patients with sepsis who did or did not develop AKI. [36][37][38] Moreover, in cardiac surgery, the lack of association between ICAM-1 increment and AKI can be explained, at least partly, by the observed reduction in their levels after CBP when compared with presurgery samples. Although adhesion molecules are known to have an important role in AKI pathophysiology, we speculate that postoperative systemic levels do not reflect their local expression in kidney tissue.…”

Pro-Apoptotic Effects of Plasma from Patients with Cardiorenal Syndrome on Human Tubular Cells

“…In particular, soluble isoforms of CAMs are elevated in patients with HF and reflect enhanced cell surface expression of these molecules; in addition, the levels of soluble CAMs increase with the disease severity and they are connected with clinical outcomes [20,47] . Furthermore, ICAM-1 plays an important role in the pathophysiology of AKI [19,48,49] .…”

Sepsis-Associated Acute Kidney Injury

“…An increase of E-selectin, typical of inflammatory and endothelial activation, is associated with future AKI in a longitudinal evaluation of patients after sepsis. 69 In a large multicenter study of critically ill adults, cell-cycle arrest markers tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFB7) showed superior discrimination for AKI compared with other novel biomarkers such as NGAL, interleukin-18, liver type–fatty acid binding protein, and kidney injury molecule-1 (AUC, 0.80 for TIMP-2/IGFBP7 versus <0.72 for the others). 70 In this study, the predictive performance of TIMP-2/IGFBP7 for AKI was increased further in patients with sepsis (AUC, 0.82).…”