osteoprotegerin and Sepsis

Topics: Animals; Biomarkers; Humans; Inflammation; Lipopolysaccharides; Mice; Osteoprotegerin; Respiratory Distress Syndrome; Sepsis; Vascular Diseases

Though significant progress has been made towards new diagnostic approaches for early detection of acute kidney injury (AKI) induced by different factors, there is still an urgent demand for a more specific and predictive biomarker for each type. The aim of this study is to unravel the potential diagnostic utility of circulating osteoprotegerin (OPG) in septic patients who developed AKI in the ICU, compared to cystatin C (a renal function maker) and KIM-1 (a kidney damage marker). Eighty patients (male = 43, female = 37) with ages ranging from 42 to 46 years and with sepsis, 40 of whom developed AKI, and 30 healthy controls were enrolled in this prospective study. Results revealed significant progressive elevation of OPG, along with cystatin C and KIM-1, among sepsis, severe sepsis, and sepsis-AKI patients. The progression of OPG levels paralleled the deterioration of kidney and endothelial functions from sepsis to sepsis-AKI, revealed as progressively increased levels of serum E-selectin (15.3%), endothelin-1 (ET-1) (19.6%), and decreased nitric oxide (NO) (29.7%), associated with elevations of TNF-α (25.5%) and TGF-β (18%). Their comparative prognostic validity of sepsis-AKI was assessed using ROC analysis, which revealed that OPG, KIM-1, and cystatin C showed similar AUCs (0.827-0.83) but with different sensitivities, viz., 84%, 88%, and 92%, respectively. Although cystatin showed 82% specificity, OPG showed a higher, similar specificity to KIM-1 of 85%, indicating its potential function as a marker of renal damage such as KIM-1. This study revealed a significant elevation of circulating OPG in septic patients with different levels of severity and those who progressed to AKI. Moreover, OPG showed a significant correlation to KIM-1 and cystatin, as well as conventional renal, inflammatory, and endothelial markers. Having a similar specificity to KIM-1, as evidenced by the ROC analysis, OPG has the potential to serve as a reliable biomarker of kidney damage in cases of sepsis-AKI.

Topics: Acute Kidney Injury; Adult; Biomarkers; Cystatin C; Cytokines; Female; Hepatitis A Virus Cellular Receptor 1; Humans; Inflammation Mediators; Male; Middle Aged; Osteoprotegerin; Prognosis; ROC Curve; Sepsis; Severity of Illness Index

Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its tumor necrosis factor-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to systemic inflammatory response syndrome (SIRS), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/mL, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Osteoprotegerin; Receptors, Tumor Necrosis Factor, Member 6b; ROC Curve; Sensitivity and Specificity; Sepsis; Tumor Necrosis Factor Ligand Superfamily Member 15; Young Adult