Liver Cirrhosis and Septic Shock Attenuate the Increase in Plasma Endostatin Concentrations That Is Associated with Acute Kidney Injury Requiring Dialysis

Background/Objectives: Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection. Alterations in pro- and anti-angiogenic mediators have been associated with disease severity and clinical outcomes. Endostatin, a potent endogenous inhibitor of angiogenesis, has been linked to renal dysfunction through elevated circulating concentrations. This study investigated whether plasma endostatin levels could serve as a biomarker of acute kidney injury requiring dialysis (AKI-D) and predict disease severity or clinical outcome in patients with sepsis. Methods: Plasma endostatin concentrations were quantified by enzyme-linked immunosorbent assay in 258 patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock and in 49 healthy controls. Among the patients, 99 had AKI-D, 29 had SARS-CoV-2 infection, 9 had severe malaria, 60 had liver cirrhosis, and 45 had pancreatitis. Results: Plasma endostatin concentrations were significantly higher in patients with SIRS, sepsis, or septic shock than in healthy controls. Endostatin levels were further increased in patients with AKI-D and predicted its need with 70% accuracy compared with 72% for the glomerular filtration rate and 72% when both were combined in the non-cirrhosis patients. Subsequent analyses were therefore performed separately in patients with and without AKI-D. In both subgroups, endostatin concentrations were not associated with critical disease severity, survival, or SARS-CoV-2 infection. Liver cirrhosis did not influence endostatin levels in patients not requiring dialysis; however, among patients with AKI-D, cirrhosis attenuated AKI-D-associated upregulation of plasma endostatin. In the subgroup of patients with septic shock, AKI-D was not related to a further increase in plasma endostatin levels. Notably, the nine patients with severe malaria exhibited plasma endostatin levels comparable to those of healthy controls, providing preliminary evidence that the endostatin elevation observed in sepsis was absent in malaria. Conclusions: Plasma endostatin concentrations are elevated in patients with SIRS/sepsis/septic shock compared to controls and increase further in AKI-D. However, plasma endostatin levels are not of diagnostic value for prediction of AKI-D, critical illness severity or outcome. The attenuated increase in endostatin levels observed in AKI-D patients with liver cirrhosis or septic shock suggests that circulating endostatin concentrations in AKI-D may be influenced by hepatic function and the severity of critical illness.