suPAR links a dysregulated immune response to tissue inflammation and sepsis-induced acute kidney injury.

Acute kidney injury (AKI) secondary to sepsis results in poor outcomes and conventional kidney function indicators lack diagnostic value. Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune-derived molecule implicated in inflammatory organ damage. We characterized the diagnostic ability of longitudinal serum suPAR levels to discriminate severity and course of sepsis-induced AKI (SI-AKI) in 200 critically ill patients meeting Sepsis-3 criteria. The pathophysiologic relevance of varying suPAR levels in SI-AKI was explored in a polymicrobial sepsis model in WT, (s)uPAR-knockout, and transgenic suPAR-overexpressing mice. At all time points studied, suPAR provided a robust classification of SI-AKI disease severity, with improved prediction of renal replacement therapy (RRT) and mortality compared with established kidney biomarkers. Patients with suPAR levels of greater than 12.7 ng/mL were at highest risk for RRT or death, with an adjusted odds ratio of 7.48 (95% CI, 3.00-18.63). suPAR deficiency protected mice against SI-AKI. suPAR-overexpressing mice exhibited greater kidney damage and poorer survival through inflamed kidneys, accompanied by local upregulation of potent chemoattractants and pronounced kidney T cell infiltration. Hence, suPAR allows for an innate immune-derived and kidney function-independent staging of SI-AKI and offers improved longitudinal risk stratification. suPAR promotes T cell-based kidney inflammation, while suPAR deficiency improves SI-AKI.

The role of unfractionated heparin for the antiaggregatory effect of aspirin in patients undergoing carotid endarterectomy: Results of an observational clinical study.

The aims of the present study were to examine the influence of a low-dose unfractionated heparin regime on platelet aggregation and to additionally assess the prevalence of primary aspirin resistance in patients undergoing carotid endarterectomy. Therefore, 50 patients undergoing carotid endarterectomy were enrolled. A bolus of 3000 IU unfractionated heparin was administered 2 min before carotid cross-clamping additionally to standard antiaggregatory therapy. Haemostaseological point of care testing was performed twice, prior to surgery and 10 min after unfractionated heparin administration by the use of aggregometric and viscoelastic point of care testing. Following unfractionated heparin administration, the activated partial thromboplastin time increased significantly and clotting time in viscoelastic INTEM test was shown to be significantly prolonged. In contrast, the antiaggregatory effect of aspirin was not diminished in aggregometric ASPI test. A low-dose unfractionated heparin regime during carotid endarterectomy was therefore considered to be safe, without diminishing the antiplatelet effect of aspirin. Moreover, aggregometric point of care testing was identified to be a suitable tool for the identification of patients with primary aspirin resistance ( n = 3).