Association of Endothelial Cell Activation with Acute Kidney Injury during Coronary Angiography and the Influence of Recombinant Human C1 Inhibitor—A Secondary Analysis of a Randomized, Placebo-Controlled, Double-Blind Trial

• Published in: Biomedicines
• Main Authors: Stephan Moser, Laura Araschmid, Anneza Panagiotou, Leo H. Bonati, Tobias Breidthardt, Gregor Fahrni, Christoph Kaiser, Raban Jeger, Marten Trendelenburg, Michael Osthoff
• Format: Article
• Language: English
• Published: MDPI AG 2024-08-01
• Subjects: endothelial cell activation; complement system; C1 inhibitor; contrast media; ICAM-1; VCAM-1
• Online Access: https://www.mdpi.com/2227-9059/12/9/1956

Background: Acute kidney injury (AKI) as a result of iodinated contrast media (CM) has been linked to CM-induced renal ischemia and toxic effects on endothelial cells (EC). The recombinant human C1 inhibitor (rhC1INH) has been shown to influence EC activation. Methods: Secondary analysis of 74/77 (96%) participants of a double-blind, randomized, and placebo-controlled study that assessed the effect of rhC1INH on AKI. E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), and CC-chemokin-ligand-5 (CCL5) were determined in frozen blood samples over 48 h and analyzed according to the treatment group and renal outcomes. Results: The mean age was 76.7 years, and 37 patients each received rhC1INH and placebo, respectively. In the entire study population, minor differences in median EC activation markers/CCL5 concentrations during the first 48 h compared to baseline were observed (e.g., E-selectin 27.5 ng/mL at baseline vs. 29.7 ng/mL on day 1, CCL5: 17.7 ng/mL at baseline vs. 32.2 ng/mL on day 2). Absolute changes in ICAM-1/E-selectin concentrations correlated with a higher peak change in urinary NGAL concentrations. However, AKI was not associated with significant changes in EC markers/CCL5. Last, no significant differences in serum concentrations of EC activation markers/CCL5 were evident between the placebo and the rhC1INH group. Conclusions: CM administration during coronary angiography only mildly activated ECs within the first 48 h, which does not explain subsequent AKI. The administration of rhC1INH was not associated with a reduction of EC activation or CCL5.