Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism–related vascular thrombosis with microvascular injury and its consequences

• DOI: 10.1016/j.kint.2024.07.020
• Publication Date: 2024-08-12T05:51:11Z
• Authors: Danyang Zhao; Chao Han; Elmina Mammadova-...; Kanako Watanabe-K...; Tamisa Seeko Band...; Yihong Li; Chenyu Li; Qiubo Li; Hao Long; Lyuben Lyubenov; Chongxu Shi; Donato Santovito; Christian Weber; Peter Boor; Patrick Droste; Samir Parikh; John Shapiro; Letizia De Chiara; Giulia Carangelo; Paola Romagnani; Sven Klussmann; Kai Hoehlig; Axel Vater; Hans-Joachim Anders
• Keywords: acute kidney injury; diabetes; infarct; acute kidney injury; crystals; infarct; necroinflammation; thrombosis; necroinflammation; thrombosis

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate consequences like with systemic vasculitis. microcrystal injection into kidney artery wildtype mice initiated intra-kidney immunothrombosis within a few hours followed by sudden drop glomerular filtration rate ischemic necrosis after 24 hours. Genetic deficiency either C3 or C5aR prevented drop, at as did preemptive treatment C5a C5aR. Delayed blockade still resolved clots all consequences. Thus, selective is established prospective inhibition in high-risk patients may clinically feasible safe.