Moser Stephan, Araschmid Laura, Panagiotou Anneza, Bonati Leo H, Breidthardt Tobias, Fahrni Gregor, Kaiser Christoph, Jeger Raban, Trendelenburg Marten, Osthoff Michael
Division of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland.
Department of Clinical Research, University of Basel, 4001 Basel, Switzerland.
Biomedicines. 2024 Aug 27;12(9):1956. doi: 10.3390/biomedicines12091956.
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.
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.
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.
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.
碘化造影剂（CM）导致的急性肾损伤（AKI）与CM诱导的肾缺血及对内皮细胞（EC）的毒性作用有关。重组人C1抑制剂（rhC1INH）已被证明可影响EC激活。
对一项双盲、随机、安慰剂对照研究的74/77（96%）名参与者进行二次分析，该研究评估了rhC1INH对AKI的影响。在48小时内对冷冻血样中的E选择素、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子（VCAM-1）和CC趋化因子配体5（CCL5）进行测定，并根据治疗组和肾脏结局进行分析。
平均年龄为76.7岁，分别有37名患者接受rhC1INH和安慰剂治疗。在整个研究人群中，观察到与基线相比，前48小时内EC激活标志物/CCL5浓度中位数的微小差异（例如，E选择素基线时为27.5 ng/mL，第1天为29.7 ng/mL；CCL5：基线时为17.7 ng/mL，第2天为32.2 ng/mL）。ICAM-1/E选择素浓度的绝对变化与尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）浓度的较高峰值变化相关。然而，AKI与EC标志物/CCL5的显著变化无关。最后，安慰剂组和rhC1INH组之间EC激活标志物/CCL5的血清浓度无明显差异。
冠状动脉造影期间给予CM仅在最初48小时内轻度激活EC，这无法解释随后发生的AKI。rhC1INH的给药与EC激活或CCL5的降低无关。
