KARE Biosciences, Orange, California.
Drug Discovery Center and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Curr Opin Nephrol Hypertens. 2022 Jan 1;31(1):36-46. doi: 10.1097/MNH.0000000000000750.
Severe COVID-19 disease is often complicated by acute kidney injury (AKI), which may transition to chronic kidney disease (CKD). Better understanding of underlying mechanisms is important in advancing therapeutic approaches.
SARS-CoV-2-induced endothelial injury initiates platelet activation, platelet-neutrophil partnership and release of neutrophil extracellular traps. The resulting thromboinflammation causes ischemia-reperfusion (I/R) injury to end organs. Severe COVID-19 induces a lipid-mediator storm with massive increases in thromboxane A2 (TxA2) and PGD2, which promote thromboinflammation and apoptosis of renal tubular cells, respectively, and thereby enhance renal fibrosis. COVID-19-associated AKI improves rapidly in the majority. However, 15-30% have protracted renal injury, raising the specter of transition from AKI to CKD.
In COVID-19, the lipid-mediator storm promotes thromboinflammation, ischemia-reperfusion injury and cytotoxicity. The thromboxane A2 and PGD2 signaling presents a therapeutic target with potential to mitigate AKI and transition to CKD. Ramatroban, the only dual antagonist of the thromboxane A2/TPr and PGD2/DPr2 signaling could potentially mitigate renal injury in acute and long-haul COVID. Urgent studies targeting the lipid-mediator storm are needed to potentially reduce the heavy burden of kidney disease emerging in the wake of the current pandemic.
严重的 COVID-19 疾病常伴有急性肾损伤（AKI），后者可能会进展为慢性肾脏病（CKD）。深入了解其潜在机制对于推进治疗方法至关重要。
SARS-CoV-2 诱导的内皮损伤会引发血小板激活、血小板-中性粒细胞相互作用以及中性粒细胞细胞外陷阱的释放。由此产生的血栓炎症会导致终末器官的缺血再灌注（I/R）损伤。严重的 COVID-19 会引发脂质介质风暴，导致血栓素 A2（TxA2）和 PGD2 大量增加，分别促进血栓炎症和肾小管细胞凋亡，从而增强肾纤维化。大多数 COVID-19 相关性 AKI 会迅速改善。然而，仍有 15%-30%的患者会出现持续的肾损伤，增加了从 AKI 进展为 CKD 的风险。
在 COVID-19 中，脂质介质风暴会促进血栓炎症、缺血再灌注损伤和细胞毒性。血栓素 A2 和 PGD2 信号通路提供了一个治疗靶点，有可能减轻 AKI 并防止其进展为 CKD。拉曲前列醇是血栓素 A2/TPr 和 PGD2/DPr2 信号的唯一双重拮抗剂，有可能减轻急性和长期 COVID 中的肾损伤。迫切需要针对脂质介质风暴的研究，以减轻当前大流行后出现的严重肾脏疾病负担。
