Kidney in the net of acute and long-haul coronavirus disease 2019: a potential role for lipid mediators in causing renal injury and fibrosis. Curr Opin Nephrol Hypertens 2022 Jan 01;31(1):36-46
Date
12/01/2021Pubmed ID
34846312DOI
10.1097/MNH.0000000000000750Scopus ID
2-s2.0-85122348632 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
PURPOSE OF REVIEW: 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.
RECENT FINDINGS: 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.
SUMMARY: 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.
Author List
Chiang KC, Imig JD, Kalantar-Zadeh K, Gupta AMESH terms used to index this publication - Major topics in bold
Acute Kidney InjuryFibrosis
Humans
Inflammation
Kidney
Lipids
Renal Insufficiency, Chronic
Thrombosis
