Phospholipase A2 receptor is associated with hypercoagulable status in membranous nephropathy: a narrative review

Abstract

Background and objective: Membranous nephropathy (MN) is the pathology type with the highest incidence of thrombotic events in nephrotic syndrome (NS). While patients with MN are prone to developing thromboembolic complications, the specific mechanism remains unclear. Many studies have shown a high titer of PLA2R antibody aggravates proteinuria and hypoalbuminemia and predicts a lower likelihood of clinical remission in patients with PLA2R-associated MN. Proteinuria and hypoalbuminemia also increase the risk of thrombotic events. In our previous review, we found secretory phospholipase A2 (sPLA2) may act as a ligand for PLA2R, and binding of sPLA2 to PLA2R results in damage to podocytes. sPLA2 can promote the release of AA from membrane phospholipids, and AA is closely related to blood lipid levels and coagulation cascades. The objective of this study is to explain the relationship between phospholipase A2 receptor (PLA2R) and blood hypercoagulability in MN patients and the new theory that secretory phospholipase A2 (sPLA2) and arachidonic acid (AA) may play a role in regulating blood lipid levels and the coagulation cascade in patients with PLA2R-positive MN.

Methods: Literature retrieval was conducted through China National Knowledge Infrastructure (CNKI) and PubMed. Abstract and Introduction information was then retrieved and the results from the literature searched, classified, and important information summarized. A conclusion was then reached, and a new standpoint put forward.

Key content and findings: We discussed the role of PLA2R antibody and sPLA2 in hypercoagulability in patients with MN and analyzed the following four possible mechanisms: sPLA2 can combine with PLA2R and induce podocyte apoptosis; sPLA2 may promote the production of anti-PLA2R antibodies; sPLA2 may promote the release of AA from membrane phospholipids; and AA induces platelet aggregation.

Conclusions: PLA2R may exacerbate hypercoagulability in patients with PLA2R-related MN, and sPLA2 plays an important role in the process.

Keywords: Arachidonic acid (AA); coagulation disorder; membranous nephropathy (MN); phospholipase A2 receptor (PLA2R); secretory phospholipase A2 (sPLA2).