Lipoprotein apheresis as rescue therapy in lipoprotein glomerulopathy: The role of plasmatic extracellular vesicle removal

Background: Lipoprotein glomerulopathy (LPG) is a rare disease affecting the kidney, clinically characterized by type III hyperlipoproteinemia, mutated apolipoprotein E (ApoE), the presence of glomerular lipoprotein thrombi, proteinuria in the nephrotic range, and progression toward chronic kidney disease (CKD). Objective: Evaluate the role of lipoprotein apheresis (LA) as rescue therapy in LPG. Methods: Since 2011, we have identified 6 unrelated patients living in the same geographical area of Central Italy (Tuscany Region) who share the same rare ApoE mutation. Results: Four patients, due to nephrotic syndrome associated with biopsy-proven LPG, underwent LA. LA was able to stabilize renal function even for years in three of these subjects: of note, a better prognosis was reported when less impairment of renal function was present.LA was associated with a significant decrease of the number of plasmatic extracellular vesicles (EV) released from activated and/or damaged cells. In vitro studies showed that EV isolated from plasma of LPG patients induced human glomerular endothelial cell and podocyte alterations potentially responsible for the development of nephrotic syndrome and tissue injury. Conclusion: In conclusion, we demonstrated, in unrelated LPG patients with LPG carrying the same ApoE mutation, a protective role of LA on proteinuria and progression toward CKD. This LA-associated protective effect may be at least in part related to the modulation of biologically active EVs in patients' plasma.