Rapamycin ameliorates renal pathology in anti-Fx1A induced passive Heymann nephritis

Our study focused on understanding the pathogenesis and treatment of membranous nephropathy (MN), a common cause of nephrotic syndrome (NS) characterized by glomerular basement membrane (GBM) thickening and immune complex deposition.

Through an Fx1A antibody-induced passive Heymann nephritis rat model, we observed a significant increase in kidney size, weight, and kidney-to-body weight ratio in diseased rats. However, oral administration of rapamycin mitigated renal pathology. Rats treated with rapamycin displayed kidney weights comparable to healthy rats, along with improvements in renal health indicators like proteinuria, blood urea nitrogen (BUN), and creatinine levels.

Furthermore, rapamycin-treated rats exhibited reduced inflammatory cytokine expressions (IL1b, IL6, IL10, IFNgama) comparable to healthy rats, in contrast to elevated expression levels in diseased rats. Histopathological analysis revealed diminished complement C3 and C5b-9 deposits, decreased renal tubular dilatation, and mitigated glomerular collapse upon rapamycin treatment.

Our findings indicate that rapamycin effectively improved renal pathology in anti-FX1A-induced passive Heymann nephritis, potentially suggesting a role for autophagy in modulating this condition.