Effect of Ciclosporin A on Antibody-induced Experimental Glomerulonephritis

Abstract

The effect of cyclosporin A (C YA) on the development of active and passive modeis of rat anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) was assessed. Active GN was induced by an intravenous injection of sheep anti-rat GBM globulin to preimmunized rats. After 5 days, a diffuse proliferative GN with proteinuria and linear GBM deposition of rat IgG was regularly observed. CYA treatment, commencing prior to preimmunization, significantly attenuated the glomerular lesion, reduced proteinuria, prevented linear deposition of rat IgG and reduced the serum titre of anti-sheep globulin antibody. However, treatment started after the antibody response was established failed to alter antibody production, its glomerular deposition or the outcome of the disease. CYA treatment did not effect passive anti-GBM-GN, occurring 24 h after intravenous administration of sheep anti-rat GBM globulin to unimmunized rats. Thus, CYA is able to block anti-GBM-GN when given prior to induction of disease, by preventing an active antibody response. However, it did not alter GN when the antibody response was well established, or when glomerular injury was passively induced.

Ciclosporin in Minimal-Change Glomerulopathy and in Focal Segmental Glomerular Sclerosis

“…Interfer ence with lymphokine-mediated signals between acces sory cells [20], intrarenal hemodynamic changes [21] and/or restoration of the anionic charges may advocate the antiproteinuric effect of CS. However, the fact that a reduction of proteinuria may be observed with CS in dif ferent experimental models of glomerulonephritis [35][36][37][38] as well as patients with nonimmunologically me diated glomerular disease [21] suggests that CS probably operates, at least in part, without interfering with a spe cific immunological mechanism. The preliminary results of the Italian cooperative study confirm the possibility of maintaining remission with CS in steroid-sensitive pa tients.…”

Cyclosporine A combined with medium/low dose prednisone in progressive IgA nephropathy

“…Up to 40% of IgAN patients reach end‐stage renal disease within 20 years [1,2]. Several studies have proved that steroids, angiotensin‐converting enzyme inhibitors, fish oil, cytotoxics, immunosuppressants, tonsillectomy, and vitamin E are beneficial to IgAN patients [7–12]. However, consensus about therapy is still lacking.…”