Antibody-mediated glomerulonephritis, including that resulting from immune 
complexes, is an important cause of renal failure and is in need of more 
specific and effective treatment. Binding of antibody or immune complexes to Fc 
receptors activates intracellular signal transduction pathways, including spleen 
tyrosine kinase (Syk), leading to the production of inflammatory cytokines. We 
examined the effect of R788 (fostamatinib disodium), an oral prodrug of the 
selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats. 
Treatment with R788 reduced proteinuria, tissue injury, glomerular macrophage 
and CD8+ cell numbers, and renal monocyte chemoattractant protein-1 (MCP-1) and 
IL-1beta, even when we started treatment after the onset of glomerulonephritis. 
When we administered R788 from days 4 to 10, glomerular crescents reduced by 
100% (P < 0.01) compared with the vehicle group. When we administered R788 
treatment from days 7 to 14, established glomerular crescents reversed (reduced 
by 21%, P < 0.001), and renal function was better than the vehicle group (P < 
0.001). In vitro, R406 downregulated MCP-1 production from mesangial cells and 
macrophages stimulated with aggregated IgG. These results suggest that Syk is an 
important therapeutic target for the treatment of glomerulonephritis.