Targeting Spleen Tyrosine Kinase-Bruton’s Tyrosine Kinase Axis for Immunologically Mediated Glomerulonephritis

Table 1

Effects of spleen tyrosine kinase (Syk) inhibitors on glomerulonephritis.

Clinical disease	Model	Treatment	Results	Reference
Lupus nephritis	NZB/W	Fostamatinib	As prophylactic treatment; Delayed proteinuria and azotemia; Reduced renal pathology and prolonged survival; Did not affect serum anti-DNA autoantibodies; In full-blown disease; Decreased the incidence and severity of renal pathology	[22]
	MRL/lpr	Fostamatinib	As prophylactic treatment; Prevented development of proteinuria and suppressed pathologic changes; In full-blown disease; Improved proteinuria; Decreased lymphadenopathy; Did not affect serum anti-DNA autoantibodies	[23]
Antiglomerular basement membrane nephritis	NTN	Fostamatinib	As prophylactic treatment; Improved proteinuria; Reduced glomerular fibrinoid necrosis and infiltration of inflammatory cells; Increased exogenous antibody deposition in glomeruli; Suppressed levels of both circulating and glomerulus-deposited endogenous antibodies; In full-blown disease; Improved proteinuria and serum creatinine levels; Increased exogenous antibody deposition in glomeruli; Reduced renal MCP-1 and IL-1β production	[24]
	NTN	SYK inhibitor (Celgene Corp.)	As prophylactic treatment; Prevented proteinuria, thrombosis, and platelet activation; Inhibited JNK and p38 MAPK activation; Reduced glomerular inflammation leukocyte recruitment	[25]
IgA nephropathy	In vitro	R406; siRNA	In vitro study; Decreased heat-aggregated IgA1-induced IL-6, IL-8, IFN-γ, IP-10, RANTES, and PDGF-BB production by human mesangial cells; Inhibited heat-aggregated IgA1-induced human mesangial cell proliferation	[26]