Targeting the tyrosine kinase signalling pathways for treatment of immune-mediated glomerulonephritis: from bench to bedside and beyond.

摘要: Glomerulonephritis (GN) affects patients of all ages and is an important cause morbidity mortality. Non-selective immunosuppressive drugs have been used in immune-mediated GN but often result systemic side effects occasionally fatal infective complications. There increasing evidence from both preclinical clinical studies that abnormal activation receptor non-receptor tyrosine kinase signalling pathways are implicated the pathogenesis GN. Activation spleen (SYK), Bruton's (BTK), platelet-derived growth factor (PDGFR), epidermal (EGFR) discoidin domain 1 (DDR1) demonstrated anti-GBM disease. SYK ANCA-associated SYK, BTK, PDGFR, EFGR, DDR1 Janus lupus nephritis. A representative animal model IgA nephropathy (IgAN) lacking. Based on results vitro human renal biopsy study results, a phase II trial ongoing to evaluate efficacy safety fostamatinib (an oral inhibitor) high-risk IgAN patient. Various inhibitors (TKIs) approved for cancer treatment. Clinical trials TKIs may be justified given their long-term data. In this review we will discuss current unmet medical needs treatment research as well stage development propose accelerated translational approach investigate whether selective inhibition provides safer more efficacious option