Long- and short-term treatment with imatinib attenuates the development of chronic kidney disease in experimental anti-glomerular basement membrane nephritis.

BACKGROUND: Imatinib is a selective tyrosine kinase inhibitor that can block platelet-derived growth factor (PDGF) receptor activity. Imatinib is also known as an anti-inflammatory agent. We examined the therapeutic effects of long- or short-term imatinib treatment in Wistar-Kyoto (WKY) rats with established anti-glomerular basement membrane (GBM) nephritis.
METHODS: Nephrotoxic serum (NTS) nephritis was induced in WKY rats on day 0. Groups of animals were given either imatinib or vehicle daily by intraperitoneal injection, from day 7 to day 49 in the long-term treatment study, and from day 7 to 13 in the short-term treatment study; all rats were sacrificed at day 50.
RESULTS: In long-term treatment, imatinib showed marked renoprotective effects; imatinib suppressed proteinuria, improved renal function, attenuated the development of glomerulosclerosis and tubulointerstitial injury and reduced the expression levels of collagen type I and transforming growth factor-beta (TGF-β) in renal cortex. The key finding of the present study was that short-term treatment with imatinib also significantly attenuated the development of renal injury until day 50, although the degree of renoprotection was slightly inferior to that of long-term treatment.
CONCLUSIONS: These results suggest that administration of imatinib is a promising strategy for limiting the progression of glomerulonephritis (GN) to end-stage renal failure. In particular, a short period of treatment at an early stage of GN is more beneficial in terms of cost-effectiveness and reduction of adverse effects in comparison to a continuous and long period of treatment.