Effect of camostat mesilate for the treatment of advanced diabetic nephropathy

Carnostat mesilate is a developed derivative of gabexate mesllate for oral administration and is known to be one of the most potent protease inhibitors. We administered this drug to 15 patients with advanced diabetic nephropothy at a daily dose of 600 mg for 4 to 6 weeks. All patients had been treated with conventional therapy including angtotensin-converting enzyme inhibitors, and their diseases had stabilized for at least 2 weeks before the camostat mesilate therapy. Urinary protein excretion decreased promptly from 4.8 ± 0.6 to 2.9 ± 0.4 gm/day (mean ± SEM, p < 0.01) and serum albumin level increased from 2.7 ± 0.2 gm/dl to 2.9 ± 0.2 gm/dl (mean ± SEM, p < 0.05) within 4 to 6 weeks. The amount of plasma fibrinogen significantly decreased from 419.7 ± 42.3 mg/dl to 306.6 ± 28.3 mg/dl (mean ± SEM, p < 0.01), and urinary total fibrinogen degradation product excretion over 24 hours also decreased from 26,118 ± 9,696 to 18,072 ± 7,107 μg/day (mean ± SEM, P < 0.05). The value for serum creatinine level did not change during this intervention. We suggest that camostat mesilate suppresses the hypercoagulable state originating from diabetes meilltus, and changes the permselectivity of the glomerular capillary wall. These effects of camostat mesilate may improve the prognosis of diabetic nephropathy.