Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics

The present study was conducted on 8 patients with advanced diabetic nephropathy who showed a significant reduction of proteinuria through ACE inhibition. Camostat mesilate, one of the most potent protease inhibitors developed for oral use, was administered to these patients at a daily dose of 600 mg starting after 4 weeks of ACE inhibitor administration. Laboratory data were obtained 1) just before the ACE inhibition, 2) after 4 weeks of the ACE inhibitor single treatment, and 3) after another 4 weeks of the additional treatment with camostat mesilate. The urinary protein excretion decreased from 1)10.1±1.3 to 2) 7.3±1.1, and 3) 4.6±0.9 g/day [mean±SEM; significance of difference l)-2), p<0.05; 2)-3), p<0.01], and the serum total protein values increased from 1) 5.0±0.3 to 2) 5.2±0.2, and 3) 5.4±0.3 g/dl [l)-3), p<0.05]. The plasma levels of fibrinogen, and of E fragment and D-dimer of FDP changed from 1) 476±43 to 2) 477 ±41, and 3) 374±33 mg/dl [2)-3), p<0.01], from 1) 125 ± 19 to 2) 147±27, and 3) 104± 30 ng/ml [2)-3), p<0.05], and from 1) 261 ± 60 to 2) 272 ± 86, and 3) 185 ± 56 ng/ml [2)-3), p<0.05], respectively. Although the urinary excretions of E fragment and D-dimer of FDP decreased in many patients even during ACE inhibition, their urinary excretion ratio to urinary protein fell significantly only after camostat mesilate was administered. These results suggest that camostat mesilate may suppress the intravascular over-formation of fibrinogen and fibrin, and exert inhibitory effects on the hypercoagulable state induced by advanced diabetic nephropathy. This anti-coagulatory effect might be closely related to its anti-proteinuric effect in diabetic nephropathy.