Effect of protease inhibitor on primary glomerulonephritis and the mechanism of the effect

Effect of serine protease inhibitor Camostat Mesilate (Foipan®) on primary glomerulonephritis and it's mechanism were evaluated. Forty-two patients having primary glomerulonephritis (13 cases of IgA nephropathy, 11 cases of membranous nephropathy and others), aged 18 to 81 years were selected for this study. At the start of our study, twenty-one patients had received other drugs (13 cases of dipyridamole and 13 cases of prednisolone). A control period of four weeks was established to confirm that the levels of proteinuria and renal functions were stable. Patients were orally administered with 600 mg of Camostat Mesilate per day for four weeks. Effect of Camostat Mesilate was judged by urinary protein excretion, hematuria, serum total protein, albumin, Ccr, creatinine and BUN. In order to reveal the mechanism of the effect laboratory data such as granulocyte elastase, CH50, C3, C4, fibrinogen, platelate factor 4, β3-thromboglobulin, thromboxane B2 and prostaglandin F1α were evaluated before and after the treatment. Parameters were analyzed by using paired t-test. Mean (±SEM) urinary protein excretion reduced from 4. 31 ±0.91 to 2. 80±0.43g/day (p<0.05), and score of hematuria decreased from 1.8±0.16 to 1.5 + 0.15. A significant decrease in urinary protein excretion was seen in membranous nephropathy and a significant decrease in hematuria was seen in IgA nephropathy. In combination therapy (dipyridamole, prednisolone) urinary protein excretion markedly decreased (p<10.05) and in Camostat Mesilate therapy score of hematuria markedly decreased (p<0.05). Camostat Mesilate had no effects on renal function assessed by Ccr, creatinine and BUN. During observation period there were no significant changes in serum complement titers, prostanoids, granulocyte elastase and other parameters. From our present study, Camostat Mesilate had beneficial effects on primary glomerulonephritis, although the exact mechanism of these effects of the drug could not be elucidated. We consider that proteinase inhibitors may be beneficial for the treatment of primary glomerulonephritis.