Camostat mesilate is a developed derivative of
gabexate mesilate 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 nephropathy at a daily dose of 600 mg for 4 to 6 weeks. All patients had been treated with conventional
therapy including
angiotensin-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 less than 0.01) and
serum albumin level increased from 2.7 +/- 0.2 gm/dl to 2.9 +/- 0.2 gm/dl (mean +/- SEM, p less than 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 less than 0.01), and urinary total
fibrinogen degradation product excretion over 24 hours also decreased from 26,118 +/- 9,696 to 18,072 +/- 7,107 micrograms/day (mean +/- SEM, p less than 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 mellitus, and changes the permselectivity of the glomerular capillary wall. These effects of
camostat mesilate may improve the prognosis of
diabetic nephropathy.