TY - JOUR
T1 - Anti-proteinuric and anti-coagulatory effects of camostat mesilate in azotemic diabetics
AU - Matsubara, Mitsunobu
AU - Taguma, Yoshio
AU - Saito, Takao
AU - Yoshinaga, Kaoru
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - ACE inhibition
KW - plasma D-dimer of FDP
KW - plasma E fragment of FDP
KW - plasma fibrinogen
KW - urinary FDP
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U2 - 10.14842/jpnjnephrol1959.34.411
DO - 10.14842/jpnjnephrol1959.34.411
M3 - Article
C2 - 1635286
AN - SCOPUS:0026628976
VL - 34
SP - 411
EP - 416
JO - Japanese Journal of Nephrology
JF - Japanese Journal of Nephrology
SN - 0385-2385
IS - 4
ER -