Abstract
Abnormalities of renal prostaglandins (PGs) contribute to the pathogenesis of diabetic nephropathy through changes in renal hemodynamics. Our recent studies have demonstrated that urinary excretion ratio of 6-keto-PGF 1 α (6KF) to TXB 2 is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). In the present study, we evaluated the clinical effects of some drugs on renal PG metabolism and diabetic nephropathy. Ozagrel, a specific thromboxane synthetase inhibitor, reduced urinary TXB 2 excretion, resulting in the improvement of the decreased urinary 6KF/TXB 2 ratio in NIDDM patients. Urinary albumin excretion was decreased and creatinine clearance (Ccr) was increased during ozagrel administration. The similar beneficial effect was also found in the administration of cilostazol, a phosphodiesterase inhibitor, whereas a stable analogue of PGI 2, beraprost sodium, reduced urinary albumin excretion in relation to the reduction of platelet aggregation rate. In conclusion, the drugs modulating renal and platelet PG S metabolism with direction to an increase in 6KF/TXB 2 ratio and an inhibition against platelet function might be beneficial for the treatment of diabetic nephropathy.
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