Prostaglandins and diabetic nephropathy.
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-PGF1 alpha (6KF) to TXB2 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 TXB2 excretion, resulting in the improvement of the decreased urinary 6KF/TXB2 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 phosphodiesteraase inhibitor, whereas a stable analogue of PGI2, berprost sodium, reduced urinary albumin excretion in relation to the reduction of platelet aggregation rate. In conclusion, the drugs modulating renal and platelet PGs metabolism with direction to an increase in 6KF/TXB2 ratio and an inhibition against platelet function might be beneficial for the treatment of diabetic nephropathy.
Umeda
F
F
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kuroki
T
T
Nawata
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000419:Albuminuria; D000077407:Cilostazol; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000652:urine; D015232:Dinoprostone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008689:Methacrylates / Q000494:pharmacology*; D008954:Models, Biological; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000652:urine*; D013777:Tetrazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D008689:Methacrylates; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D013777:Tetrazoles; C048081:beraprost; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C034364:ozagrel; D000077407:Cilostazol