Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy.
We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), TXB2 (a stable metabolite of TXA2) and PGE2 in NIDDM patients was comparable with that in control subjects. However, the urinary 6-keto-PGF1 alpha/TXB2 ratio in NIDDM patients with both micro- and macroalbuminuria was significantly (P less than 0.001) lower than that in the controls. By a single administration of OKY-046 (40 mg, i.v.) to the diabetic patients, urinary TXB2 excretion significantly (P less than 0.05) decreased from 169.7 +/- 23.9 to 140.2 +/- 17.9 ng/gCr, but urinary 6-keto-PGF1 alpha and PGE2 excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio thus significantly (P less than 0.01) increased from 1.02 +/- 0.13 to 1.73 +/- 0.41 as associated with significant increments in urine volume (P less than 0.05), urinary sodium excretion (P less than 0.01) and creatinine clearance (P less than 0.05). Of 14 diabetic patients, 7 with macroalbuminuria (albumin index exceeding 100 mg/gCr) were orally given OKY-046 (600 mg/day) for 8 weeks. After this period, the urinary albumin index significantly (P less than 0.05) decreased from 524.9 +/- 149.6 to 317.6 +/- 90.6 mg/gCr.(ABSTRACT TRUNCATED AT 250 WORDS)
Tajiri
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Inoguchi
T
T
Umeda
F
F
Nawata
H
H
D000419:Albuminuria; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008689:Methacrylates / Q000627:therapeutic use*; D008875:Middle Aged; D011453:Prostaglandins / Q000652:urine*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D011453:Prostaglandins; D003404:Creatinine; D013930:Thromboxane-A Synthase; C034364:ozagrel