Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy

Diabetes Res Clin Pract. 1990 Nov-Dec;10(3):231-9. doi: 10.1016/0168-8227(90)90066-3.

Abstract

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)

MeSH terms

  • Albuminuria*
  • Creatinine / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / urine
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine
  • Female
  • Humans
  • Kidney / physiopathology
  • Male
  • Methacrylates / therapeutic use*
  • Middle Aged
  • Prostaglandins / urine*
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Methacrylates
  • Prostaglandins
  • Creatinine
  • Thromboxane-A Synthase
  • ozagrel