Effects of cilostazol, a phosphodiesterase inhibitor, on urinary excretion of albumin and prostaglandins in non-insulin-dependent diabetic patients.
Microalbuminuria is characteristic in diabetic nephropathy and is thought to be influenced by renal hemodynamics, especially by the metabolism of prostaglandins (PGs) in glomruli. To reduce urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM), we administered 100 mg of cilostazol, a phosphodiesterase inhibitor, daily for 3 months. The urinary albumin index (UAI: microgram albumin/mg creatinine) decreased significantly after 3 months of administering cilostazol. Urinary excretions of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2, decreased significantly after treatment. However, it had no effects on urinary excretions of PGE2 and 6-keto PGF1 alpha (6KF), a stable metabolite of prostacyclin. The ratio 6KF/TXB2 has been known to reflect the renal metabolism of PGs. In this study, urinary 6KF/TXB2 ratio increased significantly in parallel with a significant reduction of UAI. Cilostazol had no adverse effects on the control of blood glucose and lipids. In conclusion, cilostazol has a beneficial effect on UAI in patients with NIDDM by reducing renal production of TXB2., which increases 6KF/TXB2 ratio.
Watanabe
J
J
Fukuoka Medical Association Hospital, Seijinbyo Center, Japan.
Sako
Y
Y
Umeda
F
F
Nawata
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine*; D000118:Acetylglucosaminidase / Q000652:urine; D000284:Administration, Oral; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy*; D015415:Biomarkers / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D000077407:Cilostazol; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013929:Thromboxane B2 / Q000652:urine*; D001613:beta 2-Microglobulin / Q000652:urine
D015121:6-Ketoprostaglandin F1 alpha; D000118:Acetylglucosaminidase; D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D000077407:Cilostazol; D006442:Glycated Hemoglobin; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D013929:Thromboxane B2; D001613:beta 2-Microglobulin