Renal hemodynamics and urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in newly diagnosed type I diabetic patients.
We have studied the functional importance of renal eicosanoids in renal hemodynamics of seven newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients by treatment with two structurally unrelated inhibitors of cyclooxygenase (i.e., piroxicam and sulindac). Glomerular filtration rate (GFR), renal plasma flow (RPF), daily urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of prostacyclin), and thromboxane B2 (TXB2, the stable hydrolysis product of thromboxane A2) were measured before, during, and after piroxicam (all patients) or sulindac (3 patients) treatment. Urinary excretion of 6-keto-PGF1 alpha was significantly increased (P less than .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB2 was unchanged. The baseline value of GFR was significantly (P less than .01) higher in diabetic compared with normal volunteers, whereas baseline RPF was comparable in both groups. Piroxicam (20 mg/day) reduced urinary excretion of 6-keto-PGF1 alpha and TXB2 by 65.7 +/- 26 and 64.6 +/- 33%, respectively. These biochemical changes were temporally associated with the approximately 19% decrease in GFR (P less than .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF1 alpha were still significantly (P less than .05) reduced, whereas urinary excretion of TXB2 returned to control values. In contrast, urinary excretion of eicosanoids and renal function were not affected by sulindac (0.4 g/day) treatment. No functional changes were detected in healthy subjects despite a similar suppression of renal cyclooxygenase activity when they were treated with piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)
Gambardella
S
S
Department of Medicine, University of Rome, La Sapienza, Italy.
Andreani
D
D
Cancelli
A
A
Di Mario
U
U
Cardamone
I
I
Stirati
G
G
Cinotti
G A
GA
Pugliese
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine*; D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D010894:Piroxicam / Q000627:therapeutic use; D013467:Sulindac / Q000627:therapeutic use; D013928:Thromboxane A2 / Q000652:urine*
D010894:Piroxicam; D013467:Sulindac; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine