Diabetes, Vol 37, Issue 8 1044-1048, Copyright © 1988 by American Diabetes Association
Renal hemodynamics and urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in newly diagnosed type I diabetic patients
S Gambardella, D Andreani, A Cancelli, U Di Mario, I Cardamone, G Stirati, GA Cinotti and F Pugliese
Department of Medicine, University of Rome, La Sapienza, Italy.
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)