Renal Hemodynamics and Urinary Excretion of 6-Keto-Prostaglandin F_1α 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 F_1α (6-keto-PGF_1α, 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-PGF_1α was significantly increased (P < .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB₂ was unchanged. The baseline value of GFR was significantly (P < .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-PGF_1α and TXB₂ by 65.7 ± 26 and 64.6 ± 33%, respectively. These biochemical changes were temporally associated with the ∼ 19% decrease in GFR (P < .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF_1α were still significantly (P < .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.We conclude that altered GFR in newly diagnosed IDDM patients may depend, at least partially, on altered renal synthesis of vasodilator prostacyclin.