SHORT REPORTS Effects of Thromboxane Synthesis Inhibitor Triflusal on Renal Hemodynamics in Microalbuminuric Diabetic Patients Enric Esmatjes, MD Jesus I. Conget, MD Joan Gaya, MD Maria R. Fernandez, MD Jorge P. Ferrer, MD Francisca Rivera, MD Enric Vilardell, MD Triflusal (2-acetoxy-4-trifluormethylbenzoic acid) is a platelet-antiaggregant drug that selectively inhibits thromboxane synthesis with little effect on prostacyclin production. In this study, we evaluated the effect of 5- day administration of 900 mg/day triflusal on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary albumin excretion (UAE), thromboxane B 2 (TXB 2 ), 6-ketoprostaglandin F 1u (PGF 1a ), and PGE 2 in nine normotensive insulin-dependent diabetic patients with UAE between 30 and 103 fxg/min. Plasma TXB, and plasma renin activity (PRA) were also determined. After administration of triflusal, we observed a reduction in microalbuminuria (59 ± 25 vs. 33 ± 22 |xg/min, P < 0.01), an increase in RPF (648 ± 119 vs. 722 ± 134 m l • min" 1 • 1.73 m~ 2 , P < 0.01), and a reduction in filtration fraction (0.24 ± 0.04 vs. 0.20 ± 0.03, P < 0.01). Triflusal produced a significant reduction in both plasma TXB 2 (130 ± 39 vs. 52 ± 32 pg/ml, P < 0.02) and urine TXB 2 (523 ± 249 vs. 312 ± 11 pg/min, P < 0.02), without changes in PRA and UAE of 6-keto-PGF,,, and PGE,. Metabolic control and arterial blood pressure did not change during the study. These results suggest that platelet-antiaggregant therapy can reduce microalbuminuria in diabetic patients. This effect could be mediated by a reduction in the transglomerular hydraulic pressure through a vasodilation of efferent arterioles secondary to renal thromboxane synthesis inhibition. Diabetes Care 13:1114-17, 1990 G lomerular filtration rate (GFR) and renal plasma flow (RPF) are increased in short-term insulin- dependent diabetes mellitus (IDDM). Experi- mental and epidemiological data, as well as the- oretical considerations, indicate an important influence of these early glomerular hemodynamic abnormalities on the development and progression of diabetic ne- phropathy (1). Among the recent therapeutic interven- tions intended to reduce glomerular hyperfiltration, it has been demonstrated that treatment with a specific thromboxane synthetase inhibitor (2) or a platelet-inhib- itor regimen of dipyridamole and aspirin (3) reduced microalbuminuria excretion and improved the evolution of diabetic nephropathy in IDDM patients, suggesting that renal thromboxane is related to glomerular abnor- malities. In the 1970s, a platelet-antiaggregant drug, triflusal (2-acetoxy-4-trifluormethylbenzoic acid; J. Uriach, Bar- celona, Spain), was developed. Like acetylsalicylic acid (ASA), it inhibits platelet cyclooxygenase activity, but in contrast to ASA, it has a negligible effect on vessel cy- clooxogenase at therapeutic concentrations (4). This drug prevents the formation of aggregatory thromboxane (TXA 2 ) in platelets without changing the antiaggregatory prostacyclin (PGI 2 ) vascular synthesis. The antiaggre- gant effect of triflusal has been clinically demonstrated under pathological conditions, including diabetes mel- litus (5), but its effect on renal hemodynamics has never been evaluated. The aim of this study was to evaluate the possible effect of short-term administration of triflu- sal on microalbuminuria, renal hemodynamics, and vasodilator and vasoconstrictor renal prostaglandin syn- thesis in patients with IDDM and incipient nephropathy. RESEARCH DESIGN AND METHODS Nine IDDM patients (4 women, 5 men) were recruited consecutively among outpatients fulfilling the following criteria: persistent microalbuminuria (defined as a uri- nary albumin excretion [UAE] rate between 30 and 150 ixg/min in 2 consecutive sterile ketone-free 24-h collec- tions of urine), age <40 yr, onset of IDDM at <31 yr of age, normotension (diastolic blood pressure <85 mmHg), no medication other than insulin, and no his- tory of allergic reactions to drugs or peptic ulcer disease. No other antiprostaglandin agents were taken through- out the study. Patients had a mean ± SD age of 24 ± 8 yr, diabetes duration 9.5 ± 8.4 yr, HbA! level 10.4 ± 1.6%, body mass index 22.0 ± 2.6 kg/m 2 , and insulin dosage 0.77 ± 0.12 U • kg" 1 • 24 " 1 . Informed consent was given by the subjects, and the study pro- tocol was approved by the local ethical committee. On admission to the hospital, patients continued their usual insulin schedule and were given a normocalorie- free diet. After 3 days of adapting to inpatient physical activity, two consecutive 24-h control urine samples were collected in a container with 0.1 M Tris-HCI, pH 7.4 (days 1 and 2). Aliquots of this urine were frozen at -20°C until assayed. UAE was determined in both sam- ples, and TXB 2 , 6-ketoprostaglandin F 1a (6-keto-PGF 1a ), prostaglandin E 2 (PGE 2 ), sodium, and potassium were determined in the day 2 sample. On the morning of the 3rd day of the study, after overnight rest and fasting, an antecubital vein was catheterized. Blood samples were obtained 30 min later for plasma renin activity (PRA), plasma TXB 2 , plasma 6-keto-PGF 1a , and glycosylated hemoglobin determinations. Samples were collected in tubes with EDTA and lysine acetylsalicylate, and the plasma obtained was frozen at — 20°C until assayed. GFR and RPF were determined by plasma disappear- 1114 DIABETES CARE, VOL. 13, NO. 11, NOVEMBER 1990