Increased renal TXA 2 synthesis in diabetes mellitus: Simultaneous determination of urinary TXB 2 and 2,3-dinor-TXB 2

Abstract

The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E 2, TXB 2 and 2,3-dinor-TXB 2, a major urinary metabolite of TXA 2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA 1>11% excreted less KAL. Urinary PGE 2 excretion (7.6 ± 2.8 ng/mg creatinine, mean ± SE) was significantly lower in DM compared to C (17.5 ± 3.9, p<0.05), while DM excreted more TXB 2 (0.57 ± 0.09, p<0.01) and 2,3-dinor-TXB 2 (0.56 ± 0.12, N.S.) than C (0.19 ± 0.02 or 0.33 ± 0.01). DM with or without mild proteinuria demonstrated lower PGE 2, but higher TXB 2 and 2,3-dinor-TXB 2 excretion. A positive correlation of TXB 2/2,3-dinor-TXB 2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 μg/mg creatinine, TXB 2 and 2,3-dinor-TXB 2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB 2 to PGE 2 or 2,3-dinor-TXB 2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB 2 to 2,3-dinor-TXB 2 may indicate an augmented renal, in addition to platelet, TXA 2 synthesis. An excessive vasoconstrictive and proaggregatory TXA 2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE 2, may have profound effects on renal functions such as protein excretion in DM.