Infusion of radiocontrast agents induces exaggerated release of urinary endothelin in patients with impaired renal function

Background. The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure. Methods. We measured plasma endothelin-1^.(ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 ± 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 ± 0.5 mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25 h, at a rate of 100 ml/h; starting from 5 h before the infusion of CM. Results. Plasma ET in group R (5.2 ± 1.4 pg/ml) was significantly higher than in group N (0.9 ± 0.3; P < 0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 ± 2.4 mg/g Cr) was significantly higher than in group N (1.5 ± 0. 4 mg/g Cr; P < 0.05). Urinary excretion levels of N-acetyl-β -D-glucosaminidase (NAG) and β2-microglobulin (β2M) were also significantly higher in group R (0.8 ± 0.2 mU/g Cr and 670 ± 400 mg/g Cr, respectively) than in group N (0.3 ± 0.1 and 7.5 ± 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 ± 2.6 mg/g Cr on the next day and returned to baseline level on the third day. NAG and β2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and β2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5 mg/dl), caused by infusion of the amount of half-normal saline used. Conclusions. In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure.