URINARY-EXCRETION OF ENDOTHELIN-1 IN NORMAL SUBJECTS AND PATIENTS WITH RENAL-DISEASE

To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity (LI) in 17 patients with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-LI excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was significantly (P < 0.005) greater than that of normal subjects (77 +/- 5 ng). In patients with renal disease, ET-1-LI clearance (C(ET)) exceeded creatinine clearance (C(CR)); C(ET)/C(CR) (305 +/- 81%) was significantly (P < 0.005) greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion of ET-1-LI in patients with renal disease showed significant correlation with that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P < 0.05), beta-2-microglobulin (r = 0.614, P < 0.01) and albumin (r = 0.484, P < 0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not affect urinary ET-1 excretion rate. These data suggest that urinary excretion of ET-1 derives mainly from renal tubular secretion at least in patients with renal disease, and that degradation and/or reabsorption of ET-1 at the tubular site may also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET-1 should serve as a potential marker for renal injury.