ENDOTHELIN IN PATIENTS WITH CHRONIC-RENAL-FAILURE

To investigate the pathophysiological significance of endothelin-1 (ET-1) in renal failure, we measured plasma and urine concentrations of ET-1-like immunoreactivity (LI) by radioimmunoassay (RIA). The plasma ET-1-LI level was significantly increased in hemodialyzed and nonhemodialyzed patients with chronic renal failure (CRF). The increase in the plasma ET-1-LI level in CRF was much larger than that in other diseases in which the plasma ET-1-LI level was reported to be increased. The urine ET-1-LI level was lower, and daily excreted amounts of ET-1-LI were smaller in CRF patients than in normal subjects. These findings indicate that the increased plasma level of ET-1-LI in CRF results from the decreased clearance rate of ET-1-LI in the kidney. Gel permeation chromatographic analysis revealed that ET-1-LI in plasma from CRF consisted of small and large molecular forms of ET-1-LI. The small molecular form is presumably ET-1, and large molecular forms are big ET-1 and another component with the molecular weight of 6,000 as is the case of that in normal plasma (1). However, the ratio of the smaller to large molecular forms of ET-1-LI in CRF was 1:13 and was quite different from that in normal plasma (1:4). These observations clearly indicate that the elevation of plasma ET-1-LI level in CRF was mainly due to the increase in the large molecular form of ET-1-LI.