INCREASED RENAL EXCRETION OF ENDOTHELIN-1 IN NEPHROTIC PATIENTS

Background. Renal function is influenced by direct and indirect action of endothelins. They reduce renal blood flow and glomerular filtratio n. The aim of the present study was to determine plasma and urinary en dothelin-1 (ET-1) in two major categories of renal patients and to com pare them with normal subjects. Methods. Endothelin-l was measured in the plasma and urine of patients with chronic renal disease and reduce d glomerular filtration rate (GFR), and in patients with proteinuria d ue to glomerular dysfunction with unaffected GFR. A group of healthy s ubjects was used as a reference. Results. Plasma endothelin-l was incr eased in all patients to 60+/-13pg/ml independent of GFR compared to 2 9+/-5pg/ml in normal subjects (P< 0.001). The endothelin-l load was de creased to 1190+/-450pg/m1/1.73m2 in patients with reduced GFR, compar ed to 2780+/-690 pg/m1/1.73 m(2) of normal subjects, whereas in patien ts with glomerular damage and normal GFR, it was increased to 5480 +/- 1910 pg/ml/1.73 m(2) (P < 0.01). ET-1 was found to be excreted and re absorbed by the renal tubules by the same mechanisms as sodium and pot assium, because its secretion fraction changes in parallel to those of the above ions. The excreted endothelin increased to 730+/-420 and 71 0+/-250pg/ml/1.73m(2) (P < 0.01) in the two categories of patients res pectively, compared to 290+/-100 pg/ml/1.73 m(2) in the normal group. The excretion fraction of patients with normal GFR was similar to norm al subjects, while it appeared to increase in patients with reduced GF R (P<0.01). Conclusions. In the development of renal disease the plasm a endothelin concentration is independent of the renal filtration capa bility and endothelin may be involved in functional and anatomical cha nges of the kidney as a causal factor or resulting from the renal dise ase.