Increased renal excretion of endothelin-1 in nephrotic patients

Abstract

BACKGROUND: Renal function is influenced by direct and indirect action of endothelins. They reduce renal blood flow and glomerular filtration. The aim of the present study was to determine plasma and urinary endothelin-1 (ET-1) in two major categories of renal patients and to compare them with normal subjects. METHODS: Endothelin-1 was measured in the plasma and urine of patients with chronic renal disease and reduced glomerular filtration rate (GFR), and in patients with proteinuria due to glomerular dysfunction with unaffected GFR. A group of healthy subjects was used as a reference. RESULTS: Plasma endothelin-1 was increased in all patients to 60 +/- 13 pg/ml independent of GFR compared to 29 +/- 5 pg/ml in normal subjects (P < 0.001). The endothelin-1 load was decreased to 1190 +/- 450 pg/ml/1.73 m2 in patients with reduced GFR, compared to 2780 +/- 690 pg/ml/1.73 m2 of normal subjects, whereas in patients with glomerular damage and normal GFR, it was increased to 5480 +/- 1910 pg/ml/1.73 m2 (P < 0.01). ET-1 was found to be excreted and reabsorbed by the renal tubules by the same mechanisms as sodium and potassium, because its secretion fraction changes in parallel to those of the above ions. The excreted endothelin increased to 730 +/- 420 and 710 +/- 250 pg/ml/1.73 m2 (P < 0.01) in the two categories of patients respectively, compared to 290 +/- 100 pg/ml/1.73 m2 in the normal group. The excretion fraction of patients with normal GFR was similar to normal subjects, while it appeared to increase in patients with reduced GFR (P < 0.01). CONCLUSIONS: In the development of renal disease the plasma endothelin concentration is independent of the renal filtration capability and endothelin may be involved in functional and anatomical changes of the kidney as a causal factor or resulting from the renal disease.