Endothelin receptors in the kidney of patients with proteinuric and non-proteinuric nephropathies.
BACKGROUND
Endothelin-1 (ET-1), which acts via the specific receptors ET-A and ET-B, has been implicated in the development of renal scarring. The activation of the endothelin system was observed in experimental models of glomerular diseases and was attributed to the toxic action of proteinuria on the tubular epithelial cells. The aim of this study was to investigate whether the endothelin system in the kidney is altered in glomerular diseases and possibly related to proteinuria.


METHODS
Thirty-seven patients with different types of glomerulonephritis and 14 controls were included. Patients presented either nephrotic syndrome (n=25) or mild proteinuria (<1g/24h, n=12). The expression of ET-A and ET-B receptors in the renal tissue was examined immunohistochemically. At the time of biopsy, urinary ET-1 was determined.


RESULTS
Both receptors were mainly localized within tubular epithelial cells, and their expression was significantly higher in patients with glomerulonephritis compared to controls. The expression of ET-B was higher in nephrotic compared to non-nephrotic patients, while no difference was observed in the expression of ET-A receptors. A significant positive correlation of the degree of proteinuria with the excreted ET-1 (r= 0.487, p<0.05) and the extent of immunostaining for ET-B receptors (r=0.420, p<0.05) was observed. The expression of ET-B receptors and the excretion of ET-1 decreased significantly in patients with remission of nephrotic syndrome after therapy.


CONCLUSIONS
This study provides evidence that the endothelin system is activated in human glomerular disease, confirming data from experimental studies. Proteinuria seems to be related to the activation of endothelin system, though further investigation is necessary to clarify this issue.
Drakopoulos
Anastasios
A
Department of Internal Medicine-Nephrology, University Hospital, Patras, Greece.
Goumenos
Dimitrios S
DS
Vlachojannis
John G
JG
Tsakas
Sotiris
S
D000328:Adult; D019332:Endothelin-1 / Q000652:urine; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D009404:Nephrotic Syndrome / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000378:metabolism* / Q000473:pathology; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B