Endothelin-1 and endothelin receptor status in kidney transplants undergoing acute rejection

Endothelin-1 (ET-1) is a potent vasoconstrictor with vasopressor and mitogenic effects. Blood samples were collected from 21 renal transplant patients undergoing acute rejection at the time of diagnostic kidney biopsy: there were 20 men and one woman, mean age 35.6 years. All patients were on triple immunosuppressive therapy with cyclosporine A, azathioprine and methylprednisolone. Twenty living kidney donors pre-uninephrectomy (11 men and nine women, mean age 34 years) served as controls. Control kidney was obtained from fresh autopsy material and normal kidney tissue from nephrectomies for malignancy. Mean plasma ET-1 was significantly increased at 1.56 +/- 0.2 pg ml(-1) during acute rejection compared to 0.74 +/- 0.06 pg ml(-1) in donors (p = 0.0009 unpaired t-test). ET(A) receptor immunolabelling was visualised in distal tubules and collecting ducts with minimal labelling in the glomeruli and blood vessels of control kidney tissue ET(A) receptor labelling was similar in kidney biopsies with acute rejection. ET(B) receptor immunolabelling was significantly increased in glomeruli (p = 0.002) and decreased in distal tubules (p = 0.004) in kidneys with acute rejection compared to control kidney tissue. While these findings may account for the oedema and hypertension observed during acute rejection, the exact significance needs to be studied further.