PATTERN OF ENDOTHELIN IMMUNOSTAINING DURING REJECTION EPISODES AFTER KIDNEY-TRANSPLANTATION

A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effect s, are investigated intrarenal ET content in 82 kidney transplant biop sies and 10 normal control kidneys. ET-immunostaining, using a polyclo nal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epitheli um. Normal kidneys showed a strong staining of endothelial cells in al l vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen . In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA tox icity, however, lead to a significant reduction of endothelial ET stai ning. Neither mean doses nor trough levels of CyA correlated closely w ith the immunostaining findings. Plasma big-ET levels were elevated du ring vascular rejection, but not in interstitial rejection and ATN. Th is study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these cha nges are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection an d during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content.