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Endothelin A Receptors Expressed in Renal Blood Vessels of Renal Transplant Patients Are Connected With Acute Tubular Necrosis or Antibody-Mediated Rejection.

BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies.

METHODS: Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale.

RESULTS: We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved.

CONCLUSIONS: The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.

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