VALUE OF SERUM-SOLUBLE TUMOR-NECROSIS-FACTOR CONCENTRATIONS IN THE DIAGNOSIS AND PROGNOSIS OF RENAL GRAFT-REJECTION

Up to the present the histological diagnosis of rejection through biop sy is still the only possibility for a definite rejection diagnosis. W e searched for a reliable non-invasive marker of renal graft rejection . By means of a highly sensitive enzyme-linked immunosorbent assay we investigated the changes in the concentration of serum soluble TNF rec eptor in kidney graft recipients with different clinical courses accor ding to their graft tolerance. sTNF-R in 19 patients with stable graft function (5.3 +/- 3.2 ng/ml) did not differ significantly from those detected in 22 healty volunteers (4.1 +/- 2.2 ng/ml). In contrast 17 p atients suffering from acute graft rejection showed highly significant ly increases (23 +/- 8.3 ng/ml, P < 0.0001). These elevated concentrat ions returned to prerejection rejection values after a 3-day anti-reje ction therapy with high-dose methylprednisolone. In 18 patients with a n irreversible, chronic kidney graft rejection we could demonstrate si gnificantly increased sTNF-R values (20 +/- 7.9 ng/ml); eight of those patients did not reflect on the anti-rejection therapy, so that the e levated concentrations remained even after the administration of high- dose corticosteroids and ATG. Additionally we found soluble TNF recept or concentrations to be increased earlier than other commonly used bio chemical parameters such as creatinine. Soluble TNF-R also proved to b e useful for the differentiation of cyclosporin nephrotoxicity. Theref ore we believe that the soluble TNF-R and its concentration course may be of diagnostic and prognostic value in kidney graft rejection, as i t supports the diagnosis of transplant rejection, indicates the reject ion event very early, and reflects the response to anti-rejection ther apy.