Value of serum soluble tumour necrosis factor concentrations in the diagnosis and prognosis of renal graft rejection.

Up to the present the histological diagnosis of rejection through biopsy is still the only possibility for a definite rejection diagnosis. We 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 receptor in kidney graft recipients with different clinical courses according 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 patients suffering from acute graft rejection showed highly significantly increases (23 +/- 8.3 ng/ml, P < 0.0001). These elevated concentrations returned to prerejection rejection values after a 3-day anti-rejection therapy with high-dose methylprednisolone. In 18 patients with an irreversible, chronic kidney graft rejection we could demonstrate significantly increased sTNF-R values (20 +/- 7.9 ng/ml); eight of those patients did not reflect on the anti-rejection therapy, so that the elevated concentrations remained even after the administration of high-dose corticosteroids and ATG. Additionally we found soluble TNF receptor concentrations to be increased earlier than other commonly used biochemical parameters such as creatinine. Soluble TNF-R also proved to be useful for the differentiation of cyclosporin nephrotoxicity. Therefore we believe that the soluble TNF-R and its concentration course may be of diagnostic and prognostic value in kidney graft rejection, as it supports the diagnosis of transplant rejection, indicates the rejection event very early, and reflects the response to anti-rejection therapy.