| Abstract: | A mouse monoclonal antibody, specific for binding with the epithelial surface antigen in human renal proximal tubules, was produced by hybridoma culture. Using this antibody, an enzyme-linked immunosorbent assay was developed to measure the human renal tubular epithelial antigen (HRTE) concentrations in serum samples from 25 normal subjects and 66 consecutive renal allograft recipients. In 46 patients treated with azathioprine and prednisone, serum HRTE was elevated more than two-fold in 56 of 62 rejection episodes 2-5 days before the clinical diagnosis was made. Of the 56 rejection episodes, the antigen level fell to baseline after treatment in 44 steroid-responsive episodes, but it remained elevated in 8 steroid-resistant rejections, and it became undetectable 3-4 days after the initial elevation in 4 episodes in which allografts were lost to rejection. In 20 patients treated with cyclosporine and prednisone, all 25 rejection episodes demonstrated a greater than two-fold increase of serum HRTE 1-6 days prior to the diagnosis of rejection. The antigen level fell to baseline in 23 reversible rejection episodes, however serum HRTE remained elevated in 2 steroid-resistant patients whose grafts were lost to rejection. Cyclosporine nephrotoxicity without rejection was confirmed in 6 episodes, each of which demonstrated a more than two-fold increase in HRTE 2-4 days before toxicity was diagnosed. When the cyclosporine dose was reduced, the antigen level decreased as the serum creatinine declined. Serial determinations of serum HRTE in renal transplant recipients can provide valuable information for the early diagnosis and management of allograft rejection and cyclosporine nephrotoxicity. |
