Diagnosis of tubular injury in renal transplant patients by a urinary assay for a proximal tubular antigen, the adenosine-deaminase-binding protein
Two murine monoclonal antibodies (URO-4 and URO-4a)--which detect different epitopes of a proximal tubular cell glycoprotein antigen, the adenosine-deaminase-binding protein (ABP)--have been formatted into a sandwich enzyme immunoassay for detection of ABP in the urine. Serial urine samples from 34 renal transplant patients during the first six months posttransplant were analyzed to determine the correlation of this test with clinical rejection and cyclosporin (CsA) nephrotoxicity. In 29/29 acute rejection episodes the ABP level was elevated, beginning 1-7 days prior to treatment of rejection. Eighteen patients were treated for rejection with courses of OKT3 or antithymocyte globulin: 0/6 whose ABP level fell to normal during therapy had rerejection; 10/12 whose ABP level remained elevated had rerejection within 7 days of therapy completion. Of 15 patients treated with CsA, 7 had no rejection or drug toxicity; all 7 had normal ABP levels. The remaining 8 had CsA nephrotoxicity, all in association with elevated ABP levels that rapidly fell to normal with decreased CsA dose. An additional 7 patients with creatinine elevations more than 6 months posttransplant were studied: 5 had chronic vascular changes on biopsy, no response to increased immunosuppression, and normal ABP levels; 2 had a cellular infiltrate on biopsy, response to increased immunosuppression, and elevated ABP levels. We conclude that the urinary ABP assay provides information useful in the management of renal transplant patients with acute and chronic rejection and CsA toxicity.