Monitoring of kidney transplant patients with tests for urinary kidney-derived antigens built on monoclonal antibodies

We have recently reported the preparation and characterization of monoclonal antibodies to antigens of the nephron of the human kidney and their use in sandwich enzyme-linked immunosorbent assay (ELISA) tests for the determination of kidney-derived urinary antigens (UA) in urine. In such tests, the antigen(s) measured are defined by the two monoclonal antibodies used: the solid-phase-adsorbed catcher and the enzyme-labeled indicator monoclonal antibody. Thirteen such tests were built, specific for antigens derived from cells of the proximal part (three tests), of the distal part (seven tests) and three tests for antigens localized over the entire length of the tubule system (pantubular antigens). These tests were applied to the urine of normal healthy subjects, of patients suffering from a variety of diseases with and without kidney involvement, and of normal healthy individuals treated with therapeutic doses of antibiotic drugs to test their nephrotoxicity. The results of these studies showed that antigen excretion, low in normal healthy persons, is enhanced in patients suffering from the acute phases of diseases and/or under treatment with nephrotoxic drugs. Enhanced excretion of UA2 and UA3 was observed in patients treated with drugs with known nephrotoxic side effects as well as in normal healthy individuals treated with therapeutic doses of antibiotic drugs. Enhanced excretion of some or of all of the antigens was always indicative of massive damage or acute phases of diseases. In the follow-ups ranging from ten to 80 days, the excretion patterns of 12 of the antigens was measured in the urine of 30 kidney transplant recipients from the transplantation unit of Beilinson Hospital. The results obtained indicate that monitoring of antigen excretion might be helpful for the early recognition of rejection episodes.