Identification of fragments of proximal and distal tubular cells in the urine of patients under cytostatic treatment by immunoelectron microscopy with monoclonal antibodies.

In an attempt to identify the origin of cellular fragments released in the urine of patients treated with potentially nephrotoxic drugs such as cytostatics, two monoclonal antibodies were applied: monoclonal antibody PM II 9 C2, directed against an antigen in distal tubular cells; and monoclonal antibody PM II 39 H11 specific for an antigen in proximal tubular cells. The specificities of both monoclonal antibodies were elaborated in the indirect as well as in the direct immunofluorescence technique. Both antibodies were then used to identify cellular fragments obtained from the urine of patients treated with cytostatic drugs by ultracentrifugation. By application of the indirect immunogold method, it was shown that material of proximal as well as distal tubular origin was shed by the damaged cells. Whereas the proximal tubular antigenic epitope recognized by PM II 39 H11 was always found in large irregular complexes of debris-containing vesicles, the distal tubular antigenic epitope recognized by PM II 9 C2 was always found associated with filament-like regular structures. This is the first report in which excretion of components of distal tubular cells is demonstrated as a consequence of the nephrotoxic side effects of cytostatic treatment. With the help of monoclonal antibodies, it has now become possible to identify and to investigate the damage inflicted on the distal part of the tubule system in addition to the well-documented proximal tubular damage.