The aims of this work are to determine (1) if early cadaver renal allograft dysfunction (acute tubular necrosis) can be predicted from allograft biopsy before transplantation; (2) if acute tubular necrosis results from improper donor selection and management, or if it results from inadequate organ preservation; (3) if the morphology of allograft acute tubular necrosis varies with the type of preservation used; and (4) if insight can be gained into the basic membrane biology of rental tubular epithelium and capillary endothelium from the studies of biopsies before and after preservation. Biopsies of kidney will be taken after cadaver nephrectomy and again after transplantation. They will be studied by light and electron microscopy to determine the presence of tubular necrosis. Abnormalities will be quantitated by morphometric analysis in the histologic sections. Ultrastructural changes in tubular epithelium and capillary endothelium will be assessed and correlated with length and method of preservation. A correlation between the biopsy morphology and the clinical outcome of the allograft will be made by plotting the daily serum creatinine against time for the first week after transplantation. The long-term objective of this work is to ascertain the cause of acute tubular necrosis in allograft kidneys so that insight into its prevention can be gained. The research project is unique in that it requires the collaborative effort of the SEOPF which has agreed to cooperate in the study. It is anticipated that about 250 biopsies will be available each year for study. This work is also unique in that it combines the morphologic expertise of the principal investigator with his clinical expertise in transplantation. The project is relevant to the management of renal failure patients because of a recent SEOPF report which demonstrated a 15 percent decrement in two year graft survival for kidneys subjected to acute tubular necrosis.
