Significant advances have been made in the understanding of the relationship between morphology and function in acute renal failure (ARF). However, two factors limit the clinical usefulness of the information obtained thus far in this important area: 1) ARF is a common life-threatening disease but occurs in only a small fraction of the very large group of patients at risk. The affected patients often have several factors predisposing to the development of ARF. Therefore, animal models in which a single very severe insult causes ARF in virtually every animal may not be completely relevant to human disease. 2) ARF is very common in transplanted kidneys and transplant patients are often biopsied as a part of therapeutic decision-making. Thus, information regarding the relationship between morphological and functional changes in transplant ARF would be of great practical significance. However, most studies of morphologic changes in ARF have been carried out in native rather than transplanted kidneys. We will study the pathology and pathophysiology of ARF in the transplanted kidney in syngeneic and allogeneic rat renal transplants. Attempts will be made to identify morphologic correlates of ischemic ARF, cyclosporine-induced ARF, and acute rejection using light microscopic morphometry and monoclonal antibody immunoperoxidase techniques. We will study combined insults as a cause of ARF in the rat using combinations of ischemia plus cyclosporine therapy, combinations similar to those that might be encountered in transplant patients who develop ARF. We will also study the protection against ARF brought about by regimens designed to alleviate medullary congestion. The morphologic correlates of protection against ARF will be studied using light, transmission and scanning electron microscopy. Renal function will be assessed by clearance and micropuncture techniques and measurements of renal blood flow. The ultimate aim of our studies is to define the pathophysiology of ARF as it is commonly encountered clinically and provide better means of preventing the disorder and of distinguishing it from acute rejection in the transplanted kidney.
