Experimental Nephritis—Other Models and Future Directions

Summary

Almost all of the advances in understanding the nephritogenic process responsible for human immune, glomerular, and tubulointerstitial renal injury have their basis in animal models. A large number of model systems are now available, with recent interest focused on producing selective glomerular cell injury. Antimesangial cell and anti-epithelial cell surface antigens participate in these processes. An almost parallel set of models are available for understanding the immune processes responsible for tubulointerstitial nephritis. These processes, which include immune deposit formation through antibody reactions with structural and cellular antigens, immune complex formation, and cellular immune reactions, are reviewed. Possible future directions for model use are described. A search for models of disease produced by antigens present only in activated or stimulated cells is suggested and should lead to a better understanding of the immunopathogenesis of vasculitis. Extensions of current model systems to better define the contribution of cytokine and growth factor cascades responsible for glomerular and renal cell contributions to injury are discussed, including the use of the isolated perfused kidney. A number of other possible extensions are mentioned, including selective immunotherapies using antibodies to the T cell receptor Vbeta gene, utilization of SCID mice for development of models of human autoimmunity, the possible role of transgenic mice, and, finally, the utilization of models of selective renal cell injury to further the understanding of renal pathophysiology.