Glomerular disease is a major cause of acute and chronic renal failure in the pediatric age group. Clinical and experimental evidence suggests that the susceptibility of the immature glomerulus to a variety of pathogenic insults, both immune and non-immune, distinctively differs from the adult's. These differences are particularly prominent in terms of a) incidence of pathology, b) functional response to a certain degree of pathologic insult, and c) recovery following an initial insult. While several investigators have examined the adaptation of the immature kidney to the chronic phase of injury, the susceptibility of the immature glomerulus to the acute effect of an insult remain largely unexplored. In particular, two important aspects of glomerular function in the young mammal, which may directly affect its susceptibility to disease, namely biosynthetic capabilities and macromolecular barrier characteristics in relation to glomerular microcirculatory dynamics, have received little attention from investigators. Examination of these aspects of glomerular function in the maturing animal will further elucidate the biology of growth of the mammalian glomerulus. Moreover, exploration for the cause of the unique disease susceptibility of immature glomeruli is hoped to provide a fruitful opportunity to test and expand our current knowledge regarding the basic pathophysiology involved in the functional derangements during glomerular injury. In the current proposal, the PI intends to address the above issues utilizing a number of techniques including: glomerular micropuncture, fractioned clearances of variously sized dextrans, and measurements of endogenous biologically active lipid mediators in kidneys of immature and mature animals, following induction of immune or non-immune experimental models of injury. These techniques will be supplemented by histologic examination of renal tissues.
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