Age and diet, particularly the intake of protein, have been suggested to influence the development, progression and ultimate outcome of human renal disease. However, the nature of this influence has been difficult to isolate. In part, this is due to the co-existence of other potentially predisposing influences. The proposed projects will use established animal models of acute and chronic renal disease to assess the effect of age and diet on the development and progression of immune and non-immune glomerular injury. The influence of these variables on glomerular function and structure will be simultaneously assessed by performing micropuncture measurements and qualitative and quantitative morphologic analyses in young versus adult animals and high versus low protein-fed animals. If differences are detected, the underlying mechanism will be further explored. It should be recognized that, in chronic renal disease nephrons become heterogeneous in structure and function. As a result, meaningful assessment of these parameters can no longer be made by whole kidney studies. Unlike acute renal disease, therefore, the relationship between these terms has yet to be established in chronic renal disease. Our studies will examine this relationship on an individual nephron basis, again by micropuncture and morphologic studies. We will also follow the progression of functional deterioration and structural changes of glomeruli by performing periodic micropuncture measurements within the same glomerulus over a period of months and subsequent structural examination of these glomeruli. It is aimed to evaluate the potential causal relationship between the early functional pattern and later glomerular changes in structure in chronic renal disease.
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