In chronic renal disease undamaged nephrons become responsible for maintaining kidney function; yet this function may continue to deteriorate even in the absence of activity of the primary kidney disease. Subtotal renal ablation, especially when combined with an unrestricted protein diet, is most effective in reproducing this state of affairs in the experimental animal. Apparently hemodynamic changes, at first compensatory, lead to increases in glomerular capillary pressures, flows, and filtration which become counterproductive, causing glomerular hypertrophy and ultimately sclerosis. It has also been shown by model building, measurement, and network analysis that the hemodynamic response to renal ablation on high protein intake may include, in its later stages, a functional loss in filtration surface caused by shunting of glomerular capillary blood flow. This finding, however, is currently based on the study of a single glomerulus. It has been suggested, moreover, that postprandial changes in glomerular blood flow and filtration rate may be more conspicuous in superficial cortical (SC) glomeruli than in juxtamedullary (JM) glomeruli. Since such hemodynamically mediated changes have been implicated in the pathogenesis of glomerular injury precipitated by renal ablation in the Munich Wistar (MW) rat, it is not unlikely that the rate of progression of glomerular injury may differ in SC and in JM glomeruli. It has also been confirmed that morphometric differences exist between SC and JM glomeruli in the normal MW rat. Accordingly, the research plan includes a two-fold study of the responses of SC and JM glomeruli to subtotal renal ablation in the presence of unrestricted protein intake: (i) A network-analytic study of the later hemodynamic responses of several glomeruli facilitated by the use of computer image analysis for the study of three-dimensional glomerular structure; and (ii) A stereologic comparison of the parameters of glomerular hypertrophy for SC and JM glomeruli.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036316-03
Application #
3234641
Study Section
Pathology A Study Section (PTHA)
Project Start
1986-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
622146454
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Shea, S M (1988) Glomerular morphometry in the Munich Wistar rat: effects of sub-total renal ablation. Microcirc Endothelium Lymphatics 4:327-36