Proliferation and remodeling of the peritubular microcirculation after nephron reduction - Association with the progression of renal lesions

Little is known about the serial changes that might occur in renal capillar ies after reduction of renal mass. In the current study, our aim was to doc ument potential alterations in the morphology and proliferation of the rena l cortical peritubular microcirculation at specific time points (7 and 60 d ays) after experimental 75% surgical nephron reduction using two strains of mice that we here demonstrate react differently to the same initial insult : one strain (C57BL6xDBA2/F1 mice) undergoes compensatory growth alone, whe reas the other (FVB/N mice) additionally develops severe tabulo-interstitia l lesions. Our data demonstrate that significant remodeling and proliferati on occur in renal cortical peritubular capillaries after experimental nephr on reduction, as assessed by microangiography using infusion of fluorescein isothiocyanate-labeled dextran, expression of the endothelial markers CD34 and Tie-2, and co-expression of CD34 and proliferating cell nuclear antige n, a surrogate marker of cell proliferation. This was accompanied by an inc rease of renal vascular endothelial growth factor protein levels and a chan ge in distribution of this protein within the kidney itself. Moreover, most of these responses were accentuated in FVB/N mice in the presence of progr essive renal disease and positively correlated with tubular epithelial cell proliferation. Hence, we have made three significant novel observations th at illuminate the complex pathophysiology of chronic kidney damage after ne phron reduction: 1) cortical peritubular capillaries grow by proliferation and remodeling, 2) vascular endothelial growth factor expression is altered , and 3) the development of tubulo-interstitial disease is genetically dete rmined.