1988
DOI: 10.1172/jci113590
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Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis.

Abstract: We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally ne… Show more

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Cited by 175 publications
(70 citation statements)
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References 47 publications
(50 reference statements)
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“…The pathological changes in each of the models were qualitatively similar to those previously described in these models and included focal thickening of glomerular and tubular basement membranes and of Bowman's capsules, as well as focal expansions of the glomerular mesangial matrix and early segmental glomerulosclerosis, focal tubular dilatation, and casts and interstitial fibrosis (Bolton et al, 1976;Couser and Stilmant, 1975;Elema and Arends, 1975;Feld et al, 1977;Fogo et al, 1988;Yoshioka et al, 1988). In general, these changes were more severe in the older rats of each group.…”
Section: Light Microscopysupporting
confidence: 61%
See 1 more Smart Citation
“…The pathological changes in each of the models were qualitatively similar to those previously described in these models and included focal thickening of glomerular and tubular basement membranes and of Bowman's capsules, as well as focal expansions of the glomerular mesangial matrix and early segmental glomerulosclerosis, focal tubular dilatation, and casts and interstitial fibrosis (Bolton et al, 1976;Couser and Stilmant, 1975;Elema and Arends, 1975;Feld et al, 1977;Fogo et al, 1988;Yoshioka et al, 1988). In general, these changes were more severe in the older rats of each group.…”
Section: Light Microscopysupporting
confidence: 61%
“…Although heterogeneity of structure and function among nephrons has been documented, the precise relationship of proteinuria to structural change in individual nephrons in these models has not been clearly established. Experimental evidence concerning heterogeneity of glomerular function among nephrons in several rat models has been largely derived from studies of the superficial nephrons that are accessible to micropuncture analysis (Allison et al, 1974;Fogo et al, 1988;Ichikawa et al, 1982;Lewy and Pesce, 1973;Yoshioka et al, 1988). However, analysis of deeper nephrons is only inferential, because they are not accessible for micropuncture.…”
mentioning
confidence: 99%
“…Adriamycin causes well-described podocyte injury in rats (21), but its nephrotoxicity in mice is strain dependent. Balb/C mice are susceptible to podocyte injury by Adriamycin (22,23), whereas other strains that have been tested normally are resistant (24). We determined that preexisting expression of podocyte COX-2 in a mouse strain (B6/D2) that otherwise is resistant to Adriamycin injury sensitized the podocytes to injury, indicated by foot process effacement and albuminuria.…”
Section: Discussionmentioning
confidence: 99%
“…12 Mechanical strain may also increase angiotensin II (AngII) production and the expression of angiotensin type 1 receptors in podocytes, 13 and AngII may directly impair the glomerular barrier sieving function-possibly through inhibited nephrin expressionindependent of its hemodynamic effects. 14 Moreover, disruption of glomerular permselectivity with eventual proteinuria and progressive glomerulosclerosis is observed in experimental models that are characterized by normal capillary glomerular pressure, such as adriamycin or puromycin nephrosis 15 and aging-associated glomerulosclerosis in male Munich-Wistar rats. 16 Thus, impaired glomerular sieving appears to initiate and perpetuate parenchymal damage, and ultimately renal scarring and insufficiency, through a common pathway that, independent of capillary pressure, results in increased protein content of the glomerular filtrate with protein overload to glomerular and tubular epithelial cells (Figure 1).…”
Section: A Concept Coming From Far Awaymentioning
confidence: 99%