Role of growth hormone in the development of experimental renal scarring

Nahas, A. Meguid El; Bassett, A. H.; Cope, G. H.; Carpentier, J. E. Le

doi:10.1038/ki.1991.175

Cited by 159 publications

(118 citation statements)

References 18 publications

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“…All semiquantitative, morphometric, and stereologic investigations were performed in a blinded manner by an observer who was unaware of the study protocol. The degree of sclerosis within the glomerular tuft as an index of progression was determined on periodic acid-Schiff-stained paraffin sections adopting the semiquantitative scoring system proposed by El Nahas et al (14). Using light microscopy at a magnification of ϫ400, the glomerular score of each animal was derived as the mean of 100 glomeruli.…”

Section: Morphologic Investigationsmentioning

confidence: 99%

“…Using light microscopy at a magnification of ϫ400, the glomerular score of each animal was derived as the mean of 100 glomeruli. The severity of glomerulosclerosis was expressed on a scale from 0 to 4 (14). The glomerular score for individual glomeruli was as follows: grade 0, normal glomerulus; grade 1, beginning mesangial expansion/ thickening of the basement membrane and/or irregular lumina of capillaries; grade 2, mild/moderate segmental hyalinosis/sclerosis involving Ͻ50% of the glomerular tuft; grade 3, diffuse glomerular hyalinosis/sclerosis involving Ͼ50% of the tuft; and grade 4, diffuse glomerulosclerosis with total tuft obliteration and collapse.…”

Section: Morphologic Investigationsmentioning

confidence: 99%

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Reversal of Glomerular Lesions Involves Coordinated Restructuring of Glomerular Microvasculature

Adamczak¹,

Gross²,

Amann³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. There is increasing evidence from both human and experimental studies that at least partial reversal of glomerulosclerosis can be achieved by glomerular remodeling. This requires substantial changes in glomerular architecture, specifically of glomerular capillaries. It was the purpose of the present study to characterize the stereologic and topologic characteristics of glomerular capillaries when partial reversal of glomerular lesions is achieved by high-dose angiotensinconverting enzyme inhibitor treatment. Sham-operated male Sprague-Dawley rats were compared with subtotally nephrectomized (SNX) rats. The latter were kept untreated for 8 wk and subsequently randomly divided into one group that was continued without treatment and another group that was treated with enalapril (48 mg/kg body wt per d administered in the drinking fluid for 4 wk). Renal morphology was evaluated after 8 or 12 wk, respectively, by stereologic techniques after pressure-controlled perfusion fixation. In SNX rats at 8 and particularly at 12 wk, the glomerulosclerosis index was significantly higher than in sham-operated rats. At 12 wk, it was lower in rats that had been treated for 4 wk with enalapril compared with untreated SNX rats, suggesting partial reversal of glomerular lesions. This was associated with a decrease in mean glomerular volume and mean glomerular tuft volume, a reduced number of capillaries per glomerulus, and reduced total length of capillaries per glomerulus but without any significant change in the length of individual capillaries. The numerical capillary density (Euler number density) as an index of topologic complexity did not change. The total capillary surface area per glomerulus was strikingly increased after subtotal nephrectomy and partially reversed after enalapril. This was accounted for primarily by fewer capillaries without any change in diameter. In parallel, the number of endothelial cells per glomerulus was strikingly increased after subtotal nephrectomy and decreased with enalapril treatment, but endothelial cell volume remained elevated. The study shows harmonious coordinate remodeling of the entire glomerulus during regression of glomerular lesions after subtotal nephrectomy. Proportionate reduction of glomerular volume and capillary number without change of individual capillary length were found. The numerical capillary density of the tuft therefore remained unchanged.For a long time, the goal of therapeutic intervention in glomerular disease was to halt progression (1). More recently, it had become apparent that glomerular lesions in progressive renal diseases can be reversed to some extent presumably if there has been no major loss of podocytes. This concept was based on clinical observations of partial reversal of basal membrane thickening and mesangial expansion in diabetic patients several years after isolated pancreas transplantation (2). Furthermore, reversal of renal lesions was seen in patients with clinically cured IgA glomerulonephritis (3) as well as in experimental studies of ...

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Section: Morphologic Investigationsmentioning

confidence: 99%

Section: Morphologic Investigationsmentioning

confidence: 99%

Reversal of Glomerular Lesions Involves Coordinated Restructuring of Glomerular Microvasculature

Adamczak¹,

Gross²,

Amann³

et al. 2004

Journal of the American Society of Nephrology

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“…Indices of renal damage (glomerulosclerosis, tubulointerstitial and vascular damage) The degree of sclerosis within the glomerular tuft as an index of progression (glomerulosclerosis damage index, GSI) was determined on PAS-stained paraffin sections adopting the semiquantitative scoring system proposed by El Nahas et al 14 Using light microscopy at a magnification of Â 400, the glomerular score of each animal was derived as the mean of 100 glomeruli. The severity of glomerulosclerosis was expressed on an arbitrary scale from 0 to 4 as described elsewhere.…”

Section: Morphological Investigationsmentioning

confidence: 99%

“…The severity of glomerulosclerosis was expressed on an arbitrary scale from 0 to 4 as described elsewhere. 14,15 Tubulointerstitial damage index (TBI) and vascular damage index (VDI) were assessed on PASstained paraffin sections at a magnification of Â 100 using a similar scoring systems with scores 0-4. 16 …”

Section: Morphological Investigationsmentioning

confidence: 99%

Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes

Gross

Koch

Mühlbauer

et al. 2006

Laboratory Investigation

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Diabetic nephropathy is the leading cause of end-stage renal disease. Dopamine receptors are involved in the regulation of renal hemodynamics and may play a role in diabetes-induced hyperfiltration. To test this hypothesis, we investigated the renal effect of a dopamine D3 receptor antagonist (D3-RA) in hypertensive type II diabetic SHR/N-cp rats. Lean and obese SHR/N-cp rats were randomly assigned to D3-RA, angiotensinconverting enzyme inhibitor (ACE-i), or D3-RA þ ACE-i treatment or control conditions. Treated animals were given the D3-RA A-437203 (10 mg/kg/body weight (BW)/day) or the ACE-i trandolapril (0.3 mg/kg BW/day) or a combination of both. At 6 months following perfusion, fixed kidneys were analyzed by morphological and stereological methods. Indices of renal damage (glomerulosclerosis, glomerulosclerosis damage index (GSI), tubulointerstitial and vascular damage), glomerular geometry and functional variables such as urinary albumin excretion, glomerular filtration rate, blood pressure, blood chemistry and BW were determined. The GSI (score 0-4) was significantly higher (Po0.05) in untreated diabetic animals (1.6270.3) compared to nondiabetic controls (0.470.2) and the treatment groups (D3-RA: 0.3170.12; ACE-i: 0.2970.1; combination treatment: 0.1270.01). Urinary albumin excretion (mg/24 h) was higher in untreated diabetic controls (102719) compared to nondiabetic controls (31712) and the treatment groups (D3-RA: 44715; ACE-i: 41713; combination treatment: 1578). Mean glomerular volume was higher in untreated diabetic animals compared to nondiabetic controls and to the treatment groups. Desmin expression, a marker of podocyte damage, was elevated in untreated diabetic controls and diminished in all treatment groups. These data suggest that in a model of type II diabetes, the dopamine D3-RA had a beneficial effect on renal morphology and albuminuria, which was comparable in magnitude to that of ACE-i treatment.

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“…Indices of renal damage (glomerulosclerosis, tubulointerstitial and vascular damage) The degree of sclerosis within the glomerular tuft as an index of progression was determined on PASstained paraffin sections adopting the semiquantitative scoring system proposed by el Nahas et al 21 Using light microscopy at a magnification of Â 400, the glomerular score of each animal was derived as the mean of 100 glomeruli. The severity of glomerulosclerosis was expressed on an arbitrary scale from 0 to 4 as described in detail.…”

Section: Morphological Investigationsmentioning

confidence: 99%

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

Groß

Ritz

Schoof

et al. 2004

Laboratory Investigation

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The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague-Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA þ cells were significantly more frequent and expression of TGF-b and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/Ncp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.

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Role of growth hormone in the development of experimental renal scarring

Cited by 159 publications

References 18 publications

Reversal of Glomerular Lesions Involves Coordinated Restructuring of Glomerular Microvasculature

Reversal of Glomerular Lesions Involves Coordinated Restructuring of Glomerular Microvasculature

Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

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