Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis

Bonnet, Fabrice; Deprele, Carole; Sassolas, Agnès; Moulin, Philippe; Alamartine, Éric; Berthezéne, F; Berthoux, F

doi:10.1016/s0272-6386(01)80120-7

Cited by 263 publications

(160 citation statements)

References 18 publications

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“…There is increasing evidence that obesity is a potent risk factor for progression. [42][43][44] In the present study, obese SHR/N-cp rats had significantly higher plasma leptin concentrations. Leptin is a potential progression promoter 45 and enhances the effect of TGF-b.…”

Section: Discussionsupporting

confidence: 56%

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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Section: Discussionsupporting

confidence: 56%

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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“…[48][49][50] Our obese SHR/N cp rats had high plasma leptin concentration. In contrast, plasma leptin concentration in STZ-induced diabetes animals was low.…”

Section: Comparison Of Stz and Shr/n-cp Model ML Gross Et Almentioning

confidence: 61%

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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“…Bonnet et al showed a similar phenomenon in another recent study in 162 patients with IgA nephropathy. 2 The presence of an elevated body mass index (BMI ! 25kg=m 2 ) at the time of renal biopsy correlated with the severity of the pathological abnormalities and with the clinical progression to end stage renal failure ( Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…5 Thereafter glomerular filtration rate starts to decrease and urinary albumin excretion rises further Figure 2 The percentage of subjects remaining free of chronic renal failure after the diagnosis of IgA nephropathy according to the presence of an elevated body mass index. Source: Bonnet et al 2 Obesity and target organ damage: the kidney PE de Jong et al to macroproteinuric ranges. The same phenomenon might be present in non-diabetic subjects.…”

Section: Introductionmentioning

confidence: 99%

Obesity and target organ damage: the kidney

et al. 2002

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Obesity is a risk marker for progressive renal function loss in patients with known renal disease. There is, however, increasing evidence that obesity may also damage the kidney in otherwise healthy subjects. There appears to be an intriguing parallel between the renal effects of obesity and those of diabetes. First, an increased renal blood flow and glomerular filtration rate has been described in obesity and, second, microalbuminuria is found to be related to obesity. These two events are known to predict future loss of renal function in diabetes. The mechanism responsible for the renal damage in obesity has not been established but there is evidence suggesting that this might be related to both hormonal changes as well as low-grade inflammation.

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Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis

Cited by 263 publications

References 18 publications

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

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

Obesity and target organ damage: the kidney

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