Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

Macedo, Célia Sperandeo; Lerco, Mauro Masson; Capelletti, Sônia Maria; Silva, Reinaldo José; Pinheiro, Daniela de Oliveira; Spadella, César Tadeu

doi:10.1590/s0102-86502007000500003

Cited by 8 publications

(7 citation statements)

References 26 publications

(19 reference statements)

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“…Thus, the increased podocyte surface area would reflect the extent of podocyte hypertrophy. Macedo et al [24] reported that the control of hyperglycemia prevented glomerular basement membrane (GBM) thickening in early and late (12 months) alloxan-induced type 1 DN and also prevented a reduction in the number of podocytes. Ishikawa et al [25] previously reported that podocyte injury might provide additional prognostic information in diabetic KK- A y mice.…”

Section: New Biomarkersmentioning

confidence: 99%

The Prevalence and Management of Diabetic Nephropathy in Asia

Tomino

Gohda²

2015

Kidney Dis

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Background: Diabetic nephropathy (DN), especially type 2 diabetes, is now increasing rapidly worldwide, also in Asian countries, and is one of the major long-term vascular complications. The pathogenesis of DN involves both genetic and environmental factors. Around 30-40% of type 2 diabetic patients develop DN despite strict blood glucose and/or blood pressure control. Although it is considered that the genetic background may influence the initiation and progression of DN, the candidate genes are still obscure. Summary: To search for genes that are involved in the susceptibility of DN, a candidate gene approach was taken in the beginning before the development of genome-wide association studies. Although a candidate gene approach can detect rare genetic variants, in advance we need known or presumed pathophysiological knowledge of the specific gene. Investigations using spontaneous animal models are important to determine the pathogenesis and treatment of DN patients. There are many spontaneous animal models, such as the NOD and Akita mice for type 1 diabetes and the Ob/Ob, db/db, Tsumura Suzuki Obese Diabetics, and KK-A^y mice for type 2 diabetes. Furthermore, the toxicity of persistent hyperglycemia, the activation of reactive oxygen species, systemic and/or glomerular hypertension, microinflammation, dyslipidemia, and other factors are considered to play important roles. Diabetic patients with normoalbuminuria and normal renal function showed typical histological patterns of DN. The discovery of a specific and reliable diagnostic and prognostic biomarker other than albuminuria is urgently needed and indispensable. Since large clinical trials of oral hypoglycemic drugs in renal failure are lacking, these recommendations will need to be regularly updated after results of larger randomized trials with longer follow-up durations are available. Key Messages: It is necessary to summarize the basic and clinical features of DN patients in Asia and to use these for the treatment of such patients. Facts from East and West: The prevalence of DN is increasing in Asia and Western countries alike. The deletion (D) allele of the angiotensin-converting enzyme gene is associated with progression to end-stage renal disease in Asian patients with DN, but this association is uncertain in Europeans. An association between DN and polymorphism of the gene coding for acetyl coenzyme A carboxylase β has been reported in Asian and Western populations. Both in Japan and the US, criteria for diagnosis are a 5-year history of diabetes and persistent albuminuria. Renal biopsy should be done in patients with severe hematuria, cellular casts and - in the US - hepatitis and HIV to rule out other pathologies. Diabetic retinopathy is considered a key criterion in Japan, but the absence of it does not rule out DN in the US. Enlargement of the kidney is observed as a diagnostic criterion in Japan. The differential use of renal biopsy as diagnostic tool might account for a different prevalence between Asian countries. Some Japanese diabe...

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Section: New Biomarkersmentioning

confidence: 99%

The Prevalence and Management of Diabetic Nephropathy in Asia

Tomino

Gohda²

2015

Kidney Dis

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“…The remaining podocytes are obliged to grow and extend their foot processes to maintain coverage of the same area. Macedo et al [80] reported that control of hyperglycemia prevented GBM thickening in early and late (12 months) alloxan diabetic nephropathy and also prevented a reduction in the number of podocytes. We previously reported that podocyte injury might provide additional prognostic information in patients with IgA nephropathy, using renal biopsy tissues and the diabetic KK-Ay mice [12,81].…”

Section: Type 2 Diabetic Nephropathymentioning

confidence: 99%

Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data

Tomino

2014

Kidney Blood Press Res

435

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Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. At end of 2013, over 300,000 Japanese patients had maintenance dialysis therapy (JSDT). In Japan, the major causes of end stage kidney disease (ESKD) are chronic glomerulonephritis (particularly IgA nephropathy), type 2 diabetic nephropathy, and hypertensive nephrosclerosis. Hypertension is a major factor driving the progression of CKD to ESKD. Since many features of the pathogenesis of IgA nephropathy are still obscure, specific treatment is not yet available. However, efforts by investigators around the world have gradually clarified different aspects of the pathogenesis and treatment of IgA nephropathy. Today, around half of all diabetic patients in Japan receive medical treatment. Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of Japanese diabetic patients. The pathogenesis of diabetic nephropathy involves both genetic and environmental factors. However, the candidate genes related to the initiation and progression of the disorder are still obscure in patients with diabetic nephropathy. Regarding environmental factors, the toxicity of persistent hyperglycemia, reactive oxygen species, systemic and/or glomerular hypertension, dyslipidemia and complement are considered to play an important role. The first part of this review covers the pathogenesis of IgA nephropathy and type 2 diabetic nephropathy, and combines the clinicopathological findings in patients with our research on the ddY and KKA-y mouse models (spontaneous animal models for IgA nephropathy and diabetic nephropathy, respectively). In Japan, the major renal replacement therapies (RRT) are peritoneal dialysis (PD) and hemodialysis (HD). The second part of this review focuses on PD and HD. Based on our research findings from patients and as well as from animal models, we discuss strategies for the management of patients on PD and HD. i 2015 S. Karger AG, Basel

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“…However, glomerular structure in type 2 diabetes has been studied less extensively although this form of diabetes is a more common cause of end stage kidney disease. Macedo et al [6] reported that the control of hyperglycemia prevented glomerular basement membrane (GBM) thickening in early and late (12 months) alloxan diabetic nephropathy and podocyte number reduction.…”

Section: Introductionmentioning

confidence: 99%

Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

Ishikawa¹,

Ito²,

Tanimoto³

et al. 2012

JDM

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Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-A y /Ta (KK-A y ) mice which had been reported as diabetic nephropathy model. Diabetic KK-A y mice, diabetic KK/Ta mice and nondiabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-A y mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-A y mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-A y mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-A y mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-A y mice. This finding confirmed our previous report that KK-A y mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.

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Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

Cited by 8 publications

References 26 publications

The Prevalence and Management of Diabetic Nephropathy in Asia

The Prevalence and Management of Diabetic Nephropathy in Asia

Pathogenesis and Treatment of Chronic Kidney Disease: A Review of Our Recent Basic and Clinical Data

Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

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