Dataset Information

The relationship between obesity and diabetic nephropathy in China.

ABSTRACT:

Background

The epidemic of diabetic nephropathy (DN) has been paralleled by rapid increases in both obesity and diabetes in China. The aim of this study was to investigate the natural history of DN and the association of obesity and renal function with diabetes.

Methods

In total, 264 patients with renal biopsy-confirmed DN were examined from 2002 to 2008 and followed up to June 2008 in our institute. Among these, 129 patients were classified into a Kidney Disease Outcomes Quality Initiative (K/DOQI) stage I subgroup. Weight status, clinico-histopathological features, the development of end-stage renal disease (ESRD) and increased proteinuria were evaluated at the baseline of biopsy and during the follow up. Lean, overweight and obese phenotypes were defined as body mass index (BMI) less than 25 kg/m2, 25-28 kg/m2, and more than 28 kg/m2 over, respectively.

Results

In the patients with renal biopsy-confirmed DN, BMI was 25.5?±?3.39 kg/m2, with 122 (46.2%), 83 (31.4%) and 59 (22.3%) having lean, overweight and obese phenotypes, respectively. Mean proteinuria was 3.09?±?2.32 g/24 h, serum creatinine was 2.02?±?2.02 mg/dL, and creatinine clearance rate (Ccr) was 96.0?±?54.0 mL/min/1.73 m2. Compared with obese patients, lean patients had a lower Ccr, a higher percentage of anemia, more renal lesions and higher risk for ESRD (HR?=?1.812, P?=?0.048). The weight in obese patients decreased significantly after 27 months, and lean patients had a longer duration of diabetes than obese patients. Regarding patients at K/DOQI stage I, patients with DN showed similar duration of diabetes regardless of weight status. Minimal weight loss was recorded in obese patients during follow-up, and they exhibited greater glomerular hyperfiltration and higher risk for increased proteinuria (HR?=?2.872, P?=?0.014) than lean patients.

Conclusions

In China, obesity is common in DN patients undergoing biopsy. Initial high levels of proteinuria and subsequent weight loss are the major characteristics of the natural course of DN. Obesity contributed to increased proteinuria at an early stage, while the lean phenotype was associated with ESRD development, especially at the later stages.

SUBMITTER: Chen HM

PROVIDER: S-EPMC3614546 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

The relationship between obesity and diabetic nephropathy in China.

Chen Hui-Mei HM Shen Wen-Wen WW Ge Yong-Chun YC Zhang Yi-De YD Xie Hong-Lang HL Liu Zhi-Hong ZH

BMC nephrology 20130325

<h4>Background</h4>The epidemic of diabetic nephropathy (DN) has been paralleled by rapid increases in both obesity and diabetes in China. The aim of this study was to investigate the natural history of DN and the association of obesity and renal function with diabetes.<h4>Methods</h4>In total, 264 patients with renal biopsy-confirmed DN were examined from 2002 to 2008 and followed up to June 2008 in our institute. Among these, 129 patients were classified into a Kidney Disease Outcomes Quality ...[more]

PMID: 23521842

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Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies. comparison of gene expression of human mesangial cells after 24h Tacrolimus vs. Ctrl; 4 independent experiments were conducted (4xTacrolimus 24h and 4x ctrl. 24h with Drug solvent (DMSO))

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Dataset Information

The relationship between obesity and diabetic nephropathy in China.

Background

Methods

Results

Conclusions

Publications

The relationship between obesity and diabetic nephropathy in China.

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