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Kidney Int. 2016 Jan;89(1):226-34. doi: 10.1038/ki.2015.278. Epub 2016 Jan 4.

Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes.

Author information

1
Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
2
Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
3
Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA. Electronic address: rnelson@nih.gov.
4
Department of Pediatrics, University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.
5
Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Elevated serum tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) concentrations are strongly associated with increased risk of end-stage renal disease in type 2 diabetes. However, little is known about the early glomerular structural lesions that develop in patients when these markers are elevated. Here, we examined the relationships between TNFRs and glomerular structure in 83 American Indians with type 2 diabetes. Serum TNFRs and glomerular filtration rate (GFR, iothalamate) were measured during a research exam performed within a median of 0.9 months from a percutaneous kidney biopsy. Associations of TNFRs with glomerular structural variables were quantified by Spearman's correlations and by multivariable linear regression after adjustment for age, gender, diabetes duration, hemoglobin A1c, body mass index, and mean arterial pressure. The baseline mean age was 46 years, median GFR 130 ml/min, median albumin/creatinine ratio 26 mg/g, median TNFR1 1500 pg/ml, and median TNFR2 3284 pg/ml. After multivariable adjustment, TNFR1 and TNFR2 significantly correlated inversely with the percentage of endothelial cell fenestration and the total filtration surface per glomerulus. There were significant positive correlations with mesangial fractional volume, glomerular basement membrane width, podocyte foot process width, and percentage of global glomerular sclerosis. Thus, TNFRs may be involved in the pathogenesis of early glomerular lesions in diabetic nephropathy.

KEYWORDS:

diabetic nephropathy; endothelium; kidney biopsy

PMID:
26398493
PMCID:
PMC4805514
DOI:
10.1038/ki.2015.278
[Indexed for MEDLINE]
Free PMC Article

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