title: Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes.
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.
authors.affiliation: Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Meda E
authors.initials: ME
authors.lastname: Pavkov
authors.affiliation: Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
authors.forename: E Jennifer
authors.initials: EJ
authors.lastname: Weil
authors.affiliation: Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
authors.forename: Gudeta D
authors.initials: GD
authors.lastname: Fufaa
authors.affiliation: 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.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.affiliation: Department of Pediatrics, University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Lemley
authors.affiliation: Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Monika A
authors.initials: MA
authors.lastname: Niewczas
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood*; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*
chemical_list: D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: diabetic nephropathy; endothelium; kidney biopsy