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NDT Advance Access originally published online on September 6, 2005
Nephrology Dialysis Transplantation 2006 21(1):93-100; doi:10.1093/ndt/gfi103
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Clinical Nephrology

Novel predictors of overt nephropathy in subjects with type 1 diabetes. A nested case control study from the Pittsburgh Epidemiology of Diabetes Complications cohort

Aklilu A. Yishak1, Tina Costacou2, Gabriel Virella3, Janice Zgibor2, Linda Fried1,4, Michael Walsh2, Rhobert W. Evans2, Maria Lopes-Virella5, Valerian E. Kagan6, James Otvos7 and Trevor J. Orchard2

1 Department of Medicine, Renal Electrolyte Division, University of Pittsburgh School of Medicine, 2 Department of Epidemiology and 6 Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 4 Veterans Pittsburgh Health Care System of Pittsburgh, PA, USA, 3 Department of Microbiology and Immunology, Medical University of South Carolina, 5 Department of Medicine, Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA, 7 LipoScience, Inc., Raleigh, North Carolina, USA

Correspondence and offprint requests to: Trevor J. Orchard, MD, University of Pittsburgh, Diabetes and Lipid Research Bldg., 3512 Fifth Avenue, Pittsburgh, PA 15213. Email: tjo{at}pitt.edu

Background. Predictors of diabetic nephropathy are only partly known and traditional risk factors do not adequately explain disease risk. We thus examined novel risk factors for overt nephropathy (ON) in type 1 diabetes.

Methods. The EDC is a prospective study of childhood-onset type 1 diabetes. When first seen (1986–1988), mean age was 28 and diabetes duration 19 years. In the subsequent 10 years, 56 of 485 subjects without ON in 1986–88 developed ON. An age, duration (±3 years), and sex-matched control was identified for 47 cases. Forty-two matched pairs had available stored plasma samples obtained prior to ON onset in cases, and complete standard risk factor data.

Results. Cases had a higher baseline albumin excretion rate (AER), HbA1, pulse rate, non-HDL cholesterol, fibrinogen, small LDL and lower eGDR and LDL particle size compared to controls (all P values <0.05). Multiple measures of immune complexes were increased in cases (P<0.05), whereas borderline elevations were seen for total antioxidant reserve (P = 0.06) and retinol (P = 0.08). Multivariably, other than AER, LDL particle size and IgG-IC were predictive beyond the standard predictors.

Conclusion. Besides AER, the immunecomplexes and lipoprotein subclasses may provide additional information in the assessment of ON risk in type 1 diabetes.

Keywords: adhesion molecules; antioxidants; diabetic nephropathy; immune complexes; lipids


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