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NDT Advance Access published online on November 14, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm711
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Increased Levels of {alpha}-Defensin (-1, -2 and -3) in Type 1 Diabetic Patients with Nephropathy

M. Saraheimo1,2, C. Forsblom1,2, K. Pettersson-Fernholm1,2, A. Flyvbjerg3, P.-H. Groop1,2, J. Frystyk3 and on behalf of the FinnDiane Study Group

1 Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland 2 Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Finland 3 Medical Research Laboratories, Clinical Institute & Medical Department M (Diabetes and Endocrinology), Aarhus University, Denmark

Correspondence and offprint requests to: Correspondence and offprint requests to: Per-Henrik Groop, Folkhälsan Research Center, Biomedicum Helsinki (318b), University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014 Helsinki, Finland. Tel: +358-9-191-25459; Fax: +358-9-191-25452; E-mail: per-henrik.groop{at}helsinki.fi



  Abstract

Objective. Diabetic nephropathy is associated with low-grade inflammation and activation of the complement system. Defensins, as part of the innate immune system, may play a regulatory role in the complement cascade and may also augment the production of proinflammatory cytokines. The aim of this study was therefore to elucidate whether {alpha}-defensin is associated with diabetic nephropathy, low-grade inflammation and lipid profiles.

Research design and methods. Data were obtained from 189 patients with type 1 diabetes selected from the FinnDiane Study. Patients were divided into three groups according to their albumin excretion rate (AER) in three consecutive overnight or 24-h urine collections: normoalbuminuria (AER <20 µg/min or <30 mg/24 h), microalbuminuria (20 <AER <200 µg/min or 30 <AER <300 mg/24 h) and macroalbuminuria (>200 µg/min or >300 mg/24 h). {alpha}-Defensin was determined by a novel, solid-phase radioimmunoassay (RIA) based on a monoclonal antibody, which recognizes {alpha}-defensin isoforms 1–3.

Results. Total serum {alpha}-defensin (-1, -2 and -3) concentrations were higher (P < 0.001) in patients with macroalbuminuria compared to micro- and normoalbuminuria, but no difference was observed between normoalbuminuria and microalbuminuria. In multiple linear regression analysis {alpha}-defensin was associated with systolic blood pressure (P = 0.032), HDL-cholesterol (P = 0.013), total cholesterol (P = 0.008), age (P = 0.001) and estimated glomerular filtration rate (P = 0.001), but not with low-grade inflammatory markers.

Conclusions. Serum {alpha}-defensin (-1, -2 and -3) concentrations are increased in type 1 diabetic patients with diabetic nephropathy.

Keywords: blood lipids; diabetic nephropathy; {alpha}-defensin; low-grade inflammation

Received for publication: 27. 4.07
Accepted in revised form: 12. 9.07


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