Increased levels of alpha-defensin (-1, -2 and -3) in type 1 diabetic patients with nephropathy.
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.


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 microg/min or <30 mg/24 h), microalbuminuria (20 <AER <200 microg/min or 30 <AER <300 mg/24 h) and macroalbuminuria (>200 microg/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.
Saraheimo
M
M
Folkhälsan Research Center, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00014 Helsinki, Finland.
Forsblom
C
C
Pettersson-Fernholm
K
K
Flyvbjerg
A
A
Groop
P-H
PH
Frystyk
J
J
D000328:Adult; D000419:Albuminuria / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005387:Finland; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D023084:alpha-Defensins / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; D008055:Lipids; D023084:alpha-Defensins