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NDT Advance Access published online on December 5, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi309
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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
Received August 8, 2005
Accepted November 11, 2005

Original Article

Advanced glycation end-product peptides are associated with impaired renal function, but not with biochemical markers of endothelial dysfunction and inflammation, in non-diabetic individuals

Frank Stam 1 *, Casper G. Schalkwijk 2, Coen van Guldener 3, Piet M. ter Wee 4, and Coen D. A. Stehouwer 5

1 Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands
2 Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
3 Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine, Amphia Hospital (Langendijk), Breda, The Netherlands
4 Department of Nephrology, VU University Medical Centre, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands
5 Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands; Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands; Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

* To whom correspondence should be addressed.
Frank Stam, E-mail: f.stam{at}vumc.nl



  Abstract

Background. Patients with end-stage renal disease as well as mild renal impairment have an increased risk for the development of cardiovascular disease. It has been suggested that advanced glycation end-products (AGEs) are involved in atherogenesis, possibly through induction of endothelial dysfunction and low-grade inflammation.

Methods. In a cross-sectional, single-centre study, we investigated four groups of 20 non-diabetic subjects with a creatinine clearance ranging from normal (>90 ml/min/1.73 m2) to <31 ml/min/1.73 m2. We measured AGE-peptides, markers of endothelial dysfunction (von Willebrand factor, soluble E-selectin, plasminogen activator inhibitor-1, tissue-type plasminogen activator, soluble vascular cell adhesion molecule-1) and markers of inflammatory activity (soluble intercellular adhesion molecule-1, C-reactive protein, secretory phospholipase A2). We constructed composite endothelial dysfunction and inflammatory activity Z-scores using these markers.

Results. AGE-peptides were independently related to creatinine clearance (standardized {beta} -0.55, 95% confidence interval (CI) -0.77 to -0.34, P<0.001). AGE-peptides were not independently related to the individual markers of endothelial dysfunction and inflammation, nor to the composite endothelial dysfunction Z-score (standardized {beta} 0.08, 95% CI -0.14 to -0.30, P = 0.48) or the inflammatory activity Z-score (standardized {beta} -0.05, 95% CI -0.25 to -0.16, P = 0.66).

Conclusions. Plasma concentrations of AGE-peptides are associated with creatinine clearance but not with biochemical markers of endothelial dysfunction and inflammatory activity in non-diabetic patients over a wide range of renal function. This suggests that the atherogenic effects of AGE-peptides in individuals with renal functional impairment are not mediated by endothelial dysfunction or inflammatory activity as estimated by the markers used.

Keywords: advanced glycation end-products; cell adhesion molecules; chronic inflammation; creatinine clearance; endothelial dysfunction; von Willebrand factor.
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