Increased levels of NE-(carboxymethyl)lysine and NE-(carboxyethyl)lysine in type 1 diabetic patients with impaired renal function: Correlation with markers of endothelial dysfunction
article
Background. Diabetic and non-diabetic patients with renal failure have an increased risk for cardiovascular disease, which may be the result of uraemic toxins, including advanced glycation end-products (AGEs). The aim of the study was to investigate the levels of well-characterized AGEs, NE-(carboxymethyl)lysine (CML) and NE-(carboxyethyl)lysine (CEL) in relation to kidney function and to study the relationship of these AGEs to endothelial function and inflammation in type 1 diabetic patients. Methods. Plasma levels of CML and CEL were measured in 60 type 1 diabetic patients categorized as having normal glomerular filtration rate (GFR) (>80 ml/min, n=31) or decreased GFR (<80 ml/min, n=29) as estimated by the Cockcroft-Gault formula. To assess the relationship of these AGEs to endothelial function and inflammation, markers of endothelial function von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), tissue type-specific plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP), a marker of inflammatory activity, were determined by enzyme-linked immunosorbent assays. Results. Plasma levels of CML and CEL were increased in diabetic patients with decreased GFR as compared with patients with normal GFR [CML 4.9 (2-12.6) vs 2.9 (1.7-4.4) μmol/l, P<0.000; and CEL 1.7 (0.9-3.3) vs 1.2 (1.7-4.4) μmol/l, P=0.004, respectively). Independently of the GFR, the plasma levels of CML and CEL were significantly associated with sVCAM-1, vWf and sTM. Conclusions. Plasma levels of CML and CEL rise with deterioration of GFR. Furthermore, CML and CEL levels are associated with markers of endothelial activation independently of renal function. This suggests an involvement of these AGEs in the acceleration of cardiovascular complications in patients with renal impairment. © ERA-EDTA 2004; all rights reserved. Chemicals / CAS: C reactive protein, 9007-41-4; endothelial leukocyte adhesion molecule 1, 128875-25-2; plasminogen activator inhibitor 1, 140208-23-7; thrombomodulin, 112049-68-0; tissue plasminogen activator, 105913-11-9; von Willebrand factor, 109319-16-6; Blood Coagulation Factors; C-Reactive Protein, 9007-41-4; E-Selectin; Lysine, 56-87-1; N(6)-(1-carboxyethyl)lysine, 5746-03-2; N(6)-carboxymethyllysine, 5746-04-3; Thrombomodulin; Vascular Cell Adhesion Molecule-1
Topics
Biomedical ResearchAdvanced glycation end-productsEndothelial markersRenal impairmentadvanced glycation end productbiological markerC reactive proteinendothelial leukocyte adhesion molecule 1n (carboxyethyl)lysinen (carboxymethyl)lysineplasminogen activator inhibitor 1thrombomodulintissue plasminogen activatorunclassified drugvascular cell adhesion molecule 1von Willebrand factorblood levelcardiovascular diseasecontrolled studycorrelation analysisdisease associationdisease coursedisease markerendothelium lesionenzyme linked immunosorbent assayglomerulus filtration rateinflammationinsulin dependent diabetes mellituskidney dysfunctionkidney functionmajor clinical studypathophysiologypriority journalstatistical significanceAdultAgedBlood Coagulation FactorsC-Reactive ProteinCase-Control StudiesDiabetes Mellitus, Type 1E-SelectinEndothelium, VascularFemaleGlomerular Filtration RateHumansKidneyLysineMaleMiddle AgedThrombomodulinVascular Cell Adhesion Molecule-1
TNO Identifier
237626
ISSN
09310509
Source
Nephrology Dialysis Transplantation, 19(3), pp. 631-636.
Pages
631-636
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