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. 2019 Aug 28;13(5):855-866.
doi: 10.1093/ckj/sfz099. eCollection 2020 Oct.

Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy

Remy J H Martens  1   2 , Natascha J H Broers  1   3 , Bernard Canaud  4   5 , Maarten H L Christiaans  1 , Tom Cornelis  6 , Adelheid Gauly  4 , Marc M H Hermans  7 , Constantijn J A M Konings  8 , Frank M van der Sande  1 , Jean L J M Scheijen  2   9 , Frank Stifft  10 , Jeroen P Kooman  1   3 , Casper G Schalkwijk  2   9
Affiliations

Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy

Remy J H Martens et al. Clin Kidney J. .

Abstract

Background: End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking.

Methods: We quantified an extensive panel of free and protein-bound serum AGEs [N ∈-(carboxymethyl)lysine (CML), N ∈-(carboxyethyl)lysine (CEL), N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models.

Results: Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; n = 52) and CKD Stage 5 dialysis (CKD 5-D; n = 35) than in controls (n = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation (n = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx (n = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined.

Conclusions: AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable.

Keywords: advanced glycation endproducts; dialysis, dicarbonyls; end-stage renal disease; kidney transplantation.

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Figures

FIGURE 1
FIGURE 1
Boxplots of serum AGEs, dicarbonyls and SAF stratified according to participant group. AU, arbitrary units.
FIGURE 2
FIGURE 2
Boxplots of serum AGEs, dicarbonyls and SAF over time in incident dialysis patients. Boxplots based on (0/1/6/12 months): n = 41/41/40/35 for serum AGEs, n = 37/41/40/35 for dicarbonyls and n = 38/37/40/34 for SAF, respectively. AU, arbitrary units.
FIGURE 3
FIGURE 3
Boxplots of serum AGEs, dicarbonyls and SAF over time in kidney transplant recipients. Boxplots based on (0/3/6/12 months): n = 17/16/18/17 for serum AGEs, n = 17/16/18/17 for dicarbonyls and n = 20/16/16/17 for SAF, respectively. AU, arbitrary units.
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