TY - JOUR
T1 - Advanced glycation endproducts and dicarbonyls in end-stage renal disease
T2 - associations with uraemia and courses following renal replacement therapy
AU - Martens, Remy J. H.
AU - Broers, Natascha J. H.
AU - Canaud, Bernard
AU - Christiaans, Maarten H. L.
AU - Cornelis, Tom
AU - Gauly, Adelheid
AU - Hermans, Marc M. H.
AU - Konings, Constantijn J. A. M.
AU - van der Sande, Frank M.
AU - Scheijen, Jean L. J. M.
AU - Stifft, Frank
AU - Kooman, Jeroen P.
AU - Schalkwijk, Casper G.
N1 - Funding Information:
The studies included in this article were supported by an unrestricted grant from Fresenius Medical Care Deutsch land GmbH (study NL33129.068.10 and NL43381.068.13), a Baxter extramural grant (study NL35039.068.10) and the Dutch Kidney Foundation (study NL35039.068.10).
Funding Information:
R.J.H.M., N.J.H.B. and J.P.K. are supported by an (un)restricted grant from Fresenius Medical Care. R.J.H.M., N.J.H.B. and J.P.K. received lectures fees from Fresenius Medical Care. B.C. and A.G. are employees of Fresenius Medical Care and hold shares in the company. The other authors report no financial conflicts of interest. B.C. and A.G., who are employees of Fresenius Medical Care and hold shares in the company, reviewed the manuscript. However, the funding sources had no role in this study design, collection, preparation or analysis of data and the decision to publish. The results presented in this article have not been published previously in whole or part, except in abstract format.
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]
PY - 2020/10
Y1 - 2020/10
N2 - 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-is an element of-(carboxymethyl)lysine (CML), N-is an element of-(carboxyethyl)lysine (CEL), N-delta-(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.
AB - 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-is an element of-(carboxymethyl)lysine (CML), N-is an element of-(carboxyethyl)lysine (CEL), N-delta-(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.
KW - advanced glycation endproducts
KW - dialysis
KW - dicarbonyls
KW - end-stage renal disease
KW - kidney transplantation
KW - RESIDUAL KIDNEY-FUNCTION
KW - CARDIOVASCULAR-DISEASE
KW - EXTENDED HEMODIALYSIS
KW - SKIN AUTOFLUORESCENCE
KW - METHYLGLYOXAL LEVELS
KW - PRODUCTS
KW - DIALYSIS
KW - PLASMA
KW - PENTOSIDINE
KW - STRESS
U2 - 10.1093/ckj/sfz099
DO - 10.1093/ckj/sfz099
M3 - Article
C2 - 33123361
SN - 2048-8505
VL - 13
SP - 855
EP - 866
JO - Clinical Kidney Journal
JF - Clinical Kidney Journal
IS - 5
ER -