Background: Tissue advanced glycation end products (AGEs) accumulate in chronic kidney disease (CKD) and are a measure of cumulative metabolic stress. Measurement of tissue AGEs by skin autofluorescence (SAF) correlates well with cardiovascular outcomes in dialysis patients. SAF levels in transplant recipients relative to CKD and dialysis patients have not been previously studied, and the impact of transplantation on SAF levels in dialysis patients is unknown. Methods: SAF was measured using an AGE reader in 66 patients who had received a kidney transplant. Values were compared to those obtained in 1,707 patients with CKD stage 3 and in 115 patients on dialysis. Results: Mean SAF in transplant recipients [2.81 ± 0.64 arbitrary units (AU)] was significantly lower than in patients on haemodialysis (3.73 ± 0.88 AU) and peritoneal dialysis (3.57 ± 0.75 AU; p < 0.001), but was no different from CKD stage 3 (2.79 ± 0.66 AU; p = 0.42). In the transplant group, SAF correlated most strongly with age (r = 0.316). There was no correlation between SAF and estimated glomerular filtration rate or renal replacement therapy vintage. A small cohort of patients with SAF recorded on dialysis and following transplantation showed a drop in SAF over a mean time of 16 months after transplantation. Discussion: Tissue AGE values in kidney transplant recipients are significantly lower than in patients receiving dialysis and similar to those in patients with CKD stage 3. Our data suggest that transplantation may be associated with a reduction in tissue AGEs, and this might be an important component of the observed reduction in cardiovascular risk in transplant recipients compared to patients on dialysis.

Keywords:
Transplantation, Cardiovascular risk, Chronic kidney disease, Advanced glycation end products
1.
Jardine AG, et al: Prevention of cardiovascular disease in adult recipients of kidney transplants. Lancet 2011;378:1419-1427.
2.
Brownlee M: Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995;46:223-234.
3.
Miyata T, et al: Renal catabolism of advanced glycation end products: the fate of pentosidine. Kidney Int 1998;53:416-422.
4.
Meerwaldt R, et al: Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care 2007;30:107-112.
5.
Smit AJ, et al: Advanced glycation endproducts in chronic heart failure. Ann NY Acad Sci 2008;1126:225-230.
6.
Aronson D: Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens 2003;21:3-12.
7.
Semba RD, et al: Serum carboxymethyl- lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults. Am J Hypertens 2009;22:74-79.
8.
Di Micco L, et al: Daily dialysis reduces pulse wave velocity in chronic hemodialysis patients. Hypertens Res 2012;35:518-522.
9.
Peppa M, Raptis SA: Advanced glycation end products and cardiovascular disease. Curr Diabetes Rev 2008;4:92-100.
10.
Bansal S, et al: Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. Mol Cell Biochem 2012;361:289-296.
11.
Basta G, Schmidt AM, De Caterina R: Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res 2004;63:582-592.
12.
Godfrey AR: Impact of glucose levels on advanced glycation end products in hemodialysis. Hemodial Int 2007;11:278-285.
13.
Makita Z, et al: Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991;325:836-842.
14.
McIntyre NJ, et al: Tissue-advanced glycation end product concentration in dialysis patients. Clin J Am Soc Nephrol 2010;5:51-55.
15.
Meerwaldt R, et al: Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol 2005;16:3687-3693.
16.
Hartog JW, et al: Advanced glycation end products in kidney transplant patients: a putative role in the development of chronic renal transplant dysfunction. Am J Kidney Dis 2004;43:966-975.
17.
Hartog JW, et al: Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease. Ann NY Acad Sci 2005;1043:299-307.
18.
McIntyre NJ, et al: Skin autofluorescence and the association with renal and cardiovascular risk factors in chronic kidney disease stage 3. Clin J Am Soc Nephrol 2011;6:2356-2363.
19.
Meerwaldt R, et al: Simple noninvasive measurement of skin autofluorescence. Ann NY Acad Sci 2005;1043:290-298.
20.
Noordzij MJ, et al: Dermal factors influencing measurement of skin autofluorescence. Diabetes Technol Ther 2011;13:165-170.
21.
Meerwaldt R, et al: Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia 2005;48:1637-1644.
22.
Monami M, et al: Skin autofluorescence in type 2 diabetes: beyond blood glucose. Diabetes Res Clin Pract 2008;79:56-60.
23.
Koetsier M, et al: Reference values of skin autofluorescence. Diabetes Technol Ther 2010;12:399-403.
24.
Hartog JW, et al: Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients. Nephrol Dial Transplant 2006;21:2263-2269.
25.
Hartog JW, et al: Skin-autofluorescence is an independent predictor of graft loss in renal transplant recipients. Transplantation 2009;87:1069-1077.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.