Nephrol Dial Transplant (2000) 15: 25-28
© 2000 European Renal Association-European Dialysis and Transplant Association
Toxic Proteins
‘Carbonyl stress’ and dialysis-related amyloidosis
Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259–1193, Japan
Abstract
Advanced glycation end products (AGEs) are formed by nonenzymatic glycation and oxidation (glycoxidation) reactions. As AGE formation is related to hyperglycaemia, they have been implicated in the pathogenesis of diabetic complications. They also increase in normoglycaemic uraemic patients: AGEs, such as pentosidine and carboxymethyllysine (CML), are elevated in both the plasma proteins and skin collagen of uraemic patients, being several times greater than in normal subjects and nonuraemic diabetic patients. However, AGE concentrations do not differ between diabetics and non-diabetics in uraemia. AGE accumulation in uraemia, therefore, cannot be attributed to hyperglycaemia, or simply to the decreased removal by glomerular filtration of AGE-modified proteins as over 90% of plasma pentosidine and CML are linked to albumin. Recently, evidence has suggested that, in uraemia, the increased carbonyl compounds, derived from both carbohydrates and lipids, modify proteins both by the glycoxidation reaction (leading to augmented AGE production) and also by the lipoxidation reaction (leading to the augmentation of the advanced lipoxidation end product, ALE, production). Thus, uraemia might be a state of carbonyl overload with potentially damaging proteins (‘carbonyl stress’). Carbonyl stress in uraemia appears to be relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis. Immunohistochemical studies, with specific antibodies to AGEs and ALEs, identified carbonyl stress in long-lived ß2-microglobulin amyloid deposits. Furthermore, proteins modified with carbonyl stress exhibit several biological activities through interactions with several types of cell, e.g. monocytes/macrophages, synovial cells and osteoclasts/osteoblasts, which might partially account for dialysis arthropathies.
Notes
Correspondence and offprint requests to: Toshio Miyata, MD, PhD, lnstitute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259–1193, Japan.
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