Potential Value of CML-Hb in Predicting the Progression of Bone Cysts in Dialysis-Related Amyloidosis

Motomiya, Yoshihiro; Iwamoto, Hisahiko; Uji, Yukitaka; Higashi, Takuya; Uchimura, Tomonori; Maruyama, Ikuro

doi:10.1159/000046087

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…RAGE expressed by synovial fibroblasts may mediate some of these responses involved in DRA [158]. CML-hemoglobin has been proposed as a possible predictor of progression of bone cysts in DRA [159]. Thus, at least a close relation between AGE accumulation in renal failure and the development of dialysis related amyloidosis exists.…”

Section: Age In Renal Insufficiency Renal Replacement Therapy and Kimentioning

confidence: 99%

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

Smit¹,

Lutgers

2004

CMC

116

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Advanced glycation endproducts (AGE) are a class of compounds resulting from glycation and oxidation of proteins, lipids or nucleic acids. Glycation is the non-enzymatic addition or insertion of saccharide derivatives to these molecules. This leads to the formation of intermediary Schiff bases and Amadori products and finally to irreversible AGE. This classical view has been modified in recent years with recognition of the importance of oxidative and carbonyl stress in endogenous AGE formation. AGE may also have exogenous sources, in certain foods and tobacco smoke. A whole class of specific and non-specific receptors binding AGE has been characterized. Apart from cross-linking of proteins by AGE, the effects of receptor stimulation contribute to the development of chronic complications of conditions like diabetes mellitus, renal failure, and atherosclerosis. Possible interventions to reduce the effects of AGE accumulation include AGE formation inhibitors or breakers, or receptor blockers, but possibly also dietary interventions. Some of the problems with current assay or diagnostic techniques, and several unresolved issues on the role of AGE in disease will be discussed. Our review will focus on the clinical and pharmaceutical implications of these developments.

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Section: Age In Renal Insufficiency Renal Replacement Therapy and Kimentioning

confidence: 99%

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

Smit¹,

Lutgers

2004

CMC

116

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“…Major clinical signs of DRA in HD patients were: (i) polyarthralgia; (ii) CTS; (iii) bone cyst; and (iv) destructive spondylo‐arthropathy. Significant correlation between circulating CML‐Hb level and the progress of bone amyloid cyst, was quite recently reported and suggested that the formation of AGEs is closely involved in development and/or progress of bone amyloid cysts (16).…”

Section: Discussionmentioning

confidence: 99%

A Possible Involvement of the Carboxymethylation Process in Carpal Tunnel Syndrome in Hemodialysis Patients

Imai¹,

Yoshinaka²,

Iwamoto³

et al. 2004

Ther Apher Dial

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A median motor nerve latency (DML) is generally prolonged in the carpal tunnel syndrome (CTS) of hemodialysis patients. Meanwhile, the advanced glycation process of proteins has been reported to be involved in the pathogenesis of the dialysis related amyloidosis. To investigate the role of carboxymethylation in dialysis related CTS, we measured a circulating carboxymethyllysine-hemoglobin (CML-Hb) level and nerve conduction velocity in 44 hemodialysis patients. The circulating CML-Hb level was 6.56 +/- 3.18 nmol CML/mg Hb, median motor nerve conduction velocity (NCV) was 49.8 +/- 4.64 m/s, median DML was 4.44 +/- 1.06 ms, and difference between median DML and ulnar DML (Delta DML) was 1.68 +/- 1.09 ms. Median and ulnar nerve NCV showed no correlation with circulating CML-Hb level. Both median DML and Delta DML were significantly correlated with CML-Hb (r = 0.429, P = 0.003, r = 0.472, P = 0.001). This study provided additional clinical evidence of an involvement of an advanced glycation process in the pathogenesis in CTS in hemodialysis patients.

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“…Future studies are required to show whether serum levels of AGE or CML can be used to predict severity or duration of a chronic inflammatory disease and thus predict the occurrence or progression of AA amyloidosis, as it was demonstrated for A␤2M amyloidosis. 35 Statistical analyses failed to show any correlation between serum or splenic CML levels and amounts of RAGE mRNA, indicating that transcription of RAGE does not depend on CML levels only. At least three different ligands, which occur during amyloidogenesis, compete for binding to RAGE: SAA1.1, AA fibril protein, and CML.…”

Section: Prevalence and Pathogenesis Of Ages In Amyloidosismentioning

confidence: 96%

Advanced Glycation End Products and Receptor for Advanced Glycation End Products in AA Amyloidosis

Röcken

Kientsch-Engel

Mansfeld

et al. 2003

The American Journal of Pathology

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Advanced glycation end products (AGEs) may be involved in either amyloidogenesis or complications related to amyloid. We hypothesized that AGEs may influence the pathogenesis of AA amyloidosis, and investigated the spatial and temporal relationship between AGEs, carboxy methyl lysine (CML), the AGE receptor (RAGE), and AA amyloid in humans and mice. Specimens from patients with AL and ATTR amyloidosis served as a control. Using immunohistochemistry, AGEs, CML, and RAGE were found within amyloid deposits, more commonly in AA amyloid than in AL amyloid and not in ATTR amyloid. Western blotting showed that multiple proteins (between 12 and >60 kd) are modified, but not the AA amyloid fibril protein itself. In the murine model of AA amyloidosis, we found a marked interindividual variability with respect to local and systemic CML levels, as well as to splenic RAGE transcription. Serum levels of CML correlated with the duration of the inflammatory response but not with amounts of splenic RAGE mRNA. Other as yet unidentified variables, especially of the heterogeneous group of AGEs, probably modulate transcription of RAGE and influence amyloidogenesis. CML serum levels, in turn, may prove useful in predicting patients at risk. Advanced glycation end products (AGEs) formed by nonenzymatic glycoxidation of proteins and lipids have been implicated in complications contributing to the increased morbidity and mortality of patients suffering from diabetes and uremia. Hyperglycemia in diabetic patients, and oxidative stress and carbonyl stress in uremic patients, contribute to the formation of AGEs, which are a chemically heterogeneous group of stable covalently bound and cross-linked adducts.

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Potential Value of CML-Hb in Predicting the Progression of Bone Cysts in Dialysis-Related Amyloidosis

Cited by 3 publications

References 19 publications

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

The Clinical Relevance of Advanced Glycation Endproducts (AGE) and Recent Developments in Pharmaceutics to Reduce AGE Accumulation

A Possible Involvement of the Carboxymethylation Process in Carpal Tunnel Syndrome in Hemodialysis Patients

Advanced Glycation End Products and Receptor for Advanced Glycation End Products in AA Amyloidosis

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