N -(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis

Motomiya, Yoshihiro; Oyama, Nobuo; Iwamoto, Hisahiko; Uchimura, Tomonori; Maruyama, Ikuro

doi:10.1046/j.1523-1755.1998.00091.x

Cited by 23 publications

(16 citation statements)

References 39 publications

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“…Hence, elevated M-CSF levels may be one of the causal factors in the activation of monocytes/macrophages in long-term HD. In comparison, it is also known that increased levels of AGEs occur in HD patients [1, 4, 5, 6]; moreover, these AGEs possess an important role in the pathogenesis of HD complications [21]. The involvement of AGEs is feasible in this process, as AGE-mediated upregulation of the expression of proinflammatory cytokines and procoagulant factors, including IL-1, IL-6, IL-8, ICAM, tissue factor and tissue plasminogen activator inhibitor 1, has been described.…”

Section: Discussionmentioning

confidence: 99%

“…CML-Hb in blood was measured using a previously described method [4]. In brief, CML-human serum albumin was prepared utilizing glyoxylic acid and sodium cyanoborohydrate according to the protocol of Ahmed et al [15].…”

Section: Methodsmentioning

confidence: 99%

“…AGE substances, including N ε -(carboxymethyl)lysine (CML), have been detected in amyloid tissue specimens obtained from HD patients presenting with dialysis-related amyloidosis [2, 3]. In addition, we recently reported a significant increase in circulating carboxymethyllysine-hemoglobin (CML-Hb) in dialysis patients, particularly in patients with dialysis-related amyloidosis [4]. …”

Section: Introductionmentioning

confidence: 99%

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Marked Increases in Macrophage Colony-Stimulating Factor and Interleukin-18 in Maintenance Hemodialysis Patients: Comparative Study of Advanced Glycation End Products, Carboxymethyllysine and Pentosidine

Uchimura

Motomiya²,

Okamura

et al. 2002

Nephron

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Background: Recent studies have demonstrated the crucial involvement of advanced glycation end products (AGEs) in major complications of long-term hemodialysis (HD) patients. HD, in a clinical setting, is characterized by increased production of proinflammatory cytokines. AGEs and cytokines are presumed to be responsible for the development of major complications in long-term HD. We therefore investigate here the relationship between a newly identified cytokine, interleukin-18 (IL-18), and two AGEs, carboxymethyllysine-hemoglobin (CML-Hb) and pentosidine. Methods: CML-Hb, pentosidine macrophage colony-stimulating factor (M-CSF), and IL-18 were evaluated in 35 patients undergoing stable maintenance HD. CML-Hb and pentosidine were measured by a dot blot and competitive ELISA. Cytokines were measured with a cytokine-specific ELISA. Results: Circulating levels of CML-Hb and pentosidine were elevated in HD patients as compared to controls. The serum values of M-CSF and IL-18 were significantly increased in the HD patients in comparison to controls. Moreover, these two AGEs and serum values of M-CSF, M-CSF and IL-18 showed significant correlation by simple and multiple regression analysis. Conclusion: Elevation of circulating IL-18 levels was demonstrated in maintenance HD patients relative to controls. A correlative increase in M-CSF and IL-18 suggests the presence of a primed state of monocytes/macrophages in HD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Marked Increases in Macrophage Colony-Stimulating Factor and Interleukin-18 in Maintenance Hemodialysis Patients: Comparative Study of Advanced Glycation End Products, Carboxymethyllysine and Pentosidine

Uchimura

Motomiya²,

Okamura

et al. 2002

Nephron

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“…Protein-bound CML was assessed in uremic sera by GC-MS after protein hydrolysis and derivatisation [33, 45, 51], CML-modified hemoglobin was determined by immunological methods [52]and total serum CML by a competitive ELISA [48]. As for unspecific AGEs an increase of total CML levels as well as of protein-bound CML by a factor of 3–5 was observed when compared to healthy controls (table 4).…”

Section: Serum Age Levels In Esrdmentioning

confidence: 99%

Advanced Glycation End Products in End-Stage Renal Disease and Their Removal

Schinzel

Münch

Heidland

et al. 2001

Nephron

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“…We reported previously [13]that the circulating CML-Hb levels were increased in HD patients to levels of about twice of those of healthy persons and that patients with DRA showed significantly higher levels of circulating CML-Hb than patients without DRA. In this study, we confirmed that the circulating level of CML-Hb correlated significantly with the clinical score of DRA and predicted a potential progression of amyloid cysts.…”

Section: Discussionmentioning

confidence: 97%

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

Motomiya¹,

Iwamoto²,

Uji

et al. 2001

Nephron

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Background/Aim: Carboxymethyllysine is one of the common advanced glycation end products in vivo. In a previous report, we were the first to describe the increase of circulating carboxymethyllysine-hemoglobin (CML-Hb) levels in hemodialysis patients, particularly in patients with dialysis-related amyloidosis (DRA). The aim of this study was to investigate the predictive value of CML-Hb in the progression of DRA using computed tomography images of 2-year or 3-year follow-up periods of patients with amyloid bone cysts at the hip joint. Methods: Circulating CML-Hb levels were measured as previously reported, and computed tomography scanning was conducted from 1996 to 1998 or 1999 in 57 hemodialysis patients whose original renal disease had been confirmed to be nondiabetic. Patients who showed a new growth of cysts or a growth rate of 30% or more were classified as progressive cases, while the other patients were classified as nonprogressive cases. Results: (1) The circulating CML-Hb levels showed a strong correlation with the DRA score by multiple regression analysis, and (2) patients with progression of amyloid cysts showed a significantly higher circulating CML-Hb level than patients without progression. Conclusion: Based upon these results, we conclude that measurement of circulating CML-Hb levels has a potential value in both judgment of the clinical state and prediction of progression of DRA in hemodialysis patients.

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N -(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis

Abstract: We suggest that CML-Hb is increased in blood from patients on maintenance hemodialysis and is thus a potential biomarker of oxidative damage in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.

Cited by 23 publications

References 39 publications

Marked Increases in Macrophage Colony-Stimulating Factor and Interleukin-18 in Maintenance Hemodialysis Patients: Comparative Study of Advanced Glycation End Products, Carboxymethyllysine and Pentosidine

Marked Increases in Macrophage Colony-Stimulating Factor and Interleukin-18 in Maintenance Hemodialysis Patients: Comparative Study of Advanced Glycation End Products, Carboxymethyllysine and Pentosidine

Advanced Glycation End Products in End-Stage Renal Disease and Their Removal

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

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