Carbamylated Hemoglobin as a Therapeutic Marker in Hemodialysis

Hasuike, Yukiko; Nakanishi, Takeshi; Maeda, K; Tanaka, Toshihiko; Inoue, Toru; Takamitsu, Yoshihiro

doi:10.1159/000058397

Cited by 17 publications

(8 citation statements)

References 17 publications

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“…111 Others have similarly demonstrated carbamylated hemoglobin could be a more accurate indicator of average urea between hemodialysis sessions than the standard indices of dialysis adequacy, Kt/V and URR. 110,112 In contrast, in a study limited by sample size (n=7), Balion et al found significant variability over time in individuals’ carbamylated hemoglobin levels, with little association with markers of dialysis adequacy. 46 …”

Section: Pathogenesismentioning

confidence: 93%

Protein Carbamylation in Kidney Disease: Pathogenesis and Clinical Implications

Kalim

Karumanchi

Thadhani

et al. 2014

American Journal of Kidney Diseases

107

101

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Carbamylation describes a non-enzymatic, posttranslational protein modification mediated by cyanate, a dissociation product of urea. When kidney function declines and urea accumulates, the burden of carbamylation naturally rises. Free amino acids may protect proteins from carbamylation, and protein carbamylation has been shown to increase in uremic patients with amino acid deficiencies. Carbamylation reactions are capable of altering the structure and functional properties of certain proteins, and have been directly implicated in the underlying mechanisms of various disease conditions. A broad range of studies has demonstrated how the irreversible binding of urea-derived cyanate to proteins in the human body causes inappropriate cellular responses leading to adverse outcomes such as accelerated atherosclerosis and inflammation. Given carbamylation’s relationship to urea and the evidence that it contributes to disease pathogenesis, measurements of carbamylated proteins may serve as useful quantitative biomarkers of time-averaged urea concentrations while also offering risk assessment in patients with kidney disease. Moreover, the link between carbamylated proteins and disease pathophysiology creates an enticing therapeutic target for reducing the rate of carbamylation. This article reviews the biochemistry of the carbamylation reaction, its role in specific diseases, and the potential diagnostic and therapeutic implications of these findings based on recent advances.

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Section: Pathogenesismentioning

confidence: 93%

Protein Carbamylation in Kidney Disease: Pathogenesis and Clinical Implications

Kalim

Karumanchi

Thadhani

et al. 2014

American Journal of Kidney Diseases

107

101

View full text Add to dashboard Cite

show abstract

“…For instance, carbamylated hemoglobin may be evaluated by measuring globin ␤ chain N-terminal carbamyl-valine residue by HPLC/UV quantification of the valine hydantoin derivative obtained after acid hydrolysis (59 ). Carbamylated hemoglobin is considered a marker of chronic renal failure (60 ) and is known to interfere with Hb A 1c measurement in patients with renal diseases (61 ).…”

Section: Carbamylation-derived Productsmentioning

confidence: 99%

Evaluation of Nonenzymatic Posttranslational Modification–Derived Products as Biomarkers of Molecular Aging of Proteins

2010

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BACKGROUND During their biological life, proteins are exposed in a cumulative fashion to irreversible nonenzymatic, late posttranslational modifications that are responsible for their molecular aging. It is now well established that these damaged proteins constitute a molecular substratum for many dysfunctions described in metabolic and age-related diseases, such as diabetes mellitus, renal insufficiency, atherosclerosis, or neurodegenerative diseases. Accordingly, the specific end products derived from these reactions are considered potentially useful biomarkers for these diseases. CONTENT The aim of this review is to give an overview of nonenzymatic posttranslational modifications of proteins and their influence in vivo, take inventory of the analytical methods available for the measurement of posttranslational modification–derived products, and assess the potential contribution of new technologies for their clinical use as biological markers of protein molecular aging. SUMMARY Despite their clinical relevance, biomarkers of posttranslational modifications of proteins have been studied only in the context of experimental clinical research, owing to the analytical complexity of their measurement. The recent implementation in clinical chemistry laboratories of mass spectrometry–based methods that provide higher specificity and sensitivity has facilitated the measurement of these compounds. These markers are not used currently by clinicians in routine practice, however, and many challenges, such as standardization, have to be confronted before these markers can be used as efficient tools in the detection and monitoring of long-term complications of metabolic and age-related diseases.

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“…No correlations were observed between these two parameters, whereas cHb was previously found to be associated with Kt/V values [5,6]. However, the results associating cHb and Kt/V were somewhat controversial [22,25,26].…”

Section: Discussionmentioning

confidence: 87%

“…Thus, carbamylated proteins have been proposed as valuable markers for the follow-up of patients with CKD. The most classical example is carbamylated hemoglobin (cHb) which has been suggested as a potential marker for the adequacy of hemodialysis therapy in CKD [5][6][7] as well as for differentiating acute from chronic renal failure [8,9]. During the course of the last decade, the development of mass spectrometry-based methods has enabled the emergence of new markers related to the carbamylation process.…”

Section: Introductionmentioning

confidence: 99%