Homocitrulline as marker of protein carbamylation in hemodialyzed patients

Jaisson, Stéphane; Kazes, Isabelle; Desmons, Aurore; Fadel, Fouad; Oudart, Jean‐Baptiste; Santos-Weiss, Izabella Castilhos Ribeiro dos; Millart, Hervé; Touré, Fatouma; Rieu, Philippe; Gillery, Philippe

doi:10.1016/j.cca.2016.06.009

Cited by 21 publications

(13 citation statements)

References 29 publications

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“…Moreover, handheld miniaturized NIR spectrometers offer great potential for on-site monitoring [13,14]. Therefore, this approach is much easier than analytical techniques classically used in the assessment of carbamoylated proteins such as LC-MS/MS [6]. Furthermore, in contrast to serum or plasma, the nail matrix does not require important preanalytical precautions, as even prolonged storage (4 • C) did not reveal significant differences for the peak intensity at 1494 nm.…”

Section: Discussionmentioning

confidence: 99%

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Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients

Bruyne

Himpe

Delanghe

et al. 2020

Toxins

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Carbamoylation is an important risk factor for accelerated atherogenesis and mortality in patients undergoing hemodialysis (HD). We intended to explore whether carbamoylation as assessed by near-infrared (NIR) analysis of nail proteins is associated with (a) plasma concentrations of representative uremic toxins and (b) mortality in HD patients. A total of 53 healthy volunteers and 84 consecutive HD patients were enrolled in this cross-sectional cohort study. Standard laboratory methods were used to measure routine parameters, whereas levels of uremic toxins were determined using reversed-phase high-performance liquid chromatography (RP-HPLC). Spectra of distal fingernail clippings were obtained using an Avantes NIR spectrometer and processed using chemometric data analysis. The second derivative of the peak intensity at 1494 nm attributed to N-H amide bands from NH2 of carbamoyl (-CONH2) groups was higher in HD patients than in control subjects (p < 0.0001). Peak intensity levels were associated with age and plasma levels of representative uremic toxins. Cox-regression analysis revealed a significant association with all-cause mortality, even after adjustment for age. In conclusion, our data revealed that carbamoylation as assessed by NIR analysis of nail proteins is associated with plasma concentrations of uremic toxins and also with mortality in HD patients. Further research to explore whether it is a surrogate marker or a hard indicator of mortality risk is warranted.

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Section: Discussionmentioning

confidence: 99%

“…Several biomarkers have been proposed to assess the extent of protein carbamoylation in biological samples. Characteristic compounds such as homocitrulline often require specialized analytical techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) [6].…”

Section: Introductionmentioning

confidence: 99%

Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients

Bruyne

Himpe

Delanghe

et al. 2020

Toxins

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“…Furthermore, elevated homocitrulline concentration was associated with poor collateral development in patients with angina and CTO, even after adjusting for other significant risk factors of coronary artery disease. Consequently, our observational study, coupled with the fact that homocitrulline levels are often used as a biomarker of renal impairment and enhanced inflammation, indicated that increasing homocitrulline levels might serve as a risk factor for poor collateral growth. Our clinical data also demonstrated a link between impaired coronary collateral development and the antiangiogenic regulation of cyanate.…”

Section: Discussionmentioning

confidence: 94%

Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Sun

Yang

Mao

et al. 2016

JAHA

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BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear.Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth.ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

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“…A first limitation of the presented method is that although the in vitro experiments have clearly demonstrated that carbamylation is responsible for the shift in the albumin peak symmetry, quantification of carbamylation‐derived products (e.g. homocitrulline) was not performed . A second limitation is that recent administration of albumin infusions could theoretically affect the obtained results.…”

Section: Discussionmentioning

confidence: 99%

Quantification of carbamylated albumin in serum based on capillary electrophoresis

et al. 2017

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Protein carbamylation, a nonenzymatic posttranslational modification promoted during uremia, is linked to a poor prognosis. In the present study, carbamylation of serum albumin was assayed using the symmetry factor on a capillary electrophoresis instrument (Helena V8). The symmetry factor has been defined as the distance from the center line of the peak to the back slope, divided by the distance from the center line of the peak to the front slope, with all measurements made at 10% of the maximum peak height. Serum albumin, creatinine, and urea concentrations were assayed using routine methods, whereas uremic toxins were determined using HPLC. In vitro carbamylation induced a marked albumin peak asymmetry. Reference values for the albumin symmetry factor were 0.69-0.92. In kidney patients, albumin peak asymmetry corresponded to the chronic kidney disease stage (p < 0.0001). The symmetry factor correlated well with serum urea (r = -0.5595, p < 0.0001) and creatinine (r = -0.5986, p < 0.0001) concentrations. Several protein-bound uremic toxins showed a significant negative correlation with the symmetry factor. Morphology of the albumin fraction was not affected by presence of glycated albumin and protein-bound antibiotics. In conclusion, the presented method provides a simple, practical way for monitoring protein carbamylation.

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Homocitrulline as marker of protein carbamylation in hemodialyzed patients

Cited by 21 publications

References 29 publications

Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients

Carbamoylated Nail Proteins as Assessed by Near-Infrared Analysis Are Associated with Load of Uremic Toxins and Mortality in Hemodialysis Patients

Cyanate‐Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion

Quantification of carbamylated albumin in serum based on capillary electrophoresis

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