Effect of Sevelamer and Nicotinamide on Albumin Carbamylation in Patients with End-Stage Kidney Disease
| العنوان: | Effect of Sevelamer and Nicotinamide on Albumin Carbamylation in Patients with End-Stage Kidney Disease |
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| المؤلفون: | Ziad A. Massy, François-Ludovic Sauvage, Gabriel Choukroun, Marie Essig, Souleiman El Balkhi, Aurélie Lenglet, Mohamad Ali Rahali, Sophie Liabeuf |
| المساهمون: | Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], CHU Limoges, Amgen Eli Lilly and Company GlaxoSmithKline, GSK Baxter International FMC Corporation, FMC Meso Scale Diagnostics, MSD, We thank Prof. Albert Fournier, who initiated this clinical study. We also thank Amiens University Hospital, and especially the Clinical Research and Innovation Directorate (for logistical support), the Clinical Research Center (for study management), and the Department of Nephrology Internal Medicine, Dialysis, Transplantation and Intensive Care. Last, we thank the patients and physicians at the 18 dialysis centers for their participation in the NICOREN trial., Ziad A. Massy reports grants and Congress Travel support from Amgen, Baxter, Otsuka, and Sanofi-Genzyme, grants from the French Government, MSD, GSK, Lilly, and FMC, and Receipt of honoraria or consultation fees for the Charities from Daichi and Astellas, outside the submitted work., HAL UVSQ, Équipe |
| المصدر: | Drugs in R&D Drugs in R&D, Springer Verlag, 2021, 21 (2), pp.231-238. ⟨10.1007/s40268-021-00350-7⟩ Drugs in R&D, 2021, 21 (2), pp.231-238. ⟨10.1007/s40268-021-00350-7⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Niacinamide, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Serum albumin, Sevelamer, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Original Research Article, Risk factor, education, Serum Albumin, 030203 arthritis & rheumatology, Pharmacology, education.field_of_study, Protein Carbamylation, biology, Nicotinamide, business.industry, Albumin, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Endocrinology, chemistry, biology.protein, Urea, Kidney Failure, Chronic, business, medicine.drug, Kidney disease |
| الوصف: | Background and Objective In end-stage kidney disease, high urea levels promote the carbamylation of lysine side chains on a variety of proteins, including albumin. Albumin carbamylation has been identified as a risk factor for mortality and sevelamer led to a decrease in urea levels in dialysis patients. In the present secondary analysis of the NICOREN trial, we investigated the putative impacts of sevelamer and nicotinamide on albumin carbamylation, and the potential correlation between carbamylation and vascular calcifications. Methods All possible carbamylation of circulating albumin were screened for with high-resolution liquid chromatography-tandem mass spectrometry. Levels of three carbamylated peptides were then measured as a guide to the extent of albumin carbamylation. Carbamylation was measured at baseline in 55 patients included in the NICOREN trial and 29 patients at 24 weeks of treatment. Calcifications on plain radiographs were quantified as the Kauppila score and the Adragao score. Results Baseline albumin carbamylation was present at three different sites in subjects with end-stage kidney disease. At baseline, we observed only a correlation between urea and the KQTA carbamylation site in these patients. Albumin carbamylation levels did not decrease after 24 weeks of treatment with either sevelamer or nicotinamide. Furthermore, the proportion of carbamylated serum albumin was not correlated with vascular calcification scores in this population. Conclusions Our results confirmed the presence of carbamylated albumin in patients with end-stage kidney disease and demonstrated the presence of carbamylation beyond the LRVP residues. The results also demonstrated the lack of impact of sevelamer or nicotinamide on albumin carbamylation levels. Therapeutic strategies to lower carbamylation load should probably be focused on direct anti-carbamylation processes and/or potentially anti-inflammatory therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s40268-021-00350-7. |
| وصف الملف: | application/pdf |
| تدمد: | 1179-6901 1174-5886 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44dbd707c6775e23ab843dce5a4de42eTest https://doi.org/10.1007/s40268-021-00350-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....44dbd707c6775e23ab843dce5a4de42e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 11796901 11745886 |
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