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Expanding the metabolic coverage using ion chromatography-mass spectrometry in metabolomics studies of immunosuppressive therapies in renal transplantation

Abstract

Renal transplantation is the most effective treatment option for patients with end-stage renal disease, representing about 70% of the transplanted organs in Brazil. However, the long-term use of immunosuppressive agents, necessary to delay organ rejection post-transplantation, results in a range of side-effects, which require constant medical monitoring. Tests currently used to evaluate renal function have low specificity, are invasive, or prone to divergent interpretations. For this reason, there is a great interest in metabolomics as an active way to discover new biomarkers and to expand the biological knowledge. In especial, polar/ionizable urinary metabolites have been highlighted in studies involving transplanted patients. However, analytical platforms commonly used in metabolomics have limited coverage for those compounds, which limits a more complete biological interpretation. In this context, the present study aims to exploring the use of ion chromatography coupled to mass spectrometry (IC-MS) to increase the number of polar/ionizable metabolites that are detectable by liquid-phase chromatography, which comprises a novel application of IC-MS that is essential to overcome a large analytical limitation in metabolomics. In a pilot study, the method developed will be used to evaluate metabolic alterations related to time after transplantation (7 and 14 days, and 1, 3, 6, 9 and 12 months after renal transplantation) in 30 patients treated with two combinations of immunosuppressive agents: (A) tacrolimus, prednisone, and everolimus; and (B) tacrolimus, prednisone, and mycophenolate sodium. Therefore, in addition to providing novel analytical protocols to expand the metabolic coverage in metabolomics studies, the present research will also contribute to better understand biological mechanisms associated to the renal function post-transplantation, leading to future improvements in the treatment and monitoring of transplanted patients. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROSSETTO, ROSILENE CRISTINA; MACEDO, ADRIANA NORI DE; DA, PEDRO LUIS ROCHA; TEDESCO-SILVA, HELIO; CARDOZO, KARINA HELENA MORAIS; CARVALHO, VALDEMIR MELECHCO; TAVARES, MARINA FRANCO MAGGI. Improving data quality in liquid chromatography-mass spectrometry metabolomics of human urine. Journal of Chromatography A, v. 1654, SEP 27 2021. Web of Science Citations: 0.
GONCALVES, LETICIA C. P.; MASSARI, JULIO; LICCIARDI, SAYMON; PRADO, FERNANDA M.; LINARES, EDLAINE; KLASSEN, ALINE; TAVARES, MARINA F. M.; AUGUSTO, OHARA; DI MASCIO, PAOLO; BECHARA, ETELVINO J. H. Singlet oxygen generation by the reaction of acrolein with peroxynitrite via a 2-hydroxyvinyl radical intermediate. Free Radical Biology and Medicine, v. 152, p. 83-90, MAY 20 2020. Web of Science Citations: 0.
CIESLAROVA, ZUZANA; MAGALDI, MARIANA; BARROS, LUCELIA ALCANTARA; DO LAGO, CLAUDIMIR LUCIO; OLIVEIRA, DANIEL ROSSADO; HELFENSTEIN FONSECA, FRANCISCO ANTONIO; IZAR, MARIA CRISTINA; LOPES, ALINE SORIANO; MAGGI TAVARES, MARINA FRANCO; KLASSEN, ALINE. Capillary electrophoresis with dual diode array detection and tandem mass spectrometry to access cardiovascular biomarkers candidates in human urine: Trimethylamine-N-Oxide and L-carnitine. Journal of Chromatography A, v. 1583, p. 136-142, JAN 4 2019. Web of Science Citations: 4.

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