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

Grant number: 17/12149-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2017
Effective date (End): August 06, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Marina Franco Maggi Tavares
Grantee:Adriana Nori de Macedo
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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 interpretation of the results. 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 analyzed in metabolomics by liquid-phase chromatography, which constitutes 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.