The Metabolomics Signature Associated with Responsiveness to Steroid Therapy in Focal Segmental Glomerulosclerosis: A Pilot Study



Título del documento: The Metabolomics Signature Associated with Responsiveness to Steroid Therapy in Focal Segmental Glomerulosclerosis: A Pilot Study
Revista: Revista de investigación clínica
Base de datos: PERIÓDICA
Número de sistema: 000454202
ISSN: 0034-8376
Autores: 1
2
2
3
Instituciones: 1Sharif University of Technology, Department of Chemistry, Teherán. Iran
2Shahid Beheshti University of Medical Sciences, Chronic Kidney Disease Research Center, Teherán. Iran
3Shahid Beheshti University of Medical Sciences, Urology-Nephrology Research Center, Teherán. Iran
Año:
Periodo: Mar-Abr
Volumen: 71
Número: 2
Paginación: 106-115
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés Background Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods Urine was collected from biopsy-proven FSGS patients eligible for monotherapy with prednisolone. Patients were followed for 6-8 weeks and categorized as SS or SR. Metabolite profile of urine samples was analyzed by one-dimensional 1H-nuclear magnetic resonance (1H-NMR). Predictive biomarker candidates and their diagnostic importance impaired molecular pathways in SR patients, and the common target molecules between biomarker candidates and drug were predicted. Results Homovanillic acid, 4-methylcatechol, and tyrosine were suggested as the significant predictive biomarker candidates, while L-3,4-dihydroxyphenylalanine, norepinephrine, and gentisic acid had high accuracy as well. Tyrosine metabolism was the most important pathway that is perturbed in SR patients. Common targets of the action of biomarker candidates and prednisolone were molecules that contributed in apoptosis. Conclusion Urine metabolites including homovanillic acid, 4-methylcatechol, and tyrosine may serve as potential non-invasive predictive biomarkers for evaluating the responsiveness of FSGS patients
Disciplinas: Medicina
Palabras clave: Nefrología,
Farmacología,
Glomeruloesclerosis focal y segmentaria,
Biomarcadores,
Prednisolona,
Resistencia a esteroides,
Metabolómica
Keyword: Nephrology,
Pharmacology,
Focal segmental glomerulosclerosis,
Biomarkers,
Prednisolone,
Steroid resistance,
Metabolomics
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