The metabolomics signature associated with responsiveness to steroid therapy in focal segmental glomerulosclerosis: A pilot study

Chashmniam, S ; Sharif University of Technology | 2019

993 Viewed
  1. Type of Document: Article
  2. DOI: 10.24875/RIC18002668
  3. Publisher: Instituto Nacional de la Nutricion Salvador Zubiran , 2019
  4. Abstract:
  5. 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
  6. Keywords:
  7. Focal segmental glomerulosclerosis ; Predictive biomarker ; Prednisolone ; Steroid resistance ; Steroid sensitivity ; 4 methylcatechol ; Caspase 3 ; Qentisic acid ; Homovanillic acid ; Levodopa ; Nerve growth factor ; Noradrenalin ; Protein Bax ; Protein bcl 2 ; Tumor necrosis factor ; Tyrosine ; Biological marker ; Qlucocorticoid ; Amino acid metabolism ; Clinical article ; Estimated glomerular filtration rate ; Female ; Focal glomerulosclerosis ; Follow up ; Human ; Male ; Monotherapy ; Proton nuclear magnetic resonance ; Steroid therapy ; Urine sampling ; Metabolism ; Pathophysiology ; Pilot study ; Procedures ; Treatment outcome ; Young adult ; Adult ; Biomarkers ; Female ; Glomerulosclerosis, Focal Segmental ; Glucocorticoids ; Humans ; Metabolomics ; Middle Aged ; Pilot Projects
  8. Source: Revista de Investigacion Clinica ; Volume 71, Issue 2 , 2019 , Pages 106-115 ; 00348376 (ISSN)
  9. URL: https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=86702