ISSN 1006-298X      CN 32-1425/R

Chinese Journal of Nephrology, Dialysis & Transplantation ›› 2022, Vol. 31 ›› Issue (2): 133-138.DOI: 10.3969/j.issn.1006-298X.2022.02.006

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Influence of gene polymorphism on efficacy of roxadustat in patients with chronic kidney disease

  

  • Online:2022-04-28 Published:2022-04-21

Abstract: Objective:By exploring relationship among CYP2C8 (cytochrome enzyme) and UGT1A9 (uridine diphosphate glucuronyltransferase) genotypes, roxadustat trough concentration and hemoglobin response rate in patients with chronic kidney disease, analyse effect of gene polymorphisms on metabolism of roxadustat and efficacy of anemia.
Methodology:Twentytwo chronic kidney disease patients not receiving dialysis and complicated with renal anemia were enrolled. The genotypes were detected by polymerase chain reactionrestriction fragment length polymorphism (PCRRFLP) method. The hemoglobin concentration of patients after roxadustat treatment for 4~8 weeks was measured, and an increase in hemoglobin of ≥10 g/L from the baseline value was defined as “hemoglobin response”. The trough concentrations of roxadustat were detected by liquid chromatographytandem mass spectrometry (LCMS/MS), and the differences in drug trough concentrations of patients in each genotype group were compared. Drug trough concentrations of patients with different genotype and different efficacy were analyzed.
Results:The elevated hemoglobin values and rosalostat concentrations in UGT1A9 rs2070959 locus AA group were significantly lower than that in AG group (P<005), but there was no difference in hemoglobin response rate between the two groups (P>005). There was no significant difference in hemoglobin elevation before and after treatment, hemoglobin response rate, and mean trough concentration between UGT1A9 rs3832043 locus genotype groups (P>005). No different genotypes were detected at CYP2C8related loci. The trough concentration of roxadustat in hemoglobin response group was significantly higher than that in nonresponse group (P<005).
Conclusion:UGT1A9 gene polymorphism significantly affects efficacy and trough concentration of roxadustat. The anemic efficacy of roxadustat is related to trough concentration of drug.


Key words: renal anemia, roxadustat, genetic polymorphism