The reduced function allele SLCO1B1 c.521T>C is of no practical relevance for the renal graft function over the first post-transplant year in patients treated with mycophenolic acid.
Humans
Kidney Transplantation
/ adverse effects
Mycophenolic Acid
/ adverse effects
Male
Female
Middle Aged
Glomerular Filtration Rate
/ drug effects
Adult
Liver-Specific Organic Anion Transporter 1
/ genetics
Alleles
Immunosuppressive Agents
/ adverse effects
Polymorphism, Single Nucleotide
Aged
Cohort Studies
Graft Rejection
/ genetics
Journal
Pharmacogenetics and genomics
ISSN: 1744-6880
Titre abrégé: Pharmacogenet Genomics
Pays: United States
ID NLM: 101231005
Informations de publication
Date de publication:
01 Sep 2024
01 Sep 2024
Historique:
medline:
5
8
2024
pubmed:
5
8
2024
entrez:
5
8
2024
Statut:
ppublish
Résumé
It is unclear whether renal transplant recipients treated with mycophenolic acid (MPA) who carry the reduced-function allele at polymorphism SLCO1B1 c.521T>C differ from their wild-type peers regarding renal outcomes and tolerability. We aimed to estimate the effect of this polymorphism on the graft function (estimated glomerular filtration rate, eGFR) over the first 12 post-transplant months in patients on MPA-based maintenance immunosuppression. In a 12-month observational cohort study, consecutive adult patients were repeatedly assessed for eGFR. The SLCO1B1 c.521C>T variant allele carriers (exposed) and wild-type subjects (controls) were balanced on a range of demographic, medical, and genetic variables at baseline, and eGFR trajectory was estimated with further adjustment for time-varying covariates. A subset of patients were assessed for exposure to MPA 5-7 days after the transplantation. The adjusted eGFR slopes from day 1 to day 28 (daily), and from day 28 to day 365 (monthly) were practically identical in exposed (n = 86) and control (n = 168) patients [geometric means ratios (GMR) = 0.99, 95% confidence interval (CI) = 0.92-1.06 and GMR = 0.98, 0.94-1.01, respectively]. The rates of adverse renal outcomes and possible MPA-related adverse effects were low, and similar in exposed and controls [rate ratios (RR) = 0.94, 0.49-1.84 and RR = 1.08, 0.74-1.58, respectively]. The pharmacokinetic analysis did not signal meaningful differences regarding exposure to MPA, overall (exposed n = 23, control n = 45), if cotreated with cyclosporine (n = 17 vs. n = 26) or with tacrolimus (n = 8 vs. n = 17). In patients treated with MPA, variant allele SLCO1B1 c.521T>C appears of no practical relevance regarding the 12-month renal graft function, MPA safety and exposure to MPA at early steady-state.
Identifiants
pubmed: 39101384
doi: 10.1097/FPC.0000000000000539
pii: 01213011-202409000-00002
doi:
Substances chimiques
Mycophenolic Acid
HU9DX48N0T
Liver-Specific Organic Anion Transporter 1
0
SLCO1B1 protein, human
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
226-235Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
Oshiro C, Mangravite L, Klein T, Altman R. PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenet Genomics 2010; 20:211–216.
Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 2009; 158:693–705.
Ramsey LB, Gong L, Lee S, Wagner JB, Zhou X, Sangkuhl K, et al. PharmVar GeneFocus: SLCO1B1. Clin Pharmacol Ther 2023; 113:782–793.
Gene-specific information tables for SLCO1B1. PharmGKB. https://www.pharmgkb.org/page/slco1b1RefMaterials. [Accessed 15 December 2023]
Farasyn T, Crowe A, Hatley O, Neuhoff S, Alam K, Kanyo J, et al. Preincubation with everolimus and sirolimus reduces organic anion-transporting polypeptide (OATP)1B1 – and 1B3 – mediated transport independently of mTOR kinase inhibition: implication in assessing OATP1B1 – and OAT1B3 mediated drug-drug interactions. J Pharm Sci 2019; 108:3443–3456.
Michelon H, Konig J, Durrbach A, Quteineh L, Verstuyft C, Furlan V, et al. SLCO1B1 genetic polymorphism influences mycophenolic and tolerance in renal transplant recipients. Pharmacogenomics 2010; 11:1703–1713.
Picard N, Yee SW, Woillard JB, Lebranchu Y, Le Meur Y, Giacomini KM, et al. The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clin Pharmacol Ther 2010; 87:100–108.
Tett SE, Saint-Marcoux F, Staatz CE, et al. Mycophenolate. Clinical pharmacokinetics, formulations, and methods for assessing drug exposure. Transplant Rev 2011; 5:47–57.
Bergan S, Brunet M, Hesselink DA, Johnson-Davis KL, Kunicki PK, Lemaitre F, et al. Personalized therapy for mycophenolate: consensus report by the International Association on Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit 2021; 43:150–200.
Lamba V, Sanhavi K, Fish A, Altman RB, Klein TE. PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics 2014; 24:73–79.
Dalla Vecchia Genvigir F, Cerda A, Dominguez Crespo Hirata T, Hirata MH, Dominguez Crespo Hirata R. Mycophenolic acid pharmacogenomics in kidney transplantation. J Transl Genet Genom 2020; 4:320–355.
Takuathung MN, Sakuludomkan W, Koonrungsesomboon N. The impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of mycophenolic acid: a systematic review and meta-analysis. Clin Pharmacokinet 2021; 60:1291–1302.
Liu J, Zhu Y, Zhang J, Wei J, Zheng M, Gui Z, et al. Influence of SLCO1B1 polymorphisms on the pharmacokinetics of mycophenolic acid in renal transplant recipients. Curr Drug Metab 2023; 24:114–123.
Bouamar R, Hesselink DA, van Schaik RHN, Weimar W, van der Heiden IP, de Fijter JW, et al. Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients. Pharmacogenet Genomics 2012; 22:399–407.
Miura M, Satoh S, Knoue K. Influence of SLCO1B1, 13B, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant patients. Eur J Clin Pharmacol 2007; 63:1161–1169.
Sun SS, Shao K, Lu JQ, An H-M, Shi H-Q, Zhou P-J, et al. Influence of calcineurin inhibitors and genetic polymorphism of transporters on enterohepatic circulation and exposure of mycophenolic acid in Chinese adult renal allograft patients. J Clin Pharmacol 2023; 63:410–420.
Varnell CD, Fukuda T, Kirby CL, Martin LJ, Warshaw BL, Patel HP, et al. Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: influence of genes and drugs. Pediatr Transplant 2017; 21. doi: 10.1111/petr.13033.
doi: 10.1111/petr.13033
Hilbrands L, Budde K, Bellini MI, Diekmann F, Furian L, Grinyó J, et al. Allograft function as endpoint for clinical trials in kidney transplantation. Transpl Int 2022; 35:10139.
Schold JD, Nordyke RJ, Wu Z, Corvino F, Wang W, Mohan S. Clinical events and renal function in the first year predict long-term kidney transplant survival. Kidney360 2022; 3:714–727.
Hernan MA, Robins JM. Using big data to emulate a target trial when a randomized trial is not available. Am J Epidemiol 2016; 183:758–764.
Ratitch B, Bell J, Mallinckrodt C, Bartlett JW, Goel N, Molenberghs G, et al. Choosing estimands in clinical trials: putting the ICH E9(R1) into perspective. Ther Innov Regul Sci 2020; 54:324–341.
Božina N, Lalić Z, Nađ Škegro S, et al. Steady-state pharmacokinetics of mycophenolic acid in renal transplant patients: exploratory analysis of the effects of cyclosporine, recipients’ and donors’ ABCC2 gene variants, and their interactions. Eur J Clin Pharmacol 2017; 73:1129–1140.
Borić Bilušić A, Božina N, Lalić Z, et al. Loss of function ABCG2 c.421C>A (rs2231142) polymorphism increases steady-state exposure to mycophenolic acid in stable renal transplant recipients: an exploratory matched cohort study. Adv Ther 2023; 40:601–618.
Huling JD, Greifer N, Chen G. Independence weights for causal inference with continuous treatments. J Am Stat Assoc 2023:; 1–14. doi: 10.1080/01621459.2023.2213485.
doi: 10.1080/01621459.2023.2213485
Huling JD, Mak S. Energy balancing of covariate distributions. arXiv 2020: 2004.13962. https://doi.org/10.48550/arXiv.2004.13962.
Greifer N. WeightIt: Weighting for Covariate Balance in Observational Studies. https://github.com/ngreifer/WeightIt. [Accessed 16 November 2023]
R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.
Goodrich B, Gabry J, Ali I, Brilleman S. rstanarm: Bayesian applied regression modeling via Stan. R package version 2.21.4. https://mc-stan.org/rstanarm/. [Accessed 15 November 2023]
Gaunt TR, Rodriquez S, Day INM. Cubic exact solution for the estimation of pairwise haplotype frequencies: implications for linkage disequlibrium analysesand a web tool ‘CubeX’. BMC Bioinf 2007; 8:428.
Schneeweiss S. Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf 2006; 15:291–303.
Heine D. The episensr package: basic sensitivity analysis for epidemiological results. R package version 1.2. https://dhaine.github.io/episensr/. [Accessed 15 November 2023]
Shah S, Harwood SM, Dohler B, Opelz G, Yaqoob MM. Inosine monophosphate dehydrogenase polymorphisms and renal allograft outome. Transplantation 2012; 94:486–491.
Mehta Cherikh W, Sood P, Hariharan S. Kidney allograft surveillance biopsy practices across US transplant centers: a UNOS survey. Clin Transplant 2017; 31. doi: https://doi.org/10.1111/ctr.12945.
doi: 10.1111/ctr.12945
Lee DM, Abecassis MM, Friedewald JJ, Rose S, First MR. Kidney graft surveillance biopsy utilization and trends: results from a survey of high-volume transplant centers. Transplant Proc 2020; 52:3085–3089.
Sobiak J, Resztak M. A systematic review of multiple linear regression-based limited sampling strategies for mycophenolic acid area under the concentration-time curve estimation. Eur J Drug Metab Pharmacokinetics. 2021; 46:721–742.
Dekkers OM, Vandenbroucke JP, Cevallos M, Renehan AG, Altman DG, Egger M. COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology. PLoS Med 2019; 16:e1002742.