Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients

Su, Lan; Yin, Lu; Yang, Jinkun; Sun, Lin

doi:10.1097/md.0000000000016113

Cited by 7 publications

(12 citation statements)

References 19 publications

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“…Thus, these techniques may permit inhibition of the differentiation of LLPCs. Further; NGS analysis of antibody reactivity to transplanted grafts can be applied to predict the antibodies that cause AMR (28)(29)(30)(31)(32)(33)(34)(35)(36). This knowledge, combined with the identification of genetic polymorphisms associated with drug sensitivity, will undoubtedly contribute to the development of optimal management strategies.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Single Nucleotide Polymorphism (SNP) of CYP3A4/3A5, ABCB1 in CNI, CYP3A5 in sirolimus, TPMT in azathioprine, UGT1A9, ABCC2 in Mycophenolic acid (MPA), and MDR1 in tacrolimus affects their pharmacokinetics. Thus, NGS analysis of these SNP will likely provide useful information for developing more effective immunosuppressive therapy, which considers differences in pathology and drug susceptibility ( 35 , 36 ).…”

Section: Development Of Diagnostic Methodsmentioning

confidence: 99%

“…Significantly, in addition to the potential induction of immune tolerance of humoral immunity-associated components to transplanted grafts (35,243,247,248,(250)(251)(252), AIM and IgMenriched IVig have a tissue repair and regeneration effect through the clearance of injured tissue (42,224,(233)(234)(235). Therefore, humoral immunity associated injury after the onset of AMR, which was considered irreversible, could be recovered by clinical application of these humoral immunity-associated components.…”

Section: Clinical Potential Of Humoral Immunity-associated Components In Amrmentioning

confidence: 99%

“…In addition, it has been reported that IL-10 protects transplanted grafts from recipient immunity and exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation or MPs with proinflammatory phenotypes by increasing AIM expression. Therefore, regulation of AIM expression may be related to the induction of immune tolerance ( 35 ).…”

Section: Novel Appliable Components In Amrmentioning

confidence: 99%

“…Identifying of the antigen specificity of MBCs circulating in the peripheral blood, as measured using an ELISpot assay or in vitro assay system, will be useful to evaluate the activation of the humoral immune response to donor-specific HLA antigens (22)(23)(24)(25)(26)(27). Furthermore, microarray techniques and next-generation sequencing (NGS) may provide detailed information that will contribute to therapeutic control of AMR, including the identification of antibodies that injure transplants and individual differences in patients' susceptibilities to immunosuppressive agents (28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

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Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Matsuda¹,

Watanabe²,

Li³

2021

Front. Immunol.

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Both acute and chronic antibody-mediated allograft rejection (AMR), which are directly mediated by B cells, remain difficult to treat. Long-lived plasma cells (LLPCs) in bone marrow (BM) play a crucial role in the production of the antibodies that induce AMR. However, LLPCs survive through a T cell-independent mechanism and resist conventional immunosuppressive therapy. Desensitization therapy is therefore performed, although it is accompanied by severe side effects and the pathological condition may be at an irreversible stage when these antibodies, which induce AMR development, are detected in the serum. In other words, AMR control requires the development of a diagnostic method that predicts its onset before LLPC differentiation and enables therapeutic intervention and the establishment of humoral immune monitoring methods providing more detailed information, including individual differences in the susceptibility to immunosuppressive agents and the pathological conditions. In this study, we reviewed recent studies related to the direct or indirect involvement of immunocompetent cells in the differentiation of naïve-B cells into LLPCs, the limitations of conventional methods, and the possible development of novel control methods in the context of AMR. This information will significantly contribute to the development of clinical applications for AMR and improve the prognosis of patients who undergo organ transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Development Of Diagnostic Methodsmentioning

confidence: 99%

Section: Clinical Potential Of Humoral Immunity-associated Components In Amrmentioning

confidence: 99%

Section: Novel Appliable Components In Amrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Matsuda¹,

Watanabe²,

Li³

2021

Front. Immunol.

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Rapid clearance of tacrolimus blood concentration triggered by variant pharmacogenes

Šimičević

Canjuga

Zibar

et al. 2022

Clinical Pharmacy Therapeu

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Tacrolimus (TAC) is a macrocyclic lactone that acts as a calcineurin inhibitor. It is indicated as prophylaxis of transplant rejection in adult kidney or liver allograft recipients and as treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients. Tacrolimus has significant interindividual pharmacokinetic variability and a narrow therapeutic index. Its administration should be based on clinical assessments of graft rejection prevention and toxicity in each individual patient, supported by whole blood TAC trough concentration (C 0 ) monitoring, that is therapeutic drug monitoring (TDM). 1 It has variable absorption after oral administration and first-pass metabolism, which are two major factors affecting its efficacy and safety. Metabolism principally occurs in the liver and small intestine through CYP3A4 and CYP3A5 enzymes. 1 Furthermore, TAC is the substrate for the transport efflux membrane protein P-glycoprotein (MDR1 and ABCB1) in the intestine, which regulates TAC absorption, and, consequently oral bioavailability. P-glycoprotein expressed in the liver and kidney effluxes TAC into bile and urine. 1 According to clinical practice, the targeted TAC C 0 in the blood is about 10 ng/ml, depending on individual patient characteristics, transplantation type and time after transplantation. 2 Over the last twenty years, clinical studies have clearly indicated the relationship between the pharmacokinetics of immunosuppressive agents and the genetic variability of their metabolic enzymes and transporters, which plays a significant role in their metabolism. 3-5 According to upto-date knowledge, TAC bioavailability is considerably impacted by hepatic and intestinal CYP3A-dependent metabolism that is altered by CYP3A genetic variants. Therefore, CYP3A4 and CYP3A5 singlenucleotide polymorphisms (SNPs) are suggested to notably cause TAC clearance interindividual variability. 6 Seven years ago, based on published evidence supporting this relationship, the CPIC published guidelines for the CYP3A5 genotype and tacrolimus dosing

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Effects of CYP3A422 and POR28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies

Li,

Wang,

et al. 2024

BMC Nephrol

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Purpose This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). Results The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). Conclusions CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.

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Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients

Cited by 7 publications

References 19 publications

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Rapid clearance of tacrolimus blood concentration triggered by variant pharmacogenes

Effects of CYP3A422 and POR28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies

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Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients

Cited by 7 publications

References 19 publications

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells

Rapid clearance of tacrolimus blood concentration triggered by variant pharmacogenes

Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies

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Effects of CYP3A422 and POR28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies