CYP3A5andCYP3A4, but notABCB1polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients

2014 ◽  
Vol 15 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Mateusz Kurzawski ◽  
Justyna Dąbrowska ◽  
Krzysztof Dziewanowski ◽  
Leszek Domański ◽  
Magdalena Perużyńska ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Trough Concentrations ◽  
Tacrolimus Dose

Pretransplant Tacrolimus Dose Requirements Predict Early Posttransplant Dose Requirements in Blood Group AB0-Incompatible Kidney Transplant Recipients

2016 ◽  
Vol 38 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Nauras Shuker ◽  
Femke M. de Man ◽  
Annelies E. de Weerd ◽  
Madelon van Agteren ◽  
Willem Weimar ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Blood Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Tacrolimus Dose

scholarly journals Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on Sirolimus In Vitro Metabolism and Trough Concentrations in Kidney Transplant Recipients

2013 ◽  
Vol 59 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Jean-Baptiste Woillard ◽  
Nassim Kamar ◽  
Sandra Coste ◽  
Lionel Rostaing ◽  
Pierre Marquet ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kidney Transplant ◽  
Calcineurin Inhibitor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Trough Concentrations ◽  
The Impact

BACKGROUND Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = −0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.

scholarly journals Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Kinga Krzyżowska ◽  
Aureliusz Kolonko ◽  
Piotr Giza ◽  
Jerzy Chudek ◽  
Andrzej Więcek
Keyword(s):  
Risk Factors ◽  
Dose Reduction ◽  
Kidney Transplant ◽  
Multiple Logistic Regression Analysis ◽  
Hemoglobin Concentration ◽  
Blood Levels ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Related Factors ◽  
Tacrolimus Dose

Background. Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods. We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily. The analysis included the first assessment of Tc trough blood levels and several demographic, anthropometric, laboratory, and comedication data. Results. The multiple logistic regression analysis showed that age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and the presence of anti-HCV antibodies independently increased the risk for first Tc level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml was 1.88 (95% CI 1.35–2.64, p<0.001) for patients with one risk factor and 2.81 (2.02–3.89, p<0.001) for patients with two risk factors. Conclusions. Initial tacrolimus dose reduction should be considered in older, overweight, or obese kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover, dose reduction of tacrolimus is especially important in patients with coexisting multiple risk factors.

Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients

2014 ◽  
Vol 28 (4) ◽  
pp. 470-478 ◽  
Author(s):  
Jeffrey J. Gaynor ◽  
Gaetano Ciancio ◽  
Giselle Guerra ◽  
Junichiro Sageshima ◽  
David Roth ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Trough Level ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Tacrolimus Dose

scholarly journals IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients

2017 ◽  
Vol 38 (3) ◽  
pp. 415-423 ◽  
Author(s):  
Mou-ze Liu ◽  
Hai-yan He ◽  
Yue-li Zhang ◽  
Yong-fang Hu ◽  
Fa-zhong He ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Gene Polymorphisms ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Dose Requirement ◽  
Ctla4 Gene ◽  
Tacrolimus Dose
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