Tacrolimus Dose in Black Renal Transplant Recipients

Vadivel, Nidyanandh; Garg, Ashwani; Holt, David W.; Chang, Rin; MacPhee, Iain

doi:10.1097/01.tp.0000259248.60448.8a

Cited by 25 publications

(23 citation statements)

References 4 publications

(1 reference statement)

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“…When analyzed separately, the difference in mean TAC trough levels was not observed in African American patients nor was there any difference demonstrated with regards to the mean TAC doses between African American CSWD and CCS patients, suggesting a lack of effect of corticosteroid withdrawal in this patient population. Furthermore, it was observed that African American patients consistently required significantly greater TAC doses than non-African American patients to maintain comparable TAC trough levels, confirming findings of previously published studies (16)(17)(18)(19). It remains unclear as to why African American patients require greater TAC doses or do not display significant corticosteroid interactions.…”

Section: Discussionsupporting

confidence: 78%

Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

Shihab

Lee

Smith

et al. 2013

American Journal of Transplantation

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As corticosteroid-sparing protocols are increasingly utilized in kidney transplant recipients, it is crucial to understand potential drug interactions between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting. This prospective, multicenter, randomized, double-blind study included 397 patients who were randomized on posttransplant day 8 to receive either placebo (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two posttransplant were significantly greater in the CSWD group whereas TAC doses were comparable to the CCS group. This interaction was not observed in the African American subgroup. Higher serum creatinine and potassium levels were also observed in the CSWD group. MMF dose was significantly reduced in the CSWD group by the investigators because of decreased WBC counts, mostly outside of study protocol criteria, despite similar incidence of neutropenia and reported cytomegalovirus infection. Understanding TAC and MMF exposure in the context of corticosteroid-sparing protocols should allow for improved dosing of immunosuppressants and better management of posttransplant patients.

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Section: Discussionsupporting

confidence: 78%

Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

Shihab

Lee

Smith

et al. 2013

American Journal of Transplantation

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“…Vadivel et al found that for patients of African descent a Tac starting dose of 0.3 mg/kg per day is probably more effective than the currently recommended starting dose of 0.2 mg/kg per day. [105] This higher dose requirement appears to result in part from the high number of CYP3A5 expressers among patients of African descent. [106] The lower exposure to Tac following standard dosing may be responsible for the higher acute rejection risk after kidney transplantation in recipients of African descent.…”

Section: Ethnic Considerationsmentioning

confidence: 99%

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Tang

Andrews

Gelder

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

117

114

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Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a~40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.ARTICLE HISTORY

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“…Low blood levels of tacrolimus minimise the risk of new onset diabetes after transplantation (NODAT) compared to higher levels. It should be recognised that there are important pharmacogenetic variations in tacrolimus metabolism and some centres reduce doses in black recipients [16].…”

Section: Guideline 31 -Ktr: Induction Immunosuppressionmentioning

confidence: 99%

Renal Association Clinical Practice Guideline on Post-operative Care of the Kidney Transplant Recipient

Baker

Jardine²,

Andrews³

2011

Nephron Clin Pract

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Tacrolimus Dose in Black Renal Transplant Recipients

Cited by 25 publications

References 4 publications

Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Renal Association Clinical Practice Guideline on Post-operative Care of the Kidney Transplant Recipient

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