Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients

Yeung, S; Tsang, Wing Pui; Tong, Kwok Lung; Wong, SM; Lee, W.; Tang, Hongying; Chan, HH; Chan, Angus C.W.

doi:10.1016/j.transproceed.2004.08.110

Cited by 5 publications

(3 citation statements)

References 6 publications

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“…Tacrolimus is an immunosuppressant drug widely used in most organ transplants 1 . Tacrolimus has successfully decreased the rejection rate and improved the outcome of many transplants 2 .…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients

Sohn

Kim

Han

et al. 2018

Sci Rep

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The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C0/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C0/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.

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“…Tacrolimus is an immunosuppressant drug widely used in most organ transplants 1 . Tacrolimus has successfully decreased the rejection rate and improved the outcome of many transplants 2 .…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients

Sohn

Kim

Han

et al. 2018

Sci Rep

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“…Mycophenolic acid (MPA) is the active metabolite of MMF and TAC arises the exposure through lack of inhibiting the enterohepatic recirculation of the MPA glucuronide and in diabetic patients with delayed gastric emptying time this can contribute to a greater pharmacological exposure to MPA, [14][15][16]. Given the known pharmacokinetic and pharmacodynamic interactions whereby TAC increases MPA exposure and CsA does not, the concomitant use of TAC and MMF allows a theoretical reduction in MMF doses after RT with good results in terms of graft and patients survival during the first year after transplantation [17]; however, avoiding, suspending, or employing doses lower than 1g could increase the risk of AR. [18,19] In our hospital, 97% of RT is from a living donor and the standard dose of 2g/day of MMF with TAC is used in the immediate post-RT period without taking into account the serum concentrations of MPA since this is impractical and economically unfeasible in our health care system considering the nonlinear absorption kinetics.…”

Section: Introductionmentioning

confidence: 99%

Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Andrade‐Sierra

Hernández-Reyes

Rojas‐Campos

et al. 2022

Preprint

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Background. The evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) in renal transplant (RT) is still limited but maintaining the dose of less than 2g could result in worse clinical outcomes in terms of acute rejection (AR). Research Question: This study aim was to determine the association between AR, infectious and non-infectious complications after RT with the dose of 1.5g vs. 2g of MMF. Design. A prospective cohort was performed with a 12-month follow-up in recipients of RT from living donors with low doses of MMF (1.5 g/day) or use of standard dosage (2 g/day). The association between adverse effects and complications and doses of MMF were examined in Cox proportional hazard models and survival free of AR, infectious diseases, and non-infectious complications was evaluated by the Kaplan-Meier test. Results. At the end of the follow-up, the incidence of infectious diseases was 52% vs. 50% (p=0.71) and AR was 5% vs. 5% (p=0.86), respectively. Survival free of GI complications requiring medical attention was higher in the low dose group compared to the standard dose (88% vs. 45%, respectively; p<0.001). Discussion. The use of 1.5 g/day of MMF is safe in Mexican population with RT from living donors without increasing the risk of AR, and it confers a reduction of adverse events.

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“…Current data, however, are subject to limitations. First, prospective data of reduced‐dose MPA are limited to small single‐center trials . Second, little is known about the relationship between changes to MPA dosing and concomitant exposure to calcineurin inhibitors (CNIs).…”

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confidence: 99%

Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry

Langone

Doria

Greenstein

et al. 2012

Clinical Transplantation

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Prospective data are lacking concerning the effect of reduced mycophenolic acid (MPA) dosing on efficacy and the influence of concomitant tacrolimus exposure. The Mycophenolic Renal Transplant (MORE) Registry is a prospective, observational study of de novo kidney transplant patients receiving MPA therapy under routine management. The effect of MPA dose reduction, interruption, or discontinuation (dose changes) was assessed in 870 tacrolimus-treated patients: 375 (43.1%) reduced tacrolimus (≤7 ng/mL at baseline) and 495 (56.9%) standard tacrolimus (>7 ng/mL); enteric-coated mycophenolate sodium 589 (67.7%) and mycophenolate mofetil 281 (32.3%). During baseline to month 1, months 1–3, months 3–6, and months 6–12, 9.3% (78/838), 16.6% (132/794), 20.7% (145/701), and 13.1% (70/535) patients, respectively, required MPA dose changes. These patients experienced an increased risk of biopsy-proven acute rejection at one yr with tacrolimus exposure either included in the model (hazard ratio [HR] 2.60, 95% CI 1.28–5.29, p = 0.008) or excluded (HR 2.58, 95% CI 1.28–5.23, p = 0.008). MPA dose changes were significantly associated with one yr graft failure when tacrolimus exposure was included (HR 2.23; 95% CI 1.01–4.89, p = 0.047) but not when tacrolimus exposure was excluded (HR 2.16; 95% CI 0.99–4.79; p = 0.054). These results suggest that reducing or discontinuing MPA can adversely affect graft outcomes regardless of tacrolimus trough levels.

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Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients

Cited by 5 publications

References 6 publications

Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients

Whole exome sequencing for the identification of CYP3A7 variants associated with tacrolimus concentrations in kidney transplant patients

Clinical impact using low dose mycophenolate mofetil with tacrolimus on acute rejection, infectious diseases and non-infectious complications in renal transplant: A Single Hospital Experience in Mexico

Does reduction in mycophenolic acid dose compromise efficacy regardless of tacrolimus exposure level? An analysis of prospective data from the Mycophenolic Renal Transplant (MORE) Registry

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