Safety and Efficacy of Low Dose and Very Low Dose Extended-Release Tacrolimus / MMF in De Novo Kidney Transplant Recipients
1Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan
2Applied Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Meeting: 2015 American Transplant Congress
Abstract number: D143
Keywords: Dosage, Immunosuppression, Kidney transplantation, Pharmacokinetics
Session Information
Session Name: Poster Session D: Kidney Immunosuppression: Drug Minimization
Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Recently, once-daily tacrolimus extended-release formulation (TACER) has been accepted in kidney transplantation, however its optimal dosing are not well evaluated. We have validated low dose (LD) and very low dose (VLD) TACER / MMF protocol in de novo kidney transplant recipients using limited sampling strategies to estimate tacrolimus exposure.
Patients and Methods: Thirty-eight Living-donor kidney transplant recipients were prospectively randomized into two group, 1) LD group (n=19) ; targeting tacrolimus area under curve profiles (TAC-AUC) 0-24 by limited sampling strategy 250ng•hr/ml during the first 1 months and reduced to 200ng•hr/ml after 3 months. 2) VLD group (n=19); targeting TAC-AUC0-24 200ng•hr/ml during the first 1 months and reduced to 150ng•hr/ml after 3 months. All administered in combination with mycophenolate mofetile (MMF), corticosteroid and basiliximab induction. MMF was started with 1250mg bid and reduced to 750mg bid at 2 weeks after transplant, and adjusted to achieve MPA-AUC0-12 between 30-60 μg•hr/L. Subclinical rejection and CNI toxicity were evaluated by protocol biopsy after 1 and 12 months.
Results: With a mean observation of 16 months (6-25), patients and graft survival are 100% in both groups. Subclinical or clinical T cell mediated rejection were observed in 0(0%) in LD group and 1(5.2%) in VLD group. CNI toxicity were observed in 1 (5.2%) in LD group and 2(10.5%) in VLD group in 1month protocol biopsies, but those findings were diminished in 1 year protocol biopsy (0% in LD and VLD group). Incidence of CMV infection was significantly reduced in VLD group (9.1%) compared to LD group (33%) respectively. Mean eGFR were equivalent between the two groups and maintained at 53.6±12.6ml/min/1.73m2 in LD group and 58.6±12.4ml/min/1.73m2 in VLD group at 1 years after transplant. Mean tacrolimus trough concentration at 1week, 1 month and 1 year after transplant was 7.7±3.0, 5.5±2.4 , 4.8±0.8 ng/ml in LD group, and 8.2±3.0, 4.8±1.0, 3.2±0.7 ng/ml in VLD group. Significant difference was observed at 1 year after transplant (p<0.05).
Conclusions: This study suggests that tacrolimus exposure with TACER combination with MMF can be safely reduced to very low level without significant increased incidence of rejection.
To cite this abstract in AMA style:
Watarai Y, Okada M, Futamura K, Ito K, Yamamoto T, Tsujita M, Hiramitsu T, Goto N, Narumi S, Kobayashi T. Safety and Efficacy of Low Dose and Very Low Dose Extended-Release Tacrolimus / MMF in De Novo Kidney Transplant Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/safety-and-efficacy-of-low-dose-and-very-low-dose-extended-release-tacrolimus-mmf-in-de-novo-kidney-transplant-recipients/. Accessed May 11, 2025.« Back to 2015 American Transplant Congress