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.

Patients and Methods: 50 Living-donor kidney transplant recipients were prospectively randomized into 2 groups, 1) LD group (n=26) ; target tacrolimus area under curve profiles (TAC-AUC) 0-24 by limited sampling strategy 250ng[bull]hr/ml during the first 1 months and reduced to 200ng[bull]hr/ml after 3 months. 2) VLD group (n=24); target TAC-AUC0-24 200ng[bull]hr/ml during the first 1 months and reduced to 150ng[bull]hr/ml after 3 months. MMF was started with 1250mg BID and reduced to 750mg BID at 2 weeks, and adjusted to MPA-AUC0-12 between 30-60 [mu]g[bull]hr/L. Subclinical rejection and CNI toxicity were evaluated by protocol biopsy after 1 and 12 months.

Results: With a mean observation of 42 months (28-59), patients and graft survival are 100% in both groups. Mean tacrolimus C0 at 1 month and 2 years after transplant was 5.5 ± 1.8, 4.7 ± 1.0 ng/ml in LD group, and 4.7 ± 1.1, 3.9 ± 1.2 ng/ml in VLD group. Significant difference in tacrolimus C0 was observed from 3 months to 1 year after transplant (p<0.05). Subclinical or clinical T cell mediated rejection were observed in 0% in LD group and 8.3% in VLD group, while incidence of CMV infection was reduced in VLD group (5.9%) compared to LD group (15.9%) . CNI toxicity were observed in 7.7% in LD group and 12.5% in VLD group in 1month protocol biopsies, but those findings were alleviated in 1 year protocol biopsy (7.1% in LD and 6.3% in VLD group). Mean eGFR were equivalent between 2 groups and maintained at 51.6 ± 11.2ml/min/1.73m² in LD group and 51.6 ± 13.8ml/min/1.73m² in VLD group at 2 years after transplant. None developed DSA in LD group but 2 patients in VLD group.

Conclusions: This study suggests that TACER combination with MMF can be safely reduced to very low level with reduced CMV infection rate and without significant increased rejection rate. However, DSA production is a great concern, so close follow-up is necessary.

CITATION INFORMATION: Narumi S., Watarai Y., Goto N., Hiramitsu T., Tsujita M., Okada M., Futamura K., Kobayashi T. Comparison of Low Dose and Very Low Dose Extended-Release Tacrolimus / MMF in De Novo Kidney Transplant Recipients- 3 Years Follow-Up Am J Transplant. 2017;17 (suppl 3).

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