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Published on: November 8, 2015
Triglyceride- and Body Weight-Based Nomogram for Early Postoperative Mycophenolate Mofetil Dose Selection Following
Tenshi Makiyama1, Kazuya Kinoshita1, Akane Morimoto1
1Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Background:
Early mycophenolic acid (MPA) exposure varies widely after kidney transplantation, and fixed initial mycophenolate mofetil (MMF) dosing may cause overexposure before therapeutic drug monitoring (TDM) becomes available. We explored routinely available pretransplant clinical variables and developed a simple pre-TDM nomogram using triglycerides (TG) and body weight to support early postoperative MMF dose selection in tacrolimus-treated recipients.
Methods:
In this single-center retrospective derivation study, 117 consecutive adult kidney transplant recipients were screened, and 116 with complete concentration profiles were analyzed. All received tacrolimus-based immunosuppression; none received cyclosporine. A model incorporating concurrent MMF dose, pretransplant body weight, and pretransplant TG was standardized to 1500 mg/day. A three-level rule (1000/1500/2000 mg/day) was evaluated using dose-proportional simulation. False discovery rate (FDR) correction, internal validation, and alternative dose-exposure assumptions were examined.
Results:
Observed MPA AUC categories were < 30, 30-60, and > 60 mg·h/L in 12.1%, 46.6%, and 41.4% of recipients, respectively. TG survived dose-adjusted multiplicity correction (q = 0.047), but not unadjusted correction. Under simulated nomogram-guided dosing, the corresponding proportions were 14.7%, 54.3%, and 31.0%, a reduction in overexposure of 10.4 percentage points (bootstrap 95% confidence interval, -18.1--3.4). Across alternative assumptions, the reduction ranged from -1.7--10.4 percentage points and target-attainment improvement was not robust; internal validation was directionally consistent but imprecise.
Conclusions:
The nomogram showed a directionally consistent but assumption-dependent reduction in simulated early MPA overexposure. It is a hypothesis-generating pre-TDM tool and should not replace AUC-guided TDM or clinical judgment. Prospective external validation is required.
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