Clinical transplantation · 2026
Triglyceride- and Body Weight-Based Nomogram for Early Postoperative Mycophenolate Mofetil Dose Selection Following Kidney Transplantation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Makiyama Tenshi, Kinoshita Kazuya, Morimoto Akane, Maruyama Michihiro
Аннотация
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.
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.
Предметные рубрики MeSH
HumansMycophenolic AcidKidney TransplantationNomogramsFemaleRetrospective StudiesImmunosuppressive AgentsFollow-Up StudiesMaleTriglyceridesMiddle AgedBody WeightGraft RejectionGraft SurvivalPrognosisAdultDrug MonitoringKidney Function TestsGlomerular Filtration RateKidney Failure, ChronicRisk FactorsPostoperative ComplicationsDose-Response Relationship, Drug