Impact of obesity on the conversion of immediate-release tacrolimus to extended-release tacrolimus in kidney transplant recipients

Clin Transplant. 2023 Dec;37(12):e15149. doi: 10.1111/ctr.15149. Epub 2023 Oct 3.

Abstract

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07 mg/kg/day for BMI < 30 and BMI ≥ 30 kg/m2 , respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11 mg/kg vs.09 mg/kg and .08 mg/kg vs. .06 mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady-state doses, and might yield more accurate steady-state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.

Keywords: immunosuppression; obesity; tacrolimus.

MeSH terms

  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation* / adverse effects
  • Longitudinal Studies
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / surgery
  • Retrospective Studies
  • Tacrolimus* / therapeutic use
  • Transplant Recipients

Substances

  • Tacrolimus
  • Immunosuppressive Agents
  • Delayed-Action Preparations