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Abstract: SA-PO855

Pharmacokinetic-Guided Dosing to Maintain Therapeutic Tacrolimus Levels During Post-Kidney Transplant Erythrocytapheresis in a Patient With Sickle Cell Anemia

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Caldwell, John, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Lazear, Danielle, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Miyagawa, Bradley, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Mizuno, Tomoyuki, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Quinn, Charles T., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Stone, Hillarey, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Hooper, David K., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Varnell, Charles D., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Introduction

To maximize renal recovery following kidney transplant (KT) in patients with sickle cell nephropathy (SCN) it is important to maintain a lower fraction of sickle hemoglobin (HbS). This can be done with erythrocytapheresis (RBCx). Tacrolimus (TAC), the primary immunosuppressive medication used after KT, is highly localized to red blood cells (RBCs) and is cleared by RBCx. This may result in subtherapeutic TAC levels and increased rejection risk. The impact of RBCx on post-KT TAC levels has not been described.

Case Description

A 16-y.o. male with ESKD secondary to SCN received a deceased donor KT. Pre-KT preparation included optimized hydroxyurea therapy and erythropoietin. He received one RBCx to target a HbS of < 10% immediately prior to KT and subsequent scheduled RBCx to maintain HbS < 20% for the first 3 months post-KT and < 30% thereafter. Pre- and post-RBCx TAC levels were measured for pharmacokinetic modeling (PK). The patient received a post-RBCx dose of TAC after each treatment; the dose was calculated based on estimated fraction of cells remaining (FCR), estimated RBC binding of TAC (85%), and the morning dose (Equation 1). Using PK, the estimated area under the curve (AUC) after RBCx with the extra TAC dose was 289 ng*h/mL which was comparable to his steady-state AUC (283 ng*h/mL) (Figure 1).

Discussion

Minimizing the risk of injury to a new allograft by minimizing HbS levels is an important aspect of post-KT care in patients with SCN. We show that a PK-guided dose of TAC after RBCx can allow highly effective treatment of SCN post-KT without compromising TAC exposure. This strategy protects the allograft by decreasing both SCN-related damage rejection risk.