Details

Autor(en) / Beteiligte

• Gueta, Itai
• Markovits, Noa
• Yarden‐Bilavsky, Havatzelet
• Raichlin, Eugenia
• Freimark, Dov
• Lavee, Jacob
• Loebstein, Ronen
• Peled, Yael

Titel

High tacrolimus trough level variability is associated with rejections after heart transplant

Ist Teil von

• American journal of transplantation, 2018-10, Vol.18 (10), p.2571-2578

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2018

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post‐HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post‐HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P = .930). Patients in the high variability group exhibited higher long‐term rejection rate (median total rejection score: 0.33 vs 0, P = .04) with no difference in rejection scores within the first year post‐HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8‐fold increased risk for any rejection beyond the first year post‐HTx (P = .011). Mortality was associated only with cardiovascular complications (P = .018), with no effect of tacrolimus through level variability. Long‐term follow‐up of heart transplant patients reveals an association between rejection rates and high first‐year variability of tacrolimus levels.