Journal Article

High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury

Sikma, M. A., van de Graaf, E. A., Meulenbelt, J., Hunault, C. C., Verhaar, M. C., Kesecioglu, J., de Lange, D. W.

2017

Overview

Purpose Lung transplant recipients often develop acute kidney injury (AKI) evolving into chronic kidney disease (CKD). The immunosuppressant tacrolimus might be associated with the emergence of AKI. We analyzed the development and recovery of kidney injury after lung transplantation and related AKI to whole-blood tacrolimus trough concentrations and other factors causing kidney injury. Methods We retrospectively studied kidney injury in 186 lung-transplantation patients at the UMC Utrecht between 2001 and 2011. Kidney function and whole-blood tacrolimus trough concentrations were determined from day 1 to 14 and at 1, 3, 6, and 12 months postoperative. Systemic inflammatory response syndrome (SIRS), septic shock, and nephrotoxic medications were evaluated as covariates for AKI. We analyzed liver injury and drug-drug interactions. Results AKI was present in 85 (46%) patients. Tacrolimus concentrations were supra-therapeutic in 135 of 186 patients (73%). AKI in the first week after transplantation was related to supra-therapeutic tacrolimus concentrations (OR 1.55; 95% CI 1.06–2.27), ≥3 other nephrotoxic drugs (OR 1.96; 95% CI 1.02–3.77), infection (OR 2.48; 95% CI 1.31–4.70), and cystic fibrosis (OR 2.17; 95% CI 1.16–4.06). Recovery rate of AKI was lower than expected (19%), and the cumulative incidence of severe CKD at 1 year was 15%. Conclusions After lung transplantation, AKI is common and often evolves into severe CKD, which is a known cause of morbidity and mortality. Supra-therapeutic whole-blood tacrolimus trough concentrations are related to the early onset of AKI. Conscientious targeting tacrolimus blood concentrations might be vital in the early phase after lung transplantation. What is known about this subject? • Lung transplant recipients often develop acute kidney injury evolving into chronic kidney disease increasing both morbidity and mortality. • To date, the pathophysiology of kidney injury after lung transplantation has not been fully elucidated. • The immunosuppressant tacrolimus is difficult to dose, especially in the unstable clinical setting, and is nephrotoxic. What this study adds: • For the first time, supra-therapeutic whole-blood tacrolimus trough concentrations are related to the emergence of acute kidney injury in the first days after lung transplantation. • Supra-therapeutic whole-blood tacrolimus trough concentrations often occur early after lung transplantation. • AKI after lung transplantation shows low recovery rates.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Acute Kidney Injury - etiology / Biomedical and Life Sciences / Biomedicine / Female / Humans / Immunosuppressive Agents - blood / Kidney diseases / Lung Transplantation - adverse effects / Lungs / Male / Medical prognosis / Pharmacokinetics and Disposition / Pharmacology / Pharmacology/Toxicology / Prescription drugs / Tacrolimus - blood / Transplants & implants