Renal Function, Adherence and Quality of Life Improvement After Conversion From Immediate to Prolonged-Release Tacrolimus in Liver Transplantation: Prospective Ten-Year Follow-Up Study

Immunosuppression non-adherence is a major cause of graft failure after liver transplantation. The aim of this study was to evaluate practice surrounding conversion from immediate-release to prolonged-release Tacrolimus formulation and to assess patient adherence and quality of life (QoL). One hundred and seven adult liver transplant recipients, receiving immediate-release Tacrolimus for a minimum of 6 months, were converted to prolonged-release formulation, based on a dose ratio of one (1:1). The median follow-up was 120 [IQR, 120–123] months. Tacrolimus dosage and blood level, liver and renal function, lipid and glucose profiles were recorded. In addition, questionnaires were submitted to evaluate adherence and QoL following conversion. No rejection was recorded. The median serum Tacrolimus blood level decreased over 1 month (5.80, [IQR, 2.0–10.8] vs. 3.8 [IQR, 1.4–8.7]; p < 0.0005). Significant improvement in renal function was noted (median GFR was 81.7 [IQR, 43.4–128.6] vs. 73.9 [IQR, 27.1–130.2]; p = 0.0002). At the end of the follow-up, conversion resulted in an overall decrease in non-adherence of 53.3% (p = 0.0001) and an improvement in QoL was reported by 76.2% of patients. Thus, 1:1 conversion from immediate to prolonged-release Tacrolimus is safe, feasible and efficient, avoiding under-therapeutic and toxic peak concentrations, improving renal function, adherence to immunosuppression and overall patient QoL. Graphical Abstract

[1]  G. Tisone,et al.  Withdrawal of Immunosuppression after Liver Transplantation , 2021 .

[2]  B. Keevil,et al.  Assessment of tacrolimus and creatinine concentration collected using Mitra microsampling devices , 2020, Annals of clinical biochemistry.

[3]  M. Berenguer,et al.  Immunosuppression in liver transplant. , 2020, Best practice & research. Clinical gastroenterology.

[4]  M. Rela,et al.  Determinants of Medication Adherence in Liver Transplant Recipients. , 2019, Journal of clinical and experimental hepatology.

[5]  G. Tisone,et al.  De novo malignancies after liver transplantation: The effect of immunosuppression-personal data and review of literature , 2019, World journal of gastroenterology.

[6]  K. Choinski,et al.  Transplant surgery enters a new era: Increasing immunosuppressive medication adherence through mobile apps and smart watches. , 2019, American journal of surgery.

[7]  D. Serraino,et al.  Survival after the diagnosis of de novo malignancy in liver transplant recipients , 2018, International journal of cancer.

[8]  D. Serraino,et al.  Risk of virus and non‐virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985–2014 , 2018, International journal of cancer.

[9]  R. Annunziato,et al.  Medication adherence and rejection rates in older vs younger adult liver transplant recipients , 2017, Clinical transplantation.

[10]  J. Neuberger,et al.  Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group , 2017, Transplantation.

[11]  S. Mittal,et al.  Everolimus with early withdrawal or reduced‐dose calcineurin inhibitors improves renal function in liver transplant recipients: A systematic review and meta‐analysis , 2017, Clinical transplantation.

[12]  L. Berben,et al.  Describing the evolution of medication nonadherence from pretransplant until 3 years post‐transplant and determining pretransplant medication nonadherence as risk factor for post‐transplant nonadherence to immunosuppressives: The Swiss Transplant Cohort Study , 2014, Transplant international : official journal of the European Society for Organ Transplantation.

[13]  D. Eckhoff,et al.  Conversion from twice daily tacrolimus capsules to once daily extended‐release tacrolimus (LCP‐Tacro): Phase 2 trial of stable liver transplant recipients , 2014, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[14]  L. Bäckman,et al.  An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients. , 2014, Annals of transplantation.

[15]  H. Katus,et al.  Increased adherence eight months after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation , 2013, Drug design, development and therapy.

[16]  M. Volk,et al.  Non-Adherence and Graft Failure in Adult Liver Transplant Recipients , 2013, Digestive Diseases and Sciences.

[17]  F. Dobbels,et al.  Improved Adherence to Tacrolimus Once-Daily Formulation in Renal Recipients: A Randomized Controlled Trial Using Electronic Monitoring , 2013, Transplantation.

[18]  D. Thorburn,et al.  Renal function, efficacy and safety postconversion from twice‐ to once‐daily tacrolimus in stable liver recipients: an open‐label multicenter study , 2012, Transplant international : official journal of the European Society for Organ Transplantation.

[19]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[20]  M. White,et al.  Pharmacokinetics in stable heart transplant recipients after conversion from twice-daily to once-daily tacrolimus formulations. , 2011, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[21]  G. Gerken,et al.  Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice‐daily tacrolimus‐based regimen to once‐daily tacrolimus extended‐release formulation , 2011, Transplant international : official journal of the European Society for Organ Transplantation.

[22]  G. Iaria,et al.  Switch from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in kidney transplantation. , 2011, Transplantation proceedings.

[23]  D. Seehofer,et al.  Once‐Daily Prolonged‐Release Tacrolimus (ADVAGRAF) Versus Twice‐Daily Tacrolimus (PROGRAF) in Liver Transplantation , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[24]  Denise A. Thompson,et al.  Medication Adherence in Older Renal Transplant Recipients , 2010, Clinical nursing research.

[25]  Minnie Sarwal,et al.  Calcineurin Inhibitor Nephrotoxicity , 2012 .

[26]  N. Ichimaru,et al.  Treatment adherence in renal transplant recipients: a questionnaire survey on immunosuppressants. , 2008, Transplantation proceedings.

[27]  Yutaka Kiyohara,et al.  Slower Decline of Glomerular Filtration Rate in the Japanese General Population: A Longitudinal 10-Year Follow-Up Study , 2008, Hypertension Research.

[28]  J. Melancon,et al.  Once-daily tacrolimus extended release formulation: experience at 2 years postconversion from a Prograf-based regimen in stable liver transplant recipients. , 2007, Transplantation.

[29]  R. Hansen,et al.  Medication adherence in chronic disease: issues in posttransplant immunosuppression. , 2007, Transplantation proceedings.

[30]  P. Hayes,et al.  Adherence to medication after liver transplantation in Scotland: A pilot study , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[31]  M. Tonelli,et al.  Progression of kidney dysfunction in the community-dwelling elderly. , 2006, Kidney international.

[32]  G. Tisone,et al.  Complete weaning off immunosuppression in HCV liver transplant recipients is feasible and favourably impacts on the progression of disease recurrence. , 2006, Journal of hepatology.

[33]  S. Florman CONVERSION OF STABLE LIVER TRANSPLANT RECIPIENTS FROM A TWICE DAILY PROGRAF BASED REGIMEN TO A ONCE DAILY MODIFIED RELEASE TACROLIMUS BASED REGIMEN , 2004, Transplantation proceedings.

[34]  P. Roderick,et al.  Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review , 2004, Transplantation.

[35]  C. Baird,et al.  The pilot study. , 2000, Orthopedic nursing.

[36]  G. Klintmalm,et al.  LATE‐ONSET ACUTE REJECTION IN ORTHOTOPIC LIVER TRANSPLANTATION—ASSOCIATED RISK FACTORS AND OUTCOME , 1992, Transplantation.

[37]  A. Rule,et al.  Structural and Functional Changes With the Aging Kidney. , 2016, Advances in chronic kidney disease.

[38]  C. Staatz,et al.  Clinical Pharmacokinetics and Pharmacodynamics of Tacrolimus in Solid Organ Transplantation , 2004, Clinical pharmacokinetics.

[39]  S. Keam,et al.  Tacrolimus: a further update of its use in the management of organ transplantation. , 2003, Drugs.