Non-Adherence and Graft Failure in Adult Liver Transplant Recipients

Lieber, Sarah R.; Volk, Michael L.

doi:10.1007/s10620-012-2412-0

Cited by 104 publications

(105 citation statements)

References 31 publications

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“…In this respect, tacrolimus SD may be an excellent surrogate not only for tacrolimus exposure, but also the ability and/or willingness to follow relatively complicated medical advice. Although adherence is generally high in lung transplant recipients, poor adherence has been shown to be associated with a greater tacrolimus level SD in liver transplant recipients (25,31). The relationships between tacrolimus SD, more conventional measures of adherence, and transplant outcomes will be a key focus of future studies.…”

Section: Discussionmentioning

confidence: 99%

“…High tacrolimus trough level variability (assessed using standard deviation (SD)) increases the risk of acute rejection early post adult lung transplant but its affect on CLAD and survival are unknown (23). In the liver and kidney transplant literature, an association has been found between high intra-patient tacrolimus level variability and late graft failure (24)(25)(26). This has not been assessed in adult lung transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

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Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Gallagher

Sarwar

Tse

et al. 2015

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Gallagher

Sarwar

Tse

et al. 2015

The Journal of Heart and Lung Transplantation

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“…On day 8, each patient was converted to once daily LCP-Tacro tablets with no dose changes allowed; the dose conversion ratio target was 0.70, and the ratio ranged from 0.66 to 0.80 (because of the nominal dosage strengths of LCP-Tacro that were available). The patients continued on a fixed dose of LCP-Tacro for the second week of the study (days [8][9][10][11][12][13][14]. Tacrolimus trough blood levels (C min values) were obtained once between days 9 and 11 and once between days 11 and 13 with at least 48 hours between the 2 measurements to ensure that tacrolimus blood concentrations remained between 5 and 15 ng/mL.…”

Section: Study Design and Conductmentioning

confidence: 99%

Conversion from twice daily tacrolimus capsules to once daily extended‐release tacrolimus (LCP‐Tacro): Phase 2 trial of stable liver transplant recipients

et al. 2014

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LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Studies in renal transplantation demonstrate greater bioavailability with similar safety and efficacy vs. twice-daily tacrolimus capsules. In this phase 2 study, adult stable liver transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCPTacro) once-daily; patients continued on LCP-Tacro once-daily for days 8-21; target trough levels were 5-15 ng/mL; 24-hour pharmacokinetic (PK) assessments were done on days 7 (baseline pre-switch), 14, and 21. A 6 month extension study phase evaluated PK and safety following a total of 52 weeks of LCP-Tacro. Fifty-seven patients completed LCP-Tacro dosing in the core study; 43 completed the extension phase. The mean conversion ratio was 0.71 (Prograf:LCP-Tacro). PK data demonstrated consistent exposure (AUC) at the lower conversion dose. C max , C max /C min ratio, percent fluctuation and swing were significantly (P<0.001) lower and T max significantly (P<0.001) longer for LCP-Tacro vs. Prograf. AUC 24 and C min correlation coefficients after 7 and 14 days of therapy were 0.93. There were no significant differences in PK parameters at week 26 vs. 14. One patient experienced an unrelated serious adverse event (SAE) during the core study and discontinued. There were six unrelated SAEs in the extension and 1 possibly related (rejection) that resolved; there were 3 discontinuations due to AEs during the extension. In this study, patients were safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allowed for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displayed significantly lower peak and peak-trough Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under the curve; AUC 24 , area under the curve at 24 hours; C 24 , concentration at 24 hours; C avg , average concentration; C max , maximum concentration; C min , minimum concentration; CV, coefficient of variation; ECG, electrocardiogram; H&C, hematology and chemistry; PK, pharmacokinetic; RGM, ratio of geometric means; SAE, serious adverse event; SE, standard error; TDD, total daily dose; T max , time of the maximum concentration.Some of the data were presented at the

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“…For liver transplantation, early allograft dysfunction (EAD), prolonged cold ischemia times and use of steatotic livers and organs from donation after cardiac death (DCD) donors may contribute to reduced graft and patient survival. [32][33][34] In both kidney and liver transplant recipients, modifiable risk factors for graft failure over the longer term include issues related to immunosuppression, such as nonadherence, 35 underimmunosuppression, 36 toxicity and adverse effects related to immunosuppression, 37 and high intrapatient variability (IPV) in immunosuppressive exposure. 38 The development of de novo donor-specific antibodies (DSAs) is also considered to be a modifiable risk factor, and has been strongly associated with nonadherence to immunosuppression in kidney transplant recipients.…”

Section: Modifiable Risk Factors For Graft Loss Posttransplantationmentioning

confidence: 99%

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

et al. 2017

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Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes. COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant. The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting. 12 Department of Gastroenterology and Hepatology, Erasmus MC, University Hospital Rotterdam, the Netherlands. 13 Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Belgium.14 Abdominal Transplant Surgery, Microbiology and Immunology Department, University Hospitals KU Leuven, Belgium. 15 Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Spain. www.transplantjournal.com S1 S olid organ transplantation has evolved from an experimental procedure to an established treatment option for many types of end-stage organ failure. Both patient and graft outcomes are continuing to improve, and 1-year patient and graft survival currently exceed 80%.1,2 However, survival rates gradually decline over the long term. In kidney transplant, 5-and 10-year graft survival rates in Europe are 77% and 56%, and for liver transplant, 64% and 54% (Figures 1 and 2). 3,4 Although most European countries have seen an increase in both living and deceased donation, transplantation is not available to all who would benefit from the procedure, and there is considerable morbidity and mortality for those listed for transplant.6 Therefore, maximizing long-term graft survival and reducing the need for retransplantation is paramount, not only in improving outcomes for the recipients but also for those awaiting a graft. The improvement in outcomes is predominantly due to reduction in (Transplantation. 2017;101:S1-S41). The authors were approached by Astellas to discuss the practical implementation o...

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Non-Adherence and Graft Failure in Adult Liver Transplant Recipients

Abstract: Non-adherence among liver transplant recipients is a common problem associated with increased risk of graft failure. SD tacrolimus can be used to measure non-adherent behavior and perhaps target patients for behavioral interventions.

Cited by 104 publications

References 31 publications

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival

Conversion from twice daily tacrolimus capsules to once daily extended‐release tacrolimus (LCP‐Tacro): Phase 2 trial of stable liver transplant recipients

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients

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