High Intrapatient Variability of Tacrolimus Concentrations Predicts Accelerated Progression of Chronic Histologic Lesions in Renal Recipients

Vanhove, Thomas; Vermeulen, Tim; Annaert, Pieter; Lerut, Evelyne; Kuypers, Dirk

doi:10.1111/ajt.13803

Cited by 111 publications

(192 citation statements)

References 27 publications

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“…Like the studies described above, race was not reported or accounted for in analyses. 15 Finally, Whelan et al, recently demonstrated that high tacrolimus intrapatient variability significantly increased the risk of acute rejection, reduced estimated glomerular filtration rates (GFRs) and increased graft loss in 366 renal transplant recipients receiving a low-exposure tacrolimus regimen. However, only 18 patients were nonwhite.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

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Fleming

et al. 2017

Transplantation

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Background Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African-American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities. Methods Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data. Results 1411 recipients were included (54.4% AA) with 39 521 concentrations utilized to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs vs non-AAs (39.9±19.8 % vs. 34.8±15.8% p<0.001). Tacrolimus variability was a significant risk factor for deleterious clinical outcomes. A 10% increase in tacrolimus CV augmented the risk of acute rejection by 20% (aHR 1.20, 1.13–1.28; p<0.001) and the risk of graft loss by 30% (aHR 1.30, 1.23–1.37; p<0.001), with significant effect modification by race for acute rejection, but not graft loss. High tacrolimus variability (CV >40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss. Conclusions These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients.

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Section: Discussionmentioning

confidence: 99%

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Taber

Fleming

et al. 2017

Transplantation

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“…111 In addition, increased IPV of tacrolimus has been associated with the development of de novo DSAs, 112 and faster progression of interstitial fibrosis. 113 In the context of liver transplantation, the clinical impact of tacrolimus variability has seldom been studied. Patients with biopsy-proven TCMR showed increased standard deviations of tacrolimus trough concentrations according to 1 report.…”

Section: Strategies For Managing Nonadherencementioning

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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“…Furthermore, in a recent study of 220 kidney transplant recipients, higher tacrolimus intrapatient variability predicted accelerated progression of chronic histologic lesions before onset of renal dysfunction. 73 The lower-dose tacrolimus plus MMF and steroid regimen used in the Symphony study is the most commonly used in clinical practice. In a subanalysis of data from this study, intrapatient variability of tacrolimus exposure of~28% was apparent with this regimen in the first 12 months.…”

Section: Variability Of Immunosuppressive Exposure In Kidney Transplamentioning

confidence: 99%

Advancing Transplantation

et al. 2017

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High Intrapatient Variability of Tacrolimus Concentrations Predicts Accelerated Progression of Chronic Histologic Lesions in Renal Recipients

Cited by 111 publications

References 27 publications

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

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

Advancing Transplantation

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