Monitoring Nonadherence and Acute Rejection With Variation in Blood Immunosuppressant Levels in Pediatric Renal Transplantation

Hsiau, Margaret; Fernández, Hilda; Gjertson, David W.; Ettenger, Robert B.; Tsai, Ethan

doi:10.1097/tp.0b013e31822dc34f

Cited by 112 publications

(170 citation statements)

References 10 publications

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“…As early as 2000, Kahan et al 71 demonstrated that patients in a higher-variability cyclosporine cohort exhibited a higher incidence of graft loss compared with patients in the lower-variability cohort. Similar findings regarding the impact of cyclosporine variability on long-term outcomes were also reported by Waiser et al 72 In a study of 46 pediatric transplant recipients, higher variability of tacrolimus exposure was associated with the presence of acute rejection, 30 and Borra et al 31 reported a significant relationship between high within-patient variability of tacrolimus exposure and long-term graft failure. 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.…”

Section: Variability Of Immunosuppressive Exposure In Kidney Transplasupporting

confidence: 69%

“…High variability of tacrolimus exposure is also considered to be a modifiable risk factor for kidney transplant recipients and has been associated with an increased risk of rejection and poor graft survival. 30,31 Another modification of our beliefs has been the assessment of patients who are nonadherent to treatment, and this is continuing to evolve. Fifteen years ago, we believed that most transplant recipients were adherent.…”

Section: The Kidney Graft Journey and Risk Managementmentioning

confidence: 99%

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Advancing Transplantation

et al. 2017

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Section: Variability Of Immunosuppressive Exposure In Kidney Transplasupporting

confidence: 69%

Section: The Kidney Graft Journey and Risk Managementmentioning

confidence: 99%

Advancing Transplantation

et al. 2017

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“…[18] Least squares means will be calculated for each group and the difference between the group means will be reported with a two-sided 95% confidence interval (CI). If the upper limit of the CI for the difference between the adjusted means (transition minus standard) for the therapy effect is less than 0, then lower variability in immunosuppressive agent levels and thus better adherence to therapy due to the new transition model is therefore proved.…”

Section: Methodsmentioning

confidence: 99%

The TRANSNephro-study examining a new transition model for post-kidney transplant adolescents and an analysis of the present health care: study protocol for a randomized controlled trial

Kreuzer

Prüfe

Bethe

et al. 2014

Trials

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BackgroundThe transition from pediatric to nephrology care is not yet a standardized procedure. The result is an increased risk of deteriorating transplant function, with the potential for premature transplant failure.Methods/DesignIn phase I of this study, we shall evaluate the current patient transition situation in all existing German pediatric and nephrology departments (n = 17), including an evaluation of the views of physicians, nurses, and psychosocial support staff regarding transition. Phase II will be a prospective, randomized study in which we compare current unstructured transition (control group) to structured transition (intervention group). The structured transition approach integrates the core elements of the Berliner TransitionsProgramm in combination with two facilitating smartphone apps. The primary endpoint of this study will be therapy adherence, as reflected by group variation coefficients of immunosuppressive agent levels. As a secondary outcome, we will compare patients’ self-reported quality of life, satisfaction of patients and their parents with each transition model, and how patient-centered healthcare components are utilized. These secondary parameters will be assessed with established instruments or with instruments developed (and pilot tested) in phase I of the project.DiscussionThe long-term goal of this work is to provide a model of structured transition from pediatric to adult care for adolescent nephrology patients, in order to improve transplant survival and patient wellbeing.Trial registrationIdentifier: Clinicaltrials.gov: ISRCTN22988897, registered on 24 April 2014).

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“…Recently, Sapir-Pichhadze et al observed that a higher Tac IPV was associated with more late allograft rejection, transplant glomerulopathy, graft loss, and death with a functioning transplant [50]. In pediatric kidney transplantation, a high Tac IPV has also been associated with increased late rejection and graft loss [51,52].…”

Section: Intrapatient Variabilitymentioning

confidence: 99%

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Andrews

Winter

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

115

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Introduction: Tacrolimus (Tac) is the cornerstone of immunosuppressive therapy after solid organ transplantation and will probably remain so. Excluding belatacept, no new immunosuppressive drugs were registered for the prevention of acute rejection during the last decade. For several immunosuppressive drugs, clinical development halted because they weren't sufficiently effective or more toxic. Areas covered: Current methods of monitoring Tac treatment, focusing on traditional therapeutic drug monitoring (TDM), controversies surrounding TDM, novel matrices, pharmacogenetic and pharmacodynamic monitoring are discussed. Expert opinion: Due to a narrow therapeutic index and large interpatient pharmacokinetic variability, TDM has been implemented for individualization of Tac dose to maintain drug efficacy and minimize the consequences of overexposure. The relationship between predose concentrations and the occurrence of rejection or toxicity is controversial. Acute cellular rejection also occurs when the Tac concentration is within the target range, suggesting that Tac whole blood concentrations don't necessarily correlate with pharmacological effect. Intracellular Tac, the unbound fraction of Tac or pharmacodynamic monitoring could be better biomarkers/tools for adequate Tac exposure -research into this has been promising. Traditional TDM, perhaps following pre-emptive genotyping for Tac-metabolizing enzymes, must suffice for a few years before these strategies can be implemented in clinical practice. ARTICLE HISTORY

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Monitoring Nonadherence and Acute Rejection With Variation in Blood Immunosuppressant Levels in Pediatric Renal Transplantation

Abstract: The TAC CV% seems to be a useful and superior marker, compared with SD alone, for assessing medication nonadherence and the possibility of allograft rejection in pediatric renal transplantation.

Cited by 112 publications

References 10 publications

Advancing Transplantation

Advancing Transplantation

The TRANSNephro-study examining a new transition model for post-kidney transplant adolescents and an analysis of the present health care: study protocol for a randomized controlled trial

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

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