Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients

Solomon, Sonia; Colovai, Adriana I.; Río, Marcela Del; Hayde, Nicole

doi:10.1007/s00467-019-04377-6

Cited by 26 publications

(27 citation statements)

References 36 publications

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“…As expected, given the inherent social desirability bias associated with self‐report metrics, tacrolimus trough CV% of approximately 30% suggested higher non‐adherence rates than the median 100% adherence reported in the MAM‐MM. The tacrolimus trough CV% rates in our population are consistent with Tacrolimus trough CV% reported in children elsewhere, although potentially slightly higher than adults 26,54,55 . The absence of association between adherence markers and conversion may reflect the challenges that healthcare professionals face in identifying non‐adherents; clinician gestalt on this is poor with a gross underestimation of non‐adherence 56‐60 .…”

Section: Discussionsupporting

confidence: 81%

Age and sex determine conversion from immediate‐release to extended‐release tacrolimus in a multi‐center cohort of Canadian pediatric renal transplant recipients

Lang

Sharma

Foster

et al. 2020

Pediatric Transplantation

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ER-Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate-release to ER-Tac. This prospective multi-center observational study followed Canadian pediatric kidney transplant recipients up to 5 years post-transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER-Tac. Sixty-six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P < 0.001). The impact of age reduced by three percent for every month after transplant (HR 0.97, CI 0.95, 0.98, P < 0.001). Girls were more likely to be converted than boys (HR 3.78, CI 1.35, 10.6, P 0.01). Adherence measures (MAM-MM and tacrolimus trough variability), individual barriers to adherence, renal function, HLA mismatch, and rejection were not significant predictors of conversion in the final regression model. ER-Tac was preferentially prescribed to older age and female patients. Female sex and adolescence are both associated with worse graft outcomes, but we found no link between individualized markers of adherence/graft risk and conversion. Clinicians appeared to be using demographic features to distinguish patients at perceived higher risk and How to cite this article: Lang S, Sharma A, Foster B, et al. Age and sex determine conversion from immediate-release to extended-release tacrolimus in a multi-center cohort of Canadian pediatric renal transplant recipients. Pediatr

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Section: Discussionsupporting

confidence: 81%

Age and sex determine conversion from immediate‐release to extended‐release tacrolimus in a multi‐center cohort of Canadian pediatric renal transplant recipients

Lang

Sharma

Foster

et al. 2020

Pediatric Transplantation

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“…Elevated CV has been associated with increased risk of rejection and dnDSA formation in pediatric kidney transplant recipients 13,48–52 . Median CV in patients with BPAR has ranged from 44–53%, compared with 24–33% in nonrejecters 13,48,51 .…”

Section: Resultsmentioning

confidence: 99%

Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective

2020

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Background Tacrolimus therapy in solid organ transplant (SOT) recipients is challenging due to its narrow therapeutic window and pharmacokinetic variability both between patients and within a single patient. Intrapatient variability (IPV) of tacrolimus trough concentrations has become a novel marker of interest for predicting transplant outcomes. The purpose of this review is to evaluate the association of tacrolimus IPV with graft and patient outcomes and identify interventions to improve IPV in SOT recipients. Methods A systematic review of the literature was performed using PubMed and Embase from database inception to September 20, 2020. Studies were eligible only if they evaluated an association between tacrolimus IPV and transplant outcomes. Both pediatric and adult studies were included. Measures of variability were limited to standard deviation, coefficient of variation, and time in therapeutic range. Results Forty‐four studies met the inclusion criteria. Studies were published between 2008 and 2020 and were observational in nature. Majority of data were published in adult kidney transplant recipients and identified an association with rejection, de novo donor specific antibody (dnDSA) formation, graft loss, and patient survival. Evaluation of IPV‐directed interventions was limited to small preliminary studies. Conclusions High tacrolimus IPV has been associated with poor outcomes including acute rejection, dnDSA formation, graft loss, and patient mortality in SOT recipients. Future research should prospectively explore IPV‐directed interventions to improve transplant outcomes.

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“…Among them, CNI is one of the main immunosuppressants used to control dnDSA. High tacrolimus variability (instability) may well result in dnDSA production in pediatric recipients [14]. It can be admitted that this study has highlighted the importance of medication adherence.…”

Section: Kidney Transplantationmentioning

confidence: 83%

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

Nakamura

Shirouzu

2021

JCM

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The advances in acute phase care have firmly established the practice of organ transplantation in the last several decades. Then, the next issues that loom large in the field of transplantation include antibody-mediated rejection (ABMR) and recurrent primary disease. Acute ABMR is a daunting hurdle in the performance of organ transplantation. The recent progress in desensitization and preoperative monitoring of donor-specific antibodies enables us to increase positive outcomes. However, chronic active ABMR is one of the most significant problems we currently face. On the other hand, recurrent primary disease is problematic for many recipients. Notably, some recipients, unfortunately, lost their vital organs due to this recurrence. Although some progress has been achieved in these two areas, many other factors remain largely obscure. In this review, these two topics will be discussed in light of recent discoveries.

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Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients

Cited by 26 publications

References 36 publications

Age and sex determine conversion from immediate‐release to extended‐release tacrolimus in a multi‐center cohort of Canadian pediatric renal transplant recipients

Age and sex determine conversion from immediate‐release to extended‐release tacrolimus in a multi‐center cohort of Canadian pediatric renal transplant recipients

Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective

Antibody-Mediated Rejection and Recurrent Primary Disease: Two Main Obstacles in Abdominal Kidney, Liver, and Pancreas Transplants

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