High Intrapatient Tacrolimus Variability Is Associated With Worse Outcomes in Renal Transplantation Using a Low-Dose Tacrolimus Immunosuppressive Regime

Whalen, Henry; Glen, J.; Harkins, Victoria; Stevens, Kate; Jardine, Alan G.; Geddes, Colin C.; Clancy, Marc

doi:10.1097/tp.0000000000001129

Cited by 79 publications

(121 citation statements)

References 20 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…However, only 18 patients were nonwhite. 16 Based on the country of origin these studies were conducted, there were likely few if any patients of African descent in these analyses. There are several other studies also demonstrating that high tacrolimus variability, measured either by standard deviation or %CV, increases the risk of acute rejection and poor graft outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Another limitation was that tacrolimus concentrations obtained during hospitalization were also included in this analysis and we used a 10-year cohort and the study time period was long in relation to other studies. 13–16 While this increased the sample-size, follow-up time and power of the analysis, it also meant that clinical care changed during the study period. This includes measurement of risk factors, including PRA, and donor marginality.…”

Section: Discussionmentioning

confidence: 99%

“…7, 8 There are a number of studies demonstrating that high intrapatient tacrolimus variability is associated with increased risk of acute rejection, graft dysfunction and graft loss. 9–16 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Taber

Fleming

et al. 2017

Transplantation

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Taber

Fleming

et al. 2017

Transplantation

View full text Add to dashboard Cite

show abstract

“…High intra‐patient variability in calcineurin inhibitors (CNI) can worsen graft outcome and lead to rejection and Donor Specific Antibody (DSA) development . Although non‐adherence to the immunosuppressive drug regimen seems to be the main reason for a high variability in drug blood levels , relationships between non‐adherence patterns and drug exposure have not been systematically characterized in the previous studies.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with the variability of calcineurin inhibitor blood levels in kidney recipients grafted for more than 1 year

Belaiche¹,

Décaudin²,

Dharancy

et al. 2017

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

A B S T R A C TThe study of calcineurin inhibitor (CNI) blood level variability to evaluate adherence in transplantation has improved over the years. The aim of our study was to assess factors associated with this variability using the coefficient of variation (CV). A cross-sectional sample of kidney recipients grafted for more than 1 year was recruited. We recorded clinical data, data from a clinical pharmacist interview and from six questionnaires measuring adherence, satisfaction, behaviours, beliefs, perception of the illness and social vulnerability. A total of 408 recipients were enrolled (61.2% male, mean age 54) and divided into two groups: low variability CV < 30% (n = 302), high variability CV ≥ 30% (n = 106). In univariate analysis, hospital-home distance, cyclosporine, time since transplantation and presence of discrepancies in drug regimen were associated with a greater risk of CV ≥ 30%. In contrast, tacrolimus QD conferred a lower risk of CV ≥ 30%. In multivariate analysis, only the presence of discrepancies remained significant: .01]; P = 0.022). Discrepancies in drug regimen appear as the main risk factor associated with CNI blood variability. The clinical pharmacist's input is an accurate and simple way of detecting non-adherence which is not revealed in self-report questionnaires.

show abstract

“…Risk of the composite outcome was 1.4 times higher in patients with high IPV, even after adjustment for confounders. The findings are not necessarily novel; a number of previous studies have demonstrated association between IPV and adverse outcomes in both adult and paediatric recipients, and in different solid organ transplant types . This study does, however, represent the largest series to date and includes a number of additional risk factors for poor transplant outcomes in multivariate analysis.…”

mentioning

confidence: 77%

Intrapatient variability in tacrolimus exposure - a useful tool for clinical practice?

Knight

2016

Transpl Int

View full text Add to dashboard Cite

High Intrapatient Tacrolimus Variability Is Associated With Worse Outcomes in Renal Transplantation Using a Low-Dose Tacrolimus Immunosuppressive Regime

Cited by 79 publications

References 20 publications

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation

Factors associated with the variability of calcineurin inhibitor blood levels in kidney recipients grafted for more than 1 year

Intrapatient variability in tacrolimus exposure - a useful tool for clinical practice?

Contact Info

Product

Resources

About