Aspirin Use and Incident Cardiovascular Disease, Kidney Failure, and Death in Stable Kidney Transplant Recipients: A Post Hoc Analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Abstract Background and Aims Biologically, the cellular activity of the mTOR complexes depends on the balance between the catabolic and the anabolic inputs. Hence, we hypothesized that the metabolic side effects of mTOR inhibitors (mTORi) in kidney transplantation depend on the baseline metabolic status of the patient. Method The analysis included all the patients that have been transplanted in our Center between June 2013 to December 2016, completed one year of follow-up and did not change medication during the first year after kidney transplantation (per-protocol population, n=298). Outcomes chosen include de novo diabetes, 1-year difference from baseline in glycated hemoglobin (HbA1c), triglycerides and total cholesterol. Kidney transplant recipients were treated either with an mTORi (either Sirolimus or Everolimus, n=134) or Mycophenolic Acid (MPA, n=164). Both drugs were always accompanied by tacrolimus and steroids. Patients were stratified according to the treatment received (mTORi versus MPA) and the baseline metabolic status (diabetes mellitus type 2 and obesity). Differences among groups were analyzed with exact Fisher test and ANOVA test with LSD post-hoc analysis. Results We observed a strong difference for 1-year change in HbA1c depending on the baseline metabolic status of the patients (P<0.001 between groups, Figure 1a). The worst results were observed for patients with baseline diabetes. Among these, obese patients treated with mTORi had the higher increase in HbA1c (3.04 ± 1.18% from baseline, P<0.01 with all groups at post-hoc analysis). De-novo diabetes was more frequent in patients taking mTORi (23.4 vs. 13.1%), albeit not significantly (P=0.100) and without differences taking into account obesity as a covariate. Triglycerides increased substantially in patients without baseline diabetes and treated with mTORi (P<0.05). Surprisingly, in diabetic patients no differences were observed in triglycerides between mTORi and MPA groups (Figure 1b). There were no differences in the increase in total cholesterol among groups (P=0.155) (Figure 1c). Conclusion We observed that the 1-year increase in HbA1c and triglycerides attributable to mTORi after kidney transplantation depends on the baseline metabolic status of the patients. We propose that the metabolic side effects of mTORi depend on the balance between anabolic and catabolic inputs of every kidney transplant recipient.

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Association between medication adherence and intrapatient variability in tacrolimus concentration among stable kidney transplant recipients

Scientific Reports ◽

10.1038/s41598-021-84868-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hyunmin Ko ◽

Hyo Kee Kim ◽

Chris Chung ◽

Ahram Han ◽

Seung-Kee Min ◽

...

Keyword(s):

Medication Adherence ◽

Kidney Transplant ◽

Controlled Trial ◽

Self Report ◽

Tacrolimus Concentration ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Hoc Analysis ◽

Intrapatient Variability ◽

Post Hoc

AbstractThis study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P = .527; dosing adherence, ρ = − 0.098, P = .352; timing adherence, ρ = − 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

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P1848SUSTAINABILITY OF ACTIVE LIFESTYLE INTERVENTION BENEFITS FOR KIDNEY TRANSPLANT RECIPIENTS AFTER STUDY COMPLETION: POST-HOC ANALYSIS OF THE CAVIAR RANDOMISED CONTROLLED TRIAL

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1848 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Joanne Driscoll ◽

Kulli Kuningas ◽

Mary Dutton ◽

Edward Day ◽

Adnan Sharif

Keyword(s):

Kidney Transplant ◽

Lifestyle Intervention ◽

Behaviour Change ◽

Behaviour Change Techniques ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplantation ◽

Post Hoc Analysis ◽

Study Completion ◽

Post Hoc

Abstract Background and Aims. CAVIAR (Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients) was a single-centre, randomised, controlled trial that recruited stable kidney transplant recipients without diabetes between 3-24 months’ post-transplantation. Participants were randomly assigned to active (personalised renal dietetic-led sessions using evidence-based behaviour change techniques) versus passive lifestyle intervention (current standard of care) for a six-month intervention period. Our findings showed encouraging clinical improvements including reduction in weight (mean difference -2.47kg [-.401 to -0.92], p=0.002), fat mass (-1.537 [-2.947 to -0.127], p=0.033) and rates of post-transplantation diabetes (7.6% versus 15.6% respectively, p=0.123). However, evidence from the general population suggests lifestyle intervention behaviour change techniques must be sustained to achieve the greatest benefit. It is unclear whether the same is true for kidney transplant recipients. Therefore, the aim of this study was to conduct a post-hoc analysis of the CAVIAR study to explore 1-year study outcomes (6-months after completion of the study interventions) to explore how clinical outcomes have evolved. Methods. The methodology of the CAVIAR study has already been summarised above and main findings published (Kuningas et al. Transplantation 2019; early online). Assessment of 1-year study outcomes was prespecified in the CAVIAR trial protocol to understand post-intervention outcomes. Between August 2015 and December 2017, 130 individuals were recruited to the trial and final study visits were conducted in February 2018. Electronic patient records were analysed for all study participants and 1-year outcome data (up to August 2019) were extracted in relation to cardio-metabolic risk outcomes where available. The trial is registered on clinicaltrials.org (identifier: NCT02233491). Results. While CAVIAR participants randomised to active versus passive lifestyle intervention demonstrated beneficial weight change in the six-month study period with a negative mean difference, in the six-month period after study completion we observed the opposite effect with a positive mean difference (+1.23 kg [-0.05 to 2.51], p=0.060). Two participants from both active and passive intervention arms subsequently developed post-transplantation diabetes in the six-months after study closure, although difference in post-transplantation diabetes rates remained clinically significant at 1-year (10.6% versus 18.8% respectively, p=0.143). There was no significant correlation between study baseline Situational Motivation Score components (intrinsic motivation, intrinsic regulation, extrinsic regulation or amotivation) and weight change either during or after CAVIAR study completion Conclusion. Our post-hoc analysis of the CAVIAR study suggest active lifestyle intervention using renal dietitian-led behaviour change techniques must be a continuous rather than a one-off strategy to sustain long-term clinical benefits and is unrelated to baseline motivation. This has implications for service delivery and workforce planning for established kidney transplant programs across Europe.

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