Infection and Malignancy Outweigh Cardiovascular Mortality in Kidney Transplant Recipients: Post Hoc Analysis of the FAVORIT Trial

2018 ◽  
Vol 131 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Larry A. Weinrauch ◽  
John A. D'Elia ◽  
Matthew R. Weir ◽  
Suphamai Bunnapradist ◽  
Peter V. Finn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cardiovascular Mortality ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals P1761SIDE EFFECTS OF MTOR INHIBITORS DEPEND ON THE BASELINE METABOLIC STATUS OF KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
David Cucchiari ◽  
Alicia Molina-Andujar ◽  
Enrique Montagud-Marrahi ◽  
Jordi Rovira ◽  
Fritz Diekmann
Keyword(s):  
Kidney Transplantation ◽  
Side Effects ◽  
Kidney Transplant ◽  
De Novo ◽  
Mtor Inhibitors ◽  
Metabolic Status ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Hoc Analysis ◽  
Post Hoc

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.

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

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.

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

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.

scholarly journals Circulating Advanced Glycation Endproducts and Long-Term Risk of Cardiovascular Mortality in Kidney Transplant Recipients

2019 ◽  
Vol 14 (10) ◽  
pp. 1512-1520
Author(s):  
Camilo G. Sotomayor ◽  
António W. Gomes-Neto ◽  
Marco van Londen ◽  
Rijk O. B. Gans ◽  
Ilja M. Nolte ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Kidney Transplant ◽  
Cardiovascular Mortality ◽  
Advanced Glycation Endproducts ◽  
Hazard Ratio ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Advanced Glycation ◽  
Mediation Analyses ◽  
Glycation Endproducts

Background and objectivesIn kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.Design, setting, participants, & measurementsProspective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε-[Carboxymethyl]lysine (CML) and Nε-[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes’s procedure.ResultsWe included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality.ConclusionsIn stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3

scholarly journals Relationship of Serum Bicarbonate Levels with 1-Year Graft Function in Kidney Transplant Recipients in Switzerland

2019 ◽  
Vol 44 (5) ◽  
pp. 1179-1188 ◽  
Author(s):  
Anna Wiegand ◽  
Nicole Graf ◽  
Marco Bonani ◽  
Diana Frey ◽  
Rudolf P. Wüthrich ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
First Year ◽  
Kidney Graft ◽  
Serum Bicarbonate ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Open Label ◽  
Post Hoc ◽  
Relationship Of

Background: Metabolic acidosis (MA) is common in kidney transplant recipients (KTRs). Several studies have shown that MA is involved in the progression of chronic kidney disease. However, it is unclear if there is also a relationship between serum bicarbonate and graft function after kidney transplantation (KTx). We hypothesized that low serum bicarbonate is associated with a lower estimated glomerular filtration rate (eGFR) 1 year after KTx. Methods: We performed a post hoc analysis of a single-center, open-label randomized trial in 90 KTRs and investigated the relationship of serum bicarbonate and graft function in the first year after KTx. Results: Prevalence of MA was high after KTx (63%) and decreased to 28% after 1 year. Bicarbonate (20.6 ± 3.0 to 22.7 ± 2.7 mmol/L) increased in the first year after transplantation whereas eGFR (53.4 ± 15.8 to 56.9 ± 18.5 mL/min/1.73 m2) did not change significantly. Higher serum bicarbonate (p = 0.029) was associated with higher eGFR in the first year after KTx. Conclusion: Prevalence of MA is high in KTRs. In the first year after KTx, serum bicarbonate was positively correlated with eGFR, suggesting a potential role of MA in kidney graft function.

scholarly journals Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996–2014)

2018 ◽  
Vol 48 (6) ◽  
pp. 472-481 ◽  
Author(s):  
Ahmed A. Awan ◽  
Jingbo Niu ◽  
Jenny S. Pan ◽  
Kevin F. Erickson ◽  
Sreedhar Mandayam ◽  
...  
Keyword(s):  
United States ◽  
Kidney Transplant ◽  
Cardiovascular Mortality ◽  
Causes Of Death ◽  
Graft Loss ◽  
Graft Function ◽  
The United States ◽  
Mortality Data ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background: Death with graft function remains an important cause of graft loss among kidney transplant recipients (KTRs). Little is known about the trend of specific causes of death in KTRs in recent years. Methods: We analyzed United States Renal Data System data (1996–2014) to determine 1- and 10-year all-cause and cause-specific mortality in adult KTRs who died with a functioning allograft. We also studied 1- and 10-year trends in the various causes of mortality. Results: Of 210,327 KTRs who received their first kidney transplant from 1996 to 2014, 3.2% died within 1 year after transplant. Cardiovascular deaths constituted the majority (24.7%), followed by infectious (15.2%) and malignant (2.9%) causes; 40.1% of deaths had no reported cause. Using 1996 as the referent year, all-cause as well as cardiovascular mortality declined, whereas mortality due to malignancy did not. For analyses of 10-year mortality, we studied 94,384 patients who received a first kidney transplant from 1996 to 2005. Of those, 22.1% died over 10 years and the causative patterns of their causes of death were similar to those associated with 1-year mortality. Conclusions: Despite the downtrend in mortality over the last 2 decades, a significant percentage of KTRs die in 10-years with a functioning graft, and cardiovascular mortality remains the leading cause of death. These data also highlight the need for diligent collection of mortality data in KTRs.

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