Summary
Long‐term data on cardiovascular (CV) outcome of renal transplant recipients (RTR) on mTOR‐i (mammalian Target Of Rapamycin‐inhibitors) are scarce. In a sub‐study of the MECANO trial we ...investigated changes in intima media thickness (IMT), CV risk profile, Major Adverse CV Events (MACE) and survival in RTR on a mTORi versus CNI based regimen. Patients (enrolled 361) were treated with (basiliximab) and triple IS (CsA‐Cyclosporine A‐(C), MPS (M), prednisolone (P)). At M6 patients were randomized (n = 224) to the CsA group (C, P, N = 89), MPS group (M, P, N = 39) EVL group (Everolimus, P, N = 96). At week 2, M6 and M 24, IMT measurements of the Common Carotid Artery were performed. Cardiovascular risk factors were assessed at baseline, 6 and 24 months of follow‐up. Seven years survival and MACE‐free survival probability were calculated by the Cardiovascular Risk Calculator for RTR. After 7 years of follow‐up, incidence of cardiovascular events and patient survival were assessed. Mean IMT at baseline (N = 192), was 0.64 ± 0.14 mm. At M6 (N = 158), 0.66 ± 0.15, M24 IMT was 0.68 ± 0.15 (N = 95). No significant differences between groups concerning IMT, true CV events and mortality, CV risk profile, predicted MACE/Mortality were found between mTORi and CNI‐based regimen after 7 years of follow‐up.
Background
Hepcidin is considered the master regulator of iron homoeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron‐restricted anaemia. Meanwhile, ...serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR), which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore, prospectively determined the association of serum hepcidin with risk of graft failure, cardiovascular mortality and all‐cause mortality in RTR.
Materials and methods
Serum hepcidin was assessed in an extensively phenotyped RTR cohort by dual‐monoclonal sandwich ELISA specific immunoassay. Statistical analyses were performed using univariate linear regression followed by stepwise backward linear regression. Cox proportional hazard regression models were performed to determine prospective associations.
Results
We included 561 RTR (age 51 ± 12 years). Mean haemoglobin (Hb) was 8·6 ± 1·0 mM. Median IQR serum hepcidin was 7·2 3·2–13·4 ng/mL. Mean estimated glomerular filtration rate was 47 ± 16 mL/min/1·73 m2. In univariate Cox regression analyses, serum hepcidin was not associated with risk of graft failure, cardiovascular mortality or all‐cause mortality. Notably, after adjustment for high sensitivity C‐reactive protein and ferritin, serum hepcidin became negatively associated with all‐cause mortality (hazard ratio 0·89; 95% confidence interval 0·80–0·99, P = 0·03).
Conclusions
In this study, we did not find an association between serum hepcidin and outcomes, that is graft failure, cardiovascular mortality or all‐cause mortality. Based on our results, it is questionable whether serum hepcidin may be used to predict a beneficial effect of hepcidin antagonists.
ABSTRACT
Background
Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between ...symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience.
Methods
Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups.
Results
A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7–22), with a burden of 20 (8–37; range 0–244). Per extra symptom, physical and mental HRQOL decreased –0.41 (–0.50; –0.31) and –0.51 (–0.59; –0.42), respectively, P < .001. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18–50 > 50–65 ≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance.
Conclusion
KRTs’ symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.
Graphical Abstract
Graphical Abstract
ABSTRACT
Background
The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries.
Methods
The European ...Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated.
Results
The total KT rate in the 40 participating countries increased with 1.9% annually 95% confidence interval (CI) 1.5, 2.2 from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East–West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.).
Conclusions
The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.
Graphical Abstract
Graphical Abstract
Insulin resistance has been implicated to underlie both excess cardiovascular disease and chronic transplant dysfunction after renal transplantation. Skeletal muscle mainly determines peripheral ...insulin resistance, and could therefore affect outcome.
All transplant recipients at our outpatient clinic with a functioning graft more than 1 year were invited to participate between 2001 and 2003. Mortality and death censored graft loss were recorded until August 2007. We used 24 hr urine creatinine excretion as measure of muscle mass. Cox regression was used to analyze the prospective data.
Six hundred four renal transplant recipients (age 51+/-12 years, 55% men) were studied. Creatinine excretion was 10.1+/-2.6 mmol/24 hr in women and 13.6+/-3.4 mmol/24 hr in men. During follow-up of 5.3 (4.7-5.7) years, 95 recipients died and 42 suffered graft loss. Determinants of creatinine excretion were weight, sex, age, height, cumulative prednisolone doses, and diabetes (r2=0.45). Creatinine excretion was associated with both mortality (3rd vs. 1st tertile Hazard ratio: 0.4 95% confidence interval 0.2-0.7, P=0.003) and graft loss (3rd vs. 1st tertile Hazard ratio: 0.4 95% confidence interval 0.1-0.9, P=0.03) independent of age, sex, serum creatinine, proteinuria, insulin resistance related factors, time after transplantation, and duration of dialysis.
Creatinine excretion as measure of muscle mass is associated with mortality and graft loss after renal transplantation, independent of insulin resistance and its related factors. We speculate that preservation of muscle mass by stimulating exercise, sufficient diet, and less use of corticosteroids may be relevant for improving prognosis in renal transplant recipients.
The recommended immunosuppressive treatment after kidney transplantation consists of tacrolimus, mycophenolate mofetil, and low‐dose corticosteroids. Drug concentrations are monitored using ...therapeutic drug monitoring (TDM), which does not necessarily correlate with pharmacodynamic activity. To find the balance between optimal efficacy and minimal toxicity, it might be more informative to monitor patients' immunological status rather than drug concentrations. We selected a panel of T‐cell‐based immune assays, which were used for immunomonitoring of 14 stable kidney transplantation patients. Whole blood was incubated with a T‐cell stimulus, after which T‐cell proliferation, T‐cell activation marker expression and cytokine production were measured to study residual immune activity in vitro (before drug intake; drug added to the incubation) and ex vivo (after drug intake). T‐cell proliferation was completely suppressed in all patients over the full day, while IL‐2, IFN‐γ, CD71, and CD154 showed fluctuations over the day with a strong inhibition (75%–25%) at 2 h post‐dose. The level of inhibition was variable between patients and could not be related to pharmacokinetic parameters or the presence of regulatory or senescence immune cells. Moreover, the level of inhibition did not correlate with the in vitro tacrolimus drug effect as studied by incubating pre‐dose blood samples with additional tacrolimus. Overall, IL‐2, IFN‐γ, CD71, and CD154 seem to be good markers to monitor residual immune activity of transplantation patients. To evaluate the correlation between these pharmacodynamic biomarkers and clinical outcome, prospective observational studies are needed.
Background
Advanced renal disease is characterized by adverse changes in renal structure; however, noninvasive techniques to diagnose and monitor these changes are currently lacking.
Purpose
To ...evaluate the reproducibility of native T1 mapping for renal tissue characterization.
Study Type
Reproducibility study.
Population
Fifteen healthy volunteers (mean age 31 years, range 19–63 years), and 11 patients with diabetic nephropathy (mean age 57 years, range 51–69 years).
Field Strength/Sequence
3T, modified Look–Locker imaging (MOLLI) 5(3)3.
Assessment
Intra‐ and interexamination reproducibility of voxel‐based T1 relaxation times of renal cortex and medulla was assessed in healthy human volunteers and diabetic nephropathy patients.
Statistical Tests
Reproducibility was evaluated using Bland–Altman and intraclass correlation coefficients (ICCs).
Results
Intra‐ and interexamination reproducibility of renal native T1 mapping showed good–strong ICCs (0.83–0.89) for renal cortex and medulla, and moderate–good ICCs (0.62–0.81) for cortex–medulla ratio in both healthy volunteers and diabetic nephropathy patients. Intra‐ and interexamination limits of agreement were respectively (–124 msec, + 82 msec) and (–134 msec, + 98 msec) for renal cortex and (–138 msec, + 107 msec) and (–118 msec, + 151 msec) for medulla. Overall T1 values for renal cortex (P = 0.277) and medulla (P = 0.973) were not significantly different between healthy volunteers and diabetic nephropathy patients, in contrast to the cortex–medulla ratio (P = 0.003).
Data Conclusion
Renal native T1 mapping is a technique with good–strong intra‐ and examination reproducibility in both healthy volunteers and diabetic nephropathy patients.
Level of Evidence: 3
Technical Efficacy: Stage 1
J. Magn. Reson. Imaging 2019;49:588–596.
ABSTRACT
Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided ...standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6–8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.
Video
10.1093/ndt/gfad258
Video
Watch the video of this contribution at https://academic.oup.com/ndt/pages/author_videos
gfad258Media1
6344621287112
Traffic crashes are the leading health threat to children in the United States, resulting in nearly 1 million injuries annually. The psychological consequences of these injuries are primarily ...unknown. The aims of this study were to estimate the prevalence of posttraumatic stress disorder (PTSD) in traffic-injured children and their parents and to identify risk factors for PTSD development.
A prospective cohort study of traffic-injured children between 3 and 18 years of age was conducted at a level 1 Pediatric Trauma Center. The children were enrolled as part of an ongoing surveillance system of traffic-related injuries. Presence and severity of PTSD were determined in the children and their parents through a validated diagnostic questionnaire 7 to 12 months after child injury.
Twenty-five percent of the children and 15% of the parents suffered diagnostic PTSD, but only 46% of the parents of affected children sought help of any form (including from friends) for their child and only 20% of affected parents sought help for themselves. Child PTSD was associated with older child age and parent PTSD. Parent PTSD was associated with younger child age, child PTSD, and parent witnessing the event. Injury severity was not predictive of PTSD.
PTSD in children and their parents is a common, yet overlooked, consequence of pediatric traffic-related injury with prevalence rates similar to those found in children exposed to violence. Physicians managing the pediatric trauma patient, regardless of injury severity or whether the injury was intentional, should screen for PTSD and refer for treatment where appropriate.
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