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Background: The pharmacokinetics of immunosuppressant drugs may change with advancing age, potentially affecting patient outcomes. Objective: To characterise the effects of age on the pharmacokinetic and exposure parameters of tacrolimus, mycophenolate, and prednisolone. Methods: Pharmacokinetic profiling, involving whole blood tacrolimus, total and free plasma mycophenolic acid (MPA), total plasma mycophenolic acid glucuronide (MPAG), and total and free plasma prednisolone, was performed in an older and younger adult cohort. Thirteen samples were drawn on a single occasion, pre-oral dose and then at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12 h post-dose. Non-compartmental analysis was conducted using the PKNCA package, and pharmacokinetic and exposure parameters were compared between age groups using a Mann–Whitney test. A regression analysis was conducted for free MPA and MPAG using significant variables of interest. Results: This exploratory study included 21 older and 18 younger adults. Dose-adjusted tacrolimus, total MPA and free prednisolone pharmacokinetic parameters were not different between age groups; however, for free MPA and MPAG, older recipients had significantly greater minimum and maximum concentrations, trough concentrations, and half-life. There was a two-fold increase in free MPA exposure in older adults (median dose-adjusted AUC0–12: 1284 vs. 684 μg h/L, p < 0.0001); MPAG exposure similarly increased. Age was significantly associated with free MPA and MPAG exposure, and free MPA exposure was associated with haematocrit (p < 0.05). Conclusion: Differences in MPA were found with advancing age and may be due to altered kidney function, haematocrit, plasma protein binding and/or drug absorption. Future research should explore specific covariate contributions to this further. [ABSTRACT FROM AUTHOR]

Aims: Exercise interventions positively affect numerous cardiometabolic risk factors. To better evaluate the health effects of exercise training, it may be more appropriate to evaluate risk factors together. The Metabolic Syndrome Severity Score (MetSSS) is a composite score representing cardiometabolic risk. Purpose: To evaluate the relationships between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS in a heterogenous sample of people with complex chronic disease. Material and Methods: Fifty-three people with kidney or liver disease and at least one feature of the metabolic syndrome (MetS) were included. Pearson correlations were conducted between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS. Linear regressions were performed for multi-level categorical variables. Independent variables with an association with MetSSS (P ≤ 0.2) were included in a multiple regression analysis. Results: The 6-minute walk test (6MWT) distance was inversely and independently associated with MetSSS [standardized beta coefficient (β) = −0.31, P = 0.04]. No relationship was found between MetSSS and physical activity or neuromuscular fitness. Mean 6MWT in the highest tertile was 550 m (range: 505–620 m) and 346 m (range: 233–408 m) in the lowest. The analysis showed a medium–large between-group effect for the difference in MetSSS for the lowest and highest tertile of 6MWT [Eta squared (η2) = 0.16, P = 0.01]. Conclusions: Exercise capacity was inversely and independently associated with MetSSS in people with complex chronic disease. Clinical trials with exercise interventions are needed to further investigate if improvements in exercise capacity result in clinically significant changes in the MetSSS. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the effects of prebiotic supplementation on the gastrointestinal microbiota in kidney transplant recipients. The study found that prebiotic supplementation led to significant improvements in gut microbial richness and diversity in these patients. The researchers also observed changes in the relative abundances of certain bacterial families and metabolic pathways. However, the study had limitations, such as a small sample size and potential confounding factors. Further research is needed to better understand the effects of prebiotic supplementation in different subpopulations of kidney transplant recipients and its impact on health outcomes. [Extracted from the article]

Aim: The benefits of dialysis in the older population remain highly debated, particularly for certain dialysis modalities. This study aimed to explore the dialysis modality utilization patterns between in‐centre haemodialysis (ICHD), peritoneal dialysis (PD) and home haemodialysis (HHD) and their association with outcomes in older persons. Methods: Older persons (≥75 years) initiating dialysis in Australia and New Zealand from 1999 to 2018 reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry were included. The main aim of the study was to characterize dialysis modality utilization patterns and describe individual characteristics of each pattern. Relationships between identified patterns and survival, causes of death and withdrawal were examined as secondary analyses, where the pattern was considered as the exposure. Results: A total of 10 306 older persons initiated dialysis over the study period. Of these, 6776 (66%) and 1535 (15%) were exclusively treated by ICHD and PD, respectively, while 136 (1%) ever received HHD during their dialysis treatment course. The remainder received both ICHD and PD: 906 (9%) started dialysis on ICHD and 953 (9%) on PD. Different individual characteristics were seen across dialysis modality utilization patterns. Median survival time was 3.0 (95%CI 2.9–3.1) years. Differences in survival were seen across groups and varied depending on the time period following dialysis initiation. Dialysis withdrawal was an important cause of death and varied according to individual characteristics and utilization patterns. Conclusion: This study showed that dialysis modality utilization patterns in older persons are associated with mortality, independent of individual characteristics. Summary at a glance: This large multinational (ANZDATA) registry study of older individuals identified variability in the modality utilization patterns following dialysis initiation (i.e. in‐centre haemodialysis, peritoneal dialysis or a combination inclusive of home haemodialysis) and differences in outcomes when evaluating the pattern of initiation. In addition, variability in the causes of death was identified, with a large proportion due to withdrawal, and some differences across the studied groups. [ABSTRACT FROM AUTHOR]

Background: The metabolic syndrome is common across many complex chronic disease groups. Advances in health technology have provided opportunities to support lifestyle interventions. Objective: The purpose of this study is to test the feasibility of a health technology-assisted lifestyle intervention in a patient-led model of care. Methods: The study is a single-center, 26-week, randomized controlled trial. The setting is specialist kidney and liver disease clinics at a large Australian tertiary hospital. The participants will be adults with a complex chronic condition who are referred for dietetic assessment and display at least one feature of the metabolic syndrome. All participants will receive an individualized assessment and advice on diet quality from a dietitian, a wearable activity monitor, and standard care. Participants randomized to the intervention group will receive access to a suite of health technologies from which to choose, including common base components (text messages) and optional components (online and mobile app-based nutrition information, an online home exercise program, and group-based videoconferencing). Exposure to the optional aspects of the intervention will be patient-led, with participants choosing their preferred level of engagement. The primary outcome will be the feasibility of delivering the program, determined by safety, recruitment rate, retention, exposure uptake, and telehealth adherence. Secondary outcomes will be clinical effectiveness, patient-led goal attainment, treatment fidelity, exposure demand, and participant perceptions. Primary outcome data will be assessed descriptively and secondary outcomes will be assessed using an analysis of covariance. This study will provide evidence on the feasibility of the intervention in a tertiary setting for patients with complex chronic disease exhibiting features of the metabolic syndrome. Results: The study was funded in 2019. Enrollment has commenced and is expected to be completed by June 2022. Data collection and follow up are expected to be completed by December 2022. Results from the analyses based on primary outcomes are expected to be submitted for publication by June 2023. Conclusions: The study will test the implementation of a health technology-assisted lifestyle intervention in a tertiary outpatient setting for a diverse group of patients with complex chronic conditions. It is novel in that it embeds patient choice into intervention exposure and will inform health service decision-makers in regards to the feasibility of scale and spread of technology-assisted access to care for a broader reach of specialist services. [ABSTRACT FROM AUTHOR]

Background: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. Methods: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9‐point Likert Scales, with 7–9 being critically important. Relative importance was determined using a best–worst scale. Means and proportions of the Likert‐scale ratings and best–worst preference scores were calculated. Results: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best–worst) scores were consistent. Conclusions: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes. [ABSTRACT FROM AUTHOR]