The association between tacrolimus exposure and tremor, headache and insomnia in adult kidney transplant recipients: A systematic review.

PURPOSE: Tremor, headache and insomnia have been linked to the immunosuppressant, tacrolimus. The aim of this systematic review was to determine if there is a correlation between tacrolimus exposure and new-onset tremor, headache and insomnia experienced by adult kidney transplant recipients. METHODS: PubMed, Embase, Cochrane Library and CINAHL databases were searched up to 11 April 2023 for published studies which reported on tacrolimus exposure in adult kidney transplant recipients, alongside information on treatment-emergent neurologic manifestations, including tremor, headache and insomnia. Review articles, case studies, conference abstracts and articles not published in English in peer-reviewed journals were excluded. The Physiotherapy Evidence Database and Newcastle-Ottawa Quality Assessment Scales were used to assess risk of bias. Extracted data was analysed via a narrative synthesis. RESULTS: Eighteen studies involving 4030 patients in total were included in the final analysis. These comprised five randomised control trials and thirteen observational studies. Studies failed to find significant association between tacrolimus trough concentrations in whole blood and the incidence of neurologic side effects such as tremor, headache and insomnia; however, in one study the incidence of toxicity requiring a dose reduction increased with increasing, supratherapeutic targeted levels. Females, especially Black females, and older age were positively associated with the prevalence of neurologic adverse effects. Results were conflicting regarding whether extended-release formulations were associated with fewer neurologic complications than immediate-release formulations. CONCLUSION: The varied study designs and criteria for reporting tremor, headache and insomnia impacted on the quality of the data for exploring the relationship between tacrolimus exposure and the onset of neurologic manifestations experienced after kidney transplantation. Studies that examine defined neurologic complications as the primary outcome, and that consider novel markers of tacrolimus exposure while assessing the potential contribution of multiple covariate factors, are required.

Incidence of Thromboembolic Complications Following Kidney Transplantation with Short and Extended Aspirin Prophylaxis: A Retrospective Single-Center Study.

BACKGROUND Aspirin prophylaxis has been associated with reduced graft-related thrombosis following kidney transplantation. Aspirin cessation, however, can increase risk of venous thromboembolic complications, including pulmonary thromboembolism and deep venous thrombosis. This single-center, retrospective, pre-post interventional study from Brisbane, Australia, aimed to compare the rate of thrombotic complications in 1208 adult kidney transplant recipients receiving postoperative aspirin for 5 days or >6 weeks. MATERIAL AND METHODS We enrolled1208 kidney transplant recipients who received 100 mg aspirin for 5 days (n=571) or >6 weeks (n=637) postoperatively. The primary outcome was venous thromboembolism (VTE) in the first 6 weeks after transplant, examined by multivariable logistic regression analysis. Secondary outcomes were renal vein/artery thrombosis, 1-month serum creatinine, rejection, myocardial infarction, stroke, blood transfusion, dialysis at day 5 and day 28, and mortality. RESULTS Sixteen (1.3%) patients experienced VTE (5-day n=8, 1.4%; >6-week n=8, 1.3%; P=0.8). Extended aspirin duration was not independently associated with a reduction in VTE (OR 0.91, 95% CI 0.32-2.57; P=0.9). Graft thrombosis was rare (n=3, 0.25%). Aspirin duration was not associated with cardiovascular events, blood transfusion, graft thrombosis, graft dysfunction, rejection, or mortality. VTE was independently associated with older age (OR 1.09, 95% CI 1.04-1.16; P=0.002), smoking (OR 3.59, 95% CI 1.20-13.2; P=0.032), younger donor age (OR 0.96, 95% CI 0.93-1.00; P=0.036), and thymoglobulin use (OR 10.5, 95% CI 3.09-32.1; P≥0.001). CONCLUSIONS Extended-duration aspirin use did not significantly reduce the incidence of VTE in the first 6 weeks following kidney transplantation. An association was identified between anti-human thymocyte immunoglobulin and VTE, which requires further assessment.

PREBIOTIC: a study protocol of a randomised controlled trial to assess prebiotic supplementation in kidney transplant recipients for preventing infections and gastrointestinal upset - a feasibility study.

BACKGROUND: Modulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients. METHODS: Sixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients' self-assessed quality of life, gastrointestinal symptoms and clinical outcomes. DISCUSSION: This trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true .

Rejection and graft outcomes in kidney transplant recipients with and without angiotensin II receptor type 1 antibodies.

AIM: Angiotensin II type 1 receptor antibody (AT1R Ab) is a non-Human Leucocyte Antigen (HLA) antibody that is maybe associated with early severe kidney transplant rejection and worse graft outcomes. This study aimed to assess the association between AT1R Ab and kidney transplant rejection and graft outcomes. METHODS: We performed a retrospective analysis of all adult kidney transplant recipients in an Australian centre who had an AT1R Ab test between 1 January 2015 to 30 June 2020. AT1R Ab positive patients were compared to AT1R Ab negative patients. Primary outcomes were rejection risk, type and histopathological severity scores. Secondary outcomes were 8-week graft function and graft loss. RESULTS: Of 965 kidney transplants that were performed during the study period, 73 patients had AT1R Ab tested; 16 (22%) were positive and 57(78%) were negative. Positive patients were on average younger and had higher level of donor-specific HLA antibodies. Rejection occurred in 13 (81%) positive patients and 41 (72%) negative patients (P = 0.45). No significant differences in rejection type or severity were found. HLA mismatch and peak panel reactive antibody ≥80%, but not AT1R Ab, independently predicted rejection. Average (132 vs. 177 mmol/L, P = 0.302) and graft loss were not significantly different between groups. CONCLUSION: The study found no evidence that AT1R Ab is associated with rejection type, severity or worse graft function. Future studies should assess its relationship with graft outcomes to help complement immunological risk assessment and potentially provide therapeutic options to alter outcomes.

Exploring Transplant Medication-Taking Behaviours in Older Adult Kidney Transplant Recipients: A Qualitative Study of Semi-Structured Interviews.

BACKGROUND: Today, older adult patients routinely undergo kidney transplantation. To support graft survival, patients must take immunosuppressant medicines for the rest of their lives. The post-transplant medication regimen is complex, and barriers to medication taking are likely confounded by both functional and intrinsic changes associated with advancing age. To develop diverse and innovative approaches to support best health outcomes in this vulnerable age group, it is imperative that the degree to which patients' needs are currently being met, be identified. AIM: The aim of this study was to examine medication-taking behaviours of kidney transplant recipients transplanted at 60 years of age or older. METHODS: This qualitative study used semi-structured patient interviews to explore how kidney transplant recipients currently manage their immunosuppressant regimen and how they cope after transplantation with the complex routine. Data were themed using the principles of Grounded Theory methodology; with interviews conducted until data saturation was reached. RESULTS: Quantitative information was collected from 14 participants who ranged in age from 66 to 77 years (at time of interview), and were prescribed a median of 13 (min: 10, max: 26) medicines. The main themes that emerged from the interview were variability in health literacy toward medicines, the importance of support networks, the need to adjust health expectations, factors that were motivators for self-care, different approaches to medication management, and different approaches to medication taking. Overall, it was found that patients prioritised medication taking above all else, and gratitude to their donor was a powerful motivator to adhere. However, strategies to support medication taking were sometimes ineffective when patients' routine changed. CONCLUSIONS: Future interventions should consider approaches to foster adaptable medication taking behaviours that stand up to changes in the day-to-day routine.

Medication taking is complicated in transplant recipients, due to the number of medicines that need to be taken and the complex nature of the treatment regimen. Challenges in older transplant recipients may be more pronounced and varied compared with younger adults. There are multiple factors that may impact medication taking in older adults and each requires consideration, including level of dependence, living arrangements, level of mobility and manual dexterity, vision and memory, and social situation. To better identify the gaps in support, patients' current perspectives around medication taking and how they cope after transplantation must be explored. Therefore, this study aimed to identify how older adult transplant recipients currently manage their anti-rejection medicine regimen. Participants described several strategies around how they manage a complex medication regimen. These included cues such as an alarm and linking the time they should take their medication to already established habits such as eating meals. Most participants discussed at length their relationships, and it seems that these relationships are often crucial to post-transplant positivity. Additionally, extreme gratitude to the donor, relative improvement in their life quality (compared with the rapid deterioration in their health when on dialysis), and fear of consequences (particularly graft failure) were important facilitators of self-care and served as timely reminders to prioritise one's own health. To foster more robust medication-taking habits, future education needs to be tailored to each individual patient and include details about how to link medication taking to already established routines (coined 'habit stacking').

Utilizing Technology for Diet and Exercise Change in Complex Chronic Conditions Across Diverse Environments (U-DECIDE): Protocol for a Randomized Controlled Trial.

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. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12620001282976; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378337. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37556.

Dialysis modality utilization patterns and mortality in older persons initiating dialysis in Australia and New Zealand.

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.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

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.

Prebiotic Supplementation in Kidney Transplant Recipients for Preventing Infections and Gastrointestinal Upset: A Randomized Controlled Feasibility Study.

OBJECTIVES: Modulating the large intestinal microbiome of kidney transplant recipients (KTRs) may reduce infectious complications. The aim of this study is to assess the feasibility of a randomized controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in KTRs. (DESIGN) AND METHODS: Acute KTRs were recruited to a double-blind, placebo-controlled, randomized trial at a single kidney transplant center. Patients were provided with prebiotics or placebo for 7 weeks. The primary outcome was feasibility, defined as recruitment of ≥80% of eligible people within 6 months. Secondary outcomes included adherence and tolerability, participant retention in trial, proportions of participants providing serum and stool specimens, self-reported quality of life, gastrointestinal symptoms, and infection events. RESULTS: During the 7-week period, 72 patients met eligibility criteria, of whom 60 (83%) consented to participate (mean ± standard deviation age 53 ± 12 years; 62% males). Fifty-six (78%) participants were randomized (27 interventions and 29 controls). Although participants receiving intervention experienced reduced gastrointestinal symptoms (-0.28 [interquartile range, IQR -0.67 to 0.08] vs. -0.07 [IQR -0.27 to 0], P = .03), both control and intervention groups were similar in adherence (67% vs. 72%, P = .36), tolerability (56% vs. 62%, P = .64), quality of life (-0.2 [IQR -0.6 to 0] vs. -0.2 [IQR -0.8 to 0], P = .82), and infection events (33% vs. 34%, P = .83). Blood and stool samples were collected from ≥90% of participants in both groups. CONCLUSIONS: It is feasible to recruit and retain acute KTRs in a randomized, placebo-controlled trial examining the effect of prebiotics on infections and gastrointestinal symptoms. This study also showed that prebiotics significantly reduced gastrointestinal symptoms.

Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical Trial.

BACKGROUND: Supervised lifestyle interventions have the potential to significantly improve physical activity and fitness in patients with CKD. METHODS: To assess the efficacy of a lifestyle intervention in patients with CKD to improve cardiorespiratory fitness and exercise capacity over 36 months, we conducted a randomized clinical trial, enrolling 160 patients with stage 3-4 CKD, with 81 randomized to usual care and 79 to a 3-year lifestyle intervention. The lifestyle intervention comprised care from a multidisciplinary team, including a nephrologist, nurse practitioner, exercise physiologist, dietitian, diabetes educator, psychologist, and social worker. The exercise training component consisted of an 8-week individualized and supervised gym-based exercise intervention followed by 34 months of a predominantly home-based program. Self-reported physical activity (metabolic equivalent of tasks [METs] minutes per week), cardiorespiratory fitness (peak O2 consumption [VO2peak]), exercise capacity (maximum METs and 6-minute walk distance) and neuromuscular fitness (grip strength and get-up-and-go test time) were evaluated at 12, 24, and 36 months. RESULTS: The intervention increased the percentage of patients meeting physical activity guideline targets of 500 MET min/wk from 29% at baseline to 63% at 3 years. At 12 months, both VO2peak and METs increased significantly in the lifestyle intervention group by 9.7% and 30%, respectively, without change in the usual care group. Thereafter, VO2peak declined to near baseline levels, whereas METs remained elevated in the lifestyle intervention group at 24 and 36 months. After 3 years, the intervention had increased the 6-minute walk distance and blunted declines in the get-up-and-go test time. CONCLUSIONS: A 3-year lifestyle intervention doubled the percentage of CKD patients meeting physical activity guidelines, improved exercise capacity, and ameliorated losses in neuromuscular and cardiorespiratory fitness.

Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment.

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n = 594,881) and SCC (n = 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk = 45.45%, 95% confidence interval = 33.14-58.19%) and SCC (absolute risk = 44.12%, 95% confidence interval = 32.08-56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve = 0.77 vs. 0.75, P = 0.0691) and SCC (area under the curve = 0.84 vs. 0.82, P = 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R2 = 0.21 vs. 0.19, P = 3.2 × 10-3; SCC R2 = 0.30 vs. 0.27, P = 4.6 × 10-4).

Pharmacokinetic and Pharmacodynamic Considerations in Relation to Calcineurin Usage in Elderly Kidney Transplant Recipients.

This review summarizes how possible age-related changes in tacrolimus and cyclosporine pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future. Advancing biological age leads to physiological changes that can affect drug absorption, distribution, metabolism and excretion, as well as immune system responsiveness. Some studies have shown that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors, suggesting that doses may need to be lowered in elderly recipients. Only one study has examined how aging effects drug target enzyme activity and demonstrated that age does not correlate with the calcineurin inhibitor half-maximal inhibitory concentration. Several studies have shown elderly kidney transplant recipients have increased risk of both morbidity and mortality, compared to younger adults due to increased susceptibility to immunosuppressant side effects, particularly cardiovascular disease, infection and malignancy. Current immunosuppressant dosing and monitoring protocols often make no adjustments for age. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established. Blood draw by micro-sampling may be useful for drug monitoring in this cohort in the future, as blood collection is minimally invasive and less painful than venepuncture. Micro-sampling could also make further pharmacokinetic, pharmacodynamics and outcome studies in the elderly more feasible.

Impact of deceased donor with acute kidney injury on subsequent kidney transplant outcomes-an ANZDATA registry analysis.

BACKGROUND: The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. MATERIAL AND METHODS: This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. RESULTS: The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68). CONCLUSION: Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

Dialysis initiation in older persons across centres and over time in Australia and New Zealand.

AIM: With improved life expectancy over time, the burden of kidney failure resulting in kidney replacement therapy (KRT) in older persons is increasing. This study aimed to describe the age distribution at dialysis initiation in Australia and New Zealand (ANZ) across centres and over time. METHODS: Adults initiating dialysis as first KRT in ANZ from 1999 to 2018 reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry were included. The primary outcomes were the age distribution and the proportion of older persons (75 years and older) initiating dialysis across centres and over time. Secondary outcomes were characterization of the older population compared with younger people and differences in dialysis modality and treatment trajectories between groups. RESULTS: Over the study period, 55 382 people initiated dialysis as first KRT, including 10 306 older persons, in 100 centres. Wide variation in age distribution across states/countries was noted, although the proportion of older persons at dialysis initiation did not significantly change over time (from 13% in 1999 to 19% in 2003, then remaining stable thereafter). Older persons were less likely to be treated with home therapies compared with younger people. Older persons were mostly Caucasians; had higher socioeconomic position, more cardiovascular comorbidities and higher eGFR at baseline; and resided in major cities. Higher proportions of older persons per centre were noted in privately funded facilities. CONCLUSION: Wide variations were noted in the proportions of older persons initiating dialysis across centres and states/country, which were associated with different case-mix across regions, particularly in terms of ethnicity, remoteness and socioeconomic advantage.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. CONCLUSIONS: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation.

BACKGROUND: There has been limited study of the prevalence of gastrointestinal symptoms and their impact on the quality of life (QOL) in kidney transplant recipients. The aim of this study was to examine the prevalence and predictors of gastrointestinal symptoms and the association with QOL in kidney transplant recipients. METHODS: All chronic kidney transplant recipients at the Princess Alexandra Hospital were provided with 3 questionnaires, the Gastrointestinal Quality of Life Index (GIQLI), the Gastrointestinal Symptoms Rating Scale (GSRS), and Structured Assessment of Gastrointestinal Symptoms (SAGIS) scale, to ascertain QOL impairment and to screen gastrointestinal symptom severity. Linear regression was used to determine the predictors of gastrointestinal QOL and gastrointestinal symptom severity. RESULTS: Of the 343 participants, the median age was 47 (interquartile range [IQR] 36-55) years, 58% were men, 79% were white, 39% had chronic glomerulonephritis, 83% had received their first graft, and median time since transplant was 6.3 (IQR 1.8-13.1) years. Using GSRS, 88% of participants reported at least 1 gastrointestinal symptom, most commonly indigestion (57%) and diarrhea (54%). Using GIQLI, 42% and 38% of participants reported mild and moderate QOL impairment, respectively. Gastrointestinal symptoms were predicted by female sex (coefficient -0.11, 95% CI -0.21 to -0.02) and mycophenolate (coefficient 0.0001, 95% CI 0.0001 to 0.0002), and were associated with poorer QOL (coefficient -0.38, 95% CI -0.45 to -0.30). Similar findings were observed using SAGIS for gastrointestinal symptoms. CONCLUSIONS: Gastrointestinal symptoms are frequent in kidney transplant recipients, particularly in women and those receiving mycophenolate, and are strongly associated with poorer QOL.

Characteristics of the gastrointestinal microbiota in paired live kidney donors and recipients.

BACKGROUND: There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery. AIM: To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation. METHODS: Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing. RESULTS: The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post-transplant, reflected in reductions of the mean (±SD) richness values (156 ± 46.5 to 116 ± 38.6, p = 0.002), and Shannon diversity (3.57 ± 0.49 to 3.14 ± 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post-transplant (26-fold increase from 0.16 ± 0.0091 to 4.6 ± 0.3; p = 0.006; FDR = 0.12). Functionally, the post-transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2-fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6-fold; p = 0.006; FDR = 0.14). CONCLUSION: Live donor kidney transplantation and standard care post-transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.

Multicenter registry analysis comparing survival on home hemodialysis and kidney transplant recipients in Australia and New Zealand.

BACKGROUND: In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. METHODS: The Australia and New Zealand Dialysis and Transplant Registry was used to include incident HHD patients on Day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan-Meier product-limit method comparing HHD patients with subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. RESULTS: The study compared 1411 HHD patients with 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared with HHD patients [LD adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.46-0.71; SCD HR = 0.65 95% CI 0.52-0.79], the risk of mortality was comparable between ECD recipients and HHD patients (HR = 0.90, 95% CI 0.73-1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared with HHD patients. CONCLUSIONS: This large registry study showed that kidney transplant offers a survival benefit compared with HHD but that this advantage is not significant for ECD recipients.