The randomized controlled trial (NAVKIDS2) of a patient navigator program created for children with chronic kidney disease.

Patient navigators enable adult patients to circumnavigate complex health systems, improving access to health care and outcomes. Here, we aimed to evaluate the effects of a patient navigation program in children with chronic kidney disease (CKD). In this multi-center, randomized controlled trial, we randomly assigned children (aged 0-16 years) with CKD stages 1-5 (including children on dialysis or with kidney transplants), from low socioeconomic status backgrounds, and/or residing in remote areas, to receive patient navigation at randomization (immediate) or at six months (waitlist). The primary outcome was self-rated health (SRH) of participating children at six months, using intention to treat analysis. Secondary outcomes included caregivers' SRH and satisfaction with health care, children's quality of life, hospitalizations, and missed school days. Repeated measures of the primary outcome from baseline to six months were analyzed using cumulative logit mixed effects models. Semi-structured interviews were thematically evaluated. Of 398 screened children, 162 were randomized (80 immediate and 82 waitlist); mean age (standard deviation) of 8.8 (4.8) years with 64.8% male. SRH was not significantly different between the immediate and wait-listed groups at six months. There were also no differences across all secondary outcomes between the two groups. Caregivers' perspectives were reflected in seven themes: easing mental strain, facilitating care coordination, strengthening capacity to provide care, reinforcing care collaborations, alleviating family tensions, inability to build rapport and unnecessary support. Thus, in children with CKD, self-rated health may not improve in response to a navigator program, but caregivers gained skills related to providing and accessing care.

Experiences of Indigenous Patients Receiving Dialysis: Systematic Review of Qualitative Studies.

RATIONALE & OBJECTIVE: Indigenous People suffer a high burden of kidney disease. Those receiving maintenance dialysis have worse outcomes compared with similarly treated non-Indigenous patients. We characterized the experiences of Indigenous patients receiving dialysis in British-colonized countries to gain insights into which aspects of kidney care may benefit from improvement. STUDY DESIGN: A systematic review of published qualitative interview studies. SETTING & STUDY POPULATIONS: Indigenous Peoples aged 18 years and over, receiving hemodialysis or peritoneal dialysis in British-colonized countries. SELECTION CRITERIA FOR STUDIES: Search terms for Indigenous Peoples, dialysis, and qualitative research were entered into Medline, Embase, PsycINFO, and CINAHL and searched from inception to January 5, 2023. DATA EXTRACTION: Characteristics of each study were extracted into Microsoft Excel for quality assessment. ANALYTICAL APPROACH: Data were analyzed using thematic synthesis. RESULTS: The analysis included 28 studies involving 471 participants from Australia, New Zealand, Canada, and the United States. We identified four themes: centrality of family and culture (continuing dialysis for family, gaining autonomy through shared involvement, balancing primary responsibility to care for family); marginalization due to structural and social inequities (falling through gaps in primary care intensifying shock, discriminated against and judged by specialists, alienated and fearful of hospitals, overwhelmed by travel, financial and regimental burdens); vulnerability in accessing health care (need for culturally responsive care, lack of language interpreters, without agency in decision-making, comorbidities compounding complexity of self-management); and distress from separation from community (disenfranchisement and sorrow when away for dialysis, inability to perpetuate cultural continuity, seeking a kidney transplant). LIMITATIONS: We only included articles published in English. CONCLUSIONS: Indigenous patients receiving dialysis experience inequities in health care that compound existing accessibility issues caused by colonization. Improving the accessibility and cultural responsiveness of dialysis and kidney transplant services in collaboration with Indigenous stakeholders holds promise to enhance the experience of Indigenous patients receiving dialysis. PLAIN-LANGUAGE SUMMARY: Worldwide Indigenous populations suffer a high incidence of chronic disease leading to lower life expectancy, particularly for kidney disease, an insidious condition requiring long-term dialysis treatment. By listening to Indigenous dialysis patients' stories, we hoped to understand how to improve their experience. We gathered 28 qualitative research studies from four countries reporting Indigenous adults' experiences of dialysis. They described lacking awareness of kidney disease, poor access to health services, systemic racism, inadequate cultural safety, and being dislocated from family, community, and culture. These findings indicate that respectful collaboration with Indigenous Peoples to craft and implement policy changes holds promise to improve prevention, integrate culturally responsive health care practices, and provide better access to local dialysis services and opportunities for kidney transplants.

Improving Diverse and Equitable Involvement of Patients and Caregivers in Research in CKD: Report of a Better Evidence and Translation-Chronic Kidney Disease (BEAT-CKD) Workshop.

Patient and caregiver involvement can enhance the uptake and impact of research, but the involvement of patients and caregivers who are underserved and marginalized is often limited. A better understanding of how to make involvement in research more broadly accessible, supportive, and inclusive for patients with chronic kidney disease (CKD) and caregivers is needed. We conducted a national workshop involving patients, caregivers, clinicians, and researchers from across Australia to identify strategies to increase the diversity of patients and caregivers involved in CKD research. Six themes were identified. Building trust and a sense of safety was considered pivotal to establishing meaningful relationships to support knowledge exchange. Establishing community and connectedness was expected to generate a sense of belonging to motivate involvement. Balancing stakeholder goals, expectations, and responsibilities involved demonstrating commitment and transparency by researchers. Providing adequate resources and support included strategies to minimize the burden of involvement for patients and caregivers. Making research accessible and relatable was about nurturing patient and caregiver interest by appealing to intrinsic motivators. Adapting to patient and caregiver needs and preferences required tailoring the approach for individuals and the target community. Strategies and actions to support these themes may support more diverse and equitable involvement of patients and caregivers in research in CKD.

Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Longitudinal associations between socioeconomic position and overall health of children with chronic kidney disease and their carers.

BACKGROUND: Disadvantaged socioeconomic position (SEP) is an important predictor of poor health in children with chronic kidney disease (CKD). The time course over which SEP influences the health of children with CKD and their carers is unknown. METHODS: This prospective longitudinal study included 377 children, aged 6-18 years with CKD (stages I-V, dialysis, and transplant), and their primary carers. Mixed effects ordinal regression was performed to assess the association between SEP and carer-rated child health and carer self-rated health over a 4-year follow-up. RESULTS: Adjusted for CKD stage, higher family household income (adjusted odds ratio (OR) (95% CI) 3.3, 1.8-6.0), employed status of primary carers (1.7, 0.9-3.0), higher carer-perceived financial status (2.6, 1.4-4.8), and carer home ownership (2.2, 1.2-4.0) were associated with better carer-rated child health. Household income also had a differential effect on the carer's self-rated health over time (p = 0.005). The predicted probabilities for carers' overall health being 'very good' among lower income groups at 0, 2, and 4 years were 0.43 (0.28-0.60), 0.34 (0.20-0.51), and 0.25 (0.12-0.44), respectively, and 0.81 (0.69-0.88), 0.84 (0.74-0.91), and 0.88 (0.76-0.94) for carers within the higher income group. CONCLUSIONS: Carers and their children with CKD in higher SEP report better overall child and carer health compared with those in lower SEP. Carers of children with CKD in low-income households had poorer self-rated health compared with carers in higher-income households at baseline, and this worsened over time. These cumulative effects may contribute to health inequities between higher and lower SEP groups over time. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

School attendance and sport participation amongst children with chronic kidney disease: a cross-sectional analysis from the Kids with CKD (KCAD) study.

BACKGROUND: School attendance and life participation, particularly sport, is a high priority for children with chronic kidney disease (CKD). This study is aimed at assessing the association between CKD stage, sports participation, and school absences in children with CKD. METHODS: Using data from the binational Kids with CKD study (ages 6-18 years, n = 377), we performed multivariable regression to evaluate the association between CKD stage, school absences, and sports participation. RESULTS: Overall, 62% of participants played sport with the most frequent sport activities engaged in being swimming (17%) and soccer (17%). Compared to children with CKD 1-2, the incidence rate ratios (IRR) (95% CI) for sports participation amongst children with CKD 3-5, dialysis, or transplant were 0.84 (0.64-1.09), 0.59 (0.39-0.90), and 0.75 (0.58-0.96), respectively. The median (IQR) days of school absences within a four-week period were 1 day (0-1), with children on dialysis reporting the highest number of school absences (9 days (5-15)), followed by transplant recipients (2 days (1-7)), children with CKD 3-5 (1 day (0-3)), and with CKD 1-2 (1 day (0-3)). Duration of CKD modified the association between CKD stage and school absences, with children with a transplant experiencing a higher number of missed school days with increasing duration of CKD, but not in children with CKD 1-5 or on dialysis (p-interaction < 0.01). CONCLUSIONS: Children receiving dialysis and with a kidney transplant had greater school absences and played fewer sports compared to children with CKD stages 1-2. Innovative strategies to improve school attendance and sport participation are needed to improve life participation of children with CKD.

Longitudinal assessment of the health-related quality of life of children and adolescents with chronic kidney disease.

In this multi-center longitudinal cohort study conducted in Australia and New Zealand, we assessed the trajectories of health-related quality of life (HRQoL) in children with chronic kidney disease (CKD) over time. A total of 377 children (aged 6-18 years) with CKD stages 1-5 (pre-dialysis), dialysis, or transplant, were followed biennially for four years. Multi Attribute Utility (MAU) scores of HRQoL were measured at baseline and at two and four years using the McMaster Health Utilities Index Mark 3 tool, a generic multi-attribute, preference-based system. A multivariable linear mixed model was used to assess the trajectories of HRQoL over time in 199 children with CKD stage 1-5, 43 children receiving dialysis and 135 kidney transplant recipients. An interaction between CKD stage at baseline and follow-up time indicated that the slopes of the HRQoL scores differed between children by CKD stage at inception. Over half of the cohort on dialysis at baseline had received a kidney transplant by the end of year four and the MAU scores of these children increased by a meaningful amount averaging 0.05 (95% confidence interval 0.01 to 0.09) per year in comparison to those who were transplant recipients at baseline. The mean difference between baseline and year two MAU scores was 0.09 (95% confidence interval -0.05, 0.23), (Cohen's d effect size 0.31). Thus, improvement in HRQoL over time of children on dialysis at baseline was likely to have been driven by their transition from dialysis to transplantation. Additionally, children with CKD stage 1-5 and transplant recipients at baseline had no changes in their disease stage or treatment modality and experienced stable HRQoL over time.

Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group.

Cardiovascular disease is the leading cause of death in patients receiving hemodialysis. Currently, there is no standardized definition of myocardial infarction (MI) for patients receiving hemodialysis. Through an international consensus process MI was established as the core CVD measure for this population in clinical trials. The Standardised Outcomes in Nephrology Group-Hemodialysis (SONG-HD) initiative convened a multidisciplinary, international working group to address the definition of MI in this population. On the basis of current evidence, the working group recommends using the Fourth Universal Definition of Myocardial Infarction with specific caveats with regard to the interpretation of "ischemic symptoms" and performing a baseline 12-lead electrocardiogram to facilitate interpretation of acute changes on subsequent tracings. The working group does not recommend obtaining baseline cardiac troponin values, though does recommend obtaining serial cardiac biomarkers in settings where ischemia is suspected. The application of an evidence-based uniform definition should increase the reliability and accuracy of trial results.

Long-term Trends in Infection-Related Mortality in Adults Treated With Maintenance Dialysis.

RATIONALE & OBJECTIVE: Infection is 1 of the top 3 causes of death in patients receiving maintenance dialysis. We evaluated the trends over time and risk factors for infection-related deaths among people receiving dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We included all adults who began dialysis between 1980 and 2018 in Australia and New Zealand. EXPOSURE: Age, sex, dialysis modality, and dialysis era. OUTCOME: Infection-related death. ANALYTICAL APPROACH: Incidence was described and standardized mortality ratios (SMR) calculated for infection-related death. Fine-Gray subdistribution hazards models were fitted, with non-infection-related death and kidney transplantation treated as competing events. RESULTS: The study comprised 46,074 patients who received hemodialysis and 20,653 who were treated with peritoneal dialysis who were followed for 164,536 and 69,846 person-years, respectively. There were 38,463 deaths during the follow-up period, 12% of which were ascribed to infection. The overall rate of mortality from infection (per 10,000 person-years) was 185 and 232 for patients treated with hemodialysis and peritoneal dialysis, respectively. The rates were 184 and 219 for males and females, respectively; and 99, 181, 255, and 292 for patients aged 18-44, 45-64, 65-74, 75 years and over, respectively. The rates were 224 and 163 for those commencing dialysis in years 1980-2005 and 2006-2018, respectively. The overall SMR declined over time, from 37.1 (95% CI, 35.5-38.8) in years 1980-2005 to 19.3 (95% CI, 18.4-20.3) in years 2006-2018, consistent with the declining 5-year SMR trend (P<0.001). Infection-related mortality was associated with being female, older age, and Aboriginal and/or a Torres Strait Islander or Maori. LIMITATIONS: Mediation analyses defining the causal relationships between infection type and infection-related death could not be undertaken as disaggregating the data was not feasible. CONCLUSIONS: The excess risk of infection-related death in patients on dialysis has improved substantially over time but remains more than 20 times higher than in the general population.

Improving Clinical Care for Children With CKD: A Report From a National Kidney Foundation Scientific Workshop.

Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) has rarely included the perspectives of providers from a variety of health care disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and a half-day workshop that convened a multidisciplinary group of physicians, allied health care professionals, and pediatric patients with CKD and their parents, with the goal of developing key clinical recommendations regarding best practices for the clinical management of pediatric patients living with CKD. The key clinical recommendations pertained to 5 broad topics: addressing the needs of patients and parents/caregivers; modifying the progression of CKD; clinical management of CKD-mineral and bone disorder and growth retardation; clinical management of anemia, cardiovascular disease, and hypertension; and transition and transfer of pediatric patients to adult nephrology care. This report describes the recommendations generated by the participants who attended the workshop.

The Impact of the COVID-19 Pandemic on Patients With CKD: Systematic Review of Qualitative Studies.

RATIONALE & OBJECTIVE: COVID-19 disproportionately affects people with comorbidities, including chronic kidney disease (CKD). We describe the impact of COVID-19 on people with CKD and their caregivers. STUDY DESIGN: A systematic review of qualitative studies. SETTING & STUDY POPULATIONS: Primary studies that reported the experiences and perspectives of adults with CKD and/or caregivers were eligible. SEARCH STRATEGY & SOURCES: MEDLINE, Embase, PsycINFO, CINAHL searched from database inception to October 2022. DATA EXTRACTION: Two authors independently screened the search results. Full texts of potentially relevant studies were assessed for eligibility. Any discrepancies were resolved by discussion with another author. ANALYTICAL APPROACH: A thematic synthesis was used to analyze the data. RESULTS: Thirty-four studies involving 1,962 participants were included. Four themes were identified: exacerbating vulnerability and distress (looming threat of COVID-19 infection, intensifying isolation, aggravating pressure on families); uncertainty in accessing health care (overwhelmed by disruption of care, confused by lack of reliable information, challenged by adapting to telehealth, skeptical about vaccine efficacy and safety); coping with self-management (waning fitness due to decreasing physical activity, diminishing ability to manage diet, difficulty managing fluid restrictions, minimized burden with telehealth, motivating confidence and autonomy); and strengthening sense of safety and support (protection from lockdown restrictions, increasing trust in care, strengthened family connection). LIMITATIONS: Non-English studies were excluded, and inability to delineate themes based on stage of kidney and treatment modality. CONCLUSIONS: Uncertainty in accessing health care during the COVID-19 pandemic exacerbated vulnerability, emotional distress, and burden, and led to reduced capacity to self-manage among patients with CKD and their caregivers. Optimizing telehealth and access to educational and psychosocial support may improve self-management and the quality and effectiveness of care during a pandemic, mitigating potentially catastrophic consequences for people with CKD. PLAIN-LANGUAGE SUMMARY: During the COVID-19 pandemic, patients with chronic kidney disease (CKD) faced barriers and challenges to accessing care and were at an increased risk of worsened health outcomes. To understand the perspectives about the impact of COVID-19 among patients with CKD and their caregivers, we conducted a systematic review of 34 studies involving 1,962 participants. Our findings demonstrated that uncertainty in accessing care during the COVID-19 pandemic exacerbated the vulnerability, distress, and burden of patients and impaired their abilities for self-management. Optimizing the use of telehealth and providing education and psychosocial services may mitigate the potential consequences for people with CKD during a pandemic.

A viewpoint describing the American Society of Transplantation rationale to conduct a comprehensive patient survey assessing unmet immunosuppressive therapy needs.

This viewpoint aims to "set the stage" and provide the rationale for the proposed development of a large-scale, comprehensive survey assessing transplant patients' perceived unmet immunosuppressive therapy needs. Research in organ transplantation has historically focused on reducing the incidence and impact of rejection on allograft survival and minimizing or eliminating the need for chronic immunosuppressive therapies. There has been less emphasis and investment in therapies to improve patient-reported outcomes including health-related quality of life and side-effects. Patient-focused drug development (PFDD) is a new and important emphasis of the Food and Drug Administration (FDA) that provides a guiding philosophy for incorporating the patient experience into drug development and evaluation. The American Society of Transplantation (AST) Board of Directors commissioned this working group to prepare for the conduct of a comprehensive patient survey assessing unmet immunosuppressive therapy needs. This paper aims to describe the basis for why it is important to conduct this survey and briefly outline the plan for broad stakeholder engagement to ensure the information gained is diverse, inclusive, and relevant for advancing PFDD in organ transplant recipients.

Baseline characteristics of participants in the NAVKIDS2 trial: a patient navigator program in children with chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD. METHODS: The NAVKIDS2 trial is a multi-center, waitlisted, randomized controlled trial of patient navigators in children with CKD conducted at five sites across Australia. Children (0-16 years) with CKD from low socioeconomic status rural or remote areas were randomized to an intervention group or a waitlisted control group (to receive intervention after 6 months). The study primary and secondary endpoints include the self-rated health (SRH) (primary), and utility-based quality of life, progression of kidney dysfunction of the child, SRH, and satisfaction with healthcare of the caregiver at 6 months post-randomization. RESULTS: The trial completed recruitment in October 2021 with expected completion of follow-up by October 2022. There were 162 patients enrolled with 80 and 82 patients randomized to the immediate intervention and waitlisted groups, respectively. Fifty-eight (36%) participants were from regional/remote areas, with a median (IQR) age of 9.5 (5.0, 13.0) years, 46% were of European Australian ethnicity, and 65% were male. A total of 109 children (67%) had CKD stages 1-5, 42 (26%) were transplant recipients, and 11 (7%) were receiving dialysis. CONCLUSION: The NAVKIDS2 trial is designed to evaluate the effectiveness of patient navigation in children with CKD from families experiencing socioeconomic disadvantage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Interventions for fatigue in people with kidney failure requiring dialysis.

BACKGROUND: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD). OBJECTIVES: We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies evaluating pharmacological and non-pharmacological interventions affecting levels of fatigue or fatigue-related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue-related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Ninety-four studies involving 8191 randomised participants were eligible. Pharmacological and non-pharmacological interventions were compared either to placebo or control, or to another pharmacological or non-pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high. In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis-Related Fatigue scale score): SMD -1.18, 95% CI -2.04 to -0.31; I2 = 87%) in HD. In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD -1.23, 95% CI -1.96 to -0.50; I2 = 93%) in HD. In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD -1.06, 95% CI -1.47, -0.65; I2 = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I2 = 59%) in HD. In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD -0.64, 95% CI -1.03 to -0.25; I2 = 75%) in HD. A wide range of heterogenous interventions and fatigue-related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data. Due to the paucity of studies, the effects of pharmacological and other non-pharmacological interventions on fatigue or fatigue-related outcomes, including non-physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive-behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta-blockers, anabolic steroids, glucose-enriched dialysate, or light therapy, were very uncertain. The effects of pharmacological and non-pharmacological treatments on death, cardiovascular diseases, vascular access, QoL, depression, anxiety, hypertension or diabetes were sparse. No studies assessed tiredness, exhaustion or asthenia. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS: Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

Synbiotics, prebiotics and probiotics for people with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability). OBJECTIVES: This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 µg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment. AUTHORS' CONCLUSIONS: We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.

Qualitative analysis of stakeholder perspectives on engaging Latinx patients in kidney-related research.

BACKGROUND: Latinx individuals are disproportionally burdened by kidney diseases compared to non-Latinx White individuals and are underrepresented in kidney-related research. We aimed to describe stakeholder perspectives on Latinx patient engagement in kidney-related research. METHODS: We conducted a thematic analysis of two online moderated discussions and an interactive online survey with open-text responses involving participants (i.e. stakeholders), with personal and/or professional experiences with Latinx patients with kidney diseases and their families/caregivers. RESULTS: Among the eight stakeholders (Female:75%; Latinx ethnicity:88%), there were three physicians, one nurse, one patient with kidney disease who received a kidney transplant, one policy maker, one Doctor of Philosophy, and one executive director of a non-profit health organization. We identified five themes. The majority of themes and their respective subthemes (in parentheses) reflected barriers to engagement: Lack of personal relevance (unable to relate to research staff and marketing resources, and unclear benefit of research to self, family, and community); fear and vulnerability (immigration concerns, stigma with seeking care, skepticism of Western medicine); logistical and financial barriers (limited opportunities to enroll in clinical trials, out-of-pocket costs, transportation issues); and distrust and asymmetry of power (related to limited English proficiency or health literacy, and provider bias). The last theme centered on stimulating interest and establishing trust in the research process. CONCLUSIONS: To overcome barriers to engagement in kidney-related research and establish trust among potential Latinx research participants, stakeholders recommended employing cultural responsiveness and community-based strategies. These strategies can help identify local health priorities, enhance research recruitment and retention strategies, and establish partnerships that continue to elevate research endeavors aiming to enhance the health of Latinx individuals with kidney diseases.

Australian Rural Caregivers' Experiences in Supporting Patients With Kidney Failure to Access Dialysis and Kidney Transplantation: A Qualitative Study.

RATIONALE & OBJECTIVE: Caregivers of patients with chronic kidney disease from rural communities play a crucial role in access to dialysis and transplantation, but they face many challenges including geographical distance, financial hardship, and limited support. This study aimed to inform strategies to overcome these challenges by describing the experiences of caregivers of patients with kidney failure from rural Australian communities in accessing kidney replacement therapy. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: 18 adult caregivers of Australian rural patients with kidney failure treated with dialysis or kidney transplantation. ANALYTICAL APPROACH: Semistructured interviews were conducted. Interview transcripts were thematically analyzed. RESULTS: The 18 participants were aged 20 to 78 years; 13 (72%) were female, and 13 (72%) were the spouse/partner of the patient. We identified 5 themes: devastating social isolation (difficult periods of separation, exclusion from peers, forced relocation); financial dependency and sacrifice (burgeoning out-of-pocket costs, disruption to work life, foregoing autonomy); ongoing psychological trauma (concern for neglect and stress on children, long-term emotional distress); overwhelmed by multifaceted roles and expectations (patient advocacy, uncertainty in navigating multiple health systems); and persistent burden of responsibility (loss of self-identity, ongoing travel requirements, scarcity of psychosocial support, unpreparedness for treatment regime). LIMITATIONS: The study was conducted in a high-income, English-speaking country with universal health insurance, which may limit the transferability of the findings. CONCLUSIONS: Australian rural caregivers of people with kidney failure treated by maintenance dialysis or transplantation experience an exhausting physical, financial, and psychological burden. Strategies to address these profound challenges are needed. PLAIN-LANGUAGE SUMMARY: This interview-based study elicited the challenges faced by people and family members who care for patients from rural towns who are receiving dialysis or kidney transplantation. The barriers and difficulties reported included traveling long distances, needing to move to larger towns and leaving their homes, feeling concerned for the long-term effects on their children, physical exhaustion, and financial issues. Additional efforts are needed to identify the means by which caregivers and their families in rural towns can obtain support to care for those with kidney failure.

D-mannose for preventing and treating urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted. OBJECTIVES: To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes). AUTHORS' CONCLUSIONS: There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.

Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease.

BACKGROUND: Anaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD. OBJECTIVES: We aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included. DATA COLLECTION AND ANALYSIS: Five authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE. MAIN RESULTS: We included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA. Compared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence). Compared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA. The effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain. None of the included studies reported life participation. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS: HIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.

Synbiotics, prebiotics and probiotics for solid organ transplant recipients.

BACKGROUND: Solid organ transplantation has seen improvements in both surgical techniques and immunosuppression, achieving prolonged survival. Essential to graft acceptance and post-transplant recovery, immunosuppressive medications are often accompanied by a high prevalence of gastrointestinal (GI) symptoms and side effects. Apart from GI side effects, long-term exposure to immunosuppressive medications has seen an increase in drug-related morbidities such as diabetes mellitus, hyperlipidaemia, hypertension, and malignancy. Non-adherence to immunosuppression can lead to an increased risk of graft failure. Recent research has indicated that any microbial imbalances (otherwise known as gut dysbiosis or leaky gut) may be associated with cardiometabolic diseases in the long term. Current evidence suggests a link between the gut microbiome and the production of putative uraemic toxins, increased gut permeability, and transmural movement of bacteria and endotoxins and inflammation. Early observational and intervention studies have been investigating food-intake patterns, various synbiotic interventions (antibiotics, prebiotics, or probiotics), and faecal transplants to measure their effects on microbiota in treating cardiometabolic diseases. It is believed high doses of synbiotics, prebiotics and probiotics are able to modify and improve dysbiosis of gut micro-organisms by altering the population of the micro-organisms. With the right balance in the gut flora, a primary benefit is believed to be the suppression of pathogens through immunostimulation and gut barrier enhancement (less permeability of the gut). OBJECTIVES: To assess the benefits and harms of synbiotics, prebiotics, and probiotics for recipients of solid organ transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 9 March 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials measuring and reporting the effects of synbiotics, prebiotics, or probiotics, in any combination and any formulation given to solid organ transplant recipients (any age and setting). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was independently carried out by two authors using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Five studies (250 participants) were included in this review. Study participants were adults with a kidney (one study) or liver (four studies) transplant. One study compared a synbiotic to placebo, two studies compared a probiotic to placebo, and two studies compared a synbiotic to a prebiotic. Overall, the quality of the evidence is poor. Most studies were judged to have unclear (or high) risk of bias across most domains. Of the available evidence, meta-analyses undertaken were of limited data from small studies. Across all comparisons, GRADE evaluations for all outcomes were judged to be very low certainty evidence. Very low certainty evidence implies that we are very uncertain about results (not estimable due to lack of data or poor quality). Synbiotics had uncertain effects on the change in microbiota composition (total plasma p-cresol), faecal characteristics, adverse events, kidney function or albumin concentration (1 study, 34 participants) compared to placebo. Probiotics had uncertain effects on GI side effects, infection rates immediately post-transplant, liver function, blood pressure, change in fatty liver, and lipids (1 study, 30 participants) compared to placebo. Synbiotics had uncertain effects on graft health (acute liver rejection) (2 studies, 129 participants: RR 0.73, 95% CI 0.43 to 1.25; 2 studies, 129 participants; I² = 0%), the use of immunosuppression, infection (2 studies, 129 participants: RR 0.18, 95% CI 0.03 to 1.17; I² = 66%), GI function (time to first bowel movement), adverse events (2 studies, 129 participants: RR 0.79, 95% CI 0.40 to 1.59; I² = 20%), serious adverse events (2 studies, 129 participants: RR 1.49, 95% CI 0.42 to 5.36; I² = 81%), death (2 studies, 129 participants), and organ function measures (2 studies; 129 participants) compared to prebiotics. AUTHORS' CONCLUSIONS: This review highlights the severe lack of high-quality RCTs testing the efficacy of synbiotics, prebiotics or probiotics in solid organ transplant recipients. We have identified significant gaps in the evidence. Despite GI symptoms and postoperative infection being the most common reasons for high antibiotic use in this patient population, along with increased morbidity and the growing antimicrobial resistance, we found very few studies that adequately tested these as alternative treatments. There is currently no evidence to support or refute the use of synbiotics, prebiotics, or probiotics in solid organ transplant recipients, and findings should be viewed with caution. We have identified an area of significant uncertainty about the efficacy of synbiotics, prebiotics, or probiotics in solid organ transplant recipients. Future research in this field requires adequately powered RCTs comparing synbiotics, prebiotics, and probiotics separately and with placebo measuring a standard set of core transplant outcomes. Six studies are currently ongoing (822 proposed participants); therefore, it is possible that findings may change with their inclusion in future updates.