Digital Physical Activity and Exercise Interventions for People Living with Chronic Kidney Disease: A Systematic Review of Health Outcomes and Feasibility.

Physical activity is essential to interrupt the cycle of deconditioning associated with chronic kidney disease (CKD). However, access to targeted physical activity interventions remain under-supported due to limited funding and specialised staff. Digital interventions may address some of these factors. This systematic review sought to examine the evidence base of digital interventions focused on promoting physical activity or exercise and their effect on health outcomes for people living with CKD. Electronic databases (PubMed, CINAHL, Embase, Cochrane) were searched from 1 January 2000 to 1 December 2023. Interventions (smartphone applications, activity trackers, websites) for adults with CKD (any stage, including transplant) which promoted physical activity or exercise were included. Study quality was assessed, and a narrative synthesis was conducted. Of the 4057 records identified, eight studies (five randomised controlled trials, three single-arm studies) were included, comprising 550 participants. Duration ranged from 12-weeks to 1-year. The findings indicated acceptability and feasibility were high, with small cohort numbers and high risk of bias. There were inconsistent measures of physical activity levels, self-efficacy, body composition, physical function, and psychological outcomes which resulted in no apparent effects of digital interventions on these domains. Data were insufficient for meta-analysis. The evidence for digital interventions to promote physical activity and exercise for people living with CKD is limited. Despite popularity, there is little evidence that current digital interventions yield the effects expected from traditional face-to-face interventions. However, 14 registered trials were identified which may strengthen the evidence-base.

Preferences of people with chronic kidney disease regarding digital health interventions that promote healthy lifestyle: qualitative systematic review with meta-ethnography.

OBJECTIVES: Diet and physical activity are crucial for people with chronic kidney disease (CKD) to maintain good health. Digital health interventions can increase access to lifestyle services. However, consumers' perspectives are unclear, which may reduce the capacity to develop interventions that align with specific needs and preferences. Therefore, this review aims to synthesise the preferences of people with CKD regarding digital health interventions that promote healthy lifestyle. DESIGN: Qualitative systematic review with meta-ethnography. DATA SOURCES: Databases Scopus, CENTRAL, MEDLINE, CINAHL and SPORTDiscus were searched between 2000 and 2023. ELIGIBILITY CRITERIA: Primary research papers that used qualitative exploration methods to explore the preferences of adults with CKD (≥18 years) regarding digital health interventions that promoted diet, physical activity or a combination of these health behaviours. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened title, abstract and full text. Discrepancies were resolved by a third reviewer. Consumers' quotes were extracted verbatim and synthesised into higher-order themes and subthemes. RESULTS: Database search yielded 5761 records. One record was identified following communication with a primary author. 15 papers were included. These papers comprised 197 consumers (mean age 51.0±7.2), including 83 people with CKD 1-5; 61 kidney transplant recipients; 53 people on dialysis. Sex was reported in 182 people, including 53% male. Five themes were generated regarding consumers' preferences for digital lifestyle interventions. These included simple instruction and engaging design; individualised interventions; virtual communities of care; education and action plans; and timely reminders and automated behavioural monitoring. CONCLUSION: Digital health interventions were considered an important mechanism to access lifestyle services. Consumers' preferences are important to ensure future interventions are tailored to specific needs and goals. Future research may consider applying the conceptual framework of consumers' preferences in this review to develop and evaluate the effect of a digital lifestyle intervention on health outcomes. PROSPERO REGISTRATION NUMBER: CRD42023411511.

Patient and Clinician Perspectives on the use of Remote Patient Monitoring in Peritoneal Dialysis.

Background: Numerous factors influence patient recruitment to, and retention on, peritoneal dialysis (PD), but a major challenge is a perceived "inaccessibility" to treating clinicians. It has been suggested that remote patient monitoring (RPM) could be a means of improving such oversight and, thereby, uptake of PD. Objective: To describe patient and clinician perspectives toward RPM and the use of applications (Apps) suitable for mobiles, tablets, or computers to support the provision of PD care. Design: Qualitative design using semi-structured interviews. Setting: All patient participants perform PD treatment at home under the oversight of an urban PD unit in Sydney, Australia. Patient and clinician interviews were conducted within the PD unit. Participants: 14 participants (5 clinicians [2 nephrologists, 3 PD nurses] and 9 patients treated with PD). Methods: Semi-structured interviews were conducted using interview guides tailored for clinician and patient participants. Transcripts were coded and analyzed by a single researcher using thematic analysis. Results: Six themes were identified: perceived benefits of RPM implementation (offering convenience and efficiency, patient assurance through increased surveillance, more complete data and monitoring adherence), uncertainty regarding data governance (protection of personal data, data reliability), reduced patient engagement (transfer of responsibility leading to complacency), changing patient-clinician relationships (reduced patient-initiated communication, the need to maintain patient independence), increased patient and clinician burden (inadequate technological literacy, overmanagement leading to frequent treatment changes), and clinician preference influencing patient behavior. Limitations: The interviews were conducted in English only and with participants from a single urban dialysis unit, which may limit generalizability. Conclusions: For patients and clinicians, advantages from the use of RPM in PD may include increased patient confidence and assurance, improved treatment oversight, more complete data capture, and overcoming barriers to data documentation. Careful patient selection and patient and clinician education may help to optimize the benefits of RPM, maintain patient independence, and reduce the risks of patient disengagement. The use of an App may support RPM; however, participants expressed concerns about increasing the burden on some patients through the use of unfamiliar technology. Human Research Ethics Committee Approval Number: CH62/6/2019-028.

Contexte: De nombreux facteurs influent sur le recrutement et la rétention des patients en dialyse péritonéale (DP); un des principaux défis étant une impression d'« inaccessibilité ¼ aux cliniciens traitants. La télésurveillance des patients (TSP) a été suggérée comme possible moyen d'améliorer le suivi et, par conséquent, l'adhésion des patients à la DP. Objectif: Décrire les points de vue des patients et des cliniciens à l'égard de la TSP et de l'utilisation d'applications adaptées aux téléphones intelligents, aux tablettes ou aux ordinateurs pour aider à la prise en charge de la DP. Type d'étude: Étude qualitative menée par le biais d'entretiens semi-structurés. Cadre: Tous les patients suivant des traitements de DP à domicile sous la supervision de l'unité de DP d'un centre urbain de Sydney (Australie). Les entretiens avec les patients et les cliniciens ont été menés au sein de l'unité de DP. Participants à l'étude: 14 participants, soit 5 cliniciens (2 néphrologues, 3 infirmières et infirmiers en DP) et 9 patients sous DP. Méthodologie: Des entretiens semi-structurés ont été menés à l'aide de guides d'entrevue adaptés aux cliniciens et aux patients participants. Les transcriptions ont été codées, puis une analyse thématique par un seul chercheur a été réalisée. Résultats: Six thèmes ont été dégagés : 1) avantages perçus de la TSP (intervention pratique et efficace, patients rassurés par une surveillance accrue, données plus complètes et meilleur suivi de l'observance); 2) incertitude quant à la gouvernance des données (protection des données personnelles, fiabilité des données); 3) réduction de la participation des patients (transfert de responsabilité menant à la complaisance); 4) évolution de la relation patient-clinicien (réduction des échanges initiés par le patient, nécessité de maintenir l'indépendance du patient); 5) fardeau accru pour le patient et le clinicien (connaissances technologiques inadéquates, gestion excessive conduisant à de fréquents changements du traitement) et; 6) comportement du patient influencé par la préférence du clinicien. Limites: Les entretiens ont été menés uniquement en anglais, auprès de participants provenant d'une seule unité de dialyse en centre urbain, ce qui pourrait limiter la généralisabilité des résultats. Conclusion: Selon les patients et les cliniciens interrogés, la TSP en contexte de DP pourrait offrir plusieurs avantages : confiance et assurance accrues pour les patients, meilleure surveillance du traitement, saisie plus complète des données et suppression des entraves liées à la documentation des données. Une sélection rigoureuse des patients et une formation adéquate du patient et du clinicien pourraient contribuer à optimiser les avantages de la TSP, à maintenir l'indépendance du patient et à réduire les risques de désengagement. L'utilisation d'une application pourrait appuyer la TSP; des participants ont cependant exprimé des inquiétudes quant à une augmentation du fardeau pour certains patients moins familiers avec ce type de technologie. Numéro d'approbation du Comité d'éthique pour la recherche sur l'être humain : CH62/6/2019 ­ 028.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.

RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.

Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. METHODS: A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy-induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. RESULTS: We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76-1.35], I 2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71-2.45), I 2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09-4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68-2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58-2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6-54.7), I 2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4-79.3), I 2 = 95.1%] light chain levels. CONCLUSION: Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.

The Impact of Clinical Presentation on Survival in Patients Requiring Hemodialysis Catheters for Acute and Unplanned Dialysis: A Prospective Observational Study.

BACKGROUND: Most studies addressing hemodialysis initiation with a dialysis catheter focus on patients entering maintenance dialysis programs and exclude other patients, such as those with acute kidney injury (AKI), making interpretation and application of the results difficult for clinicians managing patients at the time of dialysis commencement. OBJECTIVE: To compare the survival of all patients requiring a catheter for hemodialysis access according to the nature of clinical presentation. DESIGN: Prospective observational. SETTING: An Australian tertiary renal unit. PATIENTS: All patients requiring a central venous catheter (CVC) for hemodialysis access between 2005 and 2015. MEASUREMENTS: Baseline comorbidities, demographics, and nature of clinical presentation. Data regarding each episode of dialysis access insufficiency and each CVC were collected. The primary outcome was all-cause mortality. METHODS: Patients were classified into 1 of 3 groups based on physician assessment at the time of presentation: patients believed to have AKI with expected renal recovery (AKI), patients considered to be entering the maintenance dialysis program without a functioning dialysis access (Maintenance Dialysis), patients unable to perform peritoneal dialysis, or use their existing hemodialysis access (Access Failure). Time-split multivariable Cox regression analyses were used to compare survival between groups. RESULTS: A total of 557 eligible patients had complete prospective data regarding CVC use and were included in the analyses. The majority of patients were in the AKI (246/557, 44%) and Maintenance Dialysis groups (182/557, 33%) compared with the Access Failure group (129/557, 23%). During a median follow-up of 3 years, 302 (54%) of the 557 patients died. Following adjustment, risk of all-cause mortality was higher in the AKI group (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.31-3.60, P = .001) during the first 2 years after catheter insertion and lower in years 2 to 4 (HR: 0.42, 95% CI: 0.20-0.88, P = .02) than in the reference Maintenance Dialysis group. No difference in mortality risk between the Access Failure and reference group was found. LIMITATIONS: Single-center study. Possible residual confounding owing to the observational study design. CONCLUSIONS: Patients requiring acute or unplanned hemodialysis experience high mortality, and the nature of clinical presentation does influence outcomes. Most notable is the greater early mortality experienced by patients with AKI compared to other patient groups. Prospective definition of the nature of unplanned dialysis initiation is important to accurately measure and improve outcomes in this high-risk patient population. HUMAN RESEARCH ETHICS COMMITTEE APPROVAL NUMBER: CH62/6/2017-042.

CONTEXTE: La plupart des études traitant de l'initiation d'un traitement d'hémodialyse avec cathéter portent sur des patients qui s'engagent dans un program de dialyze d'entretien et excluent les autres patients, notamment ceux atteints d'insuffisance rénale aiguë (IRA). Ceci rend difficiles l'interprétation et l'application des résultats pour les cliniciens qui traitent les patients à l'amorce de la dialyze. OBJECTIF: Comparer la survie de tous les patients nécessitant un cathéter pour l'accès à l'hémodialyse selon la nature du tableau clinique. TYPE D'ÉTUDE: Étude observationnelle prospective. CADRE: L'unité de néphrologie d'un center de soins tertiaires australien. SUJETS: Tous les patients qui, entre 2005 et 2015, ont eu besoin d'un cathéter veineux central (CVC) pour l'hémodialyse. MESURES: Les maladies concomitantes existantes et les données démographiques des patients, ainsi que la nature du tableau clinique. Les données concernant chaque CVC et épisode d'accès déficient ont été recueillies. Le principal critère de jugement était la mortalité toutes causes confondues. MÉTHODOLOGIE: Les patients ont été répartis dans trois groupes selon l'évaluation du médecin au moment de la présentation : patients soupçonnés d'IRA avec récupération rénale prévue (groupe « IRA ¼), patients sans accès fonctionnel pour la dialyze considérés comme entrant dans le program de dialyze d'entretien (groupe « dialyze d'entretien ¼), et les patients incapables de pratiquer la dialyze péritonéale ou d'utiliser leur accès vasculaire existant (groupe « échec de l'accès ¼). Des régressions de Cox multivariées à temps partagé ont été utilisées pour comparer la survie entre les groupes. RÉSULTATS: Ont été inclus dans les analyses les 557 patients admissibles pour lesquels on disposait de données prospectives complètes sur l'utilization d'un CVC. La majorité des patients se trouvaient dans les groupes « IRA ¼ (246/557; 44 %) et « dialyze d'entretien ¼ (182/557; 33 %); le groupe « échec de l'accès ¼ ne représentant que 23 % des patients inclus (129/557). Au cours d'un suivi médian de trois ans, 302 patients (54 %) sont décédés. Après correction, le risque de mortalité toutes causes confondues dans les deux premières années suivant l'insertion du cathéter était plus élevé dans le groupe IRA (RR : 2,01; IC à 95 % : 1,31-3,60; P = .001) que dans le groupe référence (dialyze d'entretien); mais moins élevé après 2 à 4 ans (RR : 0.42; IC 95 % : 0.20-0.88; P = .02). Aucune différence n'a été observée entre le groupe « échec de l'accès ¼ et le groupe de référence. LIMITES: L'étude est monocentrique et la nature observationnelle de l'étude sous-tend de possibles facteurs de confusion résiduels. CONCLUSION: Les patients nécessitant une hémodialyse aiguë ou non planifiée connaissent un taux de mortalité élevé, et la nature du tableau clinique influence les résultats. Le plus remarquable étant la mortalité précoce plus élevée des patients atteints d'IRA comparativement aux autres patients. Il est important de définir la nature prospective de l'amorce non planifiée de la dialyze afin de mesurer précisément les résultats dans cette population à haut risque, et de les améliorer.

Effect of a medium cut-off dialyzer on protein-bound uremic toxins and mineral metabolism markers in patients on hemodialysis.

INTRODUCTION: Hemodialysis (HD) with medium cut-off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25-60 kDa). However, the impact of MCO dialyzers on long-term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) provided an opportunity to assess the effect of MCO dialyzers on protein-bound uremic toxins and novel markers of mineral metabolism. METHODS: This exploratory sub-study of REMOVAL-HD evaluated changes in protein-bound solutes (total and free indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor-23 [iFGF23], fetuin-A and endogenous calciprotein particles [CPP-1 and CPP-2]). Mid-week, pre-HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models. FINDINGS: Eighty-nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (-26.8% [95%CI -39.7, -11.1], p = 0.001), which was sustained at Week 24 (-21.7% [95%CI -35.7, -4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin-A, CPP-1, or CPP-2. DISCUSSION: The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole-trimethoprim and temozolomide.

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Health-Related Quality of Life in People Across the Spectrum of CKD.

INTRODUCTION: People with chronic kidney disease (CKD) experience reduced quality of life (QoL) because of the high symptom and treatment burden. Limited data exist on the factors associated with overall and domain-specific QoL across all CKD stages. METHODS: Using data from a prospective, multinational study (Australia, New Zealand, Canada, and Spain) in 1696 participants with CKD, we measured overall and domain-specific QoL (pain, self-care, activity, mobility, anxiety/depression) using the EuroQoL, 5 dimension, 3 level. Multivariable linear regression and logistic modeling were used to determine factors associated with overall and domain-specific QoL. RESULTS: QoL for patients with CKD stages 3 to 5 (n = 787; mean, 0.81; SD, 0.20) was higher than in patients on dialysis (n = 415; mean, 0.76; SD, 0.24) but lower than in kidney transplant recipients (n = 494; mean, 0.84; SD, 0.21). Factors associated with reduced overall QoL (ß [95% confidence intervals]) included being on dialysis (compared with CKD stages 3-5: -0.06 [-0.08 to -0.03]), female sex (-0.03 [-0.05 to -0.006]), lower educational attainment (- 0.04 [-0.06 to -0.02), lacking a partner (-0.04 [-0.06 to -0.02]), having diabetes (-0.05 [-0.07 to -0.02]), history of stroke (-0.09 [-0.13 to -0.05]), cardiovascular disease (-0.06 [-0.08 to -0.03]), and cancer (-0.03 [-0.06 to -0.009]). Pain (43%) and anxiety/depression (30%) were the most commonly affected domains, with dialysis patients reporting decrements in all 5 domains. Predictors for domain-specific QoL included being on dialysis, presence of comorbidities, lower education, female sex, and lack of a partner. CONCLUSIONS: Being on dialysis, women with CKD, those with multiple comorbidities, lack of a partner, and lower educational attainment were associated with lower QoL across all stages of CKD.

Patient needs and priorities for patient navigator programmes in chronic kidney disease: a workshop report.

BACKGROUND AND OBJECTIVE: Patients with early chronic kidney disease (CKD) face challenges in accessing healthcare, including delays in diagnosis, fragmented speciality care and lack of tailored education and psychosocial support. Patient navigator programmes have the potential to improve the process of care and outcomes. The objective of this study is to describe the experiences of patients on communication, access of care and self-management and their perspectives on patient navigator programmes in early CKD. DESIGN, SETTING AND PARTICIPANTS: We convened a workshop in Australia with 19 patients with CKD (all stages including CKD Stage 1 to 5 not on dialysis, 5D (dialysis), and 5T (transplant)) and five caregivers. All of them were over 18 years and English-speaking. Transcripts from the workshop were analysed thematically. RESULTS: Four themes that captured discussions were: lost in the ambiguity of symptoms and management, battling roadblocks while accessing care, emotionally isolated after diagnosis and re-establishing lifestyle and forward planning. Five themes that focussed on patient navigator programmes were: trust and credibility, respecting patient choices and readiness to accept the programme, using accessible language to promote the programme, offering multiple ways to engage and communicate and maintaining confidentiality and privacy. Of the 17 features identified as important for a patient navigator programme, the top five were delivery of education, psychosocial support, lifestyle modification, communication and decision-making support and facilitating care. CONCLUSION: Patient navigator services can address gaps in services around health literacy, communication, psychosocial support and coordination across multiple healthcare settings. In comparison to the existing navigator programmes, and other services that are aimed at addressing these gaps, credible, accessible and flexible patient navigator programmes for patients with early CKD, that support education, decision-making, access to care and self-management designed in partnership with patients, may be more acceptable to patients.

A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study.

BACKGROUND: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. METHODS: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. RESULTS: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction -0.7 g/L, 95% CI -1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ -9.1 mg/L, 95% CI -14.4 to -3.7; kappa-FLC: Δ -5.7 mg/L, 95% CI -9.8 to -1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. CONCLUSIONS: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.

Impact of supplemental private health insurance on dialysis and outcomes.

BACKGROUND: The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients ispoorly understood. AIM: We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalitiesand patient outcomes. The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients is poorly understood. We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalities and patient outcomes. METHODS: All adult patients commencing ESKD treatment in New South Wales, Australia from 2000 to 2010 were identified using the Australia and New Zealand Dialysis and Transplant Registry. Data were linked to the state hospitalisation dataset to obtain insurance status, allowing the comparisons of mortality, ESKD treatment modality and health service utilisation between privately insured and public patients. RESULTS: The cohort of 5737 patients included 38% (n = 2152) with PHI. At 1 year after ESKD treatment initiation, PHI patients had lower mortality (hazard ratio 0.84, 95% confidence interval (CI) 0.74-0.95, P = 0.01), were more likely to be receiving home haemodialysis (HD) (odds ratio (OR) 1.38, 95% CI 1.01-1.89, P = 0.04), to have been transplanted (OR 1.75, 95% CI 1.25-2.46, P = 0.001) and used fewer hospital days (incidence rate ratio 0.85, 95% CI 0.74-0.96, P = 0.01). After adjustment, PHI patients were more likely to initiate ESKD treatment with facility-based HD (OR 1.22, 95% CI 1.01-1.46, P = 0.03) but were less likely to be started on peritoneal dialysis (OR 0.81, 95% CI 0.67-0.98, P = 0.03). CONCLUSION: Our findings suggest that supplemental PHI in Australia is associated with lower-risk ESKD treatment attributes and improved health outcomes. A greater understanding of the treatment pathways that deliver these outcomes may inform treatment for the broader ESKD treatment population.

One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study).

BACKGROUND: In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown. METHODS: To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35-74 years with CKD (stages 3-5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status. RESULTS: Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3-5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding. CONCLUSIONS: FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.

End-stage kidney disease in Fiji.

BACKGROUND: Chronic kidney disease is now a leading cause of death in Fiji. The country lacks even basic statistics about the incidence of end-stage kidney disease (ESKD) and presents significant challenges to conducting clinical research. AIM: To estimate the incidence and characteristics of ESKD in Fijian adults. METHODS: A retrospective cohort study was conducted of patients admitted to Colonial War Memorial Hospital in Suva, Fiji, in 2012. Suspected ESKD cases were identified from laboratory registers of renal function tests and confirmed through medical record review. Population data were from the Fijian Bureau of Statistics. RESULTS: Screening identified 1474 suspected ESKD cases. Following removal of 763 duplicates and cases with discrepant identifiers, 711 unique cases remained. An additional 552 cases met exclusion criteria, including acute kidney injury (247), failure to be admitted (131) and pre-existing ESKD diagnosis (103), leaving 159 cases of confirmed ESKD. Median age was 57 years (interquartile range 47-65). Crude and age-adjusted ESKD incidence rates were 753 per million population (pmp) (95% confidence interval (CI) 636-870) and 793 pmp (95% CI 669-916), respectively, rising to 938 pmp (95% CI 804-1072) if African-American correction was removed. Diabetic nephropathy was the most common cause of ESKD (65.4%). CONCLUSION: The incidence of ESKD in Fiji is high. This is a substantial public health problem that is likely impacting life expectancy and quality of life. Improving screening, detection and management of kidney disease should be given more prominence in programmes to address non-communicable diseases in Fiji and the Western Pacific.

Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+) population of non-adherent endothelial forming cells (naEFCs) which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38) together with mature endothelial cell markers (VEGFR2, CD144 and CD31). These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8) or myeloid markers (CD11b and CD14) which distinguishes them from 'early' endothelial progenitor cells (EPCs). Functional studies demonstrated that these naEFCs (i) bound Ulex europaeus lectin, (ii) demonstrated acetylated-low density lipoprotein uptake, (iii) increased vascular cell adhesion molecule (VCAM-1) surface expression in response to tumor necrosis factor and (iv) in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs). Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM)-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

Incorporation of endothelial progenitor cells into mosaic pseudoislets.

Pancreatic islet transplantation is limited by extensive apoptosis and suboptimal function of the implanted islets in the longer term. Endothelial progenitor cells (EPC) may be ideal for enhancing both the survival and function of transplanted islets. Here, we describe for the first time the in vitro formation of rat mosaic pseudoislets comprised of pancreatic ß-cells with interspersed vasculogenic EPC. Bone marrow-derived EPC displayed a similar phenotype to non-adherent EPC, recently described in the human and mouse. Mosaic pseudoislet formation was enhanced by the use of an embryoid body forming medium (BPEL) and a spin protocol. Mosaic pseudoislets maintained function in vitro and may represent an enhanced cell therapy delivery approach to enhance the survival and revascularisation of transplanted islets.

Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease.

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.