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Background: Home haemodialysis (HHD) is utilized significantly less often than facility HD globally with few exceptions, despite being associated with improved survival and better quality of life. Previously HHD was exclusively offered to younger patients with a few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. Method(s): A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6 months post-transplant between HHD and facility HD patients. A total of 181 HHD patients from a major hospital network were included with 413 facility HD patients from the Australia and New Zealand Dialysis and Transplant Registry matched by age, gender and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. Result(s): After adjusting for body mass index, smoking status, racial group and comorbidities, HHD was associated with a significantly reduced risk of death compared with facility HD patients [hazard ratio 0.47 (95% confidence interval 0.30-0.74)]. Transplantation rates were comparable, with high rates of graft survival at 6 months in both groups. Haemoglobin, calcium and parathyroid hormone levels did not vary significantly. However, HHD patients had significantly lower phosphate levels. Conclusion(s): In this study, improved survival outcomes were observed in patients on home compared with facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.Copyright © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background: Podocyte loss is a key event in primary focal segmental glomerulosclerosis (FSGS). Common first-line therapy for patients with primary FSGS involves steroid therapy with or without blood pressure control; however 40-70% of patients achieve no remission. Animal studies have shown that treatment efficacy is achieved partly through preservation of podocyte number, as well as podocyte protective effects. Animal studies have also determined that podocyte number and density are predictive of FSGS severity. Therefore, this study aimed to determine if podocyte number and density can predict the response to therapy in patients with primary FSGS. Method(s): A retrospective cohort study of renal biopsies was conducted from 2009-2020 in Melbourne, Australia at a tertiary hospital (Monash Medical Centre). Patients diagnosed with primary FSGS were screened (n=84). Patients were excluded for lack of consent for samples to be used for research purposes (n=38), risks of other forms of FSGS (n=13), insufficient clinical data available (n=2), no biopsy tissue available (n=7) or <6 glomerular profiles available in the biopsy (n=5). Included patients were allocated into groups of treatment responders (n=11) or non-responders (n=8) based on urinary/serum data 6 months following initial diagnosis and commencement of treatment. Biopsies were immunofluorescently stained for podocyte-specific markers. Model-based stereology was used to estimate podometrics. Sections were re-stained with PAS to measure the glomerulosclerotic index (GSI). Result(s): Podocyte number per glomerulus in responders (347 (215-606); median (IQR)) was 45% higher than in non-responders (190; 143-263) (P=0.03). Podocyte density in responders (76; 58-142 per 106mum3 of glomerular volume) was similar to nonresponders (66; 44-88 per 106mum3 of glomerular volume) (P=0.38). GSI was significantly higher in non-responder patients (1.1; 0.6-2.3) than responders (0.6; 0.2-0.9) (P=0.04), and was significantly and nega

Background: Despite the emergence of diagnostic and clinical utility evidence in nephrology, publicly funded access to genomic testing is restricted in most health care systems. To establish genomic sequencing as a clinical test, an evaluation of cost-effectiveness is urgently required. Method(s): An economic evaluation, informed by a primary clinical study and available clinical evidence and guidelines in nephrology, was performed to evaluate the cost-effectiveness and optimal timing of exome sequencing (ES) in adults and children with suspected monogenic glomerular diseases compared with nongenomic investigations (NGIs). Six diagnostic strategies reflecting current practice and recommended models of care in Australia were modeled: (i) NGIs, (ii) late gene panel followed by ES, (iii) late ES, (iv) early gene panel, (v) early gene panel followed by ES, and (vi) early ES. Result(s): ES with targeted analysis achieved a diagnosis in 23 of 63 (36.5%) adults and 10 of 24 (41.6%) children. NGIs were estimated to diagnose 4.0% of children, with an average estimated cost of AU$6120 per child. Integrating ES as a first-line test in children was cost saving, with an incremental cost saving of AU$3230 per additional diagnosis compared with NGIs. In adults, NGIs was estimated to diagnose 8% of patients, with an average estimated cost of AU$1830 per person. In adults, integrating ES early resulted in an incremental cost per additional diagnosis of AU$5460 relative to NGIs. Conclusion(s): Early ES with targeted analysis was effective for diagnosing monogenic kidney disease, with substantial cost savings in children.Copyright © 2021

Aim: To describe the phenotypic spectrum in patients with diagnostic type 4 collagen variants, and to determine phenocopies of Alport Syndrome (AS). Background(s): AS is the second most common form of genetic kidney disease (GKD). Recently, Medicare approved testing for the three genes associated with AS. Pursuing genetic diagnosis has important clinical implications. Method(s): We compared the suspected diagnosis prior to ES with the genomic diagnosis in patients with suspected AS from a cohort of 204 patients with suspected GKD. We also compared the suspected diagnosis to the molecular diagnosis in patients who were found to have type 4 collagen variants following ES. Result(s): 80/204(39%) had diagnostic variants in genes related to kidney disease. 26/80(33%) had diagnostic type 4 collagen variants. Most patients (n = 13) had autosomal dominant (AD) COL4A3/4 nephropathy. Eleven had X-Linked dominant AS and 2 had autosomal recessive AS. ES reclassified the diagnosis in 7/26(27%) of patients with type 4 collagen variants. Furthermore, 3 patients who had clinical symptoms suspicious of AS were found to have an alternate diagnosis following ES (2 had X-linked recessive Dent Disease and 1 had AD hypoparathyroidism, sensorineural deafness and renal dysplasia). Conclusion(s): ES revealed type 4 collagen variants in 6 patients with alternate clinical diagnoses suspected at referral. Three additional patients who were thought to have AS were subsequently given an alternate diagnosis. We suggest that AS is underdiagnosed, and testing should be considered in patients with a suspected monogenic cause of hematuria. We also highlight the importance of expanding analysis to additional genes in the evaluation of patients with suspected AS, in addition to those reimbursed by Medicare. ES allows easier subsequent reanalysis of genomic data.

Rationale & Objective: Approximately 11% of people with kidney failure worldwide are treated with peritoneal dialysis (PD). This study examined PD use and practice patterns across the globe. Study Design: A cross-sectional survey. Setting & Participants: Stakeholders including clinicians, policy makers, and patient representatives in 182 countries convened by the International Society of Nephrology between July and September 2018. Outcome(s): PD use, availability, accessibility, affordability, delivery, and reporting of quality outcome measures. Analytical Approach: Descriptive statistics. Result(s): Responses were received from 88% (n = 160) of countries and there were 313 participants (257 nephrologists [82%], 22 non-nephrologist physicians [7%], 6 other health professionals [2%], 17 administrators/policy makers/civil servants [5%], and 11 others [4%]). 85% (n = 156) of countries responded to questions about PD. Median PD use was 38.1 per million population. PD was not available in 30 of the 156 (19%) countries responding to PD-related questions, particularly in countries in Africa (20/41) and low-income countries (15/22). In 69% of countries, PD was the initial dialysis modality for <=10% of patients with newly diagnosed kidney failure. Patients receiving PD were expected to pay 1% to 25% of treatment costs, and higher (>75%) copayments (out-of-pocket expenses incurred by patients) were more common in South Asia and low-income countries. Average exchange volumes were adequate (defined as 3-4 exchanges per day or the equivalent for automated PD) in 72% of countries. PD quality outcome monitoring and reporting were variable. Most countries did not measure patient-reported PD outcomes. Limitation(s): Low responses from policy makers; limited ability to provide more in-depth explanations underpinning outcomes from each country due to lack of granular data; lack of objective data. Conclusion(s): Large inter- and intraregional disparities exist in PD availability, acce

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.Copyright © 2020, The Author(s).

Introduction: The 3-day interdialytic interval (IDI) is associated with high interdialytic weight gain (IDWG), but little is known about the effect of public or religious holidays on IDWG. Consequently, we evaluated the impact of the "Christmas holiday effect" on IDWG of hemodialysis patients. Method(s): A retrospective cohort study of adult hemodialysis patients (over 18 years) was conducted across five dialysis units in Australia. Demographic and clinical data were collected from electronic medical records. IDWG was established for three time points; regular 3-day IDI, 2-day IDI preceding the Christmas holiday and a 3-day IDI that included the Christmas holiday. Paired t-tests and logistic regression were used to compare differences in mean IDWG before and after the Christmas holiday and to examine factors associated with high IDWG, respectively. Finding(s): Two hundred and fifty-two patients, 69% of whom were male, with mean (SD) age of 65.4 +/- 15.3 years, were studied. Most had end-stage kidney disease due to diabetes (44%), and they had been on hemodialysis for a median of 25.5 (IQR, 60-10) months. There was a significant increase in absolute IDWG (MD 0.21 kg, 95% CI -0.07 to 0.36; P = 0.004) and relative IDWG (MD 0.3%, 95% CI 0.10-0.40; P = 0.01) after the holiday 3-day IDI compared with the regular 3-day IDI. Older age (OR 0.12; 95% CI 0.02-0.55) and a unit increase in hemoglobin (OR 0.94; 95% CI 0.89-0.99) were associated with lower odds of high relative IDWG while speaking a language other than English increased the odds for high relative IDWG (OR 5.03; 95% CI 1.12-22.65). Conclusion(s): Absolute and relative IDWG increased significantly after the Christmas holiday. Individualizing dialysis needs may improve outcomes for these patients.Copyright © 2020 International Society for Hemodialysis

Background: End-stage kidney disease secondary to hyperoxaluria presents a major challenge for transplant physicians given concern regarding disease recurrence. Few contemporary studies have reported long-term outcomes following transplantation in this population. Method(s): This study examined the outcomes of all adult patients with end-stage kidney disease secondary to hyperoxaluria who received a kidney or combined liver-kidney transplant in Australia and New Zealand between 1965 and 2015. Patients with hyperoxaluria were propensity score matched to control patients with reflux nephropathy. The primary outcome was graft survival. Secondary outcomes included graft function, acute rejection, and patient survival. Result(s): Nineteen transplants performed in 16 patients with hyperoxaluria were matched to 57 transplants in patients with reflux nephropathy. Graft survival was inferior in patients with hyperoxaluria receiving a kidney transplant alone (subhazard ratio [SHR] = 3.83, 95% confidence interval [CI], 1.22-12.08, P = .02) but not in those receiving a combined liver-kidney transplant (SHR = 0.63, 95% CI, 0.08-5.21, P =. 67). Graft failure risk was particularly high in patients with hyperoxaluria receiving a kidney transplant alone after more than 1 year of renal replacement therapy (SHR = 8.90, 95% CI, 2.35-33.76, P = .001). Posttransplant estimated glomerular filtration rate was lower in patients with hyperoxaluria (10.97 mL/min/1.73 m2, 95% CI, 0.53-21.42, P = .04). There was no difference between groups in the risk of acute rejection or death with a functioning graft. Conclusion(s): Compared to reflux nephropathy, hyperoxaluria was associated with inferior graft survival in patients receiving a kidney transplant alone. Long-term graft function was lower in patients with hyperoxaluria, but the risks of acute rejection and death were not different.Copyright © 2020 Elsevier Inc.

Rationale & Objective: Hemodialysis (HD) is the most common form of kidney replacement therapy. This study aimed to examine the use, availability, accessibility, affordability, and quality of HD care worldwide. Study Design: A cross-sectional survey. Setting & Participants: Stakeholders (clinicians, policy makers, and consumer representatives) in 182 countries were convened by the International Society of Nephrology from July to September 2018. Outcome(s): Use, availability, accessibility, affordability, and quality of HD care. Analytical Approach: Descriptive statistics. Result(s): Overall, representatives from 160 (88%) countries participated. Median country-specific use of maintenance HD was 298.4 (IQR, 80.5-599.4) per million population (pmp). Global median HD use among incident patients with kidney failure was 98.0 (IQR, 81.5-140.8) pmp and median number of HD centers was 4.5 (IQR, 1.2-9.9) pmp. Adequate HD services (3-4 hours 3 times weekly) were generally available in 27% of low-income countries. Home HD was generally available in 36% of high-income countries. 32% of countries performed monitoring of patient-reported outcomes; 61%, monitoring of small-solute clearance; 60%, monitoring of bone mineral markers; 51%, monitoring of technique survival; and 60%, monitoring of patient survival. At initiation of maintenance dialysis, only 5% of countries used an arteriovenous access in almost all patients. Vascular access education was suboptimal, funding for vascular access procedures was not uniform, and copayments were greater in countries with lower levels of income. Patients in 23% of the low-income countries had to pay >75% of HD costs compared with patients in only 4% of high-income countries. Limitation(s): A cross-sectional survey with possibility of response bias, social desirability bias, and limited data collection preventing in-depth analysis. Conclusion(s): In summary, findings reveal substantial variations in global HD use, availability, accessibility

Aim: We report the dietary habits of people with advanced CKD and their adherence to country specific Dietary Guidelines. Background(s): Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with advanced chronic kidney disease (CKD stage 4-5) is not well described. Method(s): Participants with CKD 4-5, receiving or planning dialysis commencement within 12-months, enrolled in the FAVOURED trial completed a lifestyle questionnaire at baseline on their dietary habits of key food groups including fruit, vegetables, chicken, meat, fish, and alcohol consumption. Result(s): Of 567 participants (mean age 54.8 +/- 14.3 years, 63% male), 538 (ANZ n = 386, Malaysian n = 152) completed the dietary and lifestyle questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% consumed >=2 serves/day of fruit and 61% ate >=2 serves/day of vegetables compared to 24% and 34% of Malaysians respectively (P < 0.0001). Only 4% of ANZ participants met Australian Dietary recommendations of 2 fruit and 5 vegetable serves/day. Fish consumption was higher in Malaysians with 83% consuming >=2 serves/week compared to 21% of ANZ participants (P < 0.0001). Red meat intake was significantly higher in ANZ participants however chicken consumption was similar; 48% consumed >2 chicken serves/week and 65% ate >2 serves/week of red meat compared to 43% and 15% of Malaysians, respectively. Nearly two thirds (62%) of participants in Malaysia and ANZ did not use added salt. Alcohol was consumed by 5% of Malaysians compared with 41% of ANZ participants. Conclusion(s): Significant regional variation in dietary intake for fruit, vegetables and animal protein are described which likely reflect cultural and economic differences. Barriers to meeting recommended dietary intakes requires further study.

Aim: This patient workshop aimed to describe consumer views on key outcomes of interest to inform trial design for a multinational randomised controlled trial comparing safety, clinical and cost efficacy of standard vs incremental haemodialysis. Background(s): Haemodialysis is burdensome, costly and associated with poor quality of life. Starting haemodialysis incrementally at 2 sessions per week may benefit residual kidney function and quality of life whilst remaining safe and cost-effective. Method(s): We convened two 60-minute online workshops in Australia with patients and caregivers to identify key outcomes of interest from a list provided relating to initiation of dialysis using an incremental dialysis approach. New suggestions for key outcomes of interest were also included during the workshop. A points system was used to prioritise outcomes. We identified safety concerns and descriptive themes from the patient's priorities regarding initiation of dialysis. Result(s): This workshop involved 31 attendees (1 caregiver and 30 patients). Patients were currently, previously or soon to be dialysis dependent. All participants agreed that incremental dialysis would be preferred. The top five outcomes of interest were quality of life (56 points), residual kidney function (27 points), mortality (16 points), fluid overload (12.5 points) and ability to work (10 points). Four key themes were identified which underpinned the prioritised outcomes of interest when commencing haemodialysis: unpreparedness and pressure to adapt, disruption to daily living, threats to safety and hope/future planning. Conclusion(s): The concept of incremental haemodialysis is viewed favourably by patients with kidney failure, who considered enriched quality of life as the most important outcome to study. Clinical trials in dialysis must be informed by patient perspectives on key outcomes, trial design, safety and acceptability of intervention.

BACKGROUND: Current health-care models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalisation, mortality, clinical and patient relevant outcomes. METHOD(S): Longitudinal analyses of adult patients with diabetes and CKD (stages 3a to 5) were performed using outpatient and hospitalisation data from January 2015 to October 2018. Data was handled according to whether patients received the DKS intervention (n=196) or standard care (n=7511). The DKS provided patient-centered, coordinated multi-disciplinary assessment and management of patients. Primary analyses examined hospitalisation and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in eGFR, HbA1c, self-care and patient activation at 12months. RESULT(S): Patients who received the intervention had a higher hospitalisation rate (incidence rate ratio (IRR), 1.20; 95% CI, 1.13 to 1.30; P<0.0001), shorter median length of stay (2days [interquartile range (IQR), 6-1] versus 4days [IQR 9-1]; P<0.0001) and lower all-cause mortality rate (IRR 0.4; 95% CI, 0.29 to 0.64; P<0.0001) than those who received standard care. Improvements in overall self-care (MD 2.26, 95% CI 0.83, 3.69; P<0.001) and in statin use, foot and eye examination were observed. Mean eGFR did not significantly change after 12months (MD 1.30, 95% CI -4.17, 1.67; P=0.40) mls/min per 1.73m2. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12months follow-up respectively. CONCLUSION(S): A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD.Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background: The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) is an international, prospective study following persons treated by peritoneal dialysis (PD) to identify modifiable practices associated with improvements in PD technique and person survival. The aim of this study was to assess the representativeness of the Australian cohort included in PDOPPS compared to the complete Australian PD population, as reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Method(s): Adults with at least one PD treatment reported to ANZDATA Registry during the census period of PDOPPS Phase I (November 2014 to April 2018) were compared to the Australian PDOPPS cohort. The primary outcomes were the representativeness of centres and persons. Secondary outcomes explored the association of person characteristics with consent to study participation. Result(s): After data linkage, 511 PDOPPS participants were compared to 5616 Australians treated with PD. Within centres eligible for PDOPPS, selected centres were similar to other Australian centres. The PDOPPS participants' cohort tended to include older persons, more males, a higher proportion of Caucasians and more persons with higher socioeconomic advantage compared to the Australian PD population. Differences in distribution across sex and ethnicities between the PDOPPS cohort and the overall PD population were in part due to the selection and consent processes, during which females and non-Caucasians were more likely to not consent to PDOPPS participation. Conclusion(s): Sampling methods used in PDOPPS allowed for good national representativeness of the included centres. However, representativeness of the unweighted PDOPPS sample was suboptimal in regard to some participant characteristics.Copyright © The Author(s) 2021.

BACKGROUND: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. METHOD(S): As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). RESULT(S): Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. CONCLUSION(S): These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background: Home haemodialysis (HHD) is utilized significantly less often than facility HD globally with few exceptions, despite being associated with improved survival and better quality of life. Previously HHD was exclusively offered to younger patients with a few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. Method(s): A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6 months post-transplant between HHD and facility HD patients. A total of 181 HHD patients from a major hospital network were included with 413 facility HD patients from the Australia and New Zealand Dialysis and Transplant Registry matched by age, gender and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. Result(s): After adjusting for body mass index, smoking status, racial group and comorbidities, HHD was associated with a significantly reduced risk of death compared with facility HD patients [hazard ratio 0.47 (95% confidence interval 0.30-0.74)]. Transplantation rates were comparable, with high rates of graft survival at 6 months in both groups. Haemoglobin, calcium and parathyroid hormone levels did not vary significantly. However, HHD patients had significantly lower phosphate levels. Conclusion(s): In this study, improved survival outcomes were observed in patients on home compared with facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.Copyright © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The COVID-19 pandemic has challenged the delivery of health services. Telehealth allows delivery of care without in-person contacts and minimizes the risk of vial transmission. We aimed to describe the perspectives of kidney transplant recipients on the benefits, challenges, and risks of telehealth. We conducted five online focus groups with 34 kidney transplant recipients who had experienced a telehealth appointment. Transcripts were thematically analyzed. We identified five themes: minimizing burden (convenient and easy, efficiency of appointments, reducing exposure to risk, limiting work disruptions, and alleviating financial burden); attuning to individual context (depending on stability of health, respect patient choice of care, and ensuring a conducive environment); protecting personal connection and trust (requires established rapport with clinicians, hampering honest conversations, diminished attentiveness without incidental interactions, reassurance of follow-up, and missed opportunity to share lived experience); empowerment and readiness (increased responsibility for self-management, confidence in physical assessment, mental preparedness, and forced independence); navigating technical challenges (interrupted communication, new and daunting technologies, and cognizant of patient digital literacy). Telehealth is convenient and minimizes time, financial, and overall treatment burden. Telehealth should ideally be available after the pandemic, be provided by a trusted nephrologist and supported with resources to help patients prepare for appointments.Copyright © 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT

Aim: To compare properties of a novel asymmetrical cellulose triacetate (ATA) dialyser (Solacia 190-H, Nipro) to a commonly used high-flux polysulfone dialyser (FX-80, Fresenius) in patients undergoing long-hour (>7 hours) haemodialysis (HD). Background(s): The ATA membrane is highly porous and less prone to performance degradation, compared to a conventional high-flux membrane, potentially resulting in enhanced clearance of middle and large-middle molecules, along with protein bound solutes. Method(s): 10 long-hour home HD patients were included in this randomized cross-over trial. Patients were randomized to 4 weeks of either the 190-H or FX-80 dialyser with subsequent cross-over to the other. The removal of small (urea, phosphate and creatinine), middle and large-middle molecules (beta-2 microglobulin [B2M], indoxyl sulfate [IS], albumin) and markers of inflammation (interleukin-6 [IL-6], malondialdehyde-modified low density lipoprotein [MDA-LDL]), were evaluated during the mid-week dialysis session of the fourth week of each dialyser sequence. All results are expressed as mean differences in corresponding reduction ratios (RR) between the FX-80 and 190-H dialysers after 8 hours of dialysis. Result(s): There was no significant difference in reduction in clearance of small molecules, with a RR difference for urea -2.43 (p = 0.19), creatinine -1.82 (p = 0.28) and phosphate -2.61 (p = 0.55). Similarly, there was no difference in clearance of middle and large-middle molecules with a RR difference for B2M 2.63 (p = 0.22), IS 2.48 (p = 0.69) and albumin -0.15 (p = 0.96). There was also no difference in expression of inflammatory markers with RR for IL-6 18.8 (p = 0.44) and MDA-LDL -8.0 (p = 0.3). Conclusion(s): Our study did not demonstrate a difference in clearance of small, middle and large-middle molecules, nor the expression of markers of inflammation between the FX-80 and H-190 dialysers.

Introduction: Patients with glomerular disease experience symptoms that impair their physical and mental health while managing their treatments, diet, appointments and monitoring general and specific indicators of health and their illness. We sought to describe the perspectives of patients and their care partners on self-management in glomerular disease. Method(s): We conducted 16 focus groups involving adult patients with glomerular disease (n = 101) and their care partners (n = 34) in Australia, Hong Kong, the United Kingdom, and United States. Transcripts were analyzed thematically. Result(s): We identified the following 4 themes: empowered in autonomy (gaining confidence through understanding, taking ownership of disease and treatment, learning a positive health approach); overwhelmed by compounding treatment burdens (financially undermined and depleted, demoralized by side effects and harms, frustrated by fragmented and inflexible care, fear of possible drug harms); striving for stability and normalcy (making personal sacrifices, maximizing life participation, attentiveness to bodily signs, avoiding precarious health states, integrating medicines into routines); and necessity of health-sustaining relationships (buoyed by social support, fulfilling meaningful responsibilities, sharing and normalizing experiences, seeking a trusting and respectful alliance). Conclusion(s): Patients with glomerular disease and their care partners value their capacity for autonomy and disease ownership, stability of their health, and relationships that support self-management. Strategies directed at strengthening these factors may increase self-efficacy and improve the care and outcomes for patients with glomerular disease.Copyright © 2021 International Society of Nephrology

Background: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. Method(s): We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-Analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. Result(s): Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI)-1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from-3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (beta = 1.16, 95% CI 1.06-1.27; P < 0.0001). Conclusion(s): A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between-and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing. Copyright © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

BACKGROUND: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. METHOD(S): We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. RESULT(S): Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference=0.73mmol/L [95% confidence interval (CI) -1.12 to 2.58; P=0.44]} but variability across studies was substantial (I2=99.3%). Among individually reported samples (n=295), measured DNa was higher than prescribed DNa by 1.96mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (beta=1.16, 95% CI 1.06-1.27; P<0.0001). CONCLUSION(S): A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Introduction: Genomic testing is becoming widely available as a diagnostic tool, although widespread implementation is not yet established in nephrology. Method(s): An anonymous electronic survey was administered to investigate experience and confidence with genomic tests, perceived clinical utility of genomic services, preferences for service delivery models, and readiness for implementation among nephrologists. Questions were guided by a comprehensive literature review and published tools, including a validated theoretical framework for implementation of genomic medicine: Consolidated Framework for Implementation Research (CFIR). Result(s): Responses were received from 224 clinicians, of which 172 were eligible for analysis. Most clinicians (132 [76%]) had referred at least one patient to a genetics clinic. Despite most clinicians (136 [85%]) indicating that they believed genetic testing would be useful, only 39 (23%) indicated they felt confident to use results of genomic testing, with pediatric clinicians feeling more confident compared with adult clinicians (12 of 20 [60%] vs. 27 of 149 [18%]), P < 0.01, Fisher exact). A multidisciplinary renal genetics clinic was the preferred model among clinicians surveyed (98 of 172 [57%]). A key implementation barrier highlighted related to the hospital or organizational culture and/or environment. Specific barriers noted in quantitative and qualitative responses included inadequate staffing, learning resources, and funding. Conclusion(s): Our findings suggest support for genomic testing among nephrologists, with a strong preference for a multidisciplinary model (involving a nephrologist, clinical geneticist, and genetic counselor). Broad-ranging interventions are urgently required to shift the current culture and ensure successful implementation of genomics in nephrology, including reducing knowledge gaps, increased funding and resources, disease-specific guidelines, and streamlining of testing processes.Copyright © 2020

Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19-85 years old; 51%women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked out comes were kidney function(importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: Constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact.Copyright © 2020 by the American Society of Nephrology.

BACKGROUND: Home haemodialysis (HHD) is utilised significantly less often than facility haemodialysis globally with few exceptions despite being associated with improved survival, and better quality of life. Previously, HHD was exclusively offered to younger patients with few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. METHOD(S): A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6months post-transplant between HHD and facility haemodialysis patients. 181 HHD patients from a major hospital network were included, with 413 facility haemodialysis patients from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) matched by age, gender, and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. RESULT(S): After adjusting for BMI, smoking status, racial group, and comorbidities, HHD was associated with significantly reduced risk of death compared to facility HD patients (HR=0.47, 95% CI 0.30-0.74). Transplantation rates were comparable, with high rates of graft survival at 6months in both groups. Haemoglobin, calcium, and parathyroid hormone levels did not vary significantly. However, home HD patients had significantly lower phosphate levels. CONCLUSION(S): In this study, improved survival outcomes were observed in patients on home compared to facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain. Methods To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate.1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism. Results A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings. Conclusions In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia. Clinical Trial r

Objective: To evaluate the impact of an integrated diabetes and kidney disease model of care on health-related quality of life (HRQOL) of patients with comorbid diabetes and chronic kidney disease (CKD). Research design and methods: A longitudinal study of adult patients (over 18 years) with comorbid diabetes and CKD (stage 3a or worse) who attended a new diabetes kidney disease service was conducted at a tertiary hospital. A questionnaire consisting of demographics, clinical data, and the Kidney Disease Quality of Life (KDQOL-36) was administered at baseline and after 12 months. Paired t-tests were used to compare baseline and 12-month scores. A subgroup analysis examined the effects by patient gender. Multiple regression analysis examined the factors associated with changes in scores. Result(s): 179 patients, 36% of whom were female, with baseline mean+/-SD age of 65.9+/-11.3 years, were studied. Across all subscales, HRQOL did not significantly change over time (p value for all mean differences >0.05). However, on subgroup analysis, symptom problem list and physical composite summary scores increased among women (MD=9.0, 95% CI 1.25 to 16.67; p=0.02 and MD=4.5, 95% CI 0.57 to 8.42; p=0.03 respectively) and physical composite scores decreased among men (MD=-3.35, 95% CI -6.26 to -0.44; p=0.03). Conclusion The HRQOL of patients with comorbid diabetes and CKD attending a new codesigned, integrated diabetes and kidney disease model of care was maintained over 12 months. Given that HRQOL is known to deteriorate over time in this high-risk population, the impact of these findings on clinical outcomes warrants further investigation.Copyright © 2020 Author(s) (or their employer(s)).

Background: Peritoneal dialysis (PD) can offer patients more autonomy and flexibility compared with in-center hemodialysis (HD). However, burnout - defined as mental, emotional, or physical exhaustion that leads to thoughts of discontinuing PD - is associated with an increased risk of transfer to HD. We aimed to describe the perspectives of burnout among patients on PD and their caregivers. Method(s): In this focus group study, 81 patients and 45 caregivers participated in 14 focus groups from 9 dialysis units in Australia, Hong Kong, and the United States. Transcripts were analyzed thematically. Result(s): We identified two themes. Suffering an unrelenting responsibility contributed to burnout, as patients and caregivers felt overwhelmed by the daily regimen, perceived their life to be coming to a halt, tolerated the PD regimen for survival, and had to bear the burden and uncertainty of what to expect from PD alone. Adapting and building resilience against burnout encompassed establishing a new normal, drawing inspiration and support from family, relying on faith and hope for motivation, and finding meaning in other activities. Conclusion(s): For patients on PD and their caregivers, burnout was intensified by perceiving PD as an unrelenting, isolating responsibility that they had no choice but to endure, even if it held them back from doing other activities in life. More emphasis on developing strategies to adapt and build resilience could prevent or minimize burnout.Copyright © The Author(s) 2020.

Background: Endothelial progenitor cells (EPCs) are present in lower numbers in kidney disease patients who are dialysis-dependent and can be used to predict adverse cardiovascular events. The function of EPCs can be measured using colony forming unit (CFU) assays and the appearance of late outgrowth endothelial cells (OECs) in vitro. Specific clinical parameters can affect EPC function, yet less is known about the relationship between clinical observations and OEC function. Therefore the aim of this study was to determine if the appearance of OECs derived from dialysis-dependent patients was influenced by their clinical history. Method(s): Dialysis-dependent patients (n=20) were recruited to this study; and their age, time on dialysis, blood pressure (BP), erythropoietin (EPO), statin use and smoking status was collected as these parameters have previously demonstrated to affect circulating EPC levels. Blood (10mls) was obtained prior to a single dialysis session and peripheral blood mononuclear cells isolated and cultured. After 7 days CFU wasassessed, then cells were further cultured for 21 days or until OECs appeared (identified by cobblestone morphology). Result(s): The patient cohort had a mean age of 64.2(+/-15.5) years and 80% were male. The mean time on hemodialysis was 46 months (+/-69.6) and blood pressures of 139.1(+/-27.1)/75.2 (+/-18.9). Half of the patients received EPO, 30% were administered statins and 65% had a history of or were current smokers. Circulating %EPC of patients receiving EPO was significantly lower then patients who were not (mean diff. 1.487+/-0.538, 95% CI 0.3-2.7. p=0.0184) and high systolic blood pressure was negatively correlated with %EPC (r=-0.59, p=0.033). We observed a 45% conversion of EPCs to OECs, which was not dependent on starting %EPC (p=0.19). Both systolic (mean diff. 24.95mmHg, 95% CI 1.7-48.1, p=0.0365) and diastolic (mean diff. 18.9, 95%CI 3.2-34.6, p=0.0208) blood pressures were significantly lower in patients whe

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-beta1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.Copyright © 2020 The Authors

Background: Dialysis patients experience high rates of foot ulceration. Although risk factors for ulceration have been extensively studied in patients with diabetes, there is limited high-quality, longitudinal evidence in the dialysis population. Therefore, this study investigated risk factors for foot ulceration in a stable dialysis cohort. Method(s): We prospectively collected clinical, demographic, health status, and foot examination information on 450 adults with end-stage renal disease from satellite and home-therapy dialysis units in Melbourne, Australia over 12 months. The primary outcome was foot ulceration. Cox proportional hazard modelling and multinomial regression were used to investigate risk factors. Result(s): Among 450 dialysis patients (mean age, 67.5 years; 64.7% male; 94% hemodialysis; 50.2% diabetes), new cases of foot ulceration were identified in 81 (18%) participants. Overall, risk factors for foot ulceration were neuropathy (HR 3.02; 95% CI 1.48 to 6.15) and previous ulceration (HR 2.86; CI 1.53 to 5.34). In those without history of ulceration, nail pathology (RR 3.85; CI 1.08 to 13.75) and neuropathy (RR 2.66; CI 1.04 to 6.82) were risk factors. In those with history of ulceration, neuropathy (RR 11.23; CI 3.16 to 39.87), peripheral arterial disease (RR 7.15; CI 2.24 to 22.82) and cerebrovascular disease (RR 2.08; CI 1.04 to 4.16) were risk factors. There were 12 (2.7%) new amputations, 96 (21.3%) infections, 24 (5.3%) revascularizations, 42 (9.3%) foot-related hospitalizations, and 52 (11.6%) deaths. Conclusion(s): Neuropathy and previous ulceration are major risk factors for foot ulceration in dialysis patients. Risk factors differ between those with and without prior ulceration. The risk factors identified will help to reduce the incidence of ulceration and its associated complications.Copyright © 2019 The Author(s).

Aim: Extended-hours haemodialysis has long been regarded as the optimal form of dialysis for solute clearance. With emerging benefits of haemodiafiltration, we wanted to compare these two head-to-head. Method(s): In this randomized cross-over trial, we recruited existing nocturnal haemodialysis patients, who had not been hospitalized in the prior 3 months. After a baseline 8 h haemodialysis session, subjects were randomized to either 2 weeks of 8 h haemodialysis or 4 h haemodiafiltration with cross-over to the alternative treatment after a 2-week washout period. Subjects were additionally randomized to the Fresenius FX80 or Nipro Elisio in a parallel design. Blood and dialysate samples were collected at baseline and at the end of both study periods. Result(s): Twelve patients completed the study. Mean (SD) age and body mass index were 55.1 +/- 11.5 years and 36.4 +/- 10.8, respectively. Urea and creatinine reduction ratios were higher with extended-hours haemodialysis compared to haemodiafiltration (difference 14.0%, 95% CI = 10.6, 17.3; P < 0.001 and 9.1%, 95% CI = 11.0, 7.2; P < 0.001). Fibroblast growth factor 23 (FGF23) clearance was superior with haemodiafiltration (difference 20.1%, 95% CI = 8.7, 31.6; P = 0.001). No difference was seen in reduction ratios for phosphate, retinol binding protein, alpha-1-microglobulin, beta-2-microglobulin and fetuin with both modalities. Compared to Nipro Elisio, Fresenius FX80 dialyser achieved higher beta-2-microglobulin clearance (Period 1: difference 7.8%, 95% CI = 1.3, 14.4; P = 0.02, Period 2:7.5%, 95% CI = 1.0, 14.1; P = 0.02). Conclusion(s): Small solute clearance was superior with extended-hours haemodialysis while haemodiafiltration enhanced FGF23 clearance. Beta-2-microglobulin clearance was improved with Fresenius FX80 dialyser, but this difference is unlikely to be clinically significant.Copyright © 2018 Asian Pacific Society of Nephrology

The cellular origins of glomerulosclerosis involve activation of parietal epithelial cells (PECs) and progressive podocyte depletion. While mammalian target of rapamycin-mediated (mTORmediated) podocyte hypertrophy is recognized as an important signaling pathway in the context of glomerular disease, the role of podocyte hypertrophy as a compensatory mechanism preventing PEC activation and glomerulosclerosis remains poorly understood. In this study, we show that glomerular mTOR and PEC activation-related genes were both upregulated and intercorrelated in biopsies from patients with focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, suggesting both compensatory and pathological roles. Advanced morphometric analyses in murine and human tissues identified podocyte hypertrophy as a compensatory mechanism aiming to regulate glomerular functional integrity in response to somatic growth, podocyte depletion, and even glomerulosclerosis - all of this in the absence of detectable podocyte regeneration. In mice, pharmacological inhibition of mTOR signaling during acute podocyte loss impaired hypertrophy of remaining podocytes, resulting in unexpected albuminuria, PEC activation, and glomerulosclerosis. Exacerbated and persistent podocyte hypertrophy enabled a vicious cycle of podocyte loss and PEC activation, suggesting a limit to its beneficial effects. In summary, our data highlight a critical protective role of mTOR-mediated podocyte hypertrophy following podocyte loss in order to preserve glomerular integrity, preventing PEC activation and glomerulosclerosis.Copyright © 2019, American Society for Clinical Investigation.

Background: Self-management education needs have not been assessed in patients with complex co-morbid conditions such as diabetes and chronic kidney disease (CKD). The objectives of this study were to 1) determine the self-management education needs for patients with co-morbid diabetes and CKD and 2) co-develop an educational resource meeting the self-management education needs of patients with co-morbid diabetes and CKD. Method(s): Patients with co-morbid diabetes and CKD attending a co-designed, patient-centred outpatient diabetes and kidney clinic at a tertiary metropolitan hospital were recruited for semi-structured interviews. Maximal variation sampling was used, ensuring adequate representation of different gender, age, diabetes duration and stage of CKD. Data were thematically analysed using grounded theory. Result(s): Forty-two patients participated. Most were male (67%) and the mean age was 64.8 (11.1) years. The majority of patients preferred an educational resource in the form of a Digital Versatile Disc (DVD) and they thought that current education could be improved. In particular patients wanted further education on 1) management of diabetes and kidney disease (including nutrition and lifestyle, and prevention of the progression of kidney disease) and 2) complications of comorbid diabetes and kidney disease. Conclusion(s): Patients with co-morbid diabetes and kidney disease have education gaps on the management of, and complications of diabetes and kidney disease. Interventions aimed at improving patient education need to be delivered through education resources co-developed by patients and health staff. A targeted education resource in the form of a DVD, addressing these needs, may potentially close these gaps.Copyright © 2019 The Author(s).

Background Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. Methods In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. Results Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54-0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34-0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27-0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. Conclusion Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.Copyright © 2019 Viecelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduct

Testing angiogenic potential and function of cells in culture is important for the understanding of the mechanisms that can modulate angiogenesis, especially when discovering novel anti- or pro-angiogenic therapeutics. Commonly used angiogenic assays include tube formation, proliferation, migration, and wound healing, and although well-characterized, it is important that methodology is standardized and reproducible. Human endothelial progenitor cells (EPCs) are critical for post-natal vascular homeostasis and can be isolated from human peripheral blood. Endothelial colony forming cells (ECFCs) are a subset of EPCs and are of interest as a possible therapeutic target for hypoxic diseases such as kidney disease, as they have a high angiogenic potential. However, once ECFCs are identified in culture, the exact timing of passaging has not been well-described and the optimal conditions to perform angiogenic assays such as seeding density, growth media (GM) concentrations and end-points of these assays is widely varied in the literature. Here, we describe the process of isolating, culturing and passaging ECFCs from patients with end-stage renal disease (ESRD), aided by image analysis. We further describe optimal conditions, for human bladder endothelial cells (hBECs), challenged in angiogenic assays and confirm that cell density is a limiting factor in accurately detecting angiogenic parameters. Furthermore, we show that GM along is enough to alter the angiogenic potential of cells, seeded at the same density. Lastly, we report on the success of human ECFCs in angiogenic assays and describe the benefits of live-cell imaging combined with time-lapse microscopy for this type of investigation.Copyright © 2019 Huuskes, DeBuque, Kerr, Samuel and Ricardo.

Background To address guideline-practice gaps and improve management of patients with both diabetes and chronic kidney disease (CKD), we involved patients, health professionals and patient advocacy groups in the co-design and implementation of an integrated diabetes-kidney service. Objective In this study, we explored the experiences of patients and health-care providers, within this integrated diabetes and kidney service. Methods 5 focus groups and 2 semi-structured interviews were conducted amongst attending patients, referring primary health professionals, and attending specialist health professionals. Maximal variation sampling was used for both patients and referring primary health professionals to ensure an equal representation of males and females, and patients of different CKD stages. All discussions were audiotaped and transcribed verbatim, before being thematically analysed independently by 2 researchers. Results The mean age (SD) for specialist health professionals, primary care professionals and patients who participated was 45 (11), 44 (15) and 68 (5) years with men being 50%, 80% and 76% of the participants respectively. Key strengths of the diabetes and kidney service were noted to be better integration of care and a perception of improved health and management of health. Whilst some aspects of access such as time between referral and initial appointment and having fewer appointments improved, other aspects such as in-clinic waiting times and parking remained problematic. Specialist health professionals noted that health professional education could be improved. Patient self-management was also noted by to be an issue with some patients requesting more information and some health professionals expressing difficulty in empowering some patients. Conclusions Health professionals and patients reported that a co-designed integrated diabetes kidney service improved integration of care and improved health and management of health. However, some aspects of th

Aims: In patients with comorbid diabetes and chronic kidney disease, the extent to which patient-reported barriers to health-care and patient reported outcomes influence the quality of health care is not well established. This study explored the association between patient-reported barriers to health-care, patient activation, quality of life and diabetes self-care, with attainment of glycaemic and blood pressure (BP) targets. Method(s): This cross-sectional study recruited adults with diabetes and CKD (eGFR 20 to <60 ml/min/1.73m2) across four hospitals. We combined clinical data with results from a questionnaire comprising measures of patient-identified barriers to care, the Patient Activation Measure (PAM), 12-Item Short Form Survey (SF-12), and the Summary of Diabetes Self-Care Activity (SDSCA). Result(s): 199 patients, mean age 68.7 (SD 9.6), 70.4% male and 90.0% with type 2 diabetes were studied. Poor glycaemic control was associated with increased odds of patient reported "poor family support" (OR 4.90; 95% CI 1.80 to 13.32, p < 0.002). Poor BP control was associated with increased odds of patient reported, "not having a good primary care physician" (OR 6.01; 2.42 to 14.95, p < 0.001). The number of barriers was not associated with increased odds of poor control (all p > 0.05). Conclusion(s): Specific patient-reported barriers, lack of patient perceived family and primary care physician support, are associated with increased odds of poor glycaemic and blood pressure control respectively. Interventions addressing these barriers may improve treatment target attainment.Copyright © 2018 Elsevier Inc.

Background: Proteinuria is a common clinical presentation, the diagnostic workup for which involves many non-invasive and invasive investigations. We report on two siblings that highlight the clinically relevant functional role of cubulin for albumin resorption in the proximal tubule and supports the use of genomic sequencing early in the diagnostic work up of patients who present with proteinuria. Case presentation: An 8-year-old boy was referred with an incidental finding of proteinuria. All preliminary investigations were unremarkable. Further assessment revealed consanguineous family history and a brother with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global glomerular basement membrane thinning on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~ 4.5% of the genome. Shared regions of LCSH between the brothers were identified and their further research genomic analysis implicated a homozygous stop-gain variant in CUBN (10p12.31). Conclusion(s): CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the ability of genomic testing to identify genetic causes of nephropathy within expanding associated phenotypic spectra. Genomic sequencing, undertaken earlier in the diagnostic trajectory, may reduce the need for invasive investigations and the time to definitive diagnosis for patients and families.Copyright © 2019 The Author(s).

Introduction: Genomic technologies enable the rapid and cost-effective sequencing of DNA and have demonstrated a definitive diagnosis in several patient groups. The clinical utility of whole exome sequencing (WES) in a kidney disease cohort is not yet well established. We describe the patient characteristics and diagnostic yield of a cohort of 200 patients with suspected genetic kidney disease referred for WES via a multidisciplinary renal genetics clinic. Method(s): 200 sequential patients were recruited into a prospective observational cohort study through five tertiary academic centres in Victoria, Australia. Patients were referred by their treating nephrologist to a dedicated renal genetic service funded by the Melbourne Genomics Health Alliance. Following review by a multidisciplinary team, consisting of a nephrologist, clinical geneticist and genetic counsellor, patients were recruited for genomic sequencing, with analysis for a pre-determined list of genes of interest. We measured the diagnostic yield and its effect on short term clinical management. Result(s): Singleton WES was performed on 123 adult patients and 83 paediatric patients. Majority were female (118) and median age was 27 years (range 0-73 years). 100 of these patients were isolated cases (77 had a known positive family history). From 104 exome results available to date (38 paediatric and 66 adults), 43 patients received a positive molecular diagnosis (41%) and of these 22 (51%) resulted in a change from the original clinical diagnosis. The diagnostic yield was greater in the paediatric cohort (53%) compared to the adult cohort (35%). The effects of genomic testing on clinical management is currently being analysed. Conclusion(s): Singleton WES resulted in a substantial number of positive diagnoses in both adult and paediatric patients. The ongoing analysis of this cohort will allow delineation of the sensitivity of exome sequencing to current diagnostic methods, enable health economic analysis

Background: Little is known about how patient reported barriers to health care impact the quality of life (HRQoL) of patients with comorbid disease. We investigated patient reported barriers to health care and low physical and mental well-being among people with diabetes and chronic kidney disease (CKD). Method(s): Adults with diabetes and CKD (estimated Glomerular Filtration Rate < 60 ml/min/1.73m2) were recruited and completed a questionnaire on barriers to health care, the 12-Item HRQoL Short Form Survey and clinical assessment. Low physical and mental health status were defined as mean scores < 50. Logistic regression models were used. Result(s): Three hundred eight participants (mean age 66.9 +/- 11 years) were studied. Patient reported 'impact of the disease on family and friends' (OR 2.07; 95% CI 1.14 to 3.78), 'feeling unwell' (OR 4.23; 95% CI 1.45 to 12.3) and 'having other life stressors that make self-care a low priority' (OR 2.59; 95% CI 1.20 to 5.61), were all associated with higher odds of low physical health status. Patient reported 'feeling unwell' (OR 2.92; 95% CI 1.07 to 8.01), 'low mood' (OR 2.82; 95% CI 1.64 to 4.87) and 'unavailability of home help' (OR 1.91; 95% CI 1.57 to 2.33) were all associated with higher odds of low mental health status. The greater the number of patient reported barriers the higher the odds of low mental health but not physical health status. Conclusion(s): Patient reported barriers to health care were associated with lower physical and mental well-being. Interventions addressing these barriers may improve HRQoL among people with comorbid diabetes and CKD.Copyright © 2018 The Author(s).

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems.Copyright © 2018 The Authors Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology

Objective To determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative kidney management. Design International cross sectional survey. Setting International Society of Nephrology (ISN) survey of 182 countries from July to September 2018. Participants Key stakeholders identified by ISN's national and regional leaders. Main outcome measures Markers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management. Results Responses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world's population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management-namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with i

Aim: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient-centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision-making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities. Method(s): Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0-1) for each outcome and conducted thematic analyses. Result(s): Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end-stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks. Conclusion(s): For patients with ADPKD and their caregivers, kidney function, delayed progression to end-stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient-important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.Copyright © 2019 Asian Pacific Society of Nephrology