Tunneled Hemodialysis Catheter Tip Design and Risk of Catheter Dysfunction: An Australian Nationwide Cohort Study.

RATIONALE & OBJECTIVE: Hemodialysis catheter dysfunction is an important problem for patients with kidney failure. The optimal design of the tunneled catheter tip is unknown. This study evaluated the association of catheter tip design with the duration of catheter function. STUDY DESIGN: Observational cohort study using data from the nationwide REDUCCTION trial. SETTING & PARTICIPANTS: 4,722 adults who each received hemodialysis via 1 or more tunneled central venous catheters in 37 Australian nephrology services from December 2016 to March 2020. EXPOSURE: Design of tunneled hemodialysis catheter tip, classified as symmetrical, step, or split. OUTCOME: Time to catheter dysfunction requiring removal due to inadequate dialysis blood flow assessed by the treating clinician. ANALYTICAL APPROACH: Mixed, 3-level accelerated failure time model, assuming a log-normal survival distribution. Secular trends, the intervention, and baseline differences in service, patient, and catheter factors were included in the adjusted model. In a sensitivity analysis, survival times and proportional hazards were compared among participants' first tunneled catheters. RESULTS: Among the study group, 355 of 3,871 (9.2%), 262 of 1,888 (13.9%), and 38 of 455 (8.4%) tunneled catheters with symmetrical, step, and split tip designs, respectively, required removal due to dysfunction. Step tip catheters required removal for dysfunction at a rate 53% faster than symmetrical tip catheters (adjusted time ratio, 0.47 [95% CI, 0.33-0.67) and 76% faster than split tip catheters (adjusted time ratio, 0.24 [95% CI, 0.11-0.51) in the adjusted accelerated failure time models. Only symmetrical tip catheters had performance superior to step tip catheters in unadjusted and sensitivity analyses. Split tip catheters were infrequently used and had risks of dysfunction similar to symmetrical tip catheters. The cumulative incidence of other complications requiring catheter removal, routine removal, and death before removal were similar across the 3 tip designs. LIMITATIONS: Tip design was not randomized. CONCLUSIONS: Symmetrical and split tip catheters had a lower risk of catheter dysfunction requiring removal than step tip catheters. FUNDING: Grants from government (Queensland Health, Safer Care Victoria, Medical Research Future Fund, National Health and Medical Research Council, Australia), academic (Monash University), and not-for-profit (ANZDATA Registry, Kidney Health Australia) sources. TRIAL REGISTRATION: Registered at ANZCTR with study number ACTRN12616000830493. PLAIN-LANGUAGE SUMMARY: Central venous catheters are widely used to facilitate vascular access for life-sustaining hemodialysis treatments but often fail due to blood clots or other mechanical problems that impede blood flow. A range of adaptations to the design of tunneled hemodialysis catheters have been developed, but it is unclear which designs have the greatest longevity. We analyzed data from an Australian nationwide cohort of patients who received hemodialysis via a tunneled catheter and found that catheters with a step tip design failed more quickly than those with a symmetrical tip. Split tip catheters performed well but were infrequently used and require further study. Use of symmetrical rather than step tip hemodialysis catheters may reduce mechanical failures and unnecessary procedures for patients.

Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis.

AIMS/HYPOTHESIS: Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs. METHODS: We designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained. RESULTS: The numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs. CONCLUSIONS/INTERPRETATION: At current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.

Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults.

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age.

Multifaceted Quality Improvement Interventions to Prevent Hemodialysis Catheter-Related Bloodstream Infections: A Systematic Review.

RATIONALE & OBJECTIVE: Central venous catheters (CVCs) are widely used for hemodialysis but are prone to burdensome and costly bloodstream infections. We determined whether multifaceted quality improvement interventions in hemodialysis units can prevent hemodialysis catheter-related bloodstream infections (HDCRBSI). STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: PubMed, EMBASE, and CENTRAL were searched from inception to April 23, 2022, to identify randomized trials, time-series analyses, and before-after studies that examined the effect of multifaceted quality improvement interventions on the incidence of HDCRBSI or access-related bloodstream infections (ARBSI) among people receiving hemodialysis outside of the intensive care unit (ICU). DATA EXTRACTION: Two people independently extracted data and assessed the risk of bias and quality of evidence using validated tools. ANALYTICAL APPROACH: Intervention effects, validity, and characteristics of studies with the same design were compared. Differences between study designs were described. RESULTS: We included 21 studies from 8,824 identified by our search. Among 15 studies that measured HDCRBSI, 2 methodologically heterogenous cluster randomized trials reported discordant intervention effects, 2 interrupted time-series analyses reported favorable interventions with discordant patterns of effect, and 11 before-after studies reported favorable interventions with a very high risk of bias. Among 6 studies that only measured ARBSI, 1 time-series analysis and 1 before-after study did not find a favorable intervention effect, and 4 before-after studies reported a favorable effect with a very high risk of bias. The overall quality of evidence was low for HDCRBSI and very low for ARBSI. LIMITATIONS: Nine definitions of HDCRBSI were used. Ten studies included hospital-based and satellite facilities but did not report separate intervention effects for each type of facility. CONCLUSIONS: Multifaceted quality improvement interventions may prevent HDCRBSI outside the ICU. However, evidence supporting them is of low quality, and further carefully conducted studies are warranted. REGISTRATION: Registered at PROSPERO with registration number CRD42021252290. PLAIN-LANGUAGE SUMMARY: People with kidney failure rely on central venous catheters to facilitate life-sustaining hemodialysis treatments. Unfortunately, hemodialysis catheters are a common source of problematic bloodstream infections. Quality improvement programs have effectively prevented catheter-related infections in intensive care units, but it is unclear whether they can be adapted to patients using hemodialysis catheters in the community. In a systematic review that included 21 studies, we found that most quality improvement programs were reported to be successful. However, the findings were mixed among higher-quality studies, and overall the quality of evidence was low. Ongoing quality improvement programs should be complemented by more high-quality research.

Trends in the Incidence of End-Stage Kidney Disease in Type 1 and Type 2 Diabetes in Australia, 2010-2019.

RATIONALE & OBJECTIVE: Trends in end-stage kidney disease (ESKD) among people with diabetes may inform clinical management and public health strategies. We estimated trends in the incidence of ESKD among people with type 1 and type 2 diabetes in Australia from 2010-2019 and evaluated their associated factors. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 71,700 people with type 1 and 1,112,690 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS). We estimated the incidence of kidney replacement therapy (KRT) via linkage to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the incidence of KRT or death from ESKD by linking the NDSS to the ANZDATA and the National Death Index for Australia. PREDICTORS: Calendar time, sex, age, and duration of diabetes. OUTCOME: Incidence of KRT and KRT or death from ESKD. ANALYTICAL APPROACH: Incidence of ESKD, trends over time, and associations with factors related to these trends were modeled using Poisson regression stratified by diabetes type and sex. RESULTS: The median duration of diabetes increased from 15.3 to 16.8 years in type 1 diabetes, and from 7.6 to 10.2 years in type 2 diabetes between 2010 and 2019. The incidence of KRT and KRT or death from ESKD did not significantly change over this time interval among people with type 1 diabetes. Conversely, the age-adjusted incidence of KRT and KRT or death from ESKD increased among males with type 2 diabetes (annual percent changes [APCs]: 2.52% [95% CI, 1.54 to -3.52] and 1.27% [95% CI, 0.53 2.03], respectively), with no significant change among females (0.67% [95% CI, -0.68 to 2.04] and 0.07% [95% CI, -0.81 to 0.96], respectively). After further adjustment for duration of diabetes, the incidence of ESKD fell between 2010 and 2019, with APCs of-0.09% (95% CI, -1.06 to 0.89) and-2.63% (95% CI, -3.96 to-1.27) for KRT and-0.97% (95% CI, -1.71 to-0.23) and-2.75% (95% CI, -3.62 to-1.87) for KRT or death from ESKD among males and females, respectively. LIMITATIONS: NDSS only captures 80%-90% of people with diabetes; lack of clinical covariates limits understanding of trends. CONCLUSIONS: While the age-adjusted incidence of ESKD increased for males and was stable for females over the last decade, after adjusting for increases in duration of diabetes the risk of developing ESKD has decreased for both males and females. PLAIN-LANGUAGE SUMMARY: Previous studies showed an increase in new cases of kidney failure among people with type 2 diabetes, but more recent data have not been available. Here, we report trends in the rate of kidney failure for people with type 2 diabetes from 2010 to 2019 and showed that while more people with type 2 diabetes are developing kidney failure, accounting for the fact that they are also surviving longer (and therefore have a higher chance of kidney failure) the growth in this population is not caused by a higher risk of kidney failure. Nevertheless, more people are getting kidney failure than before, which will impact health care systems for years to come.

Elevated blood lactate in COPD exacerbations associates with adverse clinical outcomes and signals excessive treatment with ß2 -agonists.

BACKGROUND AND OBJECTIVE: Raised blood lactate secondary to high dose ß2 -agonist treatment has been reported in asthma exacerbations but has not been investigated during acute exacerbations of COPD (AECOPD). We explored associations of blood lactate measurements with disease outcomes and ß2 -agonist treatments during AECOPD. METHODS: Retrospective (n = 199) and prospective studies (n = 142) of patients hospitalized with AECOPD were conducted. The retrospective cohort was identified via medical records and the prospective cohort was recruited during hospitalization for AECOPD. Baseline demographics, comorbidities, ß2 -agonist treatment, biochemical measurements and clinical outcomes were compared between patients with normal (≤2.0 mmol/L) versus elevated lactate (>2.0 mmol/L). Regression analyses examined associations of lactate measurements with ß2 -agonist dosages. RESULTS: Demographic data and comorbidities were similar between high versus normal lactate groups in both cohorts. The populations were elderly (mean >70 years), predominantly male (>60%) with reduced FEV1 (%) 48.2 ± 19 (prospective cohort). Lactate was elevated in approximately 50% of patients during AECOPD and not related to evidence of sepsis. In the prospective cohort, patients with high lactate had more tachypnoea, tachycardia, acidosis and hyperglycaemia (p < 0.05) and received more non-invasive ventilation (37% vs. 9.7%, p < 0.001, prospective cohort). There was a trend to longer hospitalization (6 vs. 5 days, p = 0.06, prospective cohort). Higher cumulative ß2 -agonist dosages were linked to elevated lactate levels (OR 1.04, p = 0.01). CONCLUSION: Elevated lactate during AECOPD was common, unrelated to sepsis and correlated with high cumulative doses of ß2 -agonists. Raised lactate may indicate excessive ß2 -agonist treatment and should now be investigated as a possible biomarker.

Impact of haemodialysis hours on outcomes in older patients.

AIM: Previous studies report an association between longer haemodialysis treatment sessions and improved survival. Worldwide, there is a trend to increasing age among prevalent patients receiving haemodialysis. This analysis aimed to determine whether the mortality benefit of longer haemodialysis treatment sessions diminishes with increasing age. METHODS: This was a retrospective cohort study of people who first commenced thrice-weekly haemodialysis aged ≥65 years, reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry from 2005 to 2015, included from 90 days after dialysis start. The primary outcome was all-cause mortality. Cox regression analysis was performed with haemodialysis session duration the exposure of interest. RESULTS: Of 8224 people who commenced haemodialysis as their first treatment for kidney failure aged ≥65 years during this period, 4727 patients died. Longer dialysis hours per session was associated with a decreased risk of death in unadjusted analyses [hazard ratio, HR, for ≥5 h versus 4 to <4.5 h: 0.81 (0.75-0.88, p < .001)]. Patients having longer dialysis sessions were younger but had greater co-morbidity. In an adjusted model including age and other variables, the survival benefit of longer hours was only partially attenuated [HR for previous comparison: 0.75 (0.69-0.82, p < .001)], and no interaction between age and hours was demonstrated (p = .89). CONCLUSION: The apparent survival benefit associated with longer haemodialysis session length appears to be preserved in patients 65 years or older. In practice, the benefit of longer dialysis hours should be carefully weighed against other factors in this patient group.

The association of frailty with chronic kidney disease in older adults using the ASPirin in reducing events in the elderly cohort.

Frailty and chronic kidney disease (CKD) both increase with age and are prevalent in older adults. However, studies in older adults examining the relationship between frailty and milder impairments of kidney function are relatively sparse. We examined the cross-sectional association of baseline estimated glomerular filtration rate (eGFR), albuminuria and CKD ([eGFR <60 ml/min/1.73 m2 ] and/or albuminuria [>3.0 mg/mmol]) with prefrailty and frailty in the ASPirin in Reducing Events in the Elderly (ASPREE) trial cohort of healthy older participants. Univariate logistic regression models measured the unadjusted odds ratios (OR) and 95% confidence intervals (CI) for prevalent combined prefrailty and frailty (respectively defined as presence of 1-2 or 3+ of 5 modified fried criteria) for the association between CKD, eGFR, albuminuria and other potential risk factors. Multivariable models calculated OR for prefrailty-frailty adjusted for potential confounders and either CKD, (i) eGFR and albuminuria measured as either continuous variables; (ii) or categorical variables; (iii). Of 17 759 eligible participants, 6934 were classified as prefrail, 389 were frail. CKD, eGFR and albuminuria were all associated with combined prefrailty-frailty on univariate analysis. In the multivariable modelling, neither CKD (reduced eGFR and/or albuminuria), nor eGFR (either continuous or categorical variables) were associated with prefrailty-frailty. However, albuminuria, either as a continuous variable (OR [95% CI] 1.07 [1.04-1.10]; p < .001), or categorical variable (OR 1.21 [1.08-1.36]; p = .001) was consistently associated with prefrailty-frailty. The complex relationship between albuminuria (which may be a biomarker for vascular inflammation), ageing, progressive CKD and frailty requires further investigation.

A codesigned integrated kidney and diabetes model of care improves patient activation among patients from culturally and linguistically diverse backgrounds.

BACKGROUND: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. METHODS: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non-CALD backgrounds spoke English only as their primary language. Paired t-tests compared baseline and 12-month patient activation scores by CALD status. RESULTS: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non-CALD backgrounds (58.5 ± 14.6) at baseline. Within-group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow-up (52.1 ± 17.6-59.4 ± 14.7), and no significant change was observed for those from non-CALD backgrounds (58.5 ± 14.6-58.8 ± 13.6). CONCLUSIONS: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. PATIENT OR PUBLIC CONTRIBUTION: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi-structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses.

A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care.

BACKGROUND: Current healthcare 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 hospitalization, mortality, clinical and patient-relevant outcomes. METHODS: Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a-5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n = 196) or standard care (n = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months. RESULTS: Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13-1.30]; P < 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1-6] versus 4 days [IQR 1-9]; P < 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29-0.64); P < 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83-3.69); P < 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI -4.17-1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively. CONCLUSIONS: 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.

Kidney transplant recipients' attitudes toward COVID-19 vaccination and barriers and enablers to vaccine acceptance.

OBJECTIVE: To identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination. METHODS: An online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination. RESULTS: The survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p < .001) and more concerned about (93.3% vs. 25.1%, p < .001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine-specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team. CONCLUSION(S): Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.

Solid pancreas transplant outcomes with increased donor and recipient ages compared with reference ages: a systematic review.

BACKGROUND: Increased recipient and donor age are associated with worse solid organ pancreas transplant outcomes. However, donor and recipient age criteria vary between jurisdictions. We systematically reviewed studies reporting the association between transplanting older recipients and donors beyond current Transplantation Society of Australia and New Zealand (TSANZ) limits with solid pancreas transplant outcomes. AIMS: To review current outcomes of solid pancreas transplantation in recipients and donors over the TSANZ reference ages. METHODS: Studies comparing transplant outcomes between a reference-age and an older-age donor (>45 years) or recipient (≥50 years) cohort for solid pancreas transplantation were included. Primary outcomes were pancreas/kidney graft and patient survival at 1 and 5 years. Secondary outcomes were post-transplant complications (graft thrombosis, acute rejection and relaparotomy rates). RESULTS: Eleven studies were included (two studies assessing solid pancreas outcomes between older vs reference-aged donors and nine studies assessing outcomes between older vs reference-aged recipients). Seven of 11 studies were judged to be at high risk of bias. Primary and secondary outcomes were not significantly different between recipient age groups in nine studies. A sensitivity analysis of older versus reference-aged studies excluding studies at high risk of bias also showed non-inferior primary and secondary outcomes at 1 year. Two studies comparing outcomes by donor age showed worse graft survival but non-inferior patient survival with older donors. CONCLUSION: Increased donor or recipient age alone should not absolutely contraindicate solid pancreas transplantation, especially if other risk predictors are minimised.

Practice patterns and predictors of outpatient care following acute kidney injury in an Australian healthcare setting.

BACKGROUND: Survivors of acute kidney injury (AKI) are at increased risk of major adverse kidney events and international guidelines recommend individuals be evaluated 3 months following AKI. AIM: We describe practice patterns and predictors of post-AKI care in an Australian tertiary hospital. METHODS: A retrospective analysis was undertaken of adults with AKI (defined by KDIGO criteria) admitted to a single centre between 2012 and 2016. The primary outcome was outpatient nephrology review at 3 months. Secondary outcomes included inpatient nephrology review, and outpatient serum creatinine and urinary protein measurements. Data were analysed using multivariable logistic and competing risk regression. RESULTS: Only 117 of 2111 (6%) patients with AKI were reviewed by a nephrologist at 3 months. Reviewed patients were more likely to have a higher discharge serum creatinine (odds ratio (OR) 1.20 per 10 µmol/L increase; 95% confidence interval (CI) 1.16-1.25) or a history of peripheral vascular disease (OR 1.77; 95% CI 1.00-3.14). They were less likely to be older (OR 0.66 per decade; 95% CI 0.57-0.76) or to have a history of liver (OR 0.47; 95% CI 0.26-0.87) or ischaemic heart (OR 0.50; 95% CI 0.27-0.94) disease. AKI stage did not predict follow up. The median time from discharge to outpatient serum creatinine testing was 12 days (interquartile range 4-47) and proteinuria was measured in 538 (25%) patients. CONCLUSIONS: A minority of admitted AKI patients receive recommended post-AKI care. Studies in other Australian institutions are required to confirm or refute these concerning findings.

A pilot study comparing the efficiency of a novel asymmetric cellulose triacetate (ATA) dialyser membrane (Solacea-190H) to a standard high flux polysulfone dialyser membrane (FX-80) in the setting of extended hours haemodialysis.

AIM: To compare small, middle and large-middle molecule clearance; and expression of markers of inflammation, between Solacea-190H (asymmetric cellulose triacetate [ATA]) and FX-80 dialysers in long-hour haemodialysis patients. METHODS: This pilot, randomized cross-over trial recruited 10 home haemodialysis patients. The total study duration was 8 weeks, using each dialyser for 4 weeks. Removal of small (urea, phosphate, creatinine and indoxyl sulfate [IS]), middle and large-middle molecules (beta-2 microglobulin [ß2M], albumin), markers of inflammation (interleukin-6 [IL-6], malondialdehyde-modified low density lipoprotein [MDA-LDL] and alpha-1 microglobulin [α1M]), was evaluated in serum and dialysate samples. RESULTS: Reduction ratios [RR] were calculated for variables at the fourth week of each dialyzer sequence and results expressed as difference in mean RR between dialyzers. There was no difference in clearance of small molecules, with difference in mean RR for urea -2.43 (95% CI -6.44, 1.57; p = .19), creatinine -1.82 (95% CI -5.50, 1.85; p = .28) and phosphate -2.61 (95% CI -12.45, 7.23; p = .55); clearance of middle and large-middle molecules with difference in mean RR (range) for ß2M 2.2 (95% CI -3.2, 7.7; p = .35), IS 1.8 (95% CI -9.5, 13; p = .72) and albumin -0.6 (95% CI -5.5, 4.2; p = .77). There was lack of induction of markers of inflammation, including IL-6 15.2 (95% CI -31.9, 62.2; p = .47), MDA-LDL -8.1 (95% CI -22.1, 5.8; p = .21) and α1M -3.50 (95% CI -29.2, 22.2; p = .76). Dialysate removal results were concurrent. CONCLUSION: This study showed no difference in clearance of small, middle and large-middle molecules, nor expression of markers of inflammation between dialysers.

Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Dietary habits in Australian, New Zealand and Malaysian patients with end stage kidney failure: A pre-specified cross-sectional study of the FAVOURED trial participants.

BACKGROUND: Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with chronic kidney disease (CKD Stage 4-5) have not been adequately investigated. We report the dietary habits of people with advanced CKD and their adherence to country-specific dietary guidelines. METHODS: Participants with CKD Stage 4-5, enrolled in the Omega-3 Fatty Acids (Fish oils) and Aspirin in Vascular access Outcomes in Renal Disease (FAVOURED) trial, completed a lifestyle questionnaire at baseline on their dietary intake. RESULTS: Of 567 participants, 538 (ANZ, n = 386; Malaysian, n = 152; mean ± SD age 54.8 ± 14.3 years, 64% male) completed the questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% (n = 189) consumed ≥2 serves day-1 of fruit and 61% (n = 235) ate ≥2 serves day-1 of vegetables compared to 24% (n = 36) and 34% (n = 52) of Malaysians, respectively (p < 0.0001). Only 4% (n = 15) of ANZ participants met Australian Dietary recommendations of two fruit and five vegetable serves day-1 . Fish consumption was higher in Malaysians with 83% (n = 126) consuming ≥2 serves week-1 compared to 21% (n = 81) of ANZ participants (p < 0.001). Red meat intake was higher in ANZ participants; however, chicken consumption was similar; 48% (n = 185) consumed >2 chicken serves week-1 and 65% (n = 251) ate >2 serves week-1 of red meat compared to 43% (n = 65) and 15% (n = 23) of Malaysians, respectively. CONCLUSIONS: Significant regional variation in dietary intake for fruit, vegetables and animal protein is described that likely reflects cultural and economic differences. Barriers to meeting recommended dietary intakes require further investigation.

Relationship Between Urinary Phosphate and All-Cause and Cardiovascular Mortality in a National Population-Based Longitudinal Cohort Study.

OBJECTIVES: High dietary phosphate intake may lead to adverse outcomes including cardiovascular disease (CVD). Urinary phosphate excretion, a marker of intestinal phosphate absorption, may be a more reliable marker of phosphate homeostasis in steady state than serum phosphate. Studies report good agreement between urine phosphate-to-creatinine ratio (uPiCr) and 24-hour urinary phosphate; however, whether uPiCr is associated with increased risk of CVD or mortality remains uncertain. This study aimed to assess the relationship between uPiCr and all-cause and CVD mortality. DESIGN AND METHODS: This is an observational longitudinal cohort study using data from the population-based national Australian Diabetes, Obesity and Lifestyle study (n = 10,014 participants). Non-linear association between uPiCr and all-cause and CVD mortality was assessed using fractional polynomial transformations. Cox proportional hazards regression models were used to estimate adjusted hazard ratios for all-cause and CVD mortality. RESULTS: Median age [interquartile range] was 50 [41-62] years, and 46% were male. Median uPiCr was 1.38 [1.02-1.79] mmol/mmol. Median follow-up time was 16.9 years with 1,735 deaths. uPiCr was associated with all-cause and CVD mortality in univariate models and when adjusted for age and gender. However, associations were not significant in multivariate models. Sensitivity analyses excluding participants with chronic kidney disease (CKD) revealed a significant J-shaped association between uPiCr and all-cause mortality. Urine phosphate alone showed an association with increased all-cause mortality in a similar J-shape relationship. CONCLUSION: Although no association between uPiCr and all-cause and CVD mortality was observed in multivariate analyses in the whole cohort, a significant relationship between uPiCr and mortality in those without CKD suggests that uPiCr may have predictive validity for future adverse outcomes in people with no CKD.

Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease.

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.

Home Versus Facility Dialysis and Mortality in Australia and New Zealand.

RATIONALE & OBJECTIVE: Mortality is an important outcome for all dialysis stakeholders. We examined associations between dialysis modality and mortality in the modern era. STUDY DESIGN: Observational study comparing dialysis inception cohorts 1998-2002, 2003-2007, 2008-2012, and 2013-2017. SETTING & PARTICIPANTS: Australia and New Zealand (ANZ) dialysis population. EXPOSURE: The primary exposure was dialysis modality: facility hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated PD (APD), or home HD. OUTCOME: The main outcome was death. ANALYTICAL METHODS: Cause-specific proportional hazards models with shared frailty and subdistribution proportional hazards (Fine and Gray) models, adjusting for available confounding covariates. RESULTS: In 52,097 patients, the overall death rate improved from ~15 deaths per 100 patient-years in 1998-2002 to ~11 in 2013-2017, with the largest cause-specific contribution from decreased infectious death. Relative to facility HD, mortality with CAPD and APD has improved over the years, with adjusted hazard ratios in 2013-2017 of 0.88 (95% CI, 0.78-0.99) and 0.91 (95% CI, 0.82-1.00), respectively. Increasingly, patients with lower clinical risk have been adopting APD, and to a lesser extent CAPD. Relative to facility HD, mortality with home HD was lower throughout the entire period of observation, despite increasing adoption by older patients and those with more comorbidities. All effects were generally insensitive to the modeling approach (initial vs time-varying modality, cause-specific versus subdistribution regression), different follow-up time intervals (5 year vs 7 year vs 10 year). There was no effect modification by diabetes, comorbidity, or sex. LIMITATIONS: Potential for residual confounding, limited generalizability. CONCLUSIONS: The survival of patients on PD in 2013-2017 appears greater than the survival for patients on facility HD in ANZ. Additional research is needed to assess whether changing clinical risk profiles over time, varied dialysis prescription, and morbidity from dialysis access contribute to these findings.

Epidemiology and Outcomes of Acute Kidney Diseases: A Comparative Analysis.

INTRODUCTION: Acute kidney diseases and disorders (AKD) encompass acute kidney injury (AKI) and subacute or persistent alterations in kidney function that occur after an initiating event. Unlike AKI, accurate estimates of the incidence and prognosis of AKD are not available and its clinical significance is uncertain. METHODS: We studied the epidemiology and long-term outcome of AKD (as defined by the KDIGO criteria), with or without AKI, in a retrospective cohort of adults hospitalized at a single centre for >24 h between 2012 and 2016 who had a baseline eGFR ≥60 mL/min/1.73 m2 and were alive at 30 days. In patients for whom follow-up data were available, the risks of major adverse kidney events (MAKEs), CKD, kidney failure, and death were examined by Cox and competing risk regression analyses. RESULTS: Among 62,977 patients, 906 (1%) had AKD with AKI and 485 (1%) had AKD without AKI. Follow-up data were available for 36,118 patients. In this cohort, compared to no kidney disease, AKD with AKI was associated with a higher risk of MAKEs (40.25 per 100 person-years; hazard ratio [HR] 2.51, 95% confidence interval [CI] 2.16-2.91), CKD (27.84 per 100 person-years); subhazard ratio [SHR] 3.18, 95% CI 2.60-3.89), kidney failure (0.56 per 100 person-years; SHR 24.84, 95% CI 5.93-104.03), and death (14.86 per 100 person-years; HR 1.52, 95% CI 1.20-1.92). Patients who had AKD without AKI also had a higher risk of MAKEs (36.21 per 100 person-years; HR 2.26, 95% CI 1.89-2.70), CKD (22.94 per 100 person-years; SHR 2.69, 95% CI 2.11-3.43), kidney failure (0.28 per 100 person-years; SHR 12.63, 95% CI 1.48-107.64), and death (14.86 per 100 person-years; HR 1.57, 95% CI 1.19-2.07). MAKEs after AKD were driven by CKD, especially in the first 3 months. CONCLUSIONS: These findings establish the burden and poor prognosis of AKD and support prioritisation of clinical initiatives and research strategies to mitigate such risk.