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

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

Postoperative Outcomes After Gastrointestinal Surgery in Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: This study evaluated the postoperative mortality and morbidity outcomes following the different subtypes of gastrointestinal (GI) surgery over a 15-year period. BACKGROUND: Patients receiving chronic kidney replacement therapy (KRT) experience higher rates of general surgery compared with other surgery types. Contemporary data on the types of surgeries and their outcomes are lacking. KRT was defined as patients requiring chronic dialysis (hemodialysis or peritoneal dilaysis) or having a functioning kidney transplant long-term. METHODS: All incident and prevalent patients aged greater than 18 years identified in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry as receiving chronic KRT were linked with jurisdictional hospital admission datasets between January 1, 2000 until December 31, 2015. Patients were categorized by their KRT modality [hemodialysis (HD), peritoneal dialysis (PD), home hemodialysis (HHD), and kidney transplant (KT)]. GI surgeries were categorized as upper gastrointestinal (UGI), bowel (small and large bowel), anorectal, hernia surgery, cholecystectomy, and appendicectomy. The primary outcome was the rates of the different surgeries, estimated using Poisson models. Secondary outcomes were risks of 30-day/in-hospital postoperative mortality risk and nonfatal outcomes and were estimated using logistic regression. Independent predictors of 30-day mortality were examined using comorbidity-adjusted Cox models. RESULTS: Overall, 46,779 patients on chronic KRT were linked to jurisdictional hospital datasets, and 9,116 patients were identified as having undergone 14,540 GI surgeries with a combined follow-up of 76,593 years. Patients on PD had the highest rates of GI surgery (8 per 100 patient years), with hernia surgery being the most frequent. Patients on PD also had the highest risk of 30-day postoperative mortality following the different types of GI surgery, with the risk being more than 2-fold higher after emergency surgery compared with elective procedures. Infective postoperative complications were more common than cardiac complications. This study also observed a U-shaped association between body mass index (BMI) and mortality, with a nadir in the 30 to 35 kg/m 2 group. CONCLUSIONS: Patients on chronic KRT have high rates of GI surgery and morbidity, particularly in those who receive PD, are older, or are either underweight or moderately obese.

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

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

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

Metformin for preventing the progression of chronic kidney disease.

BACKGROUND: Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence suggests that metformin targets a number of pathways that lead to chronic kidney damage, and long-term use may, therefore, slow the rate of kidney function decline and chronic kidney disease (CKD) progression. OBJECTIVES: To evaluate the effect of metformin therapy on kidney function decline in patients with CKD with or without diabetes mellitus and assess the safety and dose tolerability in this population. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2023 with assistance from an Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that reported kidney-related outcomes with a minimum duration of 12 months delivery of the metformin intervention and whose eligibility criteria included adult participants with either i) a diagnosis of CKD of any aetiology and/or ii) those with a diagnosis of diabetes mellitus. Comparisons included placebo, no intervention, non-pharmacological interventions, other antidiabetic medications or any other active control. Studies that included patients on any modality of kidney replacement therapy were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently carried out data extraction using a standard data extraction form. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review included 11 studies reporting on 8449 randomised participants. Studies were conducted in patient populations with Autosomal Dominant Polycystic Kidney Disease (ADPKD) (four studies) or diabetes mellitus (seven studies). Six studies compared metformin with no active control, four studies compared metformin with active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), and one study included treatment arms that randomised to either metformin, diet and lifestyle modifications, or other antidiabetic therapies. The risk of bias in included studies varied; two studies were abstract-only publications and were judged to have a high risk of bias in most domains. Other included publications were judged to have a low risk of bias in most domains. Across comparisons, GRADE evaluations for most outcomes were judged as low or very low certainty, except for those relating to side effects, tolerance, and withdrawals, which were judged as moderate certainty. The evidence suggests that compared to placebo, metformin may result in i) a slightly smaller decline in kidney function (3 studies, 505 participants: MD 1.92 mL/min, 95% CI 0.33 to 3.51; I2 = 0%; low certainty), ii) very uncertain effects on the incidence of kidney failure (1 study, 753 participants: RR 1.20, 95% CI 0.17 to 8.49), iii) little or no effect on death (3 studies, 865 participants: RR 1.00, 95% CI 0.76 to 1.32; I2 = 0%; moderate certainty), iv) little or no effect on the incidence of serious adverse events (3 studies, 576 participants: RR 1.15, 95% CI 0.76 to 1.72; I2 = 0%; moderate certainty), and v) likely higher incidence of intolerance leading to study withdrawal than placebo (4 studies, 646 participants: RR 2.19, 95% CI 1.46 to 3.27; I2 = 0%; moderate certainty). The certainty of the evidence for proteinuria was very uncertain. Compared to other active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), metformin i) demonstrated very uncertain effects on kidney function decline, ii) may result in little or no difference in death (3 studies, 5608 participants: RR 0.95 95% CI 0.63 to 1.43; I2 = 0%; low certainty), iii) probably results in little or no difference in intolerance leading to study withdrawal (3 studies, 5593 participants: RR 0.92, 95% CI, 0.79 to 1.08; I2 = 0%; moderate certainty), iv) probably results in little or no difference in the incidence of serious adverse events (2 studies, 5545 participants: RR 1.16, 95% CI 0.79 to 1.71; I2 = 0%; moderate certainty), and v) may increase the urinary albumin-creatinine ratio (2 studies, 3836 participants: MD 14.61, 95% CI 8.17 to 21.05; I2 = 0%; low certainty). No studies reported the incidence of kidney failure. AUTHORS' CONCLUSIONS: This review highlights the lack of RCTs reporting on the effects of metformin on kidney function, particularly in patients with CKD. Future research in this field requires adequately powered RCTs comparing metformin to placebo or standard care in those with CKD. Seven ongoing studies were identified in this review, and future updates, including their findings, may further inform the results of this review.

Peritoneal dialysis versus haemodialysis for people commencing dialysis.

BACKGROUND: Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials (RCTs) have evaluated PD versus HD. The benefits and harms of the two modalities remain uncertain. This review includes both RCTs and non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of PD, compared to HD, in people with kidney failure initiating dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies from 2000 to June 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. MEDLINE and EMBASE were searched for NRSIs from 2000 until 28 March 2023. SELECTION CRITERIA: RCTs and NRSIs evaluating PD compared to HD in people initiating dialysis were eligible. DATA COLLECTION AND ANALYSIS: Two investigators independently assessed if the studies were eligible and then extracted data. Risk of bias was assessed using standard Cochrane methods, and relevant outcomes were extracted for each report. The primary outcome was residual kidney function (RKF). Secondary outcomes included all-cause, cardiovascular and infection-related death, infection, cardiovascular disease, hospitalisation, technique survival, life participation and fatigue. MAIN RESULTS: A total of 153 reports of 84 studies (2 RCTs, 82 NRSIs) were included. Studies varied widely in design (small single-centre studies to international registry analyses) and in the included populations (broad inclusion criteria versus restricted to more specific participants). Additionally, treatment delivery (e.g. automated versus continuous ambulatory PD, HD with catheter versus arteriovenous fistula or graft, in-centre versus home HD) and duration of follow-up varied widely. The two included RCTs were deemed to be at high risk of bias in terms of blinding participants and personnel and blinding outcome assessment for outcomes pertaining to quality of life. However, most other criteria were assessed as low risk of bias for both studies. Although the risk of bias (Newcastle-Ottawa Scale) was generally low for most NRSIs, studies were at risk of selection bias and residual confounding due to the constraints of the observational study design. In children, there may be little or no difference between HD and PD on all-cause death (6 studies, 5752 participants: RR 0.81, 95% CI 0.62 to 1.07; I2 = 28%; low certainty) and cardiovascular death (3 studies, 7073 participants: RR 1.23, 95% CI 0.58 to 2.59; I2 = 29%; low certainty), and was unclear for infection-related death (4 studies, 7451 participants: RR 0.98, 95% CI 0.39 to 2.46; I2 = 56%; very low certainty). In adults, compared with HD, PD had an uncertain effect on RKF (mL/min/1.73 m2) at six months (2 studies, 146 participants: MD 0.90, 95% CI 0.23 to 3.60; I2 = 82%; very low certainty), 12 months (3 studies, 606 participants: MD 1.21, 95% CI -0.01 to 2.43; I2 = 81%; very low certainty) and 24 months (3 studies, 334 participants: MD 0.71, 95% CI -0.02 to 1.48; I2 = 72%; very low certainty). PD had uncertain effects on residual urine volume at 12 months (3 studies, 253 participants: MD 344.10 mL/day, 95% CI 168.70 to 519.49; I2 = 69%; very low certainty). PD may reduce the risk of RKF loss (3 studies, 2834 participants: RR 0.55, 95% CI 0.44 to 0.68; I2 = 17%; low certainty). Compared with HD, PD had uncertain effects on all-cause death (42 studies, 700,093 participants: RR 0.87, 95% CI 0.77 to 0.98; I2 = 99%; very low certainty). In an analysis restricted to RCTs, PD may reduce the risk of all-cause death (2 studies, 1120 participants: RR 0.53, 95% CI 0.32 to 0.86; I2 = 0%; moderate certainty). PD had uncertain effects on both cardiovascular (21 studies, 68,492 participants: RR 0.96, 95% CI 0.78 to 1.19; I2 = 92%) and infection-related death (17 studies, 116,333 participants: RR 0.90, 95% CI 0.57 to 1.42; I2 = 98%) (both very low certainty). Compared with HD, PD had uncertain effects on the number of patients experiencing bacteraemia/bloodstream infection (2 studies, 2582 participants: RR 0.34, 95% CI 0.10 to 1.18; I2 = 68%) and the number of patients experiencing infection episodes (3 studies, 277 participants: RR 1.23, 95% CI 0.93 to 1.62; I2 = 20%) (both very low certainty). PD may reduce the number of bacteraemia/bloodstream infection episodes (2 studies, 2637 participants: RR 0.44, 95% CI 0.27 to 0.71; I2 = 24%; low certainty). Compared with HD; It is uncertain whether PD reduces the risk of acute myocardial infarction (4 studies, 110,850 participants: RR 0.90, 95% CI 0.74 to 1.10; I2 = 55%), coronary artery disease (3 studies, 5826 participants: RR 0.95, 95% CI 0.46 to 1.97; I2 = 62%); ischaemic heart disease (2 studies, 58,374 participants: RR 0.86, 95% CI 0.57 to 1.28; I2 = 95%), congestive heart failure (3 studies, 49,511 participants: RR 1.10, 95% CI 0.54 to 2.21; I2 = 89%) and stroke (4 studies, 102,542 participants: RR 0.94, 95% CI 0.90 to 0.99; I2 = 0%) because of low to very low certainty evidence. Compared with HD, PD had uncertain effects on the number of patients experiencing hospitalisation (4 studies, 3282 participants: RR 0.90, 95% CI 0.62 to 1.30; I2 = 97%) and all-cause hospitalisation events (4 studies, 42,582 participants: RR 1.02, 95% CI 0.81 to 1.29; I2 = 91%) (very low certainty). None of the included studies reported specifically on life participation or fatigue. However, two studies evaluated employment. Compared with HD, PD had uncertain effects on employment at one year (2 studies, 593 participants: RR 0.83, 95% CI 0.20 to 3.43; I2 = 97%; very low certainty). AUTHORS' CONCLUSIONS: The comparative effectiveness of PD and HD on the preservation of RKF, all-cause and cause-specific death risk, the incidence of bacteraemia, other vascular complications (e.g. stroke, cardiovascular events) and patient-reported outcomes (e.g. life participation and fatigue) are uncertain, based on data obtained mostly from NRSIs, as only two RCTs were included.

Vitamin D status and intermediate vascular and bone outcomes in chronic kidney disease: a secondary post hoc analysis of IMPROVE-CKD.

BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and has been associated with abnormalities of mineral metabolism and vascular calcification. Vitamin D influences parathyroid hormone values and calcium and phosphate metabolism, and may play a role in vascular function and bone health. We aimed to test our hypothesis that vitamin D deficiency is associated with arterial stiffness, aortic calcification and lower bone mineral density (BMD) in patients with CKD. METHODS: A cross-sectional analysis was performed using baseline data from the IMpact of Phosphate Reduction On Vascular Endpoints in CKD (IMPROVE-CKD) study cohort. Clinical and laboratory parameters were compared between those with and without vitamin D deficiency, defined as 25-hydroxyvitamin D (25(OH)D) <50 nmol/L. Univariable and multivariable linear regression analyses were performed to assess associations between serum 25(OH)D levels and pulse wave velocity (PWV), augmentation index (AIx), abdominal aortic calcification (measured by the Agatston score) and lumbar spine BMD. RESULTS: Baseline 25(OHD) values were available in 208 out of 278 IMPROVE-CKD study participants, with a mean value of 70.1 ± 30.7 nmol/L. Of these, 57 (27%) patients had vitamin D deficiency. Those with 25(OH)D deficiency were more likely to have diabetes (56% vs 38%), cardiovascular disease (54% vs 36%) and lower serum calcium (2.29 ± 0.13 vs 2.34 ± 0.13 mmol/L). On univariable and multivariable regression analyses, baseline 25(OH)D values were not associated with PWV, the AIx, Agatston score or BMD. CONCLUSION: Baseline 25(OH)D levels were not associated with intermediate markers of vascular function and BMD in patients with CKD stages 3b and 4.

Effects of Allopurinol on the Progression of Chronic Kidney Disease.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).

Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Vitamin D Therapy in Adults With CKD: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD. STUDY DESIGN: Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023. SETTING & STUDY POPULATIONS: Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis. Recipients of a kidney transplant were excluded. SELECTION CRITERIA FOR STUDIES: RCTs with≥3 months of follow-up evaluating a vitamin D compound. DATA EXTRACTION: Data were extracted independently by three investigators. ANALYTICAL APPROACH: Treatment estimates were summarized using random effects meta-analysis. Primary review endpoints were all-cause death, cardiovascular death, and fracture. Secondary outcomes were major adverse cardiovascular events, hospitalization, bone mineral density, parathyroidectomy, progression to kidney failure, proteinuria, estimated glomerular filtration rate, hypercalcemia, hyperphosphatemia, biochemical markers of CKD-MBD, and various intermediate outcome measures of cardiovascular disease. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2 tool. Evidence certainty was adjudicated using GRADE. RESULTS: Overall, 128 studies involving 11,270 participants were included. Compared with placebo, vitamin D therapy probably had no effect on all-cause death (relative risk [RR], 1.04; 95% CI, 0.84-1.24); and uncertain effects on fracture (RR, 0.68; 95% CI, 0.37-1.23) and cardiovascular death (RR, 0.73; 95% CI, 0.31-1.71). Compared with placebo, vitamin D therapy lowered serum parathyroid hormone and alkaline phosphatase, but increased serum calcium. LIMITATIONS: Data were limited by trials with short-term follow-up periods, small sample size, and the suboptimal quality. CONCLUSIONS: Vitamin D therapy did not reduce the risk of all-cause death in people with CKD. Effects on fracture and cardiovascular and kidney outcomes were uncertain. TRIAL REGISTRATION: Registered at PROSPERO with study number CRD42017057691. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) is associated with increased risk of death, cardiovascular disease, and fractures. This excess risk is thought to be related to changes in bone and mineral metabolism, leading to the development of CKD-mineral and bone disorder (CKD-MBD) which is characterized by vascular calcification and reduced bone quality. Vitamin D is commonly used in the treatment of this condition. We reviewed randomized controlled trials examining the effect of vitamin D therapy in CKD. We found that vitamin D therapy affects serum biomarkers, including an increase in serum calcium. However, it probably has no effect on risk of all-cause death in CKD, and the effects on other clinical bone, cardiovascular, and kidney outcomes are uncertain.

Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD-results from a placebo-controlled randomized trial.

BACKGROUND: Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. METHODS: The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. RESULTS: A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6-49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4-5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval -39.2, 36.4), P = 0.65] or CPP-II [-18.3% (95% confidence interval -40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. CONCLUSIONS: Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.

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

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

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

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

Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKD.

BACKGROUND: Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD. METHODS: We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence. RESULTS: In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant. CONCLUSIONS: Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.

Trends in Rates of Surgery and Postoperative Mortality Among Patients Receiving Chronic Kidney Replacement Therapy: A Population-based Cohort Study.

OBJECTIVE: To estimate the incidence and postoperative mortality rates of surgery, and variations by age, diabetes, kidney replacement therapy (KRT) modality, and time over a 15-year period. BACKGROUND: Patients with kidney failure receiving chronic KRT (dialysis or kidney transplantation) have increased risks of postoperative mortality and morbidity. Contemporary data on the incidence and types of surgery these patients undergo are lacking. METHODS: This binational population cohort study evaluated all incident and prevalent patients receiving chronic KRT using linked data between Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admission datasets between 2000 and 2015. Patients were categorized by their KRT modality (hemodialysis, peritoneal dialysis, home hemodialysis, and kidney transplant) for each calendar year. Incidence rates for overall surgery and subtypes were estimated using Poisson models. Logistic regression was used to estimate 30-day/in-hospital mortality risk. RESULTS: Overall, 46,497 patients over a median (interquartile range) follow-up of 6.3 years (3.5-10.2 years) underwent 81,332 surgeries. The median incidence rate of surgery remained stable over this period with a median of 14.9 surgeries per 100 patient-years. Annual incidence rate was higher in older people and those with diabetes mellitus. Patients receiving hemodialysis had a higher incidence rate of surgery compared with kidney transplant recipients (15.8 vs 10.0 surgeries per 100 patient-years, respectively). Overall adjusted postoperative mortality rates decreased by >70% over the study period, and were lowest in kidney transplant recipients (1.7%, 95% confidence interval, 1.4-2.0). Postoperative mortality following emergency surgery was >3-fold higher than elective surgery (8.4% vs 2.3%, respectively). CONCLUSIONS: Patients receiving chronic KRT have high rates of surgery and morbidity. Further research into strategies to mitigate perioperative risk remain a priority.

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

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Synbiotics, prebiotics and probiotics for solid organ transplant recipients.

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

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

AIM: The benefits of dialysis in the older population remain highly debated, particularly for certain dialysis modalities. This study aimed to explore the dialysis modality utilization patterns between in-centre haemodialysis (ICHD), peritoneal dialysis (PD) and home haemodialysis (HHD) and their association with outcomes in older persons. METHODS: Older persons (≥75 years) initiating dialysis in Australia and New Zealand from 1999 to 2018 reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry were included. The main aim of the study was to characterize dialysis modality utilization patterns and describe individual characteristics of each pattern. Relationships between identified patterns and survival, causes of death and withdrawal were examined as secondary analyses, where the pattern was considered as the exposure. RESULTS: A total of 10 306 older persons initiated dialysis over the study period. Of these, 6776 (66%) and 1535 (15%) were exclusively treated by ICHD and PD, respectively, while 136 (1%) ever received HHD during their dialysis treatment course. The remainder received both ICHD and PD: 906 (9%) started dialysis on ICHD and 953 (9%) on PD. Different individual characteristics were seen across dialysis modality utilization patterns. Median survival time was 3.0 (95%CI 2.9-3.1) years. Differences in survival were seen across groups and varied depending on the time period following dialysis initiation. Dialysis withdrawal was an important cause of death and varied according to individual characteristics and utilization patterns. CONCLUSION: This study showed that dialysis modality utilization patterns in older persons are associated with mortality, independent of individual characteristics.

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.