Publications by authors named "David W Johnson"

762 Publications

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Diabetes 2021 Mar 18. Epub 2021 Mar 18.

Mater Young Adult Health Centre, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes ( = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m) and 10-year historical uACR, HbA, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACR, 29.7 ± 8.8 vs. 4.5 ± 0.5; < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m higher estimated glomerular filtration rates (modified Schwartz equation; < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8 T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1 T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8 T-cell production of KIM-1.
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http://dx.doi.org/10.2337/db20-1081DOI Listing
March 2021

Renal staffs' understanding of patients' experiences of transition from peritoneal dialysis to in-centre haemodialysis and their views on service improvement: A multi-site qualitative study in England and Australia.

PLoS One 2021 19;16(7):e0254931. Epub 2021 Jul 19.

Faculty of Medicine and Health Sciences, Keele University, Staffordshire, United Kingdom.

Introduction: Many studies have explored patients' experiences of dialysis and other treatments for kidney failure. This is the first qualitative multi-site international study of how staff perceive the process of a patient's transition from peritoneal dialysis to in-centre haemodialysis. Current literature suggests that transitions are poorly coordinated and may result in increased patient morbidity and mortality. This study aimed to understand staff perspectives of transition and to identify areas where clinical practice could be improved.

Methods: Sixty-one participants (24 UK and 37 Australia), representing a cross-section of kidney care staff, took part in seven focus groups and sixteen interviews. Data were analysed inductively and findings were synthesised across the two countries.

Results: For staff, good clinical practice included: effective communication with patients, well planned care pathways and continuity of care. However, staff felt that how they communicated with patients about the treatment journey could be improved. Staff worried they inadvertently made patients fear haemodialysis when trying to explain to them why going onto peritoneal dialysis first is a good option. Despite staff efforts to make transitions smooth, good continuity of care between modalities was only reported in some of the Australian hospitals where, unlike the UK, patients kept the same consultant. Timely access to an appropriate service, such as a psychologist or social worker, was not always available when staff felt it would be beneficial for the patient. Staff were aware of a disparity in access to kidney care and other healthcare professional services between some patient groups, especially those living in remote areas. This was often put down to the lack of funding and capacity within each hospital.

Conclusions: This research found that continuity of care between modalities was valued by staff but did not always happen. It also highlighted a number of areas for consideration when developing ways to improve care and provide appropriate support to patients as they transition from peritoneal dialysis to in-centre haemodialysis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254931PLOS
July 2021

Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.

JAMA Netw Open 2021 Jul 1;4(7):e2117542. Epub 2021 Jul 1.

Sick Kids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Importance: Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization.

Objective: To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables.

Design, Setting, And Participants: This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo.

Exposures: Intravenous magnesium sulfate therapy (40-75 mg/kg).

Main Outcomes And Measures: The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect.

Results: Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001).

Conclusions And Relevance: After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma.

Trial Registration: ClinicalTrials.gov: NCT01429415.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.17542DOI Listing
July 2021

Perspectives on ability to work from patients' receiving dialysis and caregivers: analysis of data from the global SONG initiative.

J Nephrol 2021 Jul 9. Epub 2021 Jul 9.

College of Medicine and Public Health, Flinders University, Adelaide, Australia.

Background: Patients receiving dialysis have low employment rates, which compounds poorer health and socioeconomic outcomes. Reasons for under- and unemployment remain underexplored. We aimed to describe the perspectives of patients receiving hemodialysis (HD) or peritoneal dialysis (PD) and their caregivers on ability to work.

Methods: Data was derived from adult patients' and caregivers' responses from 26 focus groups, two international Delphi surveys and two consensus workshops conducted through the Standardized Outcomes in Nephrology (SONG-HD) and SONG-PD programs. Our secondary thematic analysis identified concepts around ability to work.

Results: Five hundred four patients and 146 caregivers from 86 countries were included. We identified five themes: financial pressures and instability (with subthemes of rationing the budget with increased expenditure, losing financial independence and threatened job security); struggling to meet expectations (burdened by sociocultural norms and striving to protect independence); contending with upheaval of roles and responsibilities (forced to establish a new routine to accommodate work, symptoms disrupting work, prioritizing work and other duties, and adjusting to altered capacity to work); enabling flexibility and control (employment driving decisions about dialysis modality and schedule, workplace providing occupational safety and adaptability, requiring organizational support and planning for a future career); and finding purpose and value (accepting and redefining identity, pride and fulfillment, and protecting mental well-being).

Conclusions: Employment enabled patients to maintain their identity, independence, financial security and mental health. Symptom burden, workplace inflexibility and juggling roles are major challenges. Interventions addressing motivation, workplace flexibility and safety, and establishing goals and routines could support patients' capacities to work, thereby improving overall well-being and productivity.
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http://dx.doi.org/10.1007/s40620-021-01105-yDOI Listing
July 2021

Scope and heterogeneity of outcomes reported in randomized trials in patients receiving peritoneal dialysis.

Clin Kidney J 2021 Jul 31;14(7):1817-1825. Epub 2020 Dec 31.

Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.

Background: Randomized trials can provide evidence to inform decision-making but this may be limited if the outcomes of importance to patients and clinicians are omitted or reported inconsistently. We aimed to assess the scope and heterogeneity of outcomes reported in trials in peritoneal dialysis (PD).

Methods: We searched the Cochrane Kidney and Transplant Specialized Register for randomized trials in PD. We extracted all reported outcome domains and measurements and analyzed their frequency and characteristics.

Results: From 128 reports of 120 included trials, 80 different outcome domains were reported. Overall, 39 (49%) domains were surrogate, 23 (29%) patient-reported and 18 (22%) clinical. The five most commonly reported domains were PD-related infection [59 (49%) trials], dialysis solute clearance [51 (42%)], kidney function [45 (38%)], protein metabolism [44 (37%)] and inflammatory markers/oxidative stress [42 (35%)]. Quality of life was reported infrequently (4% of trials). Only 14 (12%) trials included a patient-reported outcome as a primary outcome. The median number of outcome measures (defined as a different measurement, aggregation and metric) was 22 (interquartile range 13-37) per trial. PD-related infection was the most frequently reported clinical outcome as well as the most frequently stated primary outcome. A total of 383 different measures for infection were used, with 66 used more than once.

Conclusions: Trials in PD include important clinical outcomes such as infection, but these are measured and reported inconsistently. Patient-reported outcomes are infrequently reported and nearly half of the domains were surrogate. Standardized outcomes for PD trials are required to improve efficiency and relevance.
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http://dx.doi.org/10.1093/ckj/sfaa224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243273PMC
July 2021

A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis.

Kidney Int 2021 Jun 28. Epub 2021 Jun 28.

School of Medicine, Faculty of Medicine and Health Sciences, Keele University, Keele, UK.

Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. Heritability of PSTR was estimated using genomic-restricted maximum-likelihood analysis, and the association of PSTR with a genome-wide polygenic risk score was also tested. The mean four hour dialysate/plasma creatinine ratio in participants was 0.70. In 2212 participants of European ancestry, no signal reached genome-wide significance but 23 single nucleotide variants at four loci demonstrated suggestive associations with PSTR. Meta-analysis of the 2850 ancestry stratified regressions revealed five single nucleotide variants at four loci with suggestive correlations with PSTR. Association across ancestry strata was consistent for rs28644184 at the KDM2B locus. The estimated heritability of PSTR was 19% and a significant permuted model polygenic risk score was associated with PSTR. Thus, this genome-wide association study of patients receiving peritoneal dialysis bolsters evidence for a genetic contribution to inter-individual variability in PSTR.
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http://dx.doi.org/10.1016/j.kint.2021.05.037DOI Listing
June 2021

Temporal changes and risk factors of death from early withdrawal within 12 months of dialysis initiation - a cohort study.

Nephrol Dial Transplant 2021 Jun 27. Epub 2021 Jun 27.

Medical School, University of Western Australia, Perth, Australia.

Background: Mortality risk is high soon after dialysis initiation in patients with kidney failure, and dialysis withdrawal is a major cause of early mortality, attributed to psychosocial or medical reasons. The temporal trends and risk factors associated with cause-specific early dialysis withdrawal within 12 months of dialysis initiation remain uncertain.

Methods: Using data from the Australian and New Zealand Dialysis and Transplant Registry, we examined the temporal trends and risk factors associated with mortality attributed to early psychosocial and medical withdrawals in incident adult dialysis patients in Australia between 2005 and 2018 using adjusted competing risk analyses.

Results: Of 32,274 incident dialysis patients, 3390 (11%) experienced death within 12 months post-dialysis initiation. Of these, 1225 (36%) were attributed to dialysis withdrawal, with 484 (14%) psychosocial withdrawals and 741 (22%) medical withdrawals. These patterns remained unchanged over the past two decades. Factors associated with increased risk of death from early psychosocial and medical withdrawals were older age, dialysis via central venous catheter, late referral, and the presence of cerebrovascular disease; while obesity and Asian ethnicity were associated with decreased risk. Risk factors associated with early psychosocial withdrawals were underweight and higher socioeconomic status. Presence of peripheral vascular disease, chronic lung disease, and cancers were associated with early medical withdrawals.

Conclusions: Death from dialysis withdrawal accounted for over 30% of early deaths in kidney failure patients initiated on dialysis and remained unchanged over the past two decades. Several shared risk factors were observed between mortality attributed to early psychosocial and medical withdrawals.
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http://dx.doi.org/10.1093/ndt/gfab207DOI Listing
June 2021

Variation in Peritoneal Dialysis-Related Peritonitis Outcomes in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Am J Kidney Dis 2021 May 28. Epub 2021 May 28.

Division of Nephrology, St. Michael's Hospital and the Keenan Research Center in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. Electronic address:

Rationale & Objective: Peritoneal dialysis (PD)-associated peritonitis is a significant PD-related complication. We describe the likelihood of cure after a peritonitis episode, exploring its association with various patient, peritonitis, and treatment characteristics.

Study Design: Observational prospective cohort study.

Setting & Participants: 1,631 peritonitis episodes (1,190 patients, 126 facilities) in Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States.

Exposure: Patient characteristics (demographics, patient history, laboratory values), peritonitis characteristics (organism category, concomitant exit-site infection), dialysis center characteristics (use of icodextrin and low glucose degradation product solutions, policies regarding antibiotic self-administration), and peritonitis treatment characteristics (antibiotic used).

Outcome: Cure, defined as absence of death, transfer to hemodialysis (HD), PD catheter removal, relapse, or recurrent peritonitis within 50 days of a peritonitis episode.

Analytical Approach: Mixed-effects logistic models.

Results: Overall, 65% of episodes resulted in a cure. Adjusted odds ratios (AOR) for cure were similar across countries (range, 54%-68%), by age, sex, dialysis vintage, and diabetes status. Compared with Gram-positive peritonitis, the odds of cure were lower for Gram-negative (AOR, 0.41 [95% CI, 0.30-0.57]), polymicrobial (AOR, 0.30 [95% CI, 0.20-0.47]), and fungal (AOR, 0.01 [95% CI, 0.00-0.07]) peritonitis. Odds of cure were higher with automated PD versus continuous ambulatory PD (AOR, 1.36 [95% CI, 1.02-1.82]), facility icodextrin use (AOR per 10% greater icodextrin use, 1.06 [95% CI, 1.01-1.12]), empirical aminoglycoside use (AOR, 3.95 [95% CI, 1.23-12.68]), and ciprofloxacin use versus ceftazidime use for Gram-negative peritonitis (AOR, 5.73 [95% CI, 1.07-30.61]). Prior peritonitis episodes (AOR, 0.85 [95% CI, 0.74-0.99]) and concomitant exit-site infection (AOR, 0.41 [95% CI, 0.26-0.64]) were associated with a lower odds of cure.

Limitations: Sample selection may be biased and generalizability may be limited. Residual confounding and confounding by indication limit inferences. Use of facility-level treatment variables may not capture patient-level treatments.

Conclusions: Outcomes after peritonitis vary by patient characteristics, peritonitis characteristics, and modifiable peritonitis treatment practices. Differences in the odds of cure across infecting organisms and antibiotic regimens suggest that organism-specific treatment considerations warrant further investigation.
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http://dx.doi.org/10.1053/j.ajkd.2021.03.022DOI Listing
May 2021

A Systematic Review of Scope and Consistency of Outcome Measures for Physical Fitness in Chronic Kidney Disease Trials.

Kidney Int Rep 2021 May 13;6(5):1280-1288. Epub 2021 Feb 13.

Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia.

Introduction: Impaired physical fitness is prevalent in people with chronic kidney disease (CKD), associating with an increased risk of mortality, falls, and hospitalization. A plethora of physical fitness outcomes have been reported in randomized trials. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in trials in CKD.

Methods: A systematic review of randomized trials reporting physical fitness outcomes in adults with CKD (not requiring kidney replacement therapy) receiving hemodialysis (HD) or peritoneal dialysis and kidney transplant recipients was conducted. Studies were identified from MEDLINE, Embase, and the Cochrane Library from 2000 to 2019. The scope, frequency, and characteristics of outcome measures were categorized and analyzed.

Results: From 111 trials, 87 tests/measurements were used to evaluate 30 outcomes measures that reported on 23 outcomes, categorized into five domains of physical fitness: neuromuscular fitness (reported in 76% of trials), exercise capacity (64%), physiological-metabolic (49%), body composition (36%), and cardiorespiratory fitness (30%). Neuromuscular fitness was examined by 37 tests/measurements including the physical function component of questionnaires (27%), one-repetition maximum (9%), and hand-grip strength (9%). Outcome measures were assessed by lab-based (58% of all trials), field-based (31%), and patient-reported measures (11%), and commonly evaluated at 12 (30%), 26 (23%) and 52 weeks (10%), respectively.

Conclusion: There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies particularly in the definitions of outcome measures. Standardization in the assessment of physical fitness will likely improve the comparability of trial outcomes and enhance clinical recommendations.
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http://dx.doi.org/10.1016/j.ekir.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116757PMC
May 2021

Recent evidence on the effect of treatment of metabolic acid on the progression of kidney disease.

Curr Opin Nephrol Hypertens 2021 May 19. Epub 2021 May 19.

Australasian Kidney Trials Network, The University of Queensland, Brisbane University of Sydney Department of Nephrology, St George Hospital, Sydney Department of Nephrology, Princess Alexandra Hospital Translational Research Institute, Brisbane The George Institute for Global Health, University of New South Wales Medicine, Sydney, Australia.

Purpose Of Review: Preclinical and epidemiological studies have shown an association between acidosis and progression of chronic kidney disease (CKD) and kidney fibrosis. This review discusses the recent trials evaluating the effect of treatment of metabolic acidosis on kidney outcomes.

Recent Findings: The emerging evidence suggests that bicarbonate treatment may slow the progression of CKD and reduce the risk of kidney failure. However, high-certainty evidence on the efficacy and safety of alkali therapy is still lacking. Ongoing studies are evaluating the effect of veverimer, a novel nonabsorbable polymer, on clinical kidney outcomes.

Summary: Recent studies indicate a potential benefit from reduction in acid load in patients with CKD. Whilst it is reasonable that clinicians institute acid-lowering interventions in CKD patients with acidosis, adequately powered trials are required to evaluate the benefit of correction of metabolic acidosis to delay kidney disease progression.
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http://dx.doi.org/10.1097/MNH.0000000000000728DOI Listing
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Western Europe.

Kidney Int Suppl (2011) 2021 May 12;11(2):e106-e118. Epub 2021 Apr 12.

Intensive Care Nephrology and Transplantation Department, Hopital Tenon, Assistance Publique-Hopitaux de Paris, Paris, France.

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates.
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http://dx.doi.org/10.1016/j.kisu.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084721PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in South Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e97-e105. Epub 2021 Apr 12.

George Institute for Global Health, University of New South Wales (UNSW), New Delhi, India.

Information about disease burden and the available infrastructure and workforce to care for patients with kidney disease was collected for the second edition of the International Society of Nephrology Global Kidney Health Atlas. This paper presents findings for the 8 countries in the South Asia region. The World Bank categorizes Afghanistan and Nepal as low-income; Bangladesh, Bhutan, India, and Pakistan as lower-middle-income; and Sri Lanka and the Maldives as upper-middle-income countries. The prevalence of chronic kidney disease (CKD) in South Asia ranged from 5.01% to 13.24%. Long-term hemodialysis and long-term peritoneal dialysis are available in all countries, but Afghanistan lacks peritoneal dialysis services. Kidney transplantation was available in all countries except Bhutan and Maldives. Hemodialysis was the dominant modality of long-term dialysis, peritoneal dialysis was more expensive than hemodialysis, and kidney transplantation overwhelmingly depended on living donors. Bhutan provided public funding for kidney replacement therapy (dialysis and transplantation); Sri Lanka, India, Pakistan, and Bangladesh had variable funding mechanisms; and Afghanistan relied solely on out-of-pocket expenditure. There were shortages of health care personnel across the entire region. Reporting was variable: Afghanistan and Sri Lanka have dialysis registries but publish no reports, whereas Bangladesh has a transplant registry. South Asia has a large, but poorly documented burden of CKD. Diabetes and hypertension are the major causes of CKD throughout the region with a higher prevalence of infectious causes in Afghanistan and a high burden of CKD of an unknown cause in Sri Lanka and parts of India. The extent and quality of care delivery is suboptimal and variable. Sustainable strategies need to be developed to address the growing burden of CKD in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084730PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Oceania and South East Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e86-e96. Epub 2021 Apr 12.

Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Oceania and South East Asia (OSEA) is a socioeconomically, culturally, and ethnically diverse region facing a rising epidemic of noncommunicable diseases, including chronic kidney disease (CKD). The second iteration of the International Society of Nephrology Global Kidney Health Atlas aimed to provide a comprehensive evaluation of kidney care in OSEA. Of the 30 countries/territories in OSEA, 15 participated in the survey, representing 98.5% of the region's population. The median prevalence of treated kidney failure in OSEA was 1352 per million population (interquartile range, 966-1673 per million population), higher than the global median of 787 per million population. Although the general availability, access, and quality of kidney replacement therapy (i.e., dialysis and transplantation) was high in OSEA, inequalities in accessibility and affordability of kidney replacement therapy across the region resulted in variability between countries. According to the survey results, in a third of the participating countries (mostly lower-income countries), less than half the patients with kidney failure were able to access dialysis, whereas it was readily available to all with minimal out-of-pocket costs in high-income countries; similar variability in access to transplantation was also recorded. Limitations in workforce and resources vary across the region and were disproportionately worse in lower-income countries. There was little advocacy for kidney disease, moderate use of registries, restricted CKD detection programs, and limited availability of routine CKD testing in some high-risk groups across the region. International collaborations, as seen in OSEA, are important initiatives to help close the gaps in CKD care provision across the region and should continue receiving support from the global nephrology community.
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http://dx.doi.org/10.1016/j.kisu.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084715PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization and services for the management of kidney failure in North and East Asia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e77-e85. Epub 2021 Apr 12.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Kidney failure (KF) is a public health problem in all regions of the world. We aim to provide comprehensive information regarding the disease burden of KF and capacity for providing optimal care in the International Society of Nephrology North and East Asia region based on data from the International Society of Nephrology Global Kidney Health Atlas project. Seven of eight jurisdictions participated, and wide variation was found in terms of KF burden and care capacity. Prevalence of long-term dialysis ranged from 88.4 per million population in mainland China to 3251 per million population in Taiwan. Hemodialysis was the predominant modality of dialysis in all jurisdictions, except for Hong Kong, where peritoneal dialysis (PD) was much more prevalent than hemodialysis. All jurisdictions provided public funding for kidney replacement therapy (dialysis and transplantation). Although the frequency and duration of hemodialysis followed a standard pattern in all investigated jurisdictions, the density of nephrologists and kidney replacement therapy centers varied according to income level. Conservative care, whether medically advised or chosen by patients, was available in most jurisdictions. All jurisdictions had official registries for KF and recognized KF as a health priority. These comprehensive data provide information about the burden of KF and capacity to provide optimal care in North and East Asia, which varied greatly across jurisdictions in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084719PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in North America and the Caribbean.

Kidney Int Suppl (2011) 2021 May 12;11(2):e66-e76. Epub 2021 Apr 12.

Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries.
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http://dx.doi.org/10.1016/j.kisu.2021.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084729PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Newly Independent States and Russia.

Kidney Int Suppl (2011) 2021 May 12;11(2):e57-e65. Epub 2021 Apr 12.

High Technology Medical Center University Clinic, Tbilisi State Medical University, Tbilisi, Georgia.

The International Society of Nephrology Global Kidney Health Atlas analyzed the current state of kidney care in Newly Independent States and Russia. Our results demonstrated that the Newly Independent States and Russia region was not an exception and showed the same effect of chronic kidney disease on health and its outcomes, facing many difficulties and challenges in terms of improving kidney care across the countries. This work summarized and presented demographics, health information systems, statistics, and national health policy of the region, as well as characteristics of the burden of chronic kidney disease and kidney failure (KF) of participating countries. Besides significant economic advancement in the region, the collected data revealed existing shortage in KF care providers, essential medications, and health product access for KF care. Moreover, there was low reporting of kidney replacement therapy (dialysis and kidney transplantation) quality indicators and low capacity for long-term hemodialysis, peritoneal dialysis, and kidney transplantation. The financial issues and funding structures for KF care across the region needs strategic support for fundamental changes and further advancement. This article emphasizes the urgent need for further effective regional and international collaborations and partnership for establishment of universal health care systems for KF management.
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http://dx.doi.org/10.1016/j.kisu.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084727PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in the Middle East.

Kidney Int Suppl (2011) 2021 May 12;11(2):e47-e56. Epub 2021 Apr 12.

Division of Nephrology, Department of Medicine, Hasheminejad Kidney Center, Iran University of Medical Sciences, Tehran, Iran.

Kidney failure is the permanent impairment of kidney function associated with increased morbidity, hospitalization, and requirement for kidney replacement therapy. A total of 11 countries in the Middle East region (84.6%) responded to the survey. The prevalence of chronic kidney disease in the region ranged from 5.2% to 10.6%, whereas prevalence of treated kidney failure ranged from 152 to 826 per million population. Overall, the incidence of kidney transplantation was highest in Iran (30.9 per million population) and lowest in Oman and the United Arab Emirates (2.2 and 3.0 per million population, respectively). Long-term hemodialysis services were available in all countries, long-term peritoneal dialysis services were available in 9 (69.2%) countries, and transplantation services were available in most countries of the region. Public funding covered the costs of nondialysis chronic kidney disease care in two-thirds of countries, and kidney replacement therapy in nearly all countries. More than half of the countries had dialysis registries; however, national noncommunicable disease strategies were lacking in most countries. The Middle East is a region with high burden of kidney disease and needs cost-effective measures through effective health care funding to be available to improve kidney care in the region. Furthermore, well-designed and sustainable health information systems are needed in the region to address current gaps in kidney care in the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084726PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Latin America.

Kidney Int Suppl (2011) 2021 May 12;11(2):e35-e46. Epub 2021 Apr 12.

Department of Nephrology, Metro South and Ipswich Nephrology and Transplant Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Latin America is a region with a widely variable socioeconomic landscape, facing a surge in noncommunicable diseases, including chronic kidney disease and kidney failure, exposing significant limitations in the delivery of care. Despite region-wide efforts to explore and address these limitations, much uncertainty remains as to the capacity, accessibility, and quality of kidney failure care in Latin America. Through this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to report on these indicators to provide a comprehensive map of kidney failure care in the region. Survey responses were received from 18 (64.2%) countries, representing 93.8% of the total population in Latin America. The median prevalence and incidence of treated kidney failure in Latin America were 715 and 157 per million population, respectively, the latter being higher than the global median (142 per million population), with Puerto Rico, Mexico, and El Salvador experiencing much of this growing burden. In most countries, public and private systems collectively funded most aspects of kidney replacement therapy (dialysis and transplantation) care, with patients incurring at least 1% to 25% of out-of-pocket costs. In most countries, >90% of dialysis patients able to access kidney replacement therapy received hemodialysis (n = 11; 5 high income and 6 upper-middle income), and only a small minority began with peritoneal dialysis (1%-10% in 67% of countries; n = 12). Few countries had chronic kidney disease registries or targeted detection programs. There is a large variability in the availability, accessibility, and quality of kidney failure care in Latin America, which appears to be subject to individual countries' funding structures, underreliance on cheap kidney replacement therapy, such as peritoneal dialysis, and limited chronic kidney disease surveillance and management initiatives.
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http://dx.doi.org/10.1016/j.kisu.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084731PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Eastern and Central Europe.

Kidney Int Suppl (2011) 2021 May 12;11(2):e24-e34. Epub 2021 Apr 12.

Division of Nephrology, Bezmialem Vakif University, Istanbul, Turkey.

Provision of adequate kidney care for patients with chronic kidney disease or kidney failure (KF) is costly and requires extensive resources. There is an inequality in the global distribution of wealth and resources needed to provide this care. In this second iteration of the International Society of Nephrology Global Kidney Health Atlas, we present data for countries in Eastern and Central Europe. In the region, the median prevalence of chronic kidney disease was 13.15% and treated KF was 764 per million population, respectively, slightly higher than the global median of 759 per million population. In most countries in the region, over 90% of dialysis patients were on hemodialysis and patients with a functioning graft represented less than one-third of total patients with treated KF. The median annual costs for maintenance hemodialysis were close to the global median, and public funding provided nearly universal coverage of the costs of kidney replacement therapy. Nephrologists were primarily responsible for KF care. All countries had the capacity to provide long-term hemodialysis, and 95% had the capacity to provide peritoneal dialysis. Home hemodialysis was generally not available. Kidney transplantation and conservative care were available across most of the region. Almost all countries had official dialysis and transplantation registries. Eastern and Central Europe is a region with a high burden of chronic kidney disease and variable capacity to deal with it. Insufficient funding and workforce shortages coupled with increasing comorbidities among aging patients and underutilization of cost-effective dialysis therapies such as peritoneal dialysis and kidney transplantation may compromise the quality of care for patients with KF. Some workforce shortages could be addressed by improving the organization of nephrological care in some countries of the region.
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http://dx.doi.org/10.1016/j.kisu.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084718PMC
May 2021

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Africa.

Kidney Int Suppl (2011) 2021 May 12;11(2):e11-e23. Epub 2021 Apr 12.

Urinary Tract Diseases Department, Faculty of Medicine and Pharmacy of Casablanca, University Hassan II of Casablanca, Casablanca, Morocco.

Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps regarding kidney care in Africa, chief of which are (i) severe workforce limitations, especially in terms of the number of nephrologists; (ii) low government funding for kidney care; (iii) limited availability, accessibility, reporting, and quality of provided kidney replacement therapy; and (iv) weak national strategies and advocacy for kidney disease. We also identified that within Africa, the availability and accessibility to kidney replacement therapy vary significantly, with North African countries faring far better than sub-Sahara African countries. The evidence suggests an urgent need to increase the workforce and government funding for kidney care, collect adequate information on the burden of kidney disease from African countries, and develop and implement strategies to enhance disease prevention and control across the continent.
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http://dx.doi.org/10.1016/j.kisu.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084720PMC
May 2021

Global variation in kidney care: national and regional differences in the care and management of patients with kidney failure.

Kidney Int Suppl (2011) 2021 May 12;11(2):e1-e3. Epub 2021 Apr 12.

Department of Nephrology, Metro South and Ipswich Nephrology and Transplant Services (MINTS), Princess Alexandra Hospital, Brisbane, Queensland, Australia.

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http://dx.doi.org/10.1016/j.kisu.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084722PMC
May 2021

Development of an international Delphi survey to establish core outcome domains for trials in adults with glomerular disease.

Kidney Int 2021 May 5. Epub 2021 May 5.

Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Outcomes relevant to treatment decision-making are inconsistently reported in trials involving glomerular disease. Here, we sought to establish a consensus-derived set of critically important outcomes designed to be reported in all future trials by using an online, international two-round Delphi survey in English. To develop this, patients with glomerular disease, caregivers and health professionals aged 18 years and older rated the importance of outcomes using a Likert scale and a Best-Worst scale. The absolute and relative importance was assessed and comments were analyzed thematically. Of 1198 participants who completed Round 1, 734 were patients/caregivers while 464 were health care professionals from 59 countries. Of 700 participants that completed Round 2, 412 were patients/caregivers and 288 were health care professionals. Need for dialysis or transplant, kidney function, death, cardiovascular disease, remission-relapse and life participation were the most important outcomes to patients/caregivers and health professionals. Patients/caregivers rated patient-reported outcomes higher while health care professionals rated hospitalization, death and remission/relapse higher. Four themes explained the reasons for their priorities: confronting death and compounded suffering, focusing on specific targets in glomerular disease, preserving meaning in life, and fostering self-management. Thus, consistent reporting of these critically important outcomes in all trials involving glomerular disease is hoped to improve patient-centered decision-making.
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http://dx.doi.org/10.1016/j.kint.2021.04.027DOI Listing
May 2021

Advanced glycation end products as predictors of renal function in youth with type 1 diabetes.

Sci Rep 2021 May 3;11(1):9422. Epub 2021 May 3.

Mater Research Institute, The University of Queensland, TRI, 37 Kent Street, Brisbane, QLD, 4102, Australia.

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFR and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (P = 1.5 × 10). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (P = 2.2 × 10), which increased with diabetes duration (51%; P < 2.2 × 10) and random blood glucose concentrations (56%; P < 2.2 × 10). HbA and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.
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http://dx.doi.org/10.1038/s41598-021-88786-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093271PMC
May 2021

Risk of asthma in children diagnosed with bronchiolitis during infancy: protocol of a longitudinal cohort study linking emergency department-based clinical data to provincial health administrative databases.

BMJ Open 2021 05 3;11(5):e048823. Epub 2021 May 3.

Research Institute, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.

Introduction: The Canadian Bronchiolitis Epinephrine Steroid Trial (CanBEST) and the Bronchiolitis Severity Cohort (BSC) study enrolled infants with bronchiolitis during the first year of life. The CanBEST trial suggested that treatment of infants with a combined therapy of high-dose corticosteroids and nebulised epinephrine reduced the risk of admission to hospital. Our study aims to-(1) quantify the risk of developing asthma by age 5 and 10 years in children treated with high-dose corticosteroid and epinephrine for bronchiolitis during infancy, (2) identify risk factors associated with development of asthma in children with bronchiolitis during infancy, (3) develop asthma prediction models for children diagnosed with bronchiolitis during infancy.

Methods And Analysis: We propose a longitudinal cohort study in which we will link data from the CanBEST and BSC study with routinely collected data from provincial health administrative databases. Our outcome is asthma incidence measured using a validated health administrative data algorithm. Primary exposure will be treatment with a combined therapy of high-dose corticosteroids and nebulised epinephrine for bronchiolitis. Covariates will include type of viral pathogen, disease severity, medication use, maternal, prenatal, postnatal and demographic factors and variables related to health service utilisation for acute lower respiratory tract infection. The risk associated with development of asthma in children treated with high-dose corticosteroid and epinephrine for bronchiolitis will be assessed using multivariable Cox proportional hazards regression models. Prediction models will be developed using multivariable logistic regression analysis and internally validated using a bootstrap approach.

Ethics And Dissemination: Our study has been approved by the ethics board of all four participating sites of the CanBEST and BSC study. Finding of the study will be disseminated to the academic community and relevant stakeholders through conferences and peer-reviewed publications.

Trial Registration Number: ISRCTN56745572; Post-results.
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http://dx.doi.org/10.1136/bmjopen-2021-048823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098926PMC
May 2021

Association of Local Unit Sampling and Microbiology Laboratory Culture Practices With the Ability to Identify Causative Pathogens in Peritoneal Dialysis-Associated Peritonitis in Thailand.

Kidney Int Rep 2021 Apr 2;6(4):1118-1129. Epub 2021 Feb 2.

St. Michael's Hospital, Toronto, Ontario, Canada.

Introduction: This describes variations in facility peritoneal dialysis (PD) effluent (PDE) culture techniques and local microbiology laboratory practices, competencies, and quality assurance associated with peritonitis, with a specific emphasis on factors associated with culture-negative peritonitis (CNP).

Methods: Peritonitis data were prospectively collected from 22 Thai PD centers between May 2016 and October 2017 as part of the Peritoneal Dialysis Outcomes and Practice Patterns Study. The first cloudy PD bags from PD participants with suspected peritonitis were sent to local and central laboratories for comparison of pathogen identification. The associations between these characteristics and CNP were evaluated.

Results: CNP was significantly more frequent in local laboratories (38%) compared with paired PDE samples sent to the central laboratory (12%,  < 0.05). Marked variations were observed in PD center practices, particularly with respect to specimen collection and processing, which often deviated from International Society for Peritoneal Dialysis Guideline recommendations, and laboratory capacities, capabilities, and certification. Lower rates of CNP were associated with PD nurse specimen collection, centrifugation of PDE, immediate transfer of samples to the laboratory, larger hospital size, larger PD unit size, availability of an on-site nephrologist, higher laboratory capacity, and laboratory ability to perform aerobic cultures, undertake standard operating procedures in antimicrobial susceptibilities, and obtain local accreditation.

Conclusion: There were large variations in PD center and laboratory capacities, capabilities, and practices, which in turn were associated with the likelihood of culturing and correctly identifying organisms responsible for causing PD-associated peritonitis. Deviations in practice from International Society for Peritoneal Dialysis guideline recommendations were associated with higher CNP rates.
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http://dx.doi.org/10.1016/j.ekir.2021.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071630PMC
April 2021

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

Am J Nephrol 2021 27;52(4):342-350. Epub 2021 Apr 27.

School of Medicine, University of Melbourne, Melbourne, Victoria, Australia.

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.
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http://dx.doi.org/10.1159/000515231DOI Listing
April 2021

Comparative Efficacy of Bronchiolitis Interventions in Acute Care: A Network Meta-analysis.

Pediatrics 2021 May;147(5)

Alberta Research Centre for Health Evidence and

Context: Uncertainty exists as to which treatments are most effective for bronchiolitis, with considerable practice variation within and across health care sites.

Objective: A network meta-analysis to compare the effectiveness of common treatments for bronchiolitis in children aged ≤2 years.

Data Sources: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to September 1, 2019.

Study Selection: A total 150 randomized controlled trials comparing a placebo or active comparator with any bronchodilator, glucocorticoid steroid, hypertonic saline solution, antibiotic, helium-oxygen therapy, or high-flow oxygen therapy were included.

Data Extraction: Data were extracted by 1 reviewer and independently verified. Primary outcomes were admission rate on day 1 and by day 7 and hospital length of stay. Strength of evidence was assessed by using Confidence in Network Meta-Analysis .

Results: Nebulized epinephrine (odds ratio: 0.64, 95% confidence interval [CI]: 0.44 to 0.93, low confidence) and nebulized hypertonic saline plus salbutamol (odds ratio: 0.44, 95% CI: 0.23 to 0.84, low confidence) reduced the admission rate on day 1. No treatment significantly reduced the admission rate on day 7. Nebulized hypertonic saline (mean difference: -0.64 days, 95% CI: -1.01 to -0.26, low confidence) and nebulized hypertonic saline plus epinephrine (mean difference: -0.91 days, 95% CI: -1.14 to -0.40, low confidence) reduced hospital length of stay.

Limitations: Because we did not report adverse events in this analysis, we cannot make inferences about the safety of these treatments.

Conclusions: Although hypertonic saline alone, or combined with epinephrine, may reduce an infant's stay in the hospital, poor strength of evidence necessitates additional rigorous trials.
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http://dx.doi.org/10.1542/peds.2020-040816DOI Listing
May 2021

Outcome measures for technique survival reported in peritoneal dialysis: A systematic review.

Perit Dial Int 2021 Apr 21:896860821989874. Epub 2021 Apr 21.

School of Medicine, 4212Keele University, Newcastle, UK.

Background: Peritoneal dialysis (PD) technique survival is an important outcome for patients, caregivers and health professionals, however, the definition and measures used for technique survival vary. We aimed to assess the scope and consistency of definitions and measures used for technique survival in studies of patients receiving PD.

Method: MEDLINE, EMBASE and CENTRAL databases were searched for randomised controlled studies (RCTs) conducted in patients receiving PD reporting technique survival as an outcome between database inception and December 2019. The definition and measures used were extracted and independently assessed by two reviewers.

Results: We included 25 RCTs with a total of 3645 participants (41-371 per trial) and follow up ranging from 6 weeks to 4 years. Terminology used included 'technique survival' (10 studies), 'transfer to haemodialysis (HD)' (8 studies) and 'technique failure' (7 studies) with 17 different definitions. In seven studies, it was unclear whether the definition included transfer to HD, death or transplantation and eight studies reported 'transfer to HD' without further definition regarding duration or other events. Of those remaining, five studies included death in their definition of a technique event, whereas death was censored in the other five. The duration of HD necessary to qualify as an event was reported in only four (16%) studies. Of the 14 studies reporting causes of an event, all used a different list of causes.

Conclusion: There is substantial heterogeneity in how PD technique survival is defined and measured, likely contributing to considerable variability in reported rates. Standardised measures for reporting technique survival in PD studies are required to improve comparability.
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http://dx.doi.org/10.1177/0896860821989874DOI Listing
April 2021

Conducting clinical trials during the COVID-19 pandemic-a collaborative trial network response.

Trials 2021 Apr 14;22(1):278. Epub 2021 Apr 14.

Australasian Kidney Trials Network, The University of Queensland, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD, 4102, Australia.

The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.
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http://dx.doi.org/10.1186/s13063-021-05200-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045567PMC
April 2021

Effectiveness of Targeted Interventions on Treatment of Infants With Bronchiolitis: A Randomized Clinical Trial.

JAMA Pediatr 2021 Apr 12. Epub 2021 Apr 12.

Children's Emergency Department, Starship Children's Hospital, Auckland, New Zealand.

Importance: In developed countries, bronchiolitis is the most common reason for infants to be admitted to the hospital, and all international bronchiolitis guidelines recommend supportive care; however, significant variation in practice continues with infants receiving non-evidence-based therapies. Deimplementation research aims to reduce the use of low-value care, and advancing science in this area is critical to delivering evidence-based care.

Objective: To determine the effectiveness of targeted interventions vs passive dissemination of an evidence-based bronchiolitis guideline in improving treatment of infants with bronchiolitis.

Design, Setting, And Participants: This international, multicenter cluster randomized clinical trial included 26 hospitals (clusters) in Australia and New Zealand providing tertiary or secondary pediatric care (13 randomized to intervention, 13 to control) during the 2017 bronchiolitis season. Data were collected on 8003 infants for the 3 bronchiolitis seasons (2014-2016) before the implementation period and 3727 infants for the implementation period (2017 bronchiolitis season, May 1-November 30). Data were analyzed from November 16, 2018, to December 9, 2020.

Interventions: Interventions were developed using theories of behavior change to target key factors that influence bronchiolitis management. These interventions included site-based clinical leads, stakeholder meetings, a train-the-trainer workshop, targeted educational delivery, other educational and promotional materials, and audit and feedback.

Main Outcomes And Measures: The primary outcome was compliance during the first 24 hours of care with no use of chest radiography, albuterol, glucocorticoids, antibiotics, and epinephrine, measured retrospectively from medical records of randomly selected infants with bronchiolitis who presented to the hospital. There were no patient-level exclusions.

Results: A total of 26 hospitals were randomized without dropouts. Analysis was by intention to treat. Baseline data collected on 8003 infants for 3 bronchiolitis seasons (2014-2016) before the implementation period were similar between intervention and control hospitals. Implementation period data were collected on 3727 infants, including 2328 boys (62%) and 1399 girls (38%), with a mean (SD) age of 6.0 (3.2) months. A total of 459 (12%) were Māori (New Zealand), and 295 (8%) were Aboriginal/Torres Strait Islander (Australia). Compliance with recommendations was 85.1% (95% CI, 82.6%-89.7%) in intervention hospitals vs 73.0% (95% CI, 65.3%-78.8%) in control hospitals (adjusted risk difference, 14.1%; 95% CI, 6.5%-21.7%; P < .001).

Conclusions And Relevance: Targeted interventions led to improved treatment of infants with bronchiolitis. This study has important implications for bronchiolitis management and the development of effective interventions to deimplement low-value care.

Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415.
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http://dx.doi.org/10.1001/jamapediatrics.2021.0295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042564PMC
April 2021
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