Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Advancing Community Care and Access to Follow-up After Acute Kidney Injury Hospitalization: Design of the AFTER AKI Randomized Controlled Trial.

Background: Acute kidney injury (AKI) is a common complication among hospitalized patients with long-term implications including chronic kidney disease (CKD). Although models are available to predict the risk of advanced CKD after AKI, there is limited evidence regarding follow-up for patients with AKI after hospital discharge, resulting in variable follow-up care. A risk-stratified follow-up approach may improve appropriateness and efficiency of management for CKD among patients at risk of declining kidney function following AKI. Objective: The objective was to compare and evaluate the use of a risk-stratified approach to follow-up care vs usual care for patients with AKI after hospital discharge. Design: This study was a pragmatic randomized controlled trial. Setting: This study was conducted in 2 large urban hospitals in Alberta, Canada. Patients: Hospitalized patients with AKI (KDIGO stage 2 or 3) not previously under the care of a nephrologist, expected to survive greater than 90 days being discharged home. Measurements: We will evaluate whether guideline-recommended CKD care processes are initiated within 90 days, including statin use, angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) use in those with proteinuria or diabetes, and nephrologist follow-up if sustained eGFR <30 mL/min/1.73 m2. We will also assess the feasibility of recruitment and the proportion of patients completing the recommended blood and urine tests at 90 days. Methods: Patients with AKI will be enrolled and randomized near the time of hospital discharge. In the intervention group, low risk patients will receive information regarding AKI, medium risk patients will additionally receive follow-up guidance sent to their primary care physician, and high-risk patients will additionally receive follow-up with a nephrologist. Participants in the intervention and usual care group will receive a requisition for urine testing and bloodwork at 90 days following hospital discharge. Telephone follow-up will be conducted for all study participants at 90 days and 1 year after hospital discharge. Bivariate tests of association will be conducted to evaluate group differences at the follow-up time points. Limitations: We expect there may be challenges with recruitment due to the significant co-existence of comorbidity in this population. Conclusions: If the trial shows a positive effect on these processes for kidney care, it will inform larger-scale trial to determine whether this intervention reduces the incidence of long-term clinical adverse events, including CKD progression, cardiovascular events, and mortality following hospitalization with AKI.

Contexte: L'insuffisance rénale aiguë (IRA) est une complication fréquente chez les patients hospitalisés qui peut avoir des conséquences à long terme, notamment l'insuffisance rénale chronique (IRC). Bien que des modèles de prédiction du risque d'IRC avancée après un épisode d'IRA soient disponibles, peu de données existent sur le suivi des patients atteints d'IRA après leur sortie de l'hôpital, ce qui se traduit par une variabilité dans les soins de suivi. Une approche de suivi stratifiée selon le risque d'IRC peut améliorer la qualité et l'efficacité de la prise en charge de l'IRC chez les patients dont la fonction rénale risque de se détériorer après un épisode d'IRA. Objectifs: Évaluer l'utilisation d'une approche de suivi post-hospitalisation stratifiée selon le risque d'IRC chez les patients atteints d'IRA et la comparer aux soins habituels. Conception: Essai contrôlé randomisé pragmatique. Cadre: Deux grands hôpitaux urbains en Alberta (Canada). Sujets: Patients hospitalisés avec une IRA (stade KDIGO 2 ou 3) qui n'étaient pas suivis auparavant par un néphrologue et dont on prévoyait la survie au-delà de 90 jours après leur sortie de l'hôpital. Mesures: Nous évaluerons si, dans les 90 jours suivant le congé, les soins d'IRC habituels recommandés par les lignes directrices seront amorcés, c'est-à-dire l'utilisation de statines, l'utilisation d'IECA/ARA chez les patients souffrant de protéinurie ou de diabète, et le suivi avec un néphrologue pour les patients avec un DFGe inférieur à 30 ml/min/1,73 m2 de façon soutenue. Nous évaluerons également la faisabilité du recrutement et la proportion de patients qui auront effectué les analyses sanguines et urinaires recommandées à 90 jours. Méthodologie: Les patients atteints d'IRA seront recrutés et randomisés au moment de leur sortie de l'hôpital. Dans le groupe d'intervention, les patients présentant un faible risque d'évolution recevront de l'information sur l'IRA, les patients présentant un risque moyennement élevé recevront en plus des conseils de suivi envoyés à leur médecin de premier recours, et les patients présentant un risque élevé feront également l'objet d'un suivi avec un néphrologue. Les participants des groupes intervention et soins habituels recevront une requête pour des analyses de sang et d'urine 90 jours après la sortie de l'hôpital. Un suivi téléphonique sera effectué auprès de tous les participants à l'étude 90 jours et un an après la sortie de l'hôpital. Des tests d'association bivariés seront effectués pour évaluer les différences entre les groupes aux points temporels de suivi. Limites: Nous nous attendons à ce que le recrutement soit difficile, considérant l'importance des comorbidités dans cette population. Conclusion: Si l'essai montre un effet positif sur ces processus de soins rénaux, il informera un essai à plus grande échelle visant à déterminer si cette intervention réduit l'incidence des événements cliniques indésirables à long terme, notamment la progression de l'IRC, les événements cardiovasculaires et la mortalité après une hospitalisation avec épisode d'IRA.

Managing Medications During "Sick Days" in Patients With Diabetes, Kidney, and Cardiovascular Conditions: A Theory-informed Approach to Intervention Design and Implementation.

OBJECTIVES: Our aim in this work was to: 1) explore barriers and enablers to patient and health-care provider (HCP) behaviours related to sick-day medication guidance (SDMG), 2) identify theory-informed strategies to advise SDMG intervention design, and 3) obtain perspectives on an eHealth tool for this purpose. METHODS: A qualitative descriptive study using qualitative conventional content analysis was undertaken. Interviews and focus groups were held with patients and HCPs from January 2021 to April 2022. Data were analyzed using the Behaviour Change Wheel and Theoretical Domains Framework to inform intervention design. RESULTS: Forty-eight people (20 patients, 13 pharmacists, 12 family physicians, and 3 nurse practitioners) participated in this study. Three interventions were designed to address the identified barriers and enablers: 1) prescriptions provided by a community-based care provider, 2) pharmacists adding a label to at-risk medications, and 3) built-in prompts for prescribing and dispensing software. Most participants accepted the concept of an eHealth tool and identified pharmacists as the ideal point-of-care provider. Challenges for an eHealth tool were raised, including credibility, privacy of data, medical liability, clinician remuneration and workload impact, and equitable access to use of the tool. CONCLUSIONS: Patients and HCPs endorsed non-technology and eHealth innovations as strategies to aid in the delivery of SDMG. These findings can guide the design of future theory-informed SDMG interventions.

Personalising haemodialysis treatment with incremental dialysis for incident patients with end-stage kidney disease: an implementation study protocol.

INTRODUCTION: Incremental dialysis is a personalised dialysis prescription based on residual kidney function that allows for the initial use of shorter duration, less frequent and less intense dialysis. It has been associated with enhanced quality of life and decreased healthcare costs when compared with conventional dialysis. While nephrologists report prescribing incremental dialysis, few dialysis programmes offer a systematic approach in offering and evaluating its use. To move evidence into practice, and in order to improve the safety and quality of providing incremental dialysis care, we have designed an implementation study. This study aims to evaluate the systematic assessment of patients starting facility-based haemodialysis for eligibility for incremental dialysis, and the prescription and monitoring of incremental dialysis treatment. METHODS AND ANALYSIS: A hybrid effectiveness and implementation study design is being used to evaluate the implementation of the programme at dialysis sites in Alberta, Canada. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to capture individual-level and organisational-level impact of the project. Clinical outcomes related to kidney function will be monitored on an ongoing basis, and patient-reported outcomes and experience measures will be collected at baseline and then quarterly throughout the first year of dialysis. ETHICS AND DISSEMINATION: The study was approved by the Health Research Ethics Board of the University of Alberta. The study is funded by the Strategic Clinical Networks of Alberta Health Services. The study will help answer important questions on the effectiveness of incremental dialysis, and inform the acceptability, adoption, feasibility, reach and sustainability of incremental dialysis within provision of haemodialysis care.

Processes of Care After Hospital Discharge for Survivors of Acute Kidney Injury: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Survivors of acute kidney injury (AKI) are at high risk of adverse outcomes. Monitoring of kidney function, screening for proteinuria, use of statins and renin-angiotensin-aldosterone system (RAAS) inhibitors, and nephrology follow-up among survivors have not been fully characterized. We examined these processes of care after discharge in survivors of hospitalized AKI. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: Adults in Alberta, Canada, admitted to the hospital between 2009 and 2017, then followed from their discharge date until 2019 for a median follow-up of 2.7 years. EXPOSURE: Hospital-acquired AKI diagnostically conforming to Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria for stage 2 or stage 3 disease, or the need for acute dialysis. OUTCOME: Outcomes after hospital discharge included the proportion of participants who had evaluation of kidney function, were seen by a specialist or general practitioner, and received postdischarge prescriptions for recommended medications for chronic kidney disease (CKD). ANALYTICAL APPROACH: Cumulative incidence curves to characterize the proportion of participants who received each process of care outcome within the first 90 days and subsequent 1-year follow-up period after hospital discharge. To avoid risks associated with multiple hypothesis testing, differences were not statistically compared across groups. RESULTS: The cohort (n=23,921) included 50.2% men (n=12,015) with a median age of 68.1 [IQR, 56.9-78.8] years. Within 90 days after discharge, 21.2% and 8.6% of patients with and without pre-existing CKD, respectively, were seen by a nephrologist; 60.1% of AKI survivors had at least 1 serum creatinine measured, but only 25.5% had an assessment for albuminuria within 90 days after discharge; 52.7% of AKI survivors with pre-existing CKD, and 51.6% with de novo CKD were prescribed a RAAS inhibitor within 4-15 months after discharge. LIMITATIONS: Retrospective data were collected as part of routine clinical care. CONCLUSIONS: The proportion of patients receiving optimal care after an episode of AKI in Alberta was low and may represent a target for improving long-term outcomes for this population. PLAIN-LANGUAGE SUMMARY: A study in Alberta, Canada, examined the care received by patients with acute kidney disease (AKI) during hospitalization and after discharge between 2007 and 2019. The results showed that a low proportion of patients with moderate to severe AKI were seen by a kidney specialist during hospitalization or within 90 days after discharge. Fewer than 25% of AKI patients had their kidney function monitored with both blood and urine tests within 90 days of discharge. Additionally, about half of AKI survivors with chronic kidney disease (CKD) were prescribed guideline recommended medications for CKD within 15 months after discharge. There is potential to improve health care delivery to these patients both in hospital and after hospital discharge.

A Systematic Bibliometric Analysis of High-Impact Articles in Critical Care Nephrology.

INTRODUCTION: Critical care nephrology is a subspecialty that merges critical care and nephrology in response to shared pathobiology, clinical care, and technological innovations. To date, there has been no description of the highest impact articles. Accordingly, we systematically identified high impact articles in critical care nephrology. METHODS: This was a bibliometric analysis. The search was developed by a research librarian. Web of Science was searched for articles published between January 1, 2000 and December 31, 2020. Articles required a minimum of 30 citations, publication in English language, and reporting of primary (or secondary) original data. Articles were screened by two reviewers for eligibility and further adjudicated by three experts. The "Top 100" articles were hierarchically ranked by adjudication, citations in the 2 years following publication and journal impact factor (IF). For each article, we extracted detailed bibliometric data. Risk of bias was assessed for randomized trials by the Cochrane Risk of Bias tool. Analyses were descriptive. RESULTS: The search yielded 2,805 articles. Following initial screening, 307 articles were selected for full review and adjudication. The Top 100 articles were published across 20 journals (median [IQR] IF 10.6 [8.9-56.3]), 38% were published in the 5 years ending in 2020 and 62% were open access. The agreement between adjudicators was excellent (intraclass correlation, 0.96; 95% CI, 0.84-0.99). Of the Top 100, 44% were randomized trials, 35% were observational, 14% were systematic reviews, 6% were nonrandomized interventional studies and one article was a consensus document. The risk of bias among randomized trials was low. Common subgroup themes were RRT (42%), AKI (30%), fluids/resuscitation (14%), pediatrics (10%), interventions (8%), and perioperative care (6%). The citations for the Top 100 articles were 175 (95-393) and 9 were cited >1,000 times. CONCLUSION: Critical care nephrology has matured as an important subspecialty of critical care and nephrology. These high impact papers have focused largely on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curricula development, to stimulate research, and for quality assurance.

Variations in Incidence and Prognosis of Stage 4 CKD Among Adults Identified Using Different Algorithms: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Clinical guidelines define chronic kidney disease (CKD) as abnormalities of kidney structure or function for>3 months. Assessment of the duration criterion may be implemented in different ways, potentially impacting estimates of disease incidence or prevalence in the population, individual diagnosis, and treatment decisions, especially for more severe cases. We investigated differences in incidence and prognosis of CKD stage G4 identified by 1 of 4 algorithms. STUDY DESIGN: Population-based cohort study in Alberta, Canada. SETTING & PARTICIPANTS: Residents>18 years old with incident CKD stage G4 (eGFR 15-29mL/min/1.73m2) diagnosed between April 1, 2015, and March 31, 2018, based on administrative and laboratory data. EXPOSURE: Four outpatient eGFR-based algorithms, increasing in stringency, for defining cohorts with CKD G4 were evaluated: (1) a single test, (2) first eGFR<30mL/min/1.73m2 and a second eGFR 15-29mL/min/1.73m2 measured>90 days apart (2 tests), (3) ≥2 eGFR measurements of<30mL/min/1.73m2 sustained for>90 days (qualifying period) and the last eGFR in the qualifying period of 15-29mL/min/1.73m2 (relaxed sustained), and (4) ≥2 consecutive measurements of 15-29mL/min/1.73m2 for>90 days (rigorous sustained). OUTCOME: Time to the earliest of death, eGFR improvement (a sustained increase in eGFR to≥30mL/min/1.73m2 for>90 days and>25% increase from the index eGFR), or kidney failure. ANALYTICAL APPROACH: For each of the 4 cohorts, incidence rates and event-specific cumulative incidence functions at 1 year from cohort entry were estimated. RESULTS: The incidence rates of CKD G4 decreased as algorithms became more stringent, from 190.7 (single test) to 79.9 (rigorous sustained) per 100,000 person-years. The 2 cohorts based on sustained reductions in eGFR were of comparable size and 1-year event-specific probabilities. The 2 cohorts based on a single test and a 2-test sequence were larger and experienced higher probabilities of eGFR improvement. LIMITATIONS: A short follow-up period of 1 year and a predominantly White population. CONCLUSIONS: The use of more stringent algorithms for defining CKD G4 results in substantially lower estimates of disease incidence, the identification of a group with a lower probability of eGFR improvement, and a higher risk of kidney failure. These findings can inform implementation decisions of disease definitions in clinical reporting systems and research studies. PLAIN-LANGUAGE SUMMARY: Although guidelines recommend>3 months to define chronic kidney disease (CKD), the methods for defining specific stages, particularly G4 (eGFR 15-29mL/min/1.73m2) when referral to nephrology services is recommended, have been implemented differently across studies and surveillance programs. We studied differences in incidence and prognosis of CKD G4 cohorts identified by 4 algorithms using administrative and outpatient laboratory databases in Alberta, Canada. We found that, compared with a single-test definition, more stringent definitions resulted in a lower disease incidence and identified a group with worse short-term kidney outcomes. These findings highlight the impact of the choice of algorithm used to define CKD G4 on disease burden estimates at the population level, on individual prognosis, and on treatment/referral decisions.

Sex as a biological variable in acute kidney injury.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the preclinical and clinical studies investigating sex as a biological variable, as well as the impact of gender, on the development of and progression of acute kidney injury (AKI). RECENT FINDINGS: Despite a matched degree of ischemia-reperfusion AKI based on measured glomerular filtration rates, male and female mice demonstrated important sex biases in cardiorenal outcomes (1). Although the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI reported that female sex is associated with increased rates of hospital acquired AKI, subsequent meta-analyses do not show increased risk of AKI in women. Recent large scale, multicenter epidemiologic studies suggest males have higher rates of hospital acquired AKI. However, women have been consistently shown to have worse renal outcomes after AKI. There may be also be gender-based differences in presentation to care and management. SUMMARY: Sex is an important biological variable in animal models of acute kidney injury. The impact of sex on AKI likely varies based on the etiology of AKI. Preclinical studies demonstrate the nuances of sex chromosomes, sex hormones and epigenetic factors on AKI, however these have not been well studied in humans. Gender may also impact processes of care, treatment and clinical outcomes related to AKI. The scientific rigor and reproducibility of translational studies benefit from the consideration of sex and gender.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study.

Rationale & Objective: To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Study Design: Retrospective cohort study. Setting & Participants: Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate <15 mL/min/1.73 m2. Exposure: AKI (defined as ≥50% or ≥0.3 mg/dL serum creatinine increase). Outcomes: The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Analytical Approach: Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). Results: There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72 mL/min/1.73 m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. Limitations: We lacked granular data, such as urine output. Conclusions: Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup.

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.

Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Managing 'sick days' in patients with chronic conditions: An exploration of patient and healthcare provider experiences.

INTRODUCTION: People with chronic medical conditions often take medications that improve long-term outcomes but which can be harmful during acute illness. Guidelines recommend that healthcare providers offer instructions to temporarily stop these medications when patients are sick (i.e., sick days). We describe the experiences of patients managing sick days and of healthcare providers providing sick day guidance to their patients. METHODS: We undertook a qualitative descriptive study. We purposively sampled patients and healthcare providers from across Canada. Adult patients were eligible if they took at least two medications for diabetes, heart disease, high blood pressure and/or kidney disease. Healthcare providers were eligible if they were practising in a community setting with at least 1 year of experience. Data were collected using virtual focus groups and individual phone interviews conducted in English. Team members analyzed transcripts using conventional content analysis. RESULTS: We interviewed 48 participants (20 patients and 28 healthcare providers). Most patients were between 50 and 64 years of age and identified their health status as 'good'. Most healthcare providers were between 45 and 54 years of age and the majority practised as pharmacists in urban areas. We identified three overarching themes that summarize the experiences of patients and healthcare providers, largely suggesting a broad spectrum in approaches to managing sick days: Individualized Communication, Tailored Sick Day Practices, and Variation in Knowledge of Sick Day Practices and Relevant Resources. CONCLUSION: It is important to understand the perspectives of both patients and healthcare providers with respect to the management of sick days. This understanding can be used to improve care and outcomes for people living with chronic conditions during sick days. PATIENT OR PUBLIC CONTRIBUTION: Two patient partners were involved from proposal development to the dissemination of our findings, including manuscript development. Both patient partners took part in team meetings and contributed to team decision-making. Patient partners also participated in data analysis by reviewing codes and theme development. Furthermore, patients living with various chronic conditions and healthcare providers participated in focus groups and individual interviews.

Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup.

Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research.

Population-Based Analysis of Nonsteroidal Anti-inflammatory Drug Prescription in Subjects With Chronic Kidney Disease.

Background: Pain is a prevalent symptom experienced by patients with chronic kidney disease (CKD) and appropriate management of pain is an important element of comprehensive care. Nonsteroidal anti-inflammatory drugs (NSAID) are known to be nephrotoxic in persons with CKD. Objective: This study examined the pattern of NSAID prescribing practices in a population based-cohort of patients with CKD. Design: Retrospective cohort study using linked population-based health care data. Setting: Entire province of Alberta, Canada. Participants: All adults in Alberta with eGFR defined CKD G3 or greater between 2009 and 2017 were included. Measurements: CKD was defined using at least 2 outpatient serum creatinine (SCr) greater than 90 days apart; the date of second SCr measurement was used as index date. We determined the incidence of hyperkalemia using the peak serum potassium. Prescription drug information was obtained from the Pharmaceutical Information Network (PIN) database. Methods: All patients were followed from the index date until March 31, 2019, with a minimum follow-up of 2 years. Prescription drug information and the follow-up laboratory testing of serum creatinine and serum potassium were obtained. Patients with kidney failure defined as eGFR < 15 mL/min per 1.73 m2, receiving chronic dialysis, or prior kidney transplant at baseline were excluded. Results: A total of 170 574 adults (mean age 76.3; 44% male) with CKD were identified and followed for a median of 7 years; 27% were dispensed at least 1 NSAID prescription. While there was a trend toward fewer prescriptions in patients with more advanced CKD (P < .001), 16% of those with CKD G4 were prescribed an NSAID. Primary care providers provided 79% of the prescriptions. Among NSAID users, 21% had a follow-up serum creatinine (SCr) within 30 days of the index prescription. Limitations: Data collected were from clinical and administrative databases not created for research purposes. The study cohort is limited to subjects who sought medical care and had a serum creatinine measurement obtained. Measurement of NSAID use is limited to those who were dispensed a prescription, over-the-counter NSAIDs use is not captured. Conclusions: Despite guidelines advocating cautious use of NSAIDs in patients with CKD, this study indicates that there is a discrepancy from best practice recommendations. Effective strategies to better support and educate prescribers, as well as patients, may help reduce inappropriate prescribing and adverse events.

Contexte: La douleur est un symptôme fréquent chez les patients atteints d'insuffisance rénale chronique (IRC); sa prise en charge appropriée est un élément important des soins complets. Les anti-inflammatoires non stéroïdiens (AINS) sont connus pour être néphrotoxiques dans cette population de patients. Objectif: Cette étude a examiné les tendances de prescription d'AINS dans une cohorte de patients atteints d'IRC. Conception: Étude de cohorte rétrospective menée à partir des données couplées de santé de la population étudiée. Cadre: L'ensemble de la province de l'Alberta (Canada). Sujets: Tous les adultes de l'Alberta dont la mesure du DFGe correspondait à une IRC de stade 3 ou plus entre 2009 et 2017. Mesures: L'IRC a été définie par au moins deux mesures espacées de plus de 90 jours du taux de créatinine sérique (Crs) en consultation externe; la date de la deuxième mesure de Crs a servi de date indice. Le pic de potassium sérique a servi à déterminer l'incidence de l'hyperkaliémie. Les renseignements sur les médicaments d'ordonnance sont tirés de la base de données du réseau d'information pharmaceutique. Méthodologie: Tous les patients ont été suivis de leur date indice jusqu'au 31 mars 2019, soit pour un minimum de deux ans. Les renseignements sur les médicaments d'ordonnance et les résultats des tests de suivi pour la créatinine et le potassium sériques ont été obtenus. Les patients qui, au moment de l'inclusion, étaient atteints d'une insuffisance rénale définie par un DFGe inférieur à 15 mL/min/1.73 m2, sous dialyze chronique ou qui avaient reçu une greffe rénale ont été exclus. Résultats: En tout, 170 574 adultes atteints d'IRC (âge moyen: 76,3 ans; 44 % d'hommes) ont été répertoriés et suivis sur une période médiane de 7 ans; 27 % avaient reçu au moins une ordonnance d'AINS. Bien qu'on ait observé une tendance à réduire les prescriptions chez les patients atteints d'un stade plus avancé d'IRC (p < 0,001), 16 % des patients atteints d'IRC G4 avaient reçu une ordonnance d'AINS. Les prestataires de soins primaires étaient responsables de 79 % des ordonnances. Parmi les utilisateurs d'AINS, 21 % avaient une mesure de suivi pour la Crs dans les 30 jours suivant la prescription indice. Limites: Les données proviennent de bases de données cliniques et administratives qui ne sont pas créées à des fins de recherche. La cohorte est limitée aux sujets ayant requis des soins médicaux et pour qui on avait une mesure de créatinine sérique. La mesure de l'utilization d'AINS est limitée aux personnes ayant reçu une ordonnance, l'utilization d'AINS en vente libre n'est pas saisie. Conclusion: Bien que les lignes directrices prônent la prudence en ce qui concerne la prescription d'AINS chez les patients atteints d'IRC, cette étude indique que la pratique diverge des recommandations. Des stratégies efficaces pour soutenir et mieux éduquer les prescripteurs et les patients pourraient contribuer à réduire les prescriptions inappropriées et les effets indésirables.

Use of sodium-glucose cotransporter 2 inhibitors in Alberta adults with chronic kidney disease: a cross-sectional study identifying care gaps to inform knowledge translation.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important kidney and cardiovascular benefits in adults with chronic kidney disease. Among adults with diabetes, we characterized the prevalence of chronic kidney disease eligible for SGLT2 inhibitor treatment, based on definitions of eligibility from trials and diabetes guidelines, and assessed the predictors of SGLT2 inhibitor use. METHODS: We conducted a cross-sectional study using linked administrative data from Alberta Health in adults with diabetes (2002-2019). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2 with severe or greater proteinuria (trial-based definition); or eGFR less than 60 mL/min/1.73 m2 or moderate or greater proteinuria regardless of eGFR (diabetes guideline-based definition). Predictors (sociodemographic characteristics, comorbidities and health care utilization) of SGLT2 inhibitor use were identified using logistic regression. RESULTS: Of 446 315 adults with diabetes, 76 630 (17.2%, guideline-based definition; 12 867 [2.9%], trial-based definition) had chronic kidney disease eligible for SGLT2 inhibitor treatment. A total of 7.1% used SGLT2 inhibitors. Older age, lower hemoglobin A1c (HbA1c) levels, female sex, lower neighbourhood income, rural residence and hospital admission were among variables associated with nonuse of SGLT2 inhibitors (adjusted odds ratios [ORs] from 0.13 [age ≥ 85 yr] to 0.92 [rural residence], p < 0.05). Family physician visits were associated with higher SGLT2 inhibitor use (adjusted OR 4.01, p < 0.001 for > 4 visits/yr). Considering all adults, both with and without diabetes, 162 012 individuals with chronic kidney disease (5% of all Alberta adults) may benefit from treatment with SGLT2 inhibitors. INTERPRETATION: Many adults with chronic kidney disease would derive heart and kidney benefits from treatment with SGLT2 inhibitors but had low SGLT2 inhibitor use as of 2019. Efforts will be needed to address lower use of SGLT2 inhibitors among female, older and lower-income adults, and to enhance primary care and promote awareness of the benefits of SGLT2 inhibitors independent of glycemic control.

Consensus Recommendations for Sick Day Medication Guidance for People With Diabetes, Kidney, or Cardiovascular Disease: A Modified Delphi Process.

RATIONALE & OBJECTIVE: Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies. STUDY DESIGN: A modified Delphi process following guidelines for conducting and reporting Delphi studies. SETTING & PARTICIPANTS: An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by 3 sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow the participants to provide their input and rapidly prioritize and refine ideas. OUTCOME: Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as >75% agreement. ANALYTICAL APPROACH: Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants. RESULTS: The final panel included 26 clinician participants from 4 countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: 5 regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; 6 regarding signs that should prompt urgent contact with a health care provider (including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever); and 14 related to scenarios and strategies for patient self-management (including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent hypoglycemia). There was consensus that renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, sodium/glucose cotransporter 2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10%-20% if blood glucose was elevated. There was consensus on 6 recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking. LIMITATIONS: Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings. CONCLUSIONS: A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies.

A study protocol for improving the delivery of acute kidney replacement therapy (KRT) to critically ill patients in Alberta - DIALYZING WISELY.

BACKGROUND: Acute kidney replacement therapy (KRT) is delivered to acutely ill patients to support organ function and life in the Intensive Care Unit (ICU). Implementing standardized acute KRT pathways can ensure its safe and effective management. At present, there is no standardized approach to the management of acute KRT in Alberta ICUs. METHODS: Dialyzing Wisely is a registry embedded, stepped-wedge, interrupted time-series evaluation of the implementation of a standardized, stakeholder-informed, and evidence-based acute KRT pathway into Alberta ICUs. The acute KRT pathway will consist of two distinct phases. First, we will implement routine monitoring of evidence-informed key performance indicators (KPIs) of acute KRT. Second, we will provide prescriber and program reports for acute KRT initiation patterns. After the implementation of both phases of the pathway, we will evaluate acute KRT performance quarterly and implement a customized suite of interventions aimed at improving performance. We will compare this with baseline and evaluate iterative post implementation effects of the care pathway. DISCUSSION: Dialyzing Wisely will implement, monitor, and report a suite of KPIs of acute KRT, coupled with a care pathway that will transform the quality of acute KRT across ICUs in Alberta. This program will provide a framework for scaling evidence-informed approaches to monitoring and management of acute KRT in other jurisdictions. We anticipate improvements in acute KRT performance, decreased healthcare system costs and improved patient quality of life by decreasing patient dependence on maintenance dialysis. TRIAL REGISTRATION: Clinicaltrials.gov , NCT05186636. Registered 11, January, 2022.

Sick Day Medication Guidance for People With Diabetes, Kidney Disease, or Cardiovascular Disease: A Systematic Scoping Review.

Rationale & Objective: Sick day medication guidance has been promoted to prevent adverse events for people with chronic conditions. Our aim was to summarize the existing sick day medication guidance and the evidence base for the effectiveness of interventions for implementing this guidance. Study Design: Scoping review of quantitative and qualitative studies. Setting & Population: Sick day medication guidance for people with chronic conditions including diabetes mellitus, kidney diseases, and cardiovascular diseases. Selection Criteria for Studies: A search of 6 bibliographic databases (Ovid MEDLINE, Ovid Embase, CINAHL, Scopus, Web of Science Core Collection, and Cochrane Library [via Wiley]) and a comprehensive gray literature search were completed in June 2021. Data Extraction: Intervention and study characteristics were extracted using standardized tools. Analytical Approach: Data were summarized descriptively, and our approach observed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. Results: The literature search identified 2,308 documents, which were screened against the eligibility criteria, leading to 74 documents that were included. The majority of the identified documents (n = 55) were guidelines or educational resources. Of the 19 primary research studies identified, 10 studies described an intervention, with only 2 examining the effect of sick day medication guidance interventions within clinical care and no studies reporting beneficial effects on clinical outcomes. Most documents (n = 58) included guidance specific to patients with diabetes mellitus, with fewer including guidance for patients with chronic kidney disease (n = 9) or heart failure (n = 2). Limitations: Risk of bias was not assessed. Conclusions: Many resources promoting sick day medication guidance have been developed; however, there is very little empirical evidence for the effectiveness of current approaches in implementing sick day medication guidance into practice. Recommendations for the use of sick day medication guidance will require further research to develop consistent, understandable, and usable approaches for its implementation within self-management strategies as well as empirical studies to demonstrate the effectiveness of these interventions.

Effect of Clinical Decision Support With Audit and Feedback on Prevention of Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Randomized Clinical Trial.

Importance: Contrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes. Objective: To determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI. Design, Setting, and Participants: A stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020. Interventions: During the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention. Main Outcomes and Measures: The primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models. Results: Of the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, -2.3% [95% CI, -0.6% to -4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, -12.0% [95% CI, -14.4% to -9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, -15.8% [95% CI, -19.7% to -12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events. Conclusions and Relevance: Among cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT03453996.

Opportunities in digital health and electronic health records for acute kidney injury care.

PURPOSE OF REVIEW: The field of digital health is evolving rapidly with applications relevant to the prediction, detection and management of acute kidney injury (AKI). This review will summarize recent publications in these areas. RECENT FINDINGS: Machine learning (ML) approaches have been applied predominantly for AKI prediction, but also to identify patients with AKI at higher risk of adverse outcomes, and to discriminate different subgroups (subphenotypes) of AKI. There have been multiple publications in this area, but a smaller number of ML models have robust external validation or the ability to run in real-time in clinical systems. Recent studies of AKI alerting systems and clinical decision support systems continue to demonstrate variable results, which is likely to result from differences in local context and implementation strategies. In the design of AKI alerting systems, choice of baseline creatinine has a strong effect on performance of AKI detection algorithms. SUMMARY: Further research is required to overcome barriers to the validation and implementation of ML models for AKI care. Simpler electronic systems within the electronic medical record can lead to improved care in some but not all settings, and careful consideration of local context and implementation strategy is recommended.