Global variations in funding and use of hemodialysis accesses: an international report using the ISN Global Kidney Health Atlas.

BACKGROUND: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. METHODS: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. RESULTS: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). CONCLUSIONS: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Global Kidney Health priorities - Perspectives from the ISN-GKHA.

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) that uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems, and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforce, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders, and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, and resource-sensitive manners. Policies to increase use of public funding for kidney care, lower cost of KRT, and increase workforce should be high-priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities.

Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol.

INTRODUCTION: Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS: This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION: Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER: CRD42023421799.

Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.

Chronic thrombotic microangiopathy presenting as acute nephrotic syndrome in a patient with renal cancer receiving tyrosine kinase inhibitor therapy.

Thrombotic microangiopathy (TMA) is a rare but serious side effect of tyrosine kinase inhibitor (TKI) therapy. Previous case reports of renal TMA have usually occurred in the first few months of TKI initiation with only very few cases occurring within 2-3 years. We report a case of a patient who was referred to the Nephrology service for nephrotic syndrome and worsening renal function after 8 years of sunitinib therapy for metastatic clear cell carcinoma of the kidney. Renal biopsy showed chronic TMA without another secondary aetiology identified. With discontinuation of sunitinib and pharmacological optimisation of his hypertension, his renal function and proteinuria both significantly improved. No relapse or recurrence of disease activity was noted after a year of follow-up. This case highlights the importance of remaining vigilant for the development of renal TMA even after an extended duration of TKI therapy.

Global variability of vascular and peritoneal access for chronic dialysis.

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries.

Ibuprofen-Induced Renal Tubular Acidosis: Case Report on a Not-So-Basic Clinical Conundrum.

Rationale: Renal tubular acidosis (RTA) is a cause of non-anion gap metabolic acidosis (NAGMA) that is infrequently diagnosed and is due to various underlying etiologies that impair the kidney's ability to retain bicarbonate or excrete acid. Ibuprofen is an over-the-counter non-steroidal anti-inflammatory medication that is used by patients widely for a variety of reasons. Although it is well known that ibuprofen and other non-steroidal anti-inflammatory drugs may have nephrotoxic effects, the role of ibuprofen as a cause of RTA and hypokalemia is not well recognized. Presenting Concerns: A 66-year-old man with chemotherapy-treated lymphoma in remission and ongoing heavy ibuprofen use for chronic pain presented to hospital with a 1-week history of increasing lethargy and otherwise unremarkable review of systems. Investigations showed acute kidney injury, hypokalemia, hyperchloremia, and NAGMA with elevated urinary pH and positive urine anion gap. Diagnoses: The final diagnosis of distal RTA secondary to ibuprofen was made after ruling out gastrointestinal bicarbonate loss and additional secondary causes of RTA, including other medications, autoimmune conditions, and obstructive uropathy. Interventions: The patient was admitted and treated with intravenous sodium bicarbonate for 24 hours with correction of hypokalemia via oral supplementation. His ibuprofen-containing medication was discontinued. Outcomes: His acute kidney injury and electrolyte abnormalities resolved within 48 hours of initiating treatment with concurrent resolution of his lethargy. He was discharged home and advised to stop taking ibuprofen. Lessons Learned: We report a case of patient with hypokalemia and NAGMA secondary to ibuprofen and highlight the importance of monitoring for this side effect in patients taking ibuprofen.

Justification: L'acidose tubulaire rénale (ATR) est une cause d'acidose métabolique à trou non anionique (AMTNA) qui est rarement diagnostiquée. L'ATR est attribuable à diverses étiologies sous-jacentes qui altèrent la capacité du rein à retenir le bicarbonate ou à excréter l'acide. L'ibuprofène est un anti-inflammatoire non stéroïdien en vente libre, ce médicament est largement utilisé par les patients pour diverses raisons. Bien qu'on sache que l'ibuprofène et d'autres anti-inflammatoires non stéroïdiens (AINS) peuvent avoir des effets néphrotoxiques, le rôle de l'ibuprofène en tant que cause d'ATR et d'hypokaliémie n'est pas bien reconnu. Présentation du cas: Un homme âgé de 66 ans en rémission d'un lymphome ayant été traité par chimiothérapie s'est présenté à l'hôpital après une semaine de léthargie croissante. Le patient prenait beaucoup d'ibuprofène pour soulager ses douleurs chroniques. La revue des systèmes était par ailleurs sans particularités. Les examens ont révélé une insuffisance rénale aiguë, une hypokaliémie, une hyperchlorémie et une AMTNA avec un pH urinaire élevé et un trou anionique urinaire positif. Diagnostic: Le diagnostic final d'acidose rénale tubulaire distale secondaire à la prise d'ibuprofène a été posé après avoir écarté une perte de bicarbonate au niveau gastro-intestinal et des causes secondaires additionnelles d'ATR, comme la prise d'autres médicaments, des maladies auto-immunes et une uropathie obstructive. Interventions: Le patient a été admis et a reçu une perfusion intraveineuse de bicarbonate de sodium pendant 24 heures avec correction de l'hypokaliémie par supplémentation orale. Le médicament contenant de l'ibuprofène a été arrêté. Résultats: L'insuffisance rénale aiguë et les anomalies électrolytiques se sont résorbées dans les 48 heures suivant le début du traitement, tout comme la léthargie. Le patient a obtenu son congé de l'hôpital avec la recommandation de cesser la prise d'ibuprofène. Enseignements tirés: Nous rapportons le cas d'un patient présentant une hypokaliémie et une AMTNA secondaire à la prise d'ibuprofène et nous soulignons l'importance de surveiller cet effet secondaire chez les patients qui prennent de l'ibuprofène.

Trends in nephrology referral patterns for patients with chronic kidney disease: Retrospective cohort study.

INTRODUCTION: Information on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD). METHODS: Retrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet ≥1 of: Estimated glomerular filtration rate (eGFR) ˂ 30 mL/min/1.73m2, persistent albuminuria (ACR ≥ 300 mg/g, PCR ≥ 500 mg/g, or Udip ≥ 2+), or progressive and persistent decline in eGFR until index nephrology visit (≥ 5 mL/min/1.73m2). RESULTS: Of 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63). CONCLUSIONS: A significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.

Impact of Home Telemonitoring and Management Support on Blood Pressure Control in Nondialysis CKD: A Systematic Review and Meta-Analysis.

Background: Hypertension is a major cause of cardiovascular disease, chronic kidney disease (CKD), and death. Several studies have demonstrated the efficacy of home blood pressure telemonitoring (HBPT) for blood pressure (BP) control and outcomes, but the effects of this intervention remain unclear in patients with CKD. Objective: To determine the impact of HBPT on cardiovascular-related and kidney disease-related outcomes in patients with CKD. Design: Systematic review and meta-analysis. Setting: All studies that met our criteria regardless of country of origin. Participants: Patients with chronic kidney disease included in studies using HBPT for BP assessment and control. Measurements: Descriptive and quantitative analysis of our primary and secondary outcomes. Methods: We searched MEDLINE, Embase, CINAHL Plus, PsycINFO, Cochrane CENTRAL, Web of Science, and gray literature from inception for observational and randomized controlled studies in nondialysis (ND) CKD using HBPT for BP control. We selected studies that used HBPT as intervention (with or without a control arm) for BP control in ND-CKD populations. The primary outcome was change in mean systolic BP (SBP) and mean diastolic BP (DBP). Results: We selected 7 studies from 1669 articles that were initially identified. Overall, pooled estimates in the mean difference (MD) for SBP and DBP were -8.8 mm Hg; 95% confidence interval (CI): -16.2 to -1.4; P = .02 and -2.4 mm Hg; 95% CI: -3.8 to -1.0; P < .001, respectively. For studies comparing intervention with usual care (UC), pooled estimate in MD for SBP was -8.0 mm Hg (P = .02) with no significant reduction for DBP (-2.6 mm Hg; P = .18). In studies without a UC arm, both SBP and DBP were not significantly reduced (P > .05). The pooled estimate in MD for estimated glomerular filtration rate showed a significant improvement (5.4 mL/min/1.73 m2; P < .001). Limitations: Heterogeneity and few available studies for inclusion limited our ability to identify a robust link between HBPT use and BP and kidney function improvement. Conclusion: Home blood pressure telemonitoring is associated with mild lowering of BP and moderately improved kidney function in patients with CKD. However, larger studies with improved designs and prolonged interventions are still needed to assess the effects of HBPT on patients' outcomes. PROSPERO registration ID: CRD42020190705.

Contexte: L'hypertension est une cause majeure de maladie cardiovasculaire, d'insuffisance rénale chronique (IRC) et de mortalité. Plusieurs études ont montré l'efficacité de la télésurveillance de la pression artérielle à domicile (TSPA) pour le contrôle de la pression artérielle (PA) et les évènements cliniques, mais les effets de cette intervention demeurent mal connus chez les patients atteints d'IRC. Objectif: Évaluer l'effet de la TSPA sur les évènements cardiovasculaires et rénaux chez les patients atteints d'IRC. Conception: Revue systématique et méta-analyse. Sources: Toutes les études satisfaisant nos critères, peu importe le pays d'origine. Sujets: Les patients atteints d'IRC inclus dans les études portant sur l'utilisation de la TSPA pour réguler la pression artérielle. Mesures: Analyse descriptive et quantitative de nos résultats primaires et secondaires. Méthodologie: Nous avons consulté les bases de données MEDLINE, embase, CINAHL plus, PsycINFO, Cochrane CENTRAL et Web of Science, de même que la littérature grise depuis leur début, à la recherche des études observationnelles contrôlées et randomisées portant sur l'utilisation de la TSPA pour contrôler la PA chez des patients atteints d'IRC non dialysés. Nous avons sélectionné les études (avec ou sans bras témoin) utilisant l'intervention (TSPA pour contrôler la PA) dans des populations de patients atteints d'IRC non dialysés. Le principal critère d'évaluation était un changement de la pression systolique moyenne (PSM) et de la pression diastolique moyenne (PDM). Résultats: Nous avons retenu sept études parmi les 1 669 articles initialement répertoriés. Dans l'ensemble, les estimations regroupées de la différence moyenne (DM) pour la PSM et la PDM étaient de −8,8 mmHg (IC 95%: −16,2 à −1,4; P = 0,02) et de −2,4 mmHg (IC 95%: −3,8 à −1,0; P < 0,001) respectivement. Dans les études qui comparaient l'intervention aux soins habituels (SH), les estimations regroupées de la DM s'établissaient à −8,0 mmHg (P = 0,02) pour la PSM, sans réduction significative pour la PDM (−2,6 mmHg; P = 0,18). Dans les études sans bras SH, aucune réduction significative n'a été observée pour la PSM et la PDM (P > 0,05). L'estimation groupée de la DM pour le débit de filtration glomérulaire estimé (DFGe) a montré une amélioration significative (5,4 ml/min/1,73 m2; P < 0,001). Limites: Le peu d'études disponibles pour inclusion et leur hétérogénéité limitent notre capacité à établir un lien robuste entre l'utilisation de la TSPA et une amélioration de la PA et de la fonction rénale. Conclusion: La TSPA est associée à une légère baisse de la PA et à une amélioration modérée de la fonction rénale chez les patients atteints d'IRC. Des études de plus grande envergure, avec des conceptions améliorées et des interventions prolongées, sont nécessaires pour mieux évaluer les effets de la TSPA sur les résultats des patients.

Warm Autoimmune Hemolytic Anemia and Pure Red Cell Aplasia during a Severe COVID-19 B.1.1.7 Infection.

Warm autoimmune hemolytic anemia (AIHA) is a rare complication of COVID-19 infection. We report a case of warm AIHA in a patient with COVID-19 pneumonia treated with methylprednisolone and several red blood cell transfusions. Despite treatment of the warm AIHA, the patient's reticulocyte count remained low, and his biochemical markers were suggestive of pure red cell aplasia, which was later attributed to a concurrent parvovirus B19 infection. This case highlights an unusual situation of two separate hematological processes caused by two separate and simultaneous viral infections.

The impact of community-based non-pharmacological interventions on cardiovascular and kidney disease outcomes in remote dwelling Indigenous communities: A scoping review protocol.

INTRODUCTION: Indigenous people represent approximately 5% of the world's population. However, they often have a disproportionately higher burden of cardiovascular disease (CVD) risk and chronic kidney disease (CKD) than their equivalent general population. Several non-pharmacological interventions (e.g., educational) have been used to reduce CVD and kidney disease risk factors in Indigenous groups. The aim of this paper is to describe the protocol for a scoping review that will assess the impact of non-pharmacological interventions carried out in Indigenous and remote dwelling populations to reduce CVD risk factors and CKD. MATERIALS AND METHODS: This scoping review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O'Malley. Both empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be assessed if they focused on interventions targeted at reducing CVD or CKD among Indigenous groups. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. Impact of interventions used will be assessed using the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. A descriptive overview, tabular summaries, and content analysis will be carried out on the extracted data. ETHICS AND DISSEMINATION: This review will collect and analyse evidence on the impact of interventions of research carried out to reduce CVD and CKD among Indigenous populations. Such evidence will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations, and a report. Also, we will disseminate our findings to the government and Indigenous leaders. Ethical approval will not be required for this scoping review as the data used will be extracted from already published studies with publicly accessible data.

Generalized Tetanus in a Canadian Farmer Following Orthopedic Surgery.

Tetanus is extremely rare in developed countries. We report the first documented case of tetanus in the province of Alberta since 2016: a farmer that developed trismus, shoulder stiffness, and fevers eight days following orthopedic surgery. Tetanus immunoglobulin elicited rapid recovery. We highlight risk factors, pathogenesis, epidemiology, and diagnostic challenges.

Impact of quality improvement initiatives to improve CKD referral patterns: a systematic review protocol.

INTRODUCTION: Chronic kidney disease (CKD) is a global-health problem. A significant proportion of referrals to nephrologists for CKD management are early and guideline-discordant, which may lead to an excess number of referrals and increased wait-times. Various initiatives have been tested to increase the proportion of guideline-concordant referrals and decrease wait times. This paper describes the protocol for a systematic review to study the impacts of quality improvement initiatives aimed at decreasing the number of non-guideline concordant referrals, increasing the number of guideline-concordant referrals and decreasing wait times for patients to access a nephrologist. METHODS AND ANALYSIS: We developed this protocol by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (2015). We will search the following empirical electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO and grey literature for studies designed to improve guideline-concordant referrals or to reduce unnecessary referrals of patients with CKD from primary care to nephrology. Our search will include all studies published from database inception to April 2021 with no language restrictions. The studies will be limited to referrals for adult patients to nephrologists. Referrals of patients with CKD from non-nephrology specialists (eg, general internal medicine) will be excluded. ETHICS AND DISSEMINATION: Ethics approval will not be required, as we will analyse data from studies that have already been published and are publicly accessible. We will share our findings using traditional approaches, including scientific presentations, open access peer-reviewed platforms, and appropriate government and public health agencies. PROSPERO REGISTRATION NUMBER: CRD42021247756.

Global eHealth capacity: secondary analysis of WHO data on eHealth and implications for kidney care delivery in low-resource settings.

OBJECTIVE: To describe the use of electronic health (eHealth) in support of health coverage for kidney care across International Society of Nephrology (ISN) regions. DESIGN: Secondary analysis of WHO survey on eHealth as well as use of data from the World Bank, and Internet World Stats on global eHealth services. SETTING: A web-based survey on the use of eHealth in support of universal health coverage. PARTICIPANTS: 125 WHO member states provided response. PRIMARY OUTCOME MEASURES: Availability of eHealth services (eg, electronic health records, telehealth, etc) and governance frameworks (policies) for kidney care across ISN regions. RESULTS: The survey conducted by the WHO received responses from 125 (64.4%) member states, representing 4.4 billion people globally. The number of mobile cellular subscriptions was <100% of the population in Africa, South Asia, North America and North East Asia; the percentage of internet users increased from 2015 to 2020 in all regions. Western Europe had the highest percentage of internet users in all the periods: 2015 (82.0%), 2019 (90.7%) and 2020 (93.9%); Africa had the least: 9.8%, 21.8% and 31.4%, respectively. The North East Asia region had the highest availability of national electronic health record system (75%) and electronic learning access in medical schools (100%), with the lowest in Africa (27% and 39%, respectively). Policies concerning governance aspects of eHealth (eg, privacy, liability, data sharing) were more widely available in high-income countries (55%-93%) than in low-income countries (0%-47%), while access to mobile health for treatment adherence was more available in low-income countries (21%) than in high-income countries (7%). CONCLUSION: The penetration of eHealth services across ISN regions is suboptimal, particularly in low-income countries. Increasing utilisation of internet communication technologies provides an opportunity to improve access to kidney education and care globally, especially in low-income countries.

Telemonitoring and Case Management for Hypertensive and Remote-Dwelling Patients With Chronic Kidney Disease-The Telemonitoring for Improved Kidney Outcomes Study (TIKO): A Clinical Research Protocol.

BACKGROUND: Hypertension, together with poorly controlled blood pressure (BP) are known risk factors for kidney disease and progression to kidney failure as well as increased cardiovascular (CV) morbidity and mortality. Several studies in patients without kidney disease have demonstrated the efficacy of home BP telemonitoring (HBPT) for BP control. OBJECTIVE: The primary aim of this study is to assess the mean difference in systolic BP (SBP) at 12 months, from baseline in remote dwelling patients with hypertension and chronic kidney disease (CKD) in Northern Alberta, Canada, comparing HBPT + usual care versus HBPT + a case manager. Other secondary objectives, including cost-effectiveness and acceptability of HBPT as well as occurrence of adverse events will also be assessed. DESIGN: This study is designed as a pragmatic randomized controlled trial (RCT) of HBPT plus clinical case management compared to HBPT with usual care. SETTING: Peace River region in Northern Alberta Region, Canada. PATIENTS: Primary care patients with CKD and hypertension. MEASUREMENTS: Eligible patients will be randomized 1:1 to HBPT + BP case management versus HBPT + usual care. In the intervention arm, BP will be measured 4 times daily for 1 week, with medications titrated up or down by the study case manager until guideline targets (systolic BP [SBP]: <130 mmHg) are achieved. Once BP is controlled, (ie, to guideline-concordant targets), this 1-week protocol will be repeated every 3 months for 1 year. Patients in the control arm will also follow the same BP measurement protocol; however, there will be no interactions with the case manager; they will share their BP readings with their primary care physicians or nurse practitioners at scheduled visits. LIMITATIONS: Potential limitations of this study include the relatively short duration of follow-up, possible technological pitfalls, and need for patients to own a smartphone and have access to the internet to participate. CONCLUSIONS: As this study will focus on a high-risk population that has been characterized by a large care gap, it will generate important evidence that would allow targeted and effective population-level strategies to be implemented to improve health outcomes for high-risk hypertensive CKD patients in Canada's remote communities. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT number: NCT04098354).

CONTEXTE: L'hypertension et la pression artérielle (PA) mal contrôlée sont des facteurs de risque reconnus pour la néphropathie et la progression vers l'insuffisance rénale, en plus de poser un risque accru de morbidité et de mortalité cardiovasculaires. Plusieurs études chez des patients sans néphropathie ont démontré l'efficacité de la télésurveillance de la PA à domicile (TSPA) pour le contrôle de la PA. OBJECTIFS: Le principal objectif est d'évaluer la différence moyenne de pression artérielle systolique (PAS) après 12 mois par rapport à sa valeur initiale chez des patients atteints d'hypertension et d'insuffisance rénale chronique (IRC) habitant les communautés éloignées du nord de l'Alberta (Canada). Cet objectif sera atteint en comparant la TSPA + soins habituels à la TSPA + gestionnaire de cas. D'autres objectifs secondaires, notamment le rapport coût/efficacité de la TSPA, son acceptation et la survenue d'événements indésirables seront également évalués. TYPE D'ÉTUDE: Cette étude est conçue comme un essai randomisé contrôlé (ERC) pragmatique comparant la TSPA + prise en charge clinique des cas à la TSPA + soins habituels. CADRE: Région de Peace River dans le nord de l'Alberta (Canada). SUJETS: Patients atteints d'IRC et d'hypertension recevant des soins de santé primaires. MESURES: Les patients admissibles seront répartis 1:1 dans le groupe TSPA + prise en charge du cas d'hypertension ou dans le groupe témoin (TSPA + soins habituels). Dans le groupe d'intervention, la PA sera mesurée quatre fois par jour pendant une semaine, avec augmentation ou réduction de la médication par le gestionnaire de cas de l'étude jusqu'à ce que la cible de référence (PAS : <130 mmHg) soit atteinte. Une fois la PA contrôlée (c.-à-d. conforme aux cibles recommandées), ce protocole sur une semaine sera répété tous les trois mois pendant un an. Les patients du groupe témoin suivront le même protocole de mesure de la PA, mais sans interactions avec le gestionnaire de cas, ils transmettront plutôt leurs mesures de PA à leur médecin de soins primaires ou aux infirmières praticiennes lors de visites prévues. LIMITES: Cette étude est notamment limitée par la durée relativement courte du suivi, de possibles difficultés technologiques et la nécessité pour les participants de posséder un téléphone intelligent et d'avoir accès à l'Internet. CONCLUSION: Puisque cette étude se penchera sur une population à risque élevé et marquée par d'importantes lacunes en matière de soins, elle générera des données importantes qui aideront à mettre en œuvre des stratégies ciblées et efficaces au niveau de la population afin d'améliorer les évènements cliniques des patients hypertendus et atteints d'IRC à haut risque habitant les communautés éloignées au Canada.

Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades.

Importance: Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied. Objective: To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time. Data Source: Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology. Study Selection: All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included. Data Extraction and Synthesis: Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine. Main Outcomes and Measures: The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis. Results: Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point. Conclusions and Relevance: The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.

Frequency, predictors, and prognosis of ejection fraction improvement in heart failure: an echocardiogram-based registry study.

AIMS: To identify variables predicting ejection fraction (EF) recovery and characterize prognosis of heart failure (HF) patients with EF recovery (HFrecEF). METHODS AND RESULTS: Retrospective study of adults referred for ≥2 echocardiograms separated by ≥6 months between 2008 and 2016 at the two largest echocardiography centres in Alberta who also had physician-assigned diagnosis of HF. Of 10 641 patients, 3124 had heart failure reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline: while mean EF declined from 30.2% on initial echocardiogram to 28.6% on the second echocardiogram in those patients with persistent HFrEF (defined by <10% improvement in EF), it improved from 26.1% to 46.4% in the 1174 patients (37.6%) with HFrecEF (defined by EF absolute improvement ≥10%). On multivariate analysis, female sex [adjusted odds ratio (aOR) 1.66, 95% confidence interval (CI) 1.40-1.96], younger age (aOR per decade 1.16, 95% CI 1.09-1.23), atrial fibrillation (aOR 2.00, 95% CI 1.68-2.38), cancer (aOR 1.52, 95% CI 1.03-2.26), hypertension (aOR 1.38, 95% CI 1.18-1.62), lower baseline ejection fraction (aOR per 1% decrease 1.07 (1.06-1.08), and using hydralazine (aOR 1.69, 95% CI 1.19-2.40) were associated with EF improvements ≥10%. HFrecEF patients demonstrated lower rates per 1000 patient years of mortality (106 vs. 164, adjusted hazard ratio, aHR 0.70 [0.62-0.79]), all-cause hospitalizations (300 vs. 428, aHR 0.87 [0.79-0.95]), all-cause emergency room (ER) visits (569 vs. 799, aHR 0.88 [0.81-0.95]), and cardiac transplantation or left ventricular assist device implantation (2 vs. 10, aHR 0.21 [0.10-0.45]) compared to patients with persistent HFrEF. Females with HFrEF exhibited lower mortality risk (aHR 0.94 [0.88-0.99]) than males after adjusting for age, time between echocardiograms, clinical comorbidities, medications, and whether their EF improved or not during follow-up. CONCLUSION: HFrecEF patients tended to be younger, female, and were more likely to have hypertension, atrial fibrillation, or cancer. HFrecEF patients have a substantially better prognosis compared to those with persistent HFrEF, even after multivariable adjustment, and female patients exhibit lower mortality risk than men within each subgroup (HFrecEF and persistent HFrEF) even after multivariable adjustment.

The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.