Implications of Implementing the 2021 CKD-EPI Equation Without Race on Managing Patients With Kidney Disease in British Columbia, Canada.

Introduction: We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada. Methods: This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years. Results: A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94). Conclusion: CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD.

Machine learning for prediction of chronic kidney disease progression: Validation of the Klinrisk model in the CANVAS Program and CREDENCE trial.

AIM: To validate the Klinrisk machine learning model for prediction of chronic kidney disease (CKD) progression in patients with type 2 diabetes in the pooled CANVAS/CREDENCE trials. MATERIALS AND METHODS: We externally validated the Klinrisk model for prediction of CKD progression, defined as 40% or higher decline in estimated glomerular filtration rate (eGFR) or kidney failure. Model performance was assessed for prediction up to 3 years with the area under the receiver operating characteristic curve (AUC), Brier scores and calibration plots of observed and predicted risks. We compared performance of the model with standard of care using eGFR (G1-G4) and urine albumin-creatinine ratio (A1-A3) Kidney Disease Improving Global Outcomes (KDIGO) heatmap categories. RESULTS: The Klinrisk model achieved an AUC of 0.81 (95% confidence interval [CI] 0.78-0.83) at 1 year, and 0.88 (95% CI 0.86-0.89) at 3 years. The Brier scores were 0.020 (0.018-0.022) and 0.056 (0.052-0.059) at 1 and 3 years, respectively. Compared with the KDIGO heatmap, the Klinrisk model had improved performance at every interval (P < .01). CONCLUSIONS: The Klinrisk machine learning model, using routinely collected laboratory data, was highly accurate in its prediction of CKD progression in the CANVAS/CREDENCE trials. Integration of the model in electronic medical records or laboratory information systems can facilitate risk-based care.

Expanding Access to High KDPI Kidney Transplant for Recipients Aged 60 y and Older: Cost Utility and Survival.

Background: Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease. Methods: We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario). Results: The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive. Conclusions: Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care.

Validation of the Klinrisk chronic kidney disease progression model in the FIDELITY population.

Background: Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk. Methods: The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk. Results: At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome (P = .31). Conclusions: Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.

Randomized Controlled Trial of the Effect of an Exercise Rehabilitation Program on Symptom Burden in Maintenance Hemodialysis: A Clinical Research Protocol.

Background: People receiving hemodialysis experience high symptom burden that contributes to low functional status and poor health-related quality of life. Management of symptoms is a priority for individuals receiving hemodialysis but limited effective treatments exist. There is emerging evidence that exercise programming can improve several common dialysis-related symptoms. Objective: The primary aim of this study is to evaluate the effect of an exercise rehabilitation program on symptom burden in individuals receiving maintenance hemodialysis. Design: Multicenter, randomized controlled, 1:1 parallel, open label, prospective blinded end point trial. Setting: Three facility-based hemodialysis units in Winnipeg, Manitoba, Canada. Participants: Adults aged 18 years or older with end-stage kidney disease receiving facility-based maintenance hemodialysis for more than 3 months, with at least 1 dialysis-related symptom as indicated by the Dialysis Symptom Index (DSI) severity score >0 (n = 150). Intervention: Supervised 26-week exercise rehabilitation program and 60 minutes of cycling during hemodialysis thrice weekly. Exercise intensity and duration were supervised and individualized by the kinesiologist as per participant baseline physical function with gradual progression over the course of the intervention. Control: Usual hemodialysis care (no exercise program). Measurements: Our primary outcome is change in symptom burden at 12 weeks as measured by the DSI severity score. Secondary outcomes include change in modified DSI severity score (includes 10 symptoms most plausible to improve with exercise), change in DSI severity score at 26 and 52 weeks; time to recover post-hemodialysis; health-related quality of life measured using EuroQol (EQ)-5D-5L; physical activity behavior measured by self-report (Godin-Shepherd questionnaire) and triaxial accelerometry; exercise capacity (shuttle walk test); frailty (Fried); self-efficacy for exercise; and 1-year hospitalization and mortality. Methods: Change in primary outcome will be compared between groups by independent 2-tailed t test or Mann-Whitney U test depending on data distribution and using generalized linear mixed models, with study time point as a random effect and adjusted for baseline DSI score. Similarly, change in secondary outcomes will be compared between groups over time using appropriate parametric and nonparametric statistical tests depending on data type and distribution. Limitations: The COVID-19 pandemic restrictions on clinical research at our institution delayed completion of target recruitment and prevented collection of accelerometry and physical function outcome data for 15 months until restrictions were lifted. Conclusions: The application of an exercise rehabilitation program to improve symptom burden in individuals on hemodialysis may ameliorate common symptoms observed in individuals on hemodialysis and result in improved quality of life and reduced disability and morbidity over the long term. Importantly, this pragmatic study, with a standardized exercise intervention that is adaptable to baseline physical function, addresses an important gap in both clinical care of hemodialysis patients and our current knowledge.

Contexte: Les personnes sous hémodialyse éprouvent un grand nombre de symptômes qui contribuent à un faible état fonctionnel et à une mauvaise qualité de vie liée à la santé. La prise en charge des symptômes est une priorité pour les personnes sous hémodialyse, mais les traitements efficaces sont limités. De nouvelles preuves montrent que l'adoption d'un programme d'exercice permettrait d'améliorer plusieurs symptômes courants liés à la dialyse. Objectifs: Le principal objectif de cette étude est d'évaluer l'effet d'un programme de rééducation par l'exercice sur le fardeau des symptômes chez les personnes recevant une hémodialyse d'entretien. Conception: Essai clinique prospectif randomisé-contrôlé, en aveugle, en parallèle 1:1 et ouvert, multicentrique. Cadre: Trois unités d'hémodialyse de Winnipeg, au Manitoba (Canada). Sujets: Des adultes atteints d'insuffisance rénale terminale qui reçoivent des traitements d'hémodialyse d'entretien en centre depuis plus de trois mois et qui présentent au moins un symptôme lié à la dialyse, tel qu'indiqué par un score de gravité de l'indice des symptômes de la dialyse (Dialysis Symptom Index) supérieur à zéro (n = 150). Intervention: Programme supervisé de rééducation par l'exercice d'une durée de 26 semaines et 60 minutes de vélo trois fois par semaine pendant l'hémodialyse. L'intensité et la durée de l'exercice ont été supervisées par un kinésiologue qui les a ensuite personnalisées en fonction de la forme physique initiale du participant en prévoyant une progression graduelle tout au long de l'intervention. Groupe témoin: Soins habituels d'hémodialyse (sans programme d'exercice). Mesures: Notre principal critère de jugement est un changement dans le fardeau lié aux symptômes après 12 semaines, tel que mesuré par le score de gravité de l'indice des symptômes de dialyse (ISD). Les critères d'évaluation secondaires comprennent un changement du score modifié de gravité de l'ISD (portant sur 10 symptômes les plus plausibles de s'améliorer avec l'exercice), la modification du score de gravité de l'ISD après 26 et 52 semaines, le temps de récupération après l'hémodialyse, la qualité de vie liée à la santé mesurée par le questionnaire EQ5D-5L, le comportement lié à l'activité physique mesuré par autoévaluation (questionnaire Godin-Shepherd) et par accéléromètre triaxial, la capacité d'effort (test de marche navette), la fragilité (Fried), le sentiment d'efficacité autodéclaré face à l'exercice, ainsi que les hospitalisations et la mortalité à un an. Méthodologie: Les changements pour le principal critère de jugement seront comparés entre les groupes par un test t bilatéral indépendant ou un test U de Mann-Whitney en fonction de la distribution des données, ainsi qu'à l'aide de modèles linéaires mixtes généralisés avec un point temporel de l'étude comme effet aléatoire et corrigé en fonction du score ISD initial. Les changements dans les résultats secondaires seront comparés entre les groupes au fil du temps à l'aide des tests statistiques paramétriques et non paramétriques appropriés selon le type de données et la distribution. Limites: Les restrictions liées à la pandémie de COVID-19 dans notre établissement ont retardé le recrutement des cibles et empêché pendant 15 mois la collecte de données sur les résultats mesurés par l'accéléromètre et les mesures de la fonction physique, soit jusqu'à ce que les restrictions soient levées. Conclusion: L'adoption d'un programme de rééducation par l'exercice visant à réduire le fardeau lié aux symptômes chez les personnes sous hémodialyse peut améliorer les symptômes courants observés dans cette population et se traduire par une amélioration de la qualité de vie et une réduction de l'invalidité et de la morbidité à long terme. Il convient de noter que cet essai pragmatique, avec son intervention d'exercice standardisée adaptable à la condition physique initiale de la personne, comble une lacune importante dans les soins cliniques des patients sous hémodialyse et dans nos connaissances actuelles.

Patient and Clinician Perspectives: To Create a Better Future for Chronic Kidney Disease, We Need to Talk About Our Kidneys.

Chronic kidney disease (CKD) affects more than one in ten people worldwide. However, results from the REVEAL-CKD study suggest that it is often not diagnosed. Many patients are therefore unaware that they have CKD, putting them at increased risk of disease progression and complications. Empowering patients with knowledge about CKD will allow them to become active participants in their own care, driving improvements in diagnosis rates and changing patient outcomes for the better. In this article, we provide patient and clinician perspectives on the importance of early CKD diagnosis and management. We present an overview of the tests commonly used to diagnose CKD in clinical practice, as well as actionable suggestions for patients, clinicians, and health policymakers that could help improve disease detection and treatment. Navdeep Tangri, a nephrologist and epidemiologist at the University of Manitoba, and Jane DeMeis, a patient living with chronic kidney disease, discuss how results from the REVEAL-CKD study highlight the need for change to improve management of chronic kidney disease. Video Abstract (MP4 141866 KB).

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Impact of a Medical Fitness Model on Incident Major Adverse Cardiovascular Events: A Prospective Cohort Study of 11 000 Members.

BACKGROUND: Cardiovascular disease remains the leading cause of disease burden and death in the world. The medical fitness model may be an alternative public health strategy to address cardiovascular risk factors with medical integrated programming. METHODS AND RESULTS: We performed a retrospective cohort study between January 1, 2005, and December 31, 2015. Adults (aged ≥18 years) who did not have a prior major adverse cardiovascular event were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of start dates in the medical fitness facility group. Multivariate Cox proportional hazards regression models were adjusted for age, sex, socioeconomic status, comorbidities, and year of index date. We stratified the medical fitness facility group into low-frequency attenders (≤1 weekly visit) and regular-frequency attenders (>1 weekly visit). Our primary outcome was a hospitalization for nonfatal myocardial infarction and stroke, heart failure, or cardiovascular death. We included 11 319 medical fitness facility members and 507 400 controls in our study. Compared with controls, members had a lower hazard risk of a major adverse cardiovascular event-plus (hazard ratio [HR], 0.88 [95% CI, 0.81-0.96]). Higher weekly attendance was associated with a lower hazard risk of a major adverse cardiovascular event-plus compared with controls, but the effect was not significant for lower weekly attendance (low-frequency attenders: HR, 0.94 [95% CI, 0.85-1.04]; regular-frequency attenders: HR, 0.77 [95% CI, 0.67-0.89]). CONCLUSIONS: Medical fitness facility membership and attendance at least once per week may lower the risk of a major adverse cardiovascular event-plus. The medical fitness model should be considered as a public health intervention, especially for individuals at risk for cardiovascular disease.

Prediction models for earlier stages of chronic kidney disease.

PURPOSE OF REVIEW: Identifying patients with risk of developing progressive chronic kidney disease (CKD) early is an important step in improving kidney care. This review discusses four recently developed models, two which predict risk of new onset disease, and two which predict progression earlier in the course of disease. RECENT FINDINGS: Several models predicting CKD incidence and progression have been recently developed and externally validated. A connecting theme across these models is the use of data beyond estimated glomerular filtration rate, allowing for greater accuracy and personalization. Two models were developed with stratification by diabetes status, displaying excellent model fit with and without variables like use of diabetes medication and hemoglobin A1C. Another model was designed to be patient facing, not requiring the knowledge of any laboratory values for use. The final model was developed using lab data and machine learning. These models demonstrated high levels of discrimination and calibration in external validation, suggesting suitability for clinical use. SUMMARY: Models that predict risk of CKD onset and progression have the potential to significantly reduce disease burden, financial cost, and environmental output from CKD through upstream disease prevention and slowed progression. These models should be implemented and evaluated prospectively in primary care settings.

Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Clinical Decision Support Tools in the Electronic Medical Record.

The integration of clinical decision support (CDS) tools into electronic medical record (EMR) systems has become common. Although there are many benefits for both patients and providers from successful integration, barriers exist that prevent consistent and effective use of these tools. Such barriers include tool alert fatigue, lack of interoperability between tools and medical record systems, and poor acceptance of tools by care providers. However, successful integration of CDS tools into EMR systems have been reported; examples of these include the Statin Choice Decision Aid, and the Kidney Failure Risk Equation (KFRE). This article reviews the history of EMR systems and its integration with CDS tools, the barriers preventing successful integration, and the benefits reported from successful integration. This article also provides suggestions and strategies for improving successful integration, making these tools easier to use and more effective for care providers.

Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors such as dapagliflozin have been proven effective for slowing chronic kidney disease (CKD) progression in large outcomes trials that mainly included patients with higher levels of albuminuria. Understanding the real-world utilization and effectiveness of these drugs among patients with CKD with lower levels of albuminuria can inform clinical decision-making in this population. METHODS: Claims data from the USA and Japan were used to describe patients with CKD and urinary albumin-to-creatinine ratio (UACR) < 200 mg/g who were eligible for dapagliflozin 10 mg treatment (initiators and untreated) following its approval for CKD. A quantile regression analysis was performed to evaluate the effect of dapagliflozin 10 mg initiation versus no initiation on estimated glomerular filtration rate (eGFR) slope in a propensity score-matched cohort, using a prevalent new-user design. RESULTS: Dapagliflozin initiators (n = 20,407) mostly had stage 3-4 CKD (69-81% across databases). The most common comorbidities were type 2 diabetes, hypertension and cardiovascular disease. At baseline, a renin-angiotensin system inhibitor was prescribed in 53-81% of patients. Eligible but untreated patients were older and had a higher eGFR and lower comorbidity burden than initiators. Following dapagliflozin initiation, the differences in median eGFR slope between initiators and matched non-initiators were 1.07 mL/min/1.73 m2/year (95% confidence interval [CI] 0.40-1.74) in all patients with UACR < 200 mg/g and 1.28 mL/min/1.73 m2/year (95% CI - 1.56 to 4.12) in patients with UACR < 200 mg/g without type 2 diabetes. CONCLUSIONS: Dapagliflozin 10 mg was prescribed to a broad range of patients with CKD. In patients with UACR < 200 mg/g, dapagliflozin initiation was associated with a clinically meaningful attenuation of eGFR slope compared with non-initiation. These findings supplement available clinical efficacy evidence and suggest that dapagliflozin effectiveness may extend to patients with CKD and UACR < 200 mg/g. Graphical Abstract and Video Abstract available for this article. (Video Abstract 245964 kb).

Impact of Canagliflozin on Kidney and Cardiovascular Outcomes by Type 2 Diabetes Duration: A Pooled Analysis of the CANVAS Program and CREDENCE Trials.

OBJECTIVE: The study was undertaken because it was unknown whether the duration of type 2 diabetes modifies the effects of sodium-glucose cotransporter 2 inhibitor canagliflozin on cardiovascular (CV) and kidney outcomes. RESEARCH DESIGN AND METHODS: This post hoc analysis of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program (N = 10,142) and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial (N = 4,401) evaluated hazard ratios and 95% CIs using Cox proportional hazards for the effects of canagliflozin on CV and kidney outcomes, including progression and regression of albuminuria over 5-year intervals of disease duration. RESULTS: Canagliflozin had ranges of benefit across intervals of diabetes duration, with no heterogeneity for major adverse CV events, CV death or heart failure hospitalization, and kidney failure requiring therapy or doubling serum creatinine. Furthermore, canagliflozin reduced albuminuria progression and increased albuminuria regression with no interaction across all diabetes duration subgroups. CONCLUSIONS: Our findings suggest that earlier treatment with canagliflozin confers consistent cardiorenal benefits to individuals with type 2 diabetes.

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis.

SIGNIFICANCE STATEMENT: Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated. BACKGROUND: Metabolic acidosis is common in CKD, but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. METHODS: In a phase 3, double-blind, placebo-controlled trial, patients with CKD (eGFR of 20-40 ml/min per 1.73 m 2 ) and metabolic acidosis (serum bicarbonate of 12-20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite end point of CKD progression, defined as the development of ESKD (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of ≥40% from baseline, or death due to kidney failure. RESULTS: The mean (±SD) baseline eGFR was 29.2±6.3 ml/min per 1.73 m 2 , and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4±2.0 mEq/L after the active treatment run-in. After randomized withdrawal, the mean serum bicarbonate was 22.0±3.0 mEq/L and 20.9±3.3 mEq/L in the veverimer and placebo groups at month 3, and this approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 0.8 to 1.2; P = 0.90). Serious and overall adverse event incidence did not differ between the groups. CONCLUSIONS: Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VALOR-CKD, NCT03710291 .

A Canadian Commentary on the NKF-ASN Task Force Recommendations on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

In 2021, a committee was commissioned by the Canadian Society of Nephrology to comment on the 2021 National Kidney Foundation-American Society of Nephrology Task Force recommendations on the use of race in glomerular filtration rate estimating equations. The committee met on numerous occasions and agreed on several recommendations. However, the committee did not achieve unanimity, with a minority group disagreeing with the scope of the commentary. As a result, this report presents the viewpoint of the majority members. We endorsed many of the recommendations from the National Kidney Foundation-American Society of Nephrology Task Force, most importantly that race should be removed from the estimated glomerular filtration rate creatinine-based equation. We recommend an immediate implementation of the new Chronic Kidney Disease Epidemiology Collaboration equation (2021), which does not discriminate among any group while maintaining precision. Additionally, we recommend that Canadian laboratories and provincial kidney organizations advocate for increased testing and access to cystatin C because the combination of cystatin C and creatinine in revised equations leads to more precise estimates. Finally, we recommend that future research studies evaluating the implementation of the new equations and changes to screening, diagnosis, and management across provincial health programs be prioritized in Canada.

Implementing a Formalized Risk-Based Approach to Determine Candidacy for Multidisciplinary CKD Care: A Descriptive Cohort Study.

Background: The kidney failure risk equation (KFRE) can be used to predict progression to end-stage kidney disease in a clinical setting. Objective: Evaluate implementation of a formalized risk-based approach in nephrologists' outpatient clinics and multidisciplinary chronic kidney disease (CKD) clinics to determine candidacy for multidisciplinary care, and the impact of CKD care selection on clinical outcomes. Design: Population-based descriptive cohort study. Setting: Alberta Kidney Care South. Patients: Adults attending or considered for a multidisciplinary CKD clinic between April 1, 2017, and March 31, 2019. Measurements: Exposure-The course of CKD care assigned by the nephrologist: management at multidisciplinary CKD clinic; management by a nephrologist or primary care physician. Primary Outcome-CKD progression, defined as commencement of kidney replacement therapy (KRT). Secondary Outcomes-Death, emergency department visits, and hospitalizations. Methods: We linked operational data from the clinics (available until March 31, 2019) with administrative health and laboratory data (available until March 31, 2020). Comparisons among patient groups, courses of care, and clinical settings with negative binomial regression count models and calculated unadjusted and fully adjusted incidence rate ratios. For the all-cause death outcome, we used Cox survival models to calculate unadjusted and fully adjusted hazard ratios. Results: Of the 1748 patients for whom a KFRE was completed, 1347 (77%) remained in or were admitted to a multidisciplinary CKD clinic, 310 (18%) were managed by a nephrologist only, and 91 (5%) were referred back for management by their primary care physician. There was a much higher kidney failure risk among patients who remained at or were admitted to a multidisciplinary CKD clinic (median 2-year risk of 34.7% compared with 3.6% and 0.8% who remained with a nephrologist or primary care physician, respectively). None of the people managed by their primary care physician alone commenced KRT, while only 2 (0.6%) managed by a nephrologist without multidisciplinary CKD care commenced KRT. The rates of emergency department visits, hospitalizations, and death were lower in those assigned to management outside the multidisciplinary CKD clinics when compared with those managed in the multidisciplinary care setting. Limitations: The follow-up period may not have been long enough to determine outcomes, and potentially limited generalizability given variability of care in multidisciplinary clinics. Conclusions: Our findings indicate that a portion of patients can be directed to less resource-intensive care without a higher risk of adverse events. Trial registration: Not applicable.

Contexte: L'équation KFRE (Kidney Failure Risk Equation) peut être utilisée en environnement clinique pour prédire le risque d'évolution vers l'insuffisance rénale terminale (IRT). Objectif: Évaluer la mise en œuvre d'une approche structurée fondée sur le risque dans les cliniques multidisciplinaires d'insuffisance rénale chronique (IRC) et les cliniques ambulatoires des néphrologues afin de déterminer l'aptitude des patients à recevoir des soins multidisciplinaires et de mesurer l'incidence des soins d'IRC reçus sur les résultats cliniques. Conception: Étude de cohorte populationnelle descriptive. Cadre: Alberta Kidney Care South. Sujets: Adultes fréquentant ou envisageant de fréquenter une clinique multidisciplinaire d'IRC entre le 1er avril 2017 et le 31 mars 2019. Mesures: Exposition­le parcours de soins d'IRC attribué par le néphrologue ­ prise en charge en clinique multidisciplinaire d'IRC; prise en charge par un néphrologue ou un médecin de premier recours. Principaux résultats­progression de l'IRC, définie comme l'amorce d'une thérapie de remplacement rénal (TRR). Résultats secondaires­décès, visites aux urgences et hospitalisations. Méthodologie: Nous avons couplé les données opérationnelles des cliniques (disponibles jusqu'au 31 mars 2019) aux données administratives de santé et aux données de laboratoire (disponibles jusqu'au 31 mars 2020). Des modèles de régression binomiale négative et des rapports des taux d'incidence non corrigés et entièrement corrigés ont servi aux comparaisons entre les groupes de patients, les parcours de soins et les environnements cliniques. Les risques relatifs non corrigés et entièrement corrigés de décès toutes causes confondues ont été calculés à l'aide de modèles de survie de Cox. Résultats: Des 1 748 patients avec une KFRE calculée, 1 347 (77 %) sont restés ou ont été admis dans une clinique multidisciplinaire d'IRC, 310 (18 %) ont été pris en charge par un néphrologue seulement et 91 (5 %) ont été orientés pour une prise en charge par leur médecin de premier recours. Le risque d'insuffisance rénale terminale était beaucoup plus élevé chez les patients restés ou admis dans une clinique multidisciplinaire d'IRC (risque médian à 2 ans : 34,7 %) que chez ceux pris en charge par un néphrologue (3,6 %) et par un médecin de premier recours (0,8 %). Aucun patient pris en charge par un médecin de premier recours n'avait amorcé une TRR; 2 personnes (0,6 %) prises en charge par un néphrologue sans soins multidisciplinaires d'IRC avaient amorcé une TRR. Les taux de visites aux urgences, d'hospitalisations et de décès étaient plus faibles chez les patients pris en charge à l'extérieur des cliniques multidisciplinaires d'IRC comparativement à ceux pris en charge dans ces cliniques. Limites: La période de suivi n'était peut-être pas été assez longue pour déterminer les résultats. La variabilité des soins dans les cliniques multidisciplinaires pourrait également limiter la généralisation des résultats. Conclusion: Nos résultats suggèrent qu'une partie des patients pourrait être dirigée vers des soins nécessitant moins de ressources sans hausser le risque d'événements indésirables.

Association of body mass index with the development of metabolic acidosis in patients with chronic kidney disease.

Aims: Higher body mass index (BMI) is associated with higher bone mass and bone serves as a buffer during the development of metabolic acidosis. The authors sought to examine the relationship between BMI and metabolic acidosis in patients with chronic kidney disease (CKD). Materials and Methods: The study utilized a large US longitudinal data repository including over 103 million patients from healthcare provider organizations to evaluate the relationship between the exposure variable (BMI) and the prevalence and incidence of metabolic acidosis among patients with estimated glomerular filtration rate <60 ml/min/1.73 m2. Incident metabolic acidosis was identified at the first of two consecutive post-index serum bicarbonate values, 10-365 days apart, between 12 and <22 mEq/L in patients with normal index serum bicarbonate. Cox proportional hazard models were adjusted for multiple variables including demographics, comorbidities, income, education, and kidney function. Results: 103,766 patients qualified for this study; 6472 (6.2%) had metabolic acidosis at index. An inverse association between BMI category and metabolic acidosis was observed for both baseline (prevalence) and new-onset (incidence) metabolic acidosis. Compared to BMI category of 18.5 to <25 kg/m2, each category of incrementally higher BMI was associated with a decreasing risk of incident metabolic acidosis; the adjusted hazard ratios (95% confidence interval) were 0.866 (0.824-0.911), 0.770 (0.729-0.813), 0.664 (0.622-0.709), and 0.612 (0.571-0.655) for BMI 25 to <30, 30 to <35, 35 to <40, and 40+ kg/m2, respectively. Conclusions: Among patients with CKD, an incremental increase in BMI was inversely associated with both the prevalence and incidence of metabolic acidosis. These associations suggest that increased body weight may protect against the development of metabolic acidosis, a risk factor for progressive loss of kidney function.

Use of Wearable and Wireless Technology in Real-World Clinical Settings to Improve Patient Outcomes in Chronic Kidney Disease: A Mixed Methods Pilot Prospective Trial.

Background: During the 30-day period prior to initiating dialysis, there is a 10-fold rise in emergency department visits and hospitalizations related to kidney failure. Objective: The Virtual Ward Incorporating Electronic Wearables (VIEWER) trial implemented a home telemonitoring system to track changes in patients' vitals and assess their adherence and the acceptability of telemonitoring in a chronic kidney disease (CKD) population. Design: A pilot prospective clinical trial using a mixed methods approach was performed. Setting: The research was conducted in Winnipeg, Manitoba. Participants: There were 2 phases: Phase 1 was a 2-week-long pilot trial consisting of 10 participants. Phase 2 was a 3-month-long trial with a total of 26 participants. Patients with an estimated glomerular filtration rate <15 and a >40% risk of beginning dialysis in the next 2 years according to the kidney failure risk equation were eligible to participate in the study. Methods: The primary quantitative outcome was adherence, defined as the proportion of daily self-assessments completed using VIEWER over the follow-up period. The usability and acceptability of VIEWER was assessed qualitatively at the end of the trial through structured questionnaires and focus groups. Results: Phase 1 participants (n = 10) had a median adherence of 77.17% for the 2-week observation period. Phase 2 participants (n = 26) showed a lower median adherence of 36% for the 3-month period. Focus group participants (n = 11) identified many positive aspects of VIEWER, including increased awareness and empowerment over health, simplicity of the data platform, and the ability to show clinical staff their health trends. Some challenges identified with VIEWER were connectivity issues with the Bluetooth, perceived inconvenience, and negative thoughts toward their health. Limitations: Limitations of the study include a small sample size, which limited our ability to measure quantitative outcomes. In addition, patients agreeing to participate in any trial are generally more highly motivated and engaged in their care than those declining participation. Therefore, our results may not be generalizable to individuals who are not interested in self-management of their health. Conclusion: Our results suggest that home telemonitoring in patients with advanced CKD is feasible using a CKD-specific platform like VIEWER. We anticipate that improved functionality with incorporation of feedback from this study will result in greater long-term adherence. A future randomized clinical trial is planned.

Contexte: Les visites aux urgences et les hospitalisations en lien avec l'insuffisance rénale augmentent d'environ dix fois dans les 30 jours qui précèdent le début de la dialyse. Objectif: L'essai VIEWER a mis en œuvre un système de télésurveillance à domicile qui permet de suivre les changements dans les paramètres vitaux des patients atteints d'insuffisance rénale chronique (IRC). L'essai permet également d'évaluer l'observance et l'acceptabilité de la télésurveillance dans cette population. Conception: Un essai clinique pilote prospectif utilisant une approche par méthodes mixtes. Cadre: Les recherches ont été menées à Winnipeg, au Manitoba. Sujets: L'essai s'est déroulé en deux phases: un essai pilote de deux semaines avec 10 participants (phase 1) et un essai de trois mois avec un total de 26 participants (phase 2). Étaient admissibles à participer: les patients présentant un DFGe inférieur à 15 ml/kg/1,73 m2 et une probabilité d'au moins 40 % d'amorcer des traitements de dialyse dans les deux ans, selon l'équation KFRE (kidney failure risk equation). Méthodologie: Le principal critère d'évaluation quantitatif était l'observance, définie par la proportion d'auto-évaluations réalisées quotidiennement à l'aide VIEWER au cours de la période de suivi. La facilité d'utilisation et l'acceptabilité de VIEWER ont été évaluées qualitativement à la fin de l'essai au moyen de questionnaires structurés et de groupes de discussion. Résultats: Les participants à la phase 1 (n=10) ont montré une observance médiane de 77,17 % pendant les deux semaines d'observation. Les participants à la phase 2 (n=26) ont montré une observance médiane inférieure, soit de 36 %, pendant les trois mois du suivi. Les participants au groupe de discussion (n=11) ont identifié plusieurs aspects positifs de VIEWER, notamment: une sensibilisation et une responsabilisation accrues à l'égard de la santé, la simplicité de la plateforme de données, et le fait de pouvoir montrer leurs tendances de santé au personnel clinique. Parmi les défis identifiés figurent des problèmes de connectivité avec Bluetooth, des désagréments perçus à son utilisation et des pensées négatives à l'égard de la santé. Limites: La faible taille des échantillons a limité notre capacité à mesurer les résultats quantitatifs. En outre, les patients qui acceptent de participer à un essai clinique sont généralement plus motivés et impliqués dans leurs soins que ceux qui refusent de participer. Par conséquent, nos résultats pourraient ne pas être généralisables aux personnes qui ne sont pas intéressées par l'autogestion de leur santé. Conclusion: Nos résultats suggèrent que la télésurveillance des patients atteints d'IRC avancée est réalisable par le biais d'une plateforme spécifique à l'IRC comme VIEWER. Nous pensons que l'amélioration de sa fonctionnalité, découlant des résultats de cette étude, se traduira par une plus grande observance à long terme. Un futur essai clinique randomisé est prévu.

Dietary potassium liberalization with fruit and vegetables versus potassium restriction in people with chronic kidney disease (DK-Lib CKD): a clinical trial protocol.

BACKGROUND: Potassium regulation in the body is primarily done in the kidney. In addition to this, hyperkalemia, occurs in approximately 10% of individuals with chronic kidney disease (CKD) and is associated with elevated all-cause mortality. Individuals with CKD are often told to restrict dietary potassium (K), however, this recommendation is based on low quality evidence. Reduced quality of life, limited dietary choices and nutritional deficiencies are all potential negative outcomes that may occur when restricting dietary K in CKD patients. There is a need for randomized controlled trials investigating the impact of dietary K modification on serum K concentrations in people with CKD. METHODS: A randomized 2-period crossover design comparing a liberalized K fruit and vegetable diet where participants will be required to consume ~ 3500 mg of dietary K daily, to a standard K restricted diet where participants will be required to consume < 2000 mg of dietary K daily. All participants will begin on a liberalized K run-in period for 2 weeks where they will receive fruit and vegetables home deliveries and for safety will have clinical chemistry, including serum potassium measurements taken after 1 week. Participants will then be randomized into either liberalized K or standard K diet for six weeks and then crossover to the other intervention for another 6 weeks after a 2-week washout period. DISCUSSION: 30 male and female CKD outpatients, ≥ 18 years of age, who have an estimated glomerular filtration rate (eGFR) between 15 and 45 ml/min/1.73m2 and serum K between 4.5 and 5.5 mEq/L. This design would have greater than 80% power to detect a difference of 0.35 mEq/L serum K between groups. Anthropometric measurements, clinical chemistry, dietary recalls, physical function assessments, as well as a quality of life assessments will also be measured in this trial. These findings will provide high quality evidence for, or against, recommendations for dietary K restriction in individuals living with CKD. The removal of K restriction could provide individuals living with CKD more dietary choice leading to improved dietary status and quality of life. TRIAL REGISTRATION: This trial has received approval from the University of Manitoba Research Ethics board (HS25191 (B2021:104)).