Effects of dietary interventions for metabolic acidosis in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND HYPOTHESIS: Metabolic acidosis is a common complication of kidney disease and can result in further disease progression. Alkali therapy has been used to treat metabolic acidosis for decades. However, some concerns have been raised regarding its safety and long-term tolerability. Existing data suggest that dietary interventions can be beneficial in the management of chronic kidney disease (CKD). This systematic review and meta-analysis aims to summarize findings from studies comparing dietary interventions with placebo/usual care/no treatment in the management of metabolic acidosis in outpatient adults with CKD. METHODS: Medline, Embase, Cochrane Central, CINAHL, and Web of Science Core Collection were searched from inception to June 2022. Our primary outcome measure was change in serum bicarbonate. Any dietary intervention looking to manipulate dietary acid load was considered as an intervention. Data screening and extraction were performed by two independent reviewers. Random effects meta-analysis was performed to pool data. RESULTS: Dietary interventions resulted in clinically significant improvement in serum bicarbonate (mean difference (MD):2.98, 95% CI: [0.77, 5.19]; I2: 91%) and higher eGFR levels (MD: 3.16, 95%CI: [0.24, 6.08], I2: 67%) compared to controls. Serum potassium, albumin and body mass index remained unchanged. Dietary interventions were reported to be safe. Subgroup analyses indicated a superiority of plant-based over non-plant-based interventions in the improvement of acid-base balance and eGFR, however, these findings are from low quality and heterogenous studies. CONCLUSION: Our findings support the beneficial effects of dietary interventions aimed at reducing acid or adding base in the management of metabolic acidosis and kidney function in adults with CKD, with no adverse effects on serum potassium and nutritional status. Well-designed clinical trials looking at the treatment of metabolic acidosis with dietary interventions with a focus on adding base through fruit and vegetables are required.

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

This is a summary of the original article 'Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan'. The slowing down of kidney function decline is important for managing chronic kidney disease (CKD) and preventing its complications. Clinical trials of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), have shown reductions in disease progression and death in patients with CKD and elevated levels of albuminuria. This summary of research provides an overview of a previously published article that aimed to find out whether dapagliflozin is also effective in patients with lower levels of albuminuria [urinary albumin-to-creatinine ratio (UACR) below 200 mg/g]. Starting dapagliflozin was associated with slower kidney function decline in patients with CKD and UACR below 200 mg/g compared with not starting. This effect was also observed in a subgroup analysis of patients without type 2 diabetes. These results suggest that the established benefits of SGLT-2is may extend to patients with lower levels of albuminuria.

Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures.

People with prior lean mass loss had a ~ 10% higher risk of MOF and ~ 22-26% higher risk of hip fracture, and the results were similar in people on anti-osteoporosis medications. Loss of lean mass is associated with increased fracture risk. Patients should be encouraged to pursue strategies to prevent loss of lean mass. BACKGROUND: Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass. OBJECTIVE: To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use. METHODS: We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40 years of age with two DXA assessments ≥ 1 year apart and minimum 0.5 years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R2 = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses. RESULTS: We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7 years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk. CONCLUSIONS: Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

Pomalidomide Use and Kidney Outcomes in Patients With Relapsed/Refractory Multiple Myeloma and Chronic Kidney Disease: A Real-World, Population-Based Cohort Study.

BACKGROUND: Pomalidomide-based regimens are the cornerstone of treatment for relapsed/refractory MM (RRMM). Despite the high incidence of chronic kidney disease (CKD) in RRMM, individuals with advanced CKD have been excluded from phase II/III RCTs, creating a gap in our understanding of the effects of pomalidomide use in patients with RRMM complicated with advanced CKD. We undertook a cohort to study to understand the efficacy safety of pomalidomide-based regimens among patients with CKD using real-world data. METHODS: Population-based, cohort study of patients ≥ 18 years with RRMM treated with pomalidomide in Ontario, Canada. Primary outcome was all-cause mortality. Secondary outcomes were time-to-major adverse kidney events (MAKE), time-to-next treatment, kidney response and safety. RESULTS: Total 748 patients with RRMM utilizing pomalidomide were included; 440 had preserved kidney function, 210 had moderate CKD (eGFR 30-59 mL/min/1.73m2), and 98 had advanced CKD (eGFR < 30 mL/min/1.73m2). Mean age was 70.2 years, 43.3% were women. Patients with advanced CKD had a higher risk of all-cause mortality compared to the preserved kidney function group (aHR 1.37, 95% CI 1.06, 1.78). MAKE was higher in advanced CKD (aHR 1.70, 95% CI 1.03, 2.35). Kidney response was similar between moderate and severe CKD groups (aOR 1.04, 95%, CI 0.56-1.90). Safety outcomes were similar between groups. CONCLUSIONS: Patients with advanced CKD and RRMM on pomalidomide-based regimens exhibited reduced survival and a higher risk for MAKE. However, the probability of experiencing some degree of kidney recovery is 50% in both moderate and severe CKD, with comparable safety outcomes.

Dapagliflozin treatment of patients with chronic kidney disease without diabetes across different albuminuria levels (OPTIMISE-CKD).

Background: We compared kidney and cardiorenal protection in patients without type 2 diabetes across urine albumin-creatinine ratio (UACR) levels after initiation on dapagliflozin for the treatment of chronic kidney disease (CKD). Methods: OPTIMISE-CKD is an observational study describing dapagliflozin treatment for CKD. Adult patients with CKD without type 2 diabetes were included in the primary analysis. Baseline UACR was grouped as normal/mildly elevated (0-29 mg/g), low (30-200 mg/g) and high (>200 mg/g). Outcomes were estimated glomerular filtration rate (eGFR) trajectories/slopes, cardiorenal complications and all-cause mortality. Results: In total, 1480 patients had low (n = 796) and high (n = 684) UACR. The two groups were similar at baseline, aged 75 and 74 years, and 42% and 39% female, respectively. After dapagliflozin initiation, an acute eGFR dip of 3 mL/min/1.73 m2 was observed, followed by a flat development in both groups. The eGFR slope [95% confidence interval (CI)] for patients with low UACR was 0.79 mL/min/1.73 m2 per year (-0.59, 2.56), and similar to patients with high UACR [0.40 mL/min/1.73 m2 per year (-0.46, 1.38)]. Risks of cardiorenal complications and all-cause mortality were similar, with adjusted hazard ratios of 0.89 (95% CI 0.66, 1.19) and 1.10 (95% CI 0.63, 1.92), respectively. Analogous results were found in those with normal/mildly elevated UACR. Conclusions: Dapagliflozin in patients without type 2 diabetes for the treatment of CKD demonstrated similar kidney protection, cardiorenal and all-cause mortality risk across UACR levels. This suggests that the efficacy of dapagliflozin found in clinical trials expands to real-world patients with CKD, regardless of albuminuria levels.

Impact of the medical fitness model on long term health outcomes in older adults.

BACKGROUND: Physical inactivity is common among older adults and is associated with poor health outcomes. Medical fitness facilities provide a medically focused approach to physical fitness and can improve physical activity in their communities. This study aimed to assess the relationship between membership in the medical fitness model and all-cause mortality, health care utilization, and major adverse cardiac events in older adults. METHODS: A propensity weighted retrospective cohort study linked individuals that attended medical fitness facilities to provincial health administrative databases. Older adults who had at least 1 year of health coverage from their index date between January 1st, 2005 to December 31st 2015 were included. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in members. Members were stratified into low frequency attenders (< 1 Weekly Visits) and regular frequency attenders (> 1 Weekly Visits). Time to event models estimated the hazard ratios (HRs) for risk of all-cause mortality and major adverse cardiac event. Negative binomial models estimated the risk ratios (RRs) for risk of hospitalizations, outpatient primary care visits and emergency department visits. RESULTS: Among 3,029 older adult members and 91,734 controls, members had a 45% lower risk of all-cause mortality (HR: 0.55, 95% CI: 0.50 - 0.61), 20% lower risk of hospitalizations (RR: 0.80, 95% CI: 0.75 - 0.84), and a 27% (HR: 0.72, 95% CI: 0.66 - 0.77), lower risk of a major adverse cardiovascular event. A dose-response effect with larger risk reductions was associated with more frequent attendance as regular frequency attenders were 4% more likely to visit a general practitioner for a routine healthcare visit (RR: 1.04, 95% CI: 1.01 - 1.07), but 23% less likely to visit the emergency department (RR: 0.87, 95% CI: 0.82 - 0.92). CONCLUSIONS: Membership at a medical fitness facility was associated with a decreased risk of mortality, health care utilization and cardiovascular events. The medical fitness model may be an alternative approach for public health strategies to promote positive health behaviors in older adult populations.

Population-wide eGFR percentiles in younger adults and clinical outcomes.

BACKGROUND AND HYPOTHESIS: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. METHODS: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. RESULTS: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. CONCLUSIONS: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.

Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

BACKGROUND: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited. AIM: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code. METHODS: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed. RESULTS: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients. CONCLUSIONS: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.

The impact of dialysate flow rate on haemodialysis adequacy: a systematic review and meta-analysis.

Background: Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain. Methods: We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800 ml/min) and lower dialysate flow rate (300 ml/min) with a standard dialysis flow rate (500 ml/min) in adults (age ≥18 years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR). Results: A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800 ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P < .00001] and URR by 3.38 (95% CI 1.97-4.78, P < .00001) compared with a dialysate flow rate of 500 ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding. Conclusion: A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates.

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.

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.

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.

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.

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.

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).

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.