Role of SGLT-2 Inhibitors in Ultrafiltration Failure in Peritoneal Dialysis: A Narrative Review.

Purpose of review: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are glucose lowering agents with protective effects on cardiovascular health and the ability to slow chronic kidney disease (CKD) progression. The benefits of SGLT-2 inhibitors have not been studied in patients with advanced CKD or on maintenance dialysis. Ultrafiltration failure is a common reason for failure of peritoneal dialysis (PD). Glucose transporters, such as SGLT-2, are involved in the progression to ultrafiltration failure, and hence, SGLT-2 inhibitors might be beneficial in patients on PD to prevent ultrafiltration failure. Source of information: Here, we review data from animal models and ongoing clinical trials of SGLT-2 inhibitors in advanced CKD, as well as considerations for a phase III trial in patients on PD. Methods: A literature search was conducted and information on clinical trials was obtained from clinicaltrials.gov. Key findings: Animal models of PD have shown upregulation of glucose transporters in the peritoneal membrane and a potential effect of SGLT-2 inhibitors on glucose absorption and ultrafiltration. Several clinical trials are currently ongoing with SGLT-2 inhibitors in patients on PD. We discuss their study designs and propose a mixed-methods, patient-centered approach to studying SGLT-2 inhibitors in PD patients. We also discuss the potential implications of SGLT-2 inhibitors on people living with kidney failure, especially in remote communities.

Motif de la revue: Les inhibiteurs du cotransporteur sodium-glucose de type 2 (SGLT-2) sont des hypoglycémiants qui ont des effets protecteurs sur la santé cardiovasculaire et qui peuvent ralentir la progression de l'insuffisance rénale chronique (IRC). Les effets bénéfiques des inhibiteurs du SGLT-2 n'ont pas été étudiés chez les patients atteints d'IRC de stade avancé ou sous dialyse d'entretien. L'échec de l'ultrafiltration est une cause fréquente d'échec de la dialyse péritonéale (DP). Les transporteurs de glucose comme les SGLT-2 sont impliqués dans l'évolution vers l'échec de l'ultrafiltration; les inhibiteurs du SGLT-2 pourraient, par conséquent, être bénéfiques pour prévenir l'échec de l'ultrafiltration chez les patients sous DP. Source de l'information: Nous avons examiné les données provenant des modèles animaux et des essais cliniques en cours sur les inhibiteurs du SGLT-2 en contexte d'IRC avancée, de même que les paramètres d'un essai de phase III chez des patients sous DP. Méthodologie: Une recherche de la littérature a été effectuée et les informations sur les essais cliniques en cours ont été obtenues à partir de clinicaltrials.gov. Principales observations: Les modèles animaux de DP ont montré une régulation positive des transporteurs de glucose au niveau de la membrane péritonéale et un possible effet des inhibiteurs de SGLT-2 sur l'absorption du glucose et l'ultrafiltration. Plusieurs essais cliniques sur les inhibiteurs du SGLT-2 sont en cours chez des patients sous DP. Nous discutons de leurs plans d'étude et nous proposons une approche mixte, centrée sur le patient, pour étudier les inhibiteurs du SGLT-2 chez les patients sous DP. Nous discutons également des implications potentielles des inhibiteurs du SGLT-2 pour les personnes vivant avec une insuffisance rénale terminale, en particulier dans les communautés éloignées.

Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial.

BACKGROUND: Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. METHODS: The SAFE-D trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centres in Canada and Australia. The trial included adults (≥18 y) undergoing dialysis with a history of non-valvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: a) recruitment of the target population within 2 years from the start of the trial; and b) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. RESULTS: From December 2019 through June 2022, 151 patients were enrolled and randomized to apixaban (n =51), warfarin (n=52) or no oral anticoagulation (n=48). Allowing for pauses related to the COVID pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (4 warfarin, 2 apixaban, 2 no oral anticoagulation). Death occurred in 15 participants (9 warfarin, 2 apixaban, 4 no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (IQR 47%-70%). CONCLUSIONS: We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.

Influence of iron deficiency definition on the efficacy of intravenous iron in heart failure: a meta-analysis of randomized trials.

BACKGROUND: Intravenous iron improves symptoms in heart failure (HF) with iron deficiency (ID) but failed to consistently show a benefit in cardiovascular outcomes. The ID definition used may influence the response to intravenous iron. The aim of this meta-analysis is to assess the influence of ID definition on the intravenous iron effect in HF. METHODS/RESULTS: We performed a random-effects meta-analysis of randomized controlled trials (RCT) on intravenous iron (vs. placebo or standard of care) in patients with HF and ID that provided data on transferrin saturation (TSAT) and ferritin subgroups on the composite outcome of cardiovascular death (CVD) or HF hospitalizations (HFH). The risk ratio (RR) and 95% confidence intervals (95% CI) were extracted on the TSAT (< 20% and ≥ 20%) and ferritin (< 100 ng/mL and ≥ 100 ng/mL) subgroups. Data from four major RCT was collected including a total of more than 5500 patients. In patients with a TSAT < 20%, intravenous iron reduced the composite outcome of CVD or HFH: RR 0.81, 95%CI 0.69-0.94, while in patients with a TSAT ≥ 20% the effect was neutral: RR 0.98, 95%CI 0.79-1.21, interaction, P = 0.05. On the other hand, ferritin levels did not modify the effect of IV iron: ferritin ≥ 100 ng/mL RR 0.84, 95%CI 0.65-1.09, and ferritin < 100 ng/mL RR 0.85, 95%CI 0.74-0.97; interaction, P = 0.96. CONCLUSIONS: Our meta-analysis suggests that the benefit of intravenous iron may be restricted to patients with TSAT < 20% regardless of ferritin levels and supports the single use of TSAT < 20% to identify patients with ID who may benefit from intravenous iron therapy.

Cardiovascular phenotypes in type 2 diabetes: Latent class analysis of the CANVAS Program and CREDENCE trial.

AIM: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis. METHODS: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes. RESULTS: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05). CONCLUSION: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability.

Meta-analysis evaluating apixaban in patients with atrial fibrillation and end-stage renal disease requiring dialysis.

Background: Warfarin is considered the primary oral anticoagulant for patients with atrial fibrillation and end-stage renal disease (ESRD) requiring dialysis. Although warfarin can offer significant stroke prevention in this population, the accompanying major bleeding risks make warfarin nearly prohibitive. Apixaban was shown to be superior to warfarin in preventing stroke or systemic embolism, with a lower risk of bleeding and mortality in a large, randomized trial of individuals with mostly normal renal function but none with ESRD. Methods: We systematically reviewed evidence comparing apixaban versus warfarin for atrial fibrillation in this population, and evaluated outcomes of stroke or systemic embolism, and major bleeding using random-effects models. The main safety outcome was major bleeding, and the main effectiveness outcome was stroke or systemic embolism. Results: We found five observational studies of 10 036 patients (2638 receiving apixaban, and 7398 receiving warfarin) meeting inclusion criteria. Pooled analysis demonstrated a significant reduction in major bleeding with apixaban as compared to warfarin (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.42-0.61; p < .0001). Apixaban was also associated with a reduction in intracranial bleeding (OR 0.58, 95% CI 0.37-0.92; p = .02) and in gastrointestinal bleeding (OR 0.61, 95% CI 0.51-0.73; p < .0001). Furthermore, apixaban was associated with a reduction in stroke/systemic embolism (OR 0.64, 95% CI 0.50-0.82; p < .0001). Conclusion: Apixaban was associated with superior outcomes and reduced adverse events compared to warfarin in observational studies of patients with atrial fibrillation on dialysis. Randomized controlled studies are needed to confirm these findings.

Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof-of-concept results from the DECIDE-CV clinical programme.

AIM: The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline-directed medical therapy (GDMT). METHODS: We retrospectively analysed consecutive patients assessed in the 'synchronized' DECIDE-CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, renin-angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline-to-last-visit change in surrogate laboratory biomarkers. RESULTS: The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin-to-creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium-glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon-like peptide 1 receptor agonists (from 8% to 45%), renin-angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin-to-creatinine ratio and N-terminal proB-type natriuretic peptide levels significantly dropped from baseline (p < .05 for all). CONCLUSIONS: Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.

Oral Anticoagulation Use in Individuals With Atrial Fibrillation and Chronic Kidney Disease: A Review.

Atrial fibrillation (AF) is highly prevalent in patients with chronic kidney disease (CKD). It is associated with an increased risk of stroke, which increases as kidney function declines. In the general population and in those with a moderate degree of CKD (creatinine clearance 30-50 mL/min), the use of oral anticoagulation to decrease the risk of stroke has been the standard of care based on a favorable risk-benefit profile that had been established in seminal randomized controlled trials. However, evidence regarding the use of oral anticoagulants for stroke prevention is less clear in patients with severe CKD (creatinine clearance <30 mL/min) and those receiving maintenance dialysis, as these individuals were excluded from such large randomized controlled trials. Nevertheless, the direct oral anticoagulants have invariably usurped vitamin K antagonists as the preferred choice for oral anticoagulation among patients with AF across all strata of CKD based on their well-defined safety and efficacy and multiple pharmacokinetic benefits (e.g., less drug-drug interactions). This review summarizes the current literature on the role of oral anticoagulation in the management of AF among patients with CKD and highlights current deficiencies in the evidence base and how to overcome them.

Medication Deprescribing in Patients Receiving Hemodialysis: A Prospective Controlled Quality Improvement Study.

Rationale & Objective: Patients treated with dialysis are commonly prescribed multiple medications (polypharmacy), including some potentially inappropriate medications (PIMs). PIMs are associated with an increased risk of medication harm (eg, falls, fractures, hospitalization). Deprescribing is a solution that proposes to stop, reduce, or switch medications to a safer alternative. Although deprescribing pairs well with routine medication reviews, it can be complex and time-consuming. Whether clinical decision support improves the process and increases deprescribing for patients treated with dialysis is unknown. This study aimed to test the efficacy of the clinical decision support software MedSafer at increasing deprescribing for patients treated with dialysis. Study Design: Prospective controlled quality improvement study with a contemporaneous control. Setting & Participants: Patients prescribed ≥5 medications in 2 outpatient dialysis units in Montréal, Canada. Exposures: Patient health data from the electronic medical record were input into the MedSafer web-based portal to generate reports listing candidate PIMs for deprescribing. At the time of a planned biannual medication review (usual care), treating nephrologists in the intervention unit additionally received deprescribing reports, and patients received EMPOWER brochures containing safety information on PIMs they were prescribed. In the control unit, patients received usual care alone. Analytical Approach: The proportion of patients with ≥1 PIMs deprescribed was compared between the intervention and control units following a planned medication review to determine the effect of using MedSafer. The absolute risk difference with 95% CI and number needed to treat were calculated. Outcomes: The primary outcome was the proportion of patients with one or more PIMs deprescribed. Secondary outcomes include the reduction in the mean number of prescribed drugs and PIMs from baseline. Results: In total, 195 patients were included (127, control unit; 68, intervention unit); the mean age was 64.8 ± 15.9 (SD), and 36.9% were women. The proportion of patients with ≥1 PIMs deprescribed in the control unit was 3.1% (4/127) vs 39.7% (27/68) in the intervention unit (absolute risk difference, 36.6%; 95% CI, 24.5%-48.6%; P < 0.0001; number needed to treat = 3). Limitations: This was a single-center nonrandomized study with a type 1 error risk. Deprescribing durability was not assessed, and the study was not powered to reduce adverse drug events. Conclusions: Deprescribing clinical decision support and patient EMPOWER brochures provided during medication reviews could be an effective and scalable intervention to address PIMs in the dialysis population. A confirmatory randomized controlled trial is needed.

Patients treated with dialysis are commonly prescribed multiple medications, some of which are potentially inappropriate medications (PIMs). PIMs can increase a patient's pill burden and are associated with an increased risk of harm (some examples include falls, fractures, and hospitalization). Deprescribing is a proposed solution that aims to highlight medications that can be stopped, reduced, or switched to a safer option, under supervision of a health care provider. We aimed to determine if a quality improvement intervention in the dialysis unit could increase deprescribing compared to usual care. The study took place in 2 outpatient hemodialysis units where usual care involves nurses and nephrologists performing medication reviews twice a year. The intervention was a deprescribing report that was generated with the help of a software tool called MedSafer, along with brochures for patients with information on PIMs they were taking. In the intervention unit, we increased the number of patients who had a medication safely deprescribed by 36.6% more than on the control unit. Although the study was small, a future larger study in dialysis patients might show that a computer software such as MedSafer can prevent harmful complications from taking too many medications.

Clinical Outcomes of Renin-Angiotensin-Aldosterone Blockade in Patients With Advanced Chronic Kidney Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The cardiovascular and renal benefits of renin-angiotensin aldosterone system (RAAS) blockade are not well established in patients with advanced chronic kidney disease (CKD). We conducted a systematic review and meta-analysis to identify potential risks and benefits from RAAS blockade in patients with CKD stage 4-5. METHODS: A Medline search from inception to November 2022 was conducted to identify randomised controlled trials (RCTs) in patients with CKD stage 4-5 (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) comparing RAAS blockade vs placebo or alternative antihypertensive therapy. Different intervention strategies were assessed (RAAS use vs nonuse, initiation vs placebo/alternative therapy, or discontinuation vs continuation). The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were all-cause mortality and major adverse cardiovascular events (MACE). The risk ratio (RR) was estimated with the use of a random-effects model. RESULTS: Nine RCTs (1150 patients) were included. RAAS blockade was associated with a significant reduction in progression to ESKD: RR 0.84 (95% confidence interval [CI] 0.74-0.96; P = 0.01). There was no benefit from RAAS blockade on all-cause mortality or MACE: RR 1.02 (95% CI 0.63-1.65; P = 0.93) and RR 0.87 (95% CI 0.49-1.57; P = 0.65), respectively. CONCLUSIONS: RAAS blockade may be considered in selected patients with CKD stage 4-5 to delay progression to ESKD.

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.

Anticoagulation in Patients with Chronic Kidney Disease.

BACKGROUND: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD. SUMMARY: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30-50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin. KEY MESSAGES: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.

Volume Status Assessment by Lung Ultrasound in End-Stage Kidney Disease: A Systematic Review.

Purpose of review: Lung ultrasound is a noninvasive bedside technique that can accurately assess pulmonary congestion by evaluating extravascular lung water. This technique is expanding and is easily available. Our primary outcome was to compare the efficacy of volume status assessment by lung ultrasound with clinical evaluation, echocardiography, bioimpedance, or biomarkers. The secondary outcomes were all-cause mortality and cardiovascular events. Sources of information: We conducted a MEDLINE literature search for observational and randomized studies with lung ultrasound in patients on maintenance dialysis. Methods: From a total of 2363 articles, we included 28 studies (25 observational and 3 randomized). The correlation coefficients were pooled for each variable of interest using the generic inverse variance method with a random effects model. Among the clinical parameters, New York Heart Association Functional Classification of Heart Failure status and lung auscultation showed the highest correlation with the number of B-lines on ultrasound, with a pooled r correlation coefficient of .57 and .36, respectively. Among echocardiographic parameters, left ventricular ejection fraction and inferior vena cava index had the strongest correlation with the number of B-lines, with a pooled r coefficient of .35 and .31, respectively. Three randomized studies compared a lung ultrasound-guided approach with standard of care on hard clinical endpoints. Although patients in the lung ultrasound group achieved better decongestion and blood pressure control, there was no difference between the 2 management strategies with respect to death from any cause or major adverse cardiovascular events. Key findings: Lung ultrasound may be considered for the identification of patients with subclinical volume overload. Trials did not show differences in clinically important outcomes. The number of studies was small and many were of suboptimal quality. Limitations: The included studies were heterogeneous and of relatively limited quality.

Motif de la revue: L'échographie pulmonaire est une technique non-invasive réalisée au chevet du patient qui permet d'évaluer avec précision la congestion pulmonaire en mesurant l'eau pulmonaire extravasculaire. Cette technique facilement accessible est de plus en plus utilisée. Notre principal critère de jugement était de comparer l'efficacité de l'évaluation de la volémie par échographie pulmonaire avec l'évaluation clinique, l'échocardiographie, la bio-impédance ou les biomarqueurs. Les critères d'évaluation secondaires étaient la mortalité toutes causes confondues et les événements cardiovasculaires. Sources: Nous avons recherché sur MEDLINE les études observationnelles et les essais randomisés où une échographie pulmonaire avait été réalisée chez des patients sous dialyse d'entretien. Méthodologie: Sur un total de 2 363 articles, nous avons retenu 28 études (25 observationnelles et 3 randomisées). Les coefficients de corrélation ont été regroupés pour chaque variable d'intérêt en utilisant la méthode générique de variance inverse avec un modèle à effets aléatoires. Les paramètres cliniques qui avaient montré les corrélations les plus élevées avec le nombre de lignes B à l'échographie étaient le statut de l'insuffisance cardiaque selon la classification de la New York Heart Association et l'auscultation pulmonaire, avec des coefficients de corrélation r regroupés respectifs de 0,57 et de 0,36. Les paramètres de l'échocardiographie qui avaient montré les plus fortes corrélations avec le nombre de lignes B étaient la fraction d'éjection du ventricule gauche et l'indice de la veine cave inférieure, avec des coefficients r regroupés respectifs de 0,35 et de 0,31. Trois essais randomisés avaient comparé une approche guidée par échographie pulmonaire aux normes de soins selon des critères cliniques stricts. Bien que les patients du groupe avec échographie pulmonaire aient montré une décongestion plus efficace et un meilleur contrôle de la pression artérielle, aucune différence n'a été observée entre les deux stratégies de prise en charge en ce qui concerne les décès de toutes causes confondues ou les événements cardiovasculaires indésirables majeurs. Principales observations: L'échographie pulmonaire pourrait être envisagée pour identifier les patients qui présentent une surcharge volumique subclinique. Les essais inclus n'ont pas montré de différences dans les résultats cliniquement pertinents. Le nombre d'études incluses était faible et plusieurs étaient de qualité sous-optimale. Limites: Les études incluses étaient hétérogènes et de qualité relativement limitée.

The Association of Ejection Fraction With Hospital-Associated Cardiac Arrest and Heart Failure Hospitalization Differs According to Baseline Estimated GFR.

Introduction: Chronic kidney disease (CKD) and left ventricular (LV) dysfunction are risk factors for cardiovascular events. We explore whether the association of LV ejection fraction (LVEF) with cardiac arrest, heart failure hospitalization, and all-cause mortality differs across stages of kidney impairment. Methods: We performed an observational cohort study of 19,032 patients from 2004 to 2014 with estimated glomerular filtration rate (eGFR) ≤90 ml/min per 1.73 m2 and without end-stage kidney disease (ESKD). Cox regression models, incorporating an interaction term for eGFR and LVEF, were fit and adjusted for relevant covariates. Results: Mean age of the patients was 67 ± 14 years, and 51% were male. The mean eGFR was 64 ± 19 ml/min per 1.73 m2 and LVEF was 54 ± 13%. Over a median follow-up of 3.0 (0.7-6.0) years there were 504 cardiac arrests, 4181 heart failure hospitalizations, and 6989 deaths. The association of LVEF with cardiac arrest and heart failure hospitalization differed according to continuous eGFR (P-interaction <0.01 for both outcomes). The association of LVEF with cardiac arrest in the lowest quartile was attenuated (adjusted hazard ration [aHR] per 5% higher LVEF 0.92; 95% confidence interval [CI] 0.88-0.96) compared to the highest eGFR quartile (aHR per 5% higher LVEF 0.85; 95% CI 0.78-0.91). The association of LVEF with heart failure hospitalization was similarly attenuated in the lowest eGFR quartile. There was no effect modification of LVEF by continuous eGFR for all-cause mortality (P-interaction 0.26). Conclusion: Among non-ESKD patients with eGFR ≤90 ml/min per 1.73 m2, the association of LVEF with cardiac arrest and heart failure hospitalization is attenuated at lower levels of kidney function. Further research is required to elucidate what factors beyond LVEF drive these observations.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis.

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

Erythropoietic response after intravenous iron in patients with heart failure and reduced ejection fraction with and without background treatment with sodium-glucose cotransporter 2 inhibitors.

AIMS: Intravenous (IV) iron increases haemoglobin/haematocrit and improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also increase haemoglobin/haematocrit and improve outcomes in heart failure by mechanisms linked to nutrient deprivation signalling and reduction of inflammation and oxidative stress. The effect of IV iron among patients using SGLT2i has not yet been studied. The aim of this study was to evaluate the changes in haemoglobin, haematocrit, and iron biomarkers in HFrEF patients treated with IV iron with and without background SGLT2i treatment. Secondary outcomes included changes in natriuretic peptides, kidney function and heart failure-associated outcomes. METHODS AND RESULTS: Retrospective, single-centre analysis of HFrEF patients with iron deficiency treated with IV iron using (n = 60) and not using (n = 60) SGLT2i, matched for age and sex. Mean age was 73 ± 12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anaemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in haemoglobin and haematocrit compared to SGLT2i non-users: haemoglobin +0.57 g/dl (95% confidence interval [CI] 0.04-1.10, p = 0.036) and haematocrit +1.64% (95% CI 0.18-3.11, p = 0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. CONCLUSION: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in haemoglobin and haematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response. Further studies are needed to ascertain the potential benefit or harm of combining these two treatments in heart failure patients.

Electronic Decision Support for Deprescribing in Patients on Hemodialysis: Clinical Research Protocol for a Prospective, Controlled, Quality Improvement Study.

Background: Patients on dialysis are commonly prescribed multiple medications (polypharmacy), many of which are potentially inappropriate medications (PIMs). Potentially inappropriate medications are associated with an increased risk of falls, fractures, and hospitalization. MedSafer is an electronic tool that generates individualized, prioritized reports with deprescribing opportunities by cross-referencing patient health data and medications with guidelines for deprescribing. Objectives: Our primary aim was to increase deprescribing, as compared with usual care (medication reconciliation or MedRec), for outpatients receiving maintenance hemodialysis, through the provision of MedSafer deprescribing opportunity reports to the treating team and patient empowerment deprescribing brochures provided directly to the patients themselves. Design: This controlled, prospective, quality improvement study with a contemporary control builds on existing policy at the outpatient hemodialysis centers where biannual MedRecs are performed by the treating nephrologist and nursing team. Setting: The study takes place on 2 of the 3 outpatient hemodialysis units of the McGill University Health Centre in Montreal, Quebec, Canada. The intervention unit is the Lachine Hospital, and the control unit is the Montreal General Hospital. Patients: A closed cohort of outpatient hemodialysis patients visit one of the hemodialysis centers multiple times per week for their hemodialysis treatment. The initial cohort of the intervention unit includes 85 patients, whereas the control unit has 153 patients. Patients who are transplanted, hospitalized during their scheduled MedRec, or die before or during the MedRec will be excluded from the study. Measurements: We will compare rates of deprescribing between the control and intervention units following a single MedRec. On the intervention unit, MedRecs will be paired with MedSafer reports (the intervention), and on the control unit, MedRecs will take place without MedSafer reports (usual care). On the intervention unit, patients will also receive deprescribing patient empowerment brochures for select medication classes (gabapentinoids, proton-pump inhibitors, sedative hypnotics and opioids for chronic non-cancer pain). Physicians on the intervention unit will be interviewed post-MedRec to determine implementation barriers and facilitators. Methods: The primary outcome will be the proportion of patients with 1 or more PIMs deprescribed on the intervention unit, as compared with the control unit, following a biannual MedRec. This study will build on existing policies aimed at optimizing medication therapy in patients undergoing maintenance hemodialysis. The electronic deprescribing decision support tool, MedSafer, will be tested in a dialysis setting, where nephrologists are regularly in contact with patients. MedRecs are an interdisciplinary clinical activity performed biannually on the hemodialysis units (in the Spring and Fall), and within 1 week following discharge from any hospitalization. This study will take place in the Fall of 2022. Semi-structured interviews will be conducted among physicians on the intervention unit to determine barriers and facilitators to implementation of the MedSafer-supplemented MedRec process and analyzed according to grounded theory in qualitative research. Limitations: Deprescribing can be limited due to nephrologists' time constraints, cognitive impairment of the hemodialyzed patient stemming from their illness and complex medication regimens, and lack of sufficient patient resources to learn about the medications they are taking and their potential harms. Conclusions: Electronic decision support can facilitate deprescribing for the clinical team by providing a nudge reminder, decreasing the time it takes to review and effectuate guideline recommendations, and by lowering the barrier of when and how to taper. Guidelines for deprescribing in the dialysis population have recently been published and incorporated into the MedSafer software. To our knowledge, this will be the first study to examine the efficacy of pairing these guidelines with MedRecs by leveraging electronic decision support in the outpatient dialysis population. Trial registration: This study was registered on Clinicaltrials.gov (NCT05585268) on October 2, 2022, prior to the enrolment of the first participant on October 3, 2022. The registration number is pending at the time of protocol submission.

Contexte: Les patients sous dialyse se voient souvent prescrire de nombreux médicaments (polypharmacie), dont plusieurs médicaments potentiellement inappropriés (MPI). Les MPI sont associés à un risque accru de chutes, de fractures et d'hospitalisations. MedSécure est un outil électronique qui génère des rapports individualisés et classés par ordre de priorité indiquant les possibilités de déprescription. L'outil fonctionne en croisant les données sur la santé des patients et les médicaments sous ordonnance avec des lignes directrices pour la déprescription. Objectifs de l'étude: L'objectif principal est de favoriser la déprescription par rapport aux soins habituels (Medication Reconciliation [MedRecs] ou bilan comparatif des médicaments) chez les patients ambulatoires recevant une hémodialyse d'entretien, en fournissant des rapports MedSécure de déprescription à l'équipe soignante et des brochures encourageant la déprescription aux patients. Conception: Cette étude prospective et contrôlée (témoin contemporain) d'amélioration de la qualité s'appuie sur la politique existante dans les centers d'hémodialyse ambulatoires où un bilan des médicaments (MedRecs) est effectué deux fois par année par le néphrologue traitant et l'équipe de soins infirmiers. Cadre: L'étude a lieu dans deux des trois unités d'hémodialyse ambulatoire du Center universitaire de santé McGill à Montréal (Québec, Canada). L'unité d'intervention est l'Hôpital de Lachine et l'unité témoin est l'Hôpital général de Montréal. Sujets: Une cohorte fermée de patients ambulatoires sous hémodialyse qui visitent plusieurs fois par semaine un center d'hémodialyse pour leurs traitements. La cohorte initiale de l'unité d'intervention compte 85 patients, tandis que l'unité témoin compte 132 patients. Seront exclus les patients qui recevront une greffe, qui seront hospitalisés pendant leur MedRecs ou qui décèderont avant ou pendant le MedRecs. Mesures: Nous comparerons les taux de déprescription entre les unités témoin et d'intervention après un seul MedRecs. Dans l'unité d'intervention, le MedRecs sera associé aux rapports MedSécure (l'intervention); dans l'unité témoin, le MedRecs aura lieu sans rapports MedSécure (soins habituels). Au sein de l'unité d'intervention, les patients recevront également des brochures encourageant la déprescription pour certaines classes de médicaments (gabapentinoïdes, inhibiteurs de la pompe à protons, hypnotiques sédatifs et opioïdes pour les douleurs chroniques non cancéreuses). Les médecins de l'unité d'intervention seront interviewés après le MedRec pour déterminer les obstacles et les facilitateurs à la mise en œuvre. Méthodologie: Le principal critère d'évaluation sera la proportion de patients dans l'unité d'intervention chez qui au moins un MPI sera déprescrit après un MedRec semestriel, par rapport à l'unité témoin. L'étude s'appuiera sur les politiques existantes visant à optimiser la médication chez les patients suivant des traitements d'hémodialyse d'entretien. L'outil électronique d'aide à la décision de déprescription MedSécure sera testé en contexte de dialyse, où les néphrologues sont régulièrement en contact avec les patients. Les MedRecs sont une activité clinique interdisciplinaire effectuée semestriellement sur les unités d'hémodialyse (au printemps et à l'automne) et dans la semaine suivant un congé de l'hôpital. Cette étude aura lieu à l'automne 2022. Des entretiens semi-structurés seront menés avec les médecins de l'unité d'intervention afin d'établir les obstacles et les facilitateurs à la mise en œuvre du processus MedRec complété par MedSécure, puis analysés selon une théorie fondée sur la recherche qualitative. Limites: La déprescription peut être limitée par des contraintes de temps des néphrologues, des troubles cognitifs résultant des maladies et des régimes médicamenteux complexes des patients sous hémodialyse ou par un manque de ressources pour éduquer les patients sur les médicaments qu'ils prennent et leurs méfaits potentiels. Conclusion: Un outil électronique d'aide à la décision peut faciliter le processus de déprescription pour l'équipe clinique en fournissant un rappel, en réduisant le temps nécessaire à l'examen et à l'application des recommandations, et en limitant les obstacles liés au moment et à la façon de réduire le nombre de médicaments. Des lignes directrices sur la déprescription dans la population des patients sous dialyse ont récemment été publiées et incorporées au logiciel MedSécure. À notre connaissance, il s'agit de la première étude à examiner l'efficacité du couplage des lignes directrices avec le MedRecs en tirant parti de l'outil électronique d'aide à la décision en contexte d'hémodialyse ambulatoire.

Bioimpedance-Guided Monitoring of Volume Status in Patients With Kidney Disease: A Systematic Review and Meta-Analysis.

Background and Objective: Bioimpedance technologies are increasingly used to determine fluid status in patients with chronic kidney disease and those with end-stage kidney disease on dialysis. We aimed to determine whether this technology improves clinical outcomes as compared with usual care. Methods: We performed a systematic review and meta-analysis of trials, comparing fluid management guided by bioimpedance technologies to standard of care in patients with chronic kidney disease. Our primary outcome was all-cause mortality. Secondary outcomes included blood pressure control, all-cause hospitalization, major adverse cardiovascular events, and change in left ventricular mass index. Results: Our search identified 819 citations of which 12 randomized controlled trials were included (2420 patients). No studies of non-dialysis-dependent chronic kidney disease patients met inclusion criteria. Mean age was 55 years and mean follow-up was 1 year. There was a statistically significant difference in all-cause mortality between both arms studied (risk ratio [RR] 0.64, 95% confidence interval [CI]: 0.44, 0.99). Better blood pressure control was observed in the bioimpedance arm of the included articles, weighted mean differences (WMD) -3.13 mm Hg (95% CI: -5.73, -0.53 mm Hg) for systolic blood pressure and WMD -2.50 mm Hg (95% CI: -4.36, -0.64 mm Hg) for diastolic blood pressure. No difference was observed concerning the other outcomes. Conclusions: Among patients on maintenance dialysis, bioimpedance-guided volume management showed decreased all-cause mortality and blood pressure but no significant difference in all-cause hospitalization, major adverse cardiac event, or change in left ventricular mass index. This may be due to a younger population sample than previous articles. Moreover, our study identified a knowledge gap by highlighting the lack of studies evaluating this technology in non-dialysis-dependent chronic kidney disease patients.

Contexte et objectif: Les technologies de bio-impédance sont de plus en plus utilisées pour déterminer le statut hydrique des patients atteints d'insuffisance rénale chronique et des patients atteints d'insuffisance rénale terminale sous dialyze. Notre objectif était de vérifier si cette technologie améliore les résultats cliniques des patients par rapport aux soins habituels. Méthodologie: Nous avons procédé à une revue systématique et à une méta-analyze d'essais comparant la gestion des fluides guidée par les technologies de bio-impédance aux normes de soins chez les patients atteints d'insuffisance rénale chronique. Le principal critère de jugement était la mortalité toutes causes confondues. La régulation de la pression artérielle, l'hospitalization toutes causes confondues, les événements cardiovasculaires majeurs indésirables et la modification de l'index de masse ventriculaire gauche constituaient les critères de jugement secondaires. Résultats: Notre recherche a permis de répertorier 819 citations, desquelles 12 essais contrôlés randomisés ont été retenus (2 420 patients). Aucune étude portant sur des patients atteints d'insuffisance rénale chronique non dépendants de la dialyze ne remplissait les critères d'inclusion. L'âge moyen des sujets était de 55 ans et le suivi moyen était d'un an. Une différence statistiquement significative a été observée entre les deux bras étudiés en ce qui concerne la mortalité toutes causes confondues (RR: 0.64; IC 95% entre: 0.44, 0.99). Une meilleure régulation de la pression artérielle a été observée dans le bras de bio-impédance des manuscrits inclus, soit une moyenne pondérée des écarts de −3.13 mm Hg (IC 95% entre: −5.73, −0.53 mm Hg) pour la pression artérielle systolique et de −2.50 mm Hg (IC 95% entre: −4.36, −0.64 mm Hg) pour la pression artérielle diastolique. Aucune différence n'a été observée pour les autres résultats. Conclusion: Chez les patients sous dialyze d'entretien, la prise en charge du volume guidée par la bio-impédance a montré une diminution de la mortalité toutes causes confondues et une meilleure régulation de la pression artérielle. Aucune différence significative n'a été cependant observée dans les hospitalisations toutes causes confondues, les événements cardiaques majeurs indésirables ou la modification de l'index de masse ventriculaire gauche. Ce résultat pourrait être attribuable au fait que l'échantillon de population était cette fois-ci plus jeune que les populations étudiées dans les manuscrits précédents. De plus, notre étude a permis d'identifier un écart dans les connaissances en soulignant le manque d'études évaluant cette technologie chez les patients atteints d'insuffisance rénale chronique non dépendants de la dialyze.