Cardiorenal Outcomes Research Articles

Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p<0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p<0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p<0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p<0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.

The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.

Patients with chronic kidney disease (CKD) are at risk of progressive loss of kidney function, heart failure, and cardiovascular death despite current proven therapies, including renin-angiotensin system inhibitors (RASi), sodium glucose co-transporter-2 inhibitors (SGLT2i), and statin-based regimens. RASi and SGLT2i reduce risk of CKD progression irrespective of primary cause of kidney disease, suggesting they target final common pathways. Targeting aldosterone overactivity with a nonsteroidal mineralocorticoid receptor antagonist (MRA) also reduces cardiorenal risk in patients with albuminuric diabetic kidney disease already treated with RASi. Together, these observations provide the rationale for trials to assess effects of inhibiting the aldosterone pathway in a broader range of patients with CKD, including those with non-diabetic causes of CKD or low albuminuria. Aldosterone synthase inhibitors (ASi) have emerged as an alternative to MRAs for aldosterone pathway inhibition. Phase II data from 586 patients with albuminuric CKD have shown that 10 mg of an ASi, vicadrostat (BI 690517), reduced urine albumin-to-creatinine ratio by ∼40% compared to placebo with or without concurrent empagliflozin treatment. MRA and ASi increase risk of hyperkalaemia. Combining their use with an SGLT2i may mitigate some of this risk, improving tolerability, and allowing a wider range of patients to be treated (including those with higher levels of blood potassium than in previous trials). The EASi-KIDNEY (NCT06531824) double-blind placebo-controlled trial will test this approach by assessing the safety and cardiorenal efficacy of vicadrostat in combination with empagliflozin in ∼11,000 patients with CKD. It will be sufficiently large to assess effects in patients with and without diabetes separately.

Computational and Human Intelligence Methods for Constructing Practical Risk Prediction Models: An Application to Cardio-Renal Outcomes in Non-Diabetic CKD Patients

AbstractThe current investigation aimed to develop a novel approach for risk prediction modeling of clinical outcomes in common diseases based on computational and human intelligence techniques with no a priori input on risk factors using real-world individual patient-level data from administrative claims. Bootstrapping multivariable Cox regression and ant colony optimization were employed to develop time-to-first-event risk prediction models of cardio-renal outcomes in patients with non-diabetic chronic kidney disease (CKD) as a demonstration case. A cohort of 504,924 non-diabetic CKD stage 3 or 4 patients enrolled from 2008 to 2018 were identified in the US administrative de-identified claims database, Optum Clinformatics® Data Mart. Initial set of potential risk factors was derived from patient-level data at baseline and included more than 540,000 variables. Risk prediction models of hospitalization for heart failure, worsening of CKD stage from baseline and a renal composite outcome of end-stage kidney disease, kidney failure or need for dialysis in non-diabetic CKD stage 3 or 4 were built. Final model optimization was conducted using human intelligence to combine clinically similar features and build equivalence classes to ensure that risk factors included in the final model were routinely collected and easily interpretable by healthcare providers. Demonstrated validity of our approach in non-diabetic CKD offers opportunities for application in other therapeutic areas, with the potential to improve overall prognosis and decrease the clinical and economic burden of common diseases. The approach enables developing practical prediction models for risk estimation in routine clinical practice.

Associations of SGLT2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Patients ≥ 18years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2years from HT initiation. After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality. Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Acute kidney injury predicts the risk of adverse cardio renal events and all cause death in southeast Asian people with type 2 diabetes

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Physical activity and cardiorenal health - from associations to interventional studies.

Clustering of traditional and kidney-specific risk factors leads to elevated cardiovascular disease (CVD) risk across the trajectory of chronic kidney disease (CKD) and transplantation. As kidney function declines, the prevalence of CVD, cardiovascular events, and mortality increases. This review considers recent evidence for the association between physical activity (PA) and exercise and cardiorenal health, and the effectiveness of interventions for the prevention and management of cardiorenal decline across the CKD spectrum. Evidence supports a beneficial dose-response effect of PA in the prevention of incident CKD, and growing evidence in prevalent CKD patients for the attenuation of kidney function decline, and a reduction in CVD risk, morbidity, and mortality. Broadly speaking, across the trajectory of CKD, the literature supports the efficacy of exercise interventions for improving cardiorespiratory fitness and aspects of cardiorenal health. The mechanisms underlying improvements indicate differential effects on traditional and non-traditional risk factors for CKD progression and CVD. To date, there is limited transfer of these findings into clinical care, although the evaluation of available evidence has led to the development of the first detailed clinical practice guideline for exercise and lifestyle in CKD. There is a lack of large-scale multi-centre randomised controlled trials, and trials exploring hard clinical outcomes and long-term effects of exercise on cardiorenal outcomes. However, research should also address the challenges of implementing programmes of exercise and PA as part of routine care in combination with addressing the shortfall in literature to improve cardiorenal outcomes in all patients with CKD.

The prognostic interplay of heart failure and chronic kidney disease in atrial fibrillation, focus on cardiorenal outcomes

Abstract Background Heart failure (HF) and chronic kidney disease (CKD) create a mutually reinforcing cycle, escalating disease development, and increasing morbidity and mortality rates. Both are common comorbidities promoting atrial fibrillation (AF) and contributing to heightened symptom burden and poorer outcomes in AF. Purpose To investigate the relationship of HF and CKD with cardiorenal outcomes in patients with AF. Methods For this analysis we included patients with known AF, treated at a tertiary centre between 01/2005 and 07/2019. The primary endpoint was a composite of cardiovascular (CV) death and hospitalization for HF (HHF). Secondary outcomes were renal death and dialysis. The multivariate model has been adjusted for age, sex, body mass index, HF, diabetes mellitus, CKD, coronary artery disease, previous myocardial infarction, and C-reactive protein. Results We included in total 7412 patients (median age 70 years, 39.7% female) with AF and followed them over a median of 4.5 years. A total of 1668 patients (22.5%) were diagnosed with HF, 806 (10.9%) with CKD and 372 (5.0%) were suffering from both conditions. Both CKD (adjusted HR 1.87, 95% CI 1.55-2.25) and HF (adjusted HR 2.57, 95% CI 2.22-2.98) were significantly associated with the composite of CV death/ HHF after multivariable adjustment. There was a significant stepwise increase in 5-year’s event rates of CV death/ HHF (no CKD &amp; no HF: 23%, HF: 61%, CKD: 63%, CKD &amp; HF: 82%; P-logrank &amp;lt;0.001). These results remained significant in the multivariate analysis, showing the highest increase in risk in patients with both HF and CKD with an adjusted HR of 3.96 (95% CI 3.34-4.68), followed by patients with only HF (adjusted HR 2.53, 95% CI 2.26 to 2.84) and only CKD (adjusted HR 2.22, 95% CI 1.87-2.63, p-value of &amp;lt;0.001, respectively). Regarding renal death/ dialysis we could observe a similar distribution of the 5-year’s event rates (no CKD &amp; no HF: 1.5%, HF: 4.0%, CKD: 11.8%, CKD &amp; HF: 17.7%; P-logrank &amp;lt;0.001). Both conditions, CKD and HF, remained independently associated with the combined endpoint of renal death/ dialysis after multivariable adjustment (only HF: adjusted HR of 2.80, 95% CI 1.84 to 4.25; only CKD: adjusted HR of 5.31, 95% CI 3.22 to 8.76; CKD &amp; HF: adjusted HR of 7.47, 95% CI 4.70 to 11.87; Figure 1). Conclusions Both CKD and HF significantly increase the risk of CV death and HHF, as well as renal death and dialysis in patients with AF. Risk assessment should expand beyond stroke and bleeding to cardiorenal complications including HHF, CV and renal death, as well as kidney failure in an unselected AF patient population.

Integrated multi-omics predictive analysis of atherosclerosis: a sub-study from the Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) trial

Abstract Background/Introduction Mineralocorticoid receptor (MR) antagonists (MRA) are beneficial in cardiorenal outcomes in randomized controlled trials but the mechanisms are unclear. MAGMA was an NHLBI sponsored randomized, double-blind, placebo controlled, 12-month trial comparing Spironolactone (n = 37) vs. placebo (n = 42) in Type 2 diabetics with CKD stages 3-4 on maximal renin-angiotensin system (RAS) blockade and a prior atherosclerotic event and/or left ventricular (LV) hypertrophy. The primary outcome of percent (%) change in total aortic wall volume (TWV) at 12 months, measured by magnetic resonance imaging (MRI), was significantly reduced by Spironolactone. Purpose/Originality The purpose of this analysis was to understand mechanistic pathways of MRAs using a multi-omics approach that could help tease out molecular mechanisms of benefit. Revealing for the first time which of these integrated pathways are predictive of the primary outcome will help design treatments for targeted interventions. Methods Plasma and peripheral blood mononuclear cells from patients randomized to Spironolactone or placebo at baseline and 3-months were measured for aptamer-based proteomic biomarkers (7,596 proteins) and 10-X platform-based single-cell RNA-sequencing (scRNAseq), respectively. Pre-selected candidate predictors were used as inputs of a predictive model of changes of TWV. We fit a Mixed-Multivariate Random Forest (RF) model, a variation of the RF supervised tree-based machine learning method to take the experimental design into account in the regression formulation. The two sources of "omics predictors" were integrated into a supervised multi-omics model to jointly explain the outcome using an extension of Sparse Generalized Canonical Correlation Analysis (SGCCA). Integrated multiome functional analyses with graphical visualizations were carried out by statistical enrichment analysis using Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA) against databases of gene ontologies, biological pathways, putative regulatory motifs, proteins, or disease annotations. Results The plasma proteome in response to Spironolactone revealed downregulation of MR targets including fibrosis, immune activation/inflammation, leukocyte activation, proliferation and pathways involved in cytokine stimulation. scRNAseq pathways revealed negative regulation of cytokines production such as IL-2 and redistribution of multiple cell types. Predictors of plaque progression involved cytokine-receptor, complement-coagulation, cell adhesion and axonal guidance targets. Multiome integrated functional analyses results of predictive pathways will be presented. Conclusions The changes in plasma proteomic profile with Spironolactone were consistent with the phenotype of reduced atherosclerosis and downregulation of multiple inflammatory, immune response and profibrotic pathways.

Validation of existing risk scores for worsening renal function in patients with newly diagnosed heart failure: a longitudinal population cohort study

Abstract Background Worsening renal function (WRF) is one of the strongest predictors of outcome in patients with heart failure (HF). The presence of WRF often influences the decision to start, up-titrate, or discontinue disease-modifying HF therapies and is one of the key determinants of suboptimal guideline-directed medical therapy. However, there are now potential cardiovascular pharmacotherapies that have favourable cardiorenal outcomes and reduce the risk of renal decline. It is therefore important to identify patients with HF early in their disease trajectory who are at risk of developing WRF. Purpose The aim of this study was to evaluate two existing WRF risk scores (the Forman risk score and the Basel risk score) in a population-based longitudinal cohort diagnosed with incident HF. Methods Data for individuals with incident HF between 2016 to 2021 were extracted and analysed from the NELSON study conducted in Tayside, Scotland. WRF was defined as a composite event of (i) having two consecutive eGFRs declined by 40% or greater; (ii) having an eGFR &amp;lt; 15mL/min/1.73m2; (iii) initiation of sustained dialysis; (iv) development of end-stage kidney disease; or (v) receiving kidney transplantation. The primary outcome was the occurrence of WRF within 180 days of diagnosis of HF. Among patients hospitalised with HF, in-hospital WRF was also assessed. The area under the curve (AUC) was used to assess the discrimination performance of the two risk scores in individuals with incident HF diagnosed as either in-patients or out-patients. Results 4076 individuals (mean age 72.8 ± 13.2; 58% male; 1081 HFrEF, 646 HFmrEF, 1348 HFpEF, and 1001 HF with unknown ejection fraction (EF)) who were WRF-free at incident HF diagnosis were identified. Of these, 2095 (51.4%) were diagnosed as in-patients, and 1981 (48.6%) were diagnosed as out-patients. 285 (7%) patients developed WRF within 180 days post HF diagnosis. Among the 2,095 HF in-patients, 75 (3.6%) developed WRF before discharge. The Forman risk score had an AUC of 0.618 (95% CI: 0.585 – 0.651) in predicting 180-day WRF, and an AUC of 0.650 (0.587 – 0.713) for in-hospital WRF. The Basel risk score showed similar discriminating performance with an AUC of 0.618 (0.585 – 0.651) for 180-day WRF, and 0.656 (0.593 – 0.719) for in hospital WRF. Conclusions In a contemporary population, conventional risk scores such as the Forman or Basel risk scores have limited discrimination in predicting WRF in incident HF. New models with better discrimination for WRF prediction are therefore needed.

Association between average glucose concentration or glucose variability and acute kidney injury among CAD patients with prediabetes

Abstract Background Prediabetes, impacting approximately 10% of adults, lacks comprehensive attention, and there is limited data on effective glycemic control strategies. Meta-analysis suggests that intensive glycemic control is linked to a lower incidence of major adverse cardiovascular events, mainly driven by decreased reinfarction and reduced microvascular complications in coronary artery disease (CAD) patients. However, despite these associations, existing evidence does not conclusively establish the efficacy of intensive glycemic control in enhancing cardio-renal outcomes. Purpose In the present study, we aimed to validate the utility of intensive glycaemic control on acute kidney injury (AKI) prevention using a prospective, pragmatic clinical data of patients with CAD. Methods This study utilized data from the Prospective Registry of the Current Status of Care for Patients with Coronary Artery Disease database, a nationwide and pragmatic registry project initiated on January 17th, 2022. Data, including demographics, medical history, and lab results, were collected from electronic medical records. The time-weighted average glucose (TWAG) and glucose variability (CV) for each patient to assess glycaemic control, and outcomes including AKI were assessed. Statistical analysis involved logistic models and sensitivity analyses. SAS 9.4 and R software were used, with p&amp;lt;0.05 considered significant. Results Between January 2022 and June 2023, 2,454 CAD patients with prediabetes were included for final analysis. Among them, the average age was 62.6 ± 10.3 years, of whom 27.1% were females. In univariate model, the incidence of AKI was 1.51 (1.36,1.68) times higher in patients with an increasing TWAG per mmol/L. After the stepwise adjusting of covariates, the OR was 1.50 (1.35,1.67). CV of glucose also had positive association with AKI. An increasing of 0.1 unit of CV increased the risk of about 44%. When adjusting the TWAG and CV of glucose at the same time, both still had positive association with AKI. A restricted cubic splines plot showed an increasing trend of the ORs for AKI as both TWAG and CV of glucose increased. Subgroups analyses also showed stable positive association between TWAG, CV and AKI. Conclusions Our study reveals an association between TWAG or CV and AKI in individuals with both CAD and prediabetes. These findings underscore the importance of continuous glucose monitoring and the implementation of intensive glycaemic control for CAD patients coexistence of prediabetes.Restricted cubic splines function

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.

Heart rate variability indices for predicting cardiorenal outcomes: A lesson from the PERL and ACCORD cohorts.

This commentary highlights the role of heart rate variability (HRV) indices in predicting diabetic kidney disease (DKD) progression, based on findings from the PERL and ACCORD trials. HRV-derived measures from routine ECGs are shown to be strong predictors of rapid kidney function decline in both type 1 and type 2 diabetes, suggesting their potential utility in identifying individuals at high risk for DKD and guiding early preventive interventions.

Superior benefits of sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors for diabetic kidney disease: A cohort study.

To compare cardiorenal outcomes of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in a national diabetic kidney disease (DKD) population. A cohort study was conducted using Taiwan's National Health Insurance Research Database and Laboratory Databases. Propensity score-matched prevalent new users of SGLT-2is (n = 1524) and DPP-4is (n = 6005) during 2017-2018 were selected from adults with DKD and an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2. Composite renal outcomes included sustained eGFR decrease, renal failure and renal mortality. Composite cardiovascular (CV) outcomes included acute myocardial infarction, stroke, hospitalization for heart failure and CV death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with DPP-4i users, SGLT-2i users had a reduced risk of composite renal endpoint (HR: 0.16; CI: 0.12-0.24), consistently for a prolonged time to 50% or higher eGFR decrease (HR 0.17; CI: 0.11-0.27), renal failure (HR: 0.14; CI: 0.08-0.23) and decreased renal death (HR: 0.10; CI: 0.01-0.70). SGLT-2i users had a better composite CV outcome than DPP-4i users (HR: 0.74; CI: 0.64-0.85), and lower risks of stroke (HR: 0.76; CI: 0.62-0.92) and hospitalization for heart failure (HR: 0.68; CI: 0.55-0.84). Findings were consistent in analyses stratified by concomitant antidiabetic agents or intervals between DKD diagnosis and study drug initiation. This study shows the superior cardiorenal benefits of SGLT-2is compared with DPP-4is in the DKD population, regardless of concomitant antidiabetic agents or time from DKD onset to study drug initiation. SGLT-2is should be prioritized in adult patients with DKD.

The Michigan Collaborative for Type 2 Diabetes (MCT2D): Development and implementation of a statewide collaborative quality initiative

BackgroundType 2 diabetes (T2D) is one of the most prevalent chronic diseases worldwide and a leading cause of cardiorenal disease and mortality. Only one-third of individuals with T2D receive care as recommended by the American Diabetes Association’s clinical practice guidelines. Effective strategies are needed to accelerate the implementation of guideline concordant T2D care.MethodsThe Michigan Collaborative for Type 2 Diabetes (MCT2D) is a statewide population health collaborative quality initiative (CQI) developed to improve the care of all people with T2D in Michigan. MCT2D has developed a learning health system with physician organizations and their constituent practices to support quality improvement initiatives focused on (1) improving use of guideline-directed pharmacotherapy to improve cardiorenal outcomes, (2) increasing evidence-based use of continuous glucose monitoring, and (3) supporting use of lower carbohydrate eating patterns.ResultsBetween 2021 and 2022, MCT2D recruited 28 of the 40 Michigan-based physician organizations participating in Blue Cross’ Physician Group Incentive Program with 336 constituent practices and 1357 physicians in primary care (304), endocrinology (21) and nephrology (11). In January 2022, baseline data included a sample of 96,140 unique individuals with T2D. The baseline HbA1c was ≤ 7.0% for 66.3% of patients (n = 32,787), while 14.9% of patients had a most recent HbA1c ≥ 8.0% (n = 7,393). The most recent body mass index (BMI) was ≥ 30.0 for 64.8% of patients (n = 38,516).DiscussionMCT2D has organized a statewide collaborative to recruit and engage a diverse and large set of physician organizations and their constituent practices. This is a promising opportunity to accelerate adoption of guideline-concordant care for people with T2D and may be a model for other state or regional collaboratives. Future directions include specific evidence-based interventions targeted at reducing diabetes-linked comorbidities and associated healthcare costs as well as strategies focused on T2D prevention among at-risk populations.

Cardiorenal Outcomes, All-Cause Mortality, and Arterial Stiffness Parameters in Stable Kidney Transplant Recipients

Cardiorenal Outcomes, All-Cause Mortality, and Arterial Stiffness Parameters in Stable Kidney Transplant Recipients

Cardiorenal Outcomes in Patients with IgAN: The FinnGen Study

Cardiorenal Outcomes in Patients with IgAN: The FinnGen Study

Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.

Cardiorenal syndrome: evolving concepts and pediatric knowledge gaps.

Cardiorenal syndrome (CRS) refers to concomitant dysfunction of both the heart and kidneys. The pathology in CRS is bidirectional. Many individuals with kidney disease will develop cardiovascular complications. Conversely, rates of acute kidney injury and chronic kidney disease are high in cardiac patients. While our understanding of CRS has greatly increased over the past 15years, most research has occurred in adult populations. Improving cardiorenal outcomes in children and adolescents requires increased collaboration and research that spans organ systems. The purpose of this review is to discuss key features of CRS and help bring to light future opportunities for pediatric-specific research.

O80 A HIGH 24-HOUR URINE SODIUM-TO-POTASSIUM RATIO IS ASSOCIATED WITH WORSE RENAL OUTCOME

Background and Objective: Low sodium and high potassium intake are advised to control blood pressure and may improve long term cardiorenal outcomes. The optimal potassium intake for patients with chronic kidney disease remains to be defined and. We investigated whether the 24-hour urine sodium-to-potassium ratio (Na/K-ratio), which incorporates estimates of both sodium and potassium intake, could predict long-term renal outcome. Methods: We selected adult outpatients of a Dutch tertiary hospital who collected at least one 24-hour urine collection between 1998-2023. Patients with a history of dialysis or kidney transplantation were excluded. We examined the need for persistent renal replacement therapy (RRT), defined as dialysis or kidney transplantation, using Cox-regression. The association between the 24-hour urine Na/K-ratio and the estimated glomerular filtration rate (eGFR) slope was assessed using linear regression in patients who had ≥3 eGFR measurements available in ≥3 years, adjusted for age, sex, baseline eGFR, diabetes mellitus and hypertension. In the Cox-regression analysis, we additionally adjusted for the interaction between the 24-hour urine Na/K-ratio and baseline eGFR. Hypertension was defined as a clinical diagnosis or an office blood pressure ≥140/90 mmHg. Results: We included 720 patients aged 50±15 years, of whom 52% were male, 58% had hypertension and 31% diabetes mellitus. The baseline eGFR was 64±34 ml/min/1.73m2. The 24-hour urine Na/K ratio was 2.5±1.2 in a median number of 1 (IQR=1-2) urine collection. During a median follow-up of 11.2±14.0 years, 29% of patients needed RRT. The median annual eGFR decline was 1.51 (IQR=0.49-3.98) ml/min/1.73m2. Every unit increase in 24-hour urine Na/K-ratio was associated with a 19% higher risk for RRT (HR 1.19, 95% CI 1.03-1.39; p=0.02) and an additional 0.44 ml/min/1.73m2 (95% CI -0.83, -0.04; p=0.03) annual eGFR decline. Conclusions: This study suggests that higher 24-hour urine Na/K-ratio is associated with faster kidney function decline and the need for RRT, independent of hypertension, in a selected group of outpatients with available 24-hour urine measurements.

Thiazide diuretics versus loop diuretics in stage 3-5 CKD: impact on cardiorenal outcomes

ABSTRACT Objectives The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3–5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3–5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Methods Using data from the National Health Insurance Research Database (January 2008 to December 2019), we focused on individuals with stage 3–5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. Results The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (p-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all p-value <0.001). Conclusion Among stage 3–5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal function. These findings highlight the need for randomized controlled trials to assess the safety of loop diuretics in this population, urging caution in their prescription without a clear clinical indication.