POCN's Chronic Kidney Disease Center of Excellence

Author: Kimberly Cantillon,

  • CKM Syndrome: Integrating Treatment Across Cardiovascular, Kidney, and Metabolic Disorders

    CKM Syndrome: Integrating Treatment Across Cardiovascular, Kidney, and Metabolic Disorders

    Cardiovascular-kidney-metabolic (CKM) syndrome links metabolic disorders like obesity and diabetes, chronic kidney disease (CKD), and cardiovascular health, leading to increased mortality, morbidity, and healthcare costs. While its prevalence indicates a public health crisis, advancements in treatment have improved outcomes. Yet, further enhancement of CKM health outcomes requires a structured approach, including clear syndrome definition, a robust management framework, and enhanced risk prediction and treatment strategies.

    Clinically, CKM syndrome manifests as cardiorenal and cardiometabolic conditions, where organ dysfunctions exacerbate each other, such as kidney issues worsening heart health. This is further complicated by adipose tissue dysfunction, which increases inflammation and insulin resistance, elevating cardiovascular risks. Management should integrate these interconnected conditions, focusing on comprehensive screening like albuminuria and implementing holistic treatments to slow kidney progression and reduce cardiovascular risks, effectively spanning the CKM conditions spectrum.

    Reference: Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023 Nov 14;148(20):1606-1635. doi: 10.1161/CIR.0000000000001184. Epub 2023 Oct 9. Erratum in: Circulation. 2024 Mar 26;149(13):e1023. PMID: 37807924.

  • Redefining Heart Failure Management: A Call for Nuanced Approaches

    Redefining Heart Failure Management: A Call for Nuanced Approaches

    Heart failure (HF), traditionally classified by left ventricular ejection fraction (LVEF) cutpoints, overlooks its continuum and nuanced treatment responses. The Heart Failure Collaboratory advocates a pragmatic shift to broadly categorize HF into reduced and non-reduced LVEF, reflecting recent guidelines’ evolution. While terms like HFmrEF lack robust evidence and may complicate treatment decisions, HFimpEF should align with HFrEF due to shared characteristics.

    Current HF treatments show varying efficacy across LVEF, challenging traditional classifications. Neurohormonal antagonists and sodium glucose co-transporter 2 inhibitors exhibit diverse treatment effects relative to LVEF, with diminishing benefits towards normal ranges. HF device interventions echo these disparities, underscoring the need for nuanced management strategies. While LVEF remains crucial in clinical practice, ongoing research should prioritize novel biomarkers and therapies for tailored interventions, enhancing outcomes across HF’s diverse landscape.

    Reference: Dimond MG, Ibrahim NE, Fiuzat M, et al. Left Ventricular Ejection Fraction and the Future of Heart Failure Phenotyping. JACC Heart Fail. 2024 Mar;12(3):451-460. doi: 10.1016/j.jchf.2023.11.005. Epub 2023 Dec 13. PMID: 38099892.

  • Semaglutide Reduces Cardiovascular Risks in Overweight, Non-Diabetic Patients: Large Trial Reveals

    Semaglutide Reduces Cardiovascular Risks in Overweight, Non-Diabetic Patients: Large Trial Reveals

    In a large-scale, multicenter trial, semaglutide, a glucagon-like peptide-1 receptor agonist, was evaluated for its ability to reduce cardiovascular risks in individuals with obesity or overweight but no diabetes. Participants, all aged 45 or older with existing cardiovascular disease and a BMI of at least 27, were randomized to receive a weekly 2.4 mg dose of semaglutide or a placebo. The primary goal was to determine if semaglutide could effectively lower the occurrence of major cardiovascular events, which included cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

    The trial enrolled 17,604 patients, split almost evenly between the semaglutide and placebo groups. Over an average follow-up of nearly 40 months and treatment duration of about 34 months, those receiving semaglutide experienced a lower rate of cardiovascular events (6.5%) compared to those on placebo (8.0%), achieving a hazard ratio of 0.80. Despite the positive outcomes, the semaglutide group had a higher rate of adverse events leading to discontinuation at 16.6%, significantly greater than the 8.2% in the placebo group. Thus, while semaglutide proved effective in reducing cardiovascular events among those with cardiovascular disease and obesity, it also led to increased adverse effects resulting in discontinuation of treatment.

    Reference: Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11. PMID: 37952131.

  • Study Shows Combining SGLT2 Inhibitors and MRAs Extends Kidney Health in Diabetic Patients

    Study Shows Combining SGLT2 Inhibitors and MRAs Extends Kidney Health in Diabetic Patients

    A study investigated the combined long-term benefits of using sodium-glucose co-transporter 2 (SGLT2) inhibitors and mineralocorticoid-receptor antagonists (MRA) for patients with type 2 diabetes and chronic kidney disease (CKD). Utilizing data from the CREDENCE and FIDELIO trials for canagliflozin and finerenone respectively, and applying these to a control group from the DAPA-CKD trial, researchers aimed to assess the improvement in event-free and overall survival.

    The results demonstrated a marked improvement in event-free survival among those treated with the combination therapy. At age 50, such patients were projected to have 16.7 years free from severe kidney events, in contrast to just 10.0 years for those treated with standard therapies like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, yielding an added benefit of 6.7 years. Assuming reduced adherence and efficacy, the combination therapy was expected to extend event-free survival by 2.5 years. This evidence supports the substantial benefit of combining an SGLT2 inhibitor and MRA in extending the period free from significant kidney complications in this patient population.

    Reference: Heerspink HJL, Vart P, Jongs N, et al. Estimated lifetime benefit of novel pharmacological therapies in patients with type 2 diabetes and chronic kidney disease: A joint analysis of randomized controlled clinical trials. Diabetes Obes Metab. 2023 Nov;25(11):3327-3336. doi: 10.1111/dom.15232. Epub 2023 Aug 14. PMID: 37580309.

  • Sotagliflozin Reduces Cardiovascular Events After Heart Failure in Type 2 Diabetes

    Sotagliflozin Reduces Cardiovascular Events After Heart Failure in Type 2 Diabetes

    A multicenter, double-blind trial assessed the efficacy of sotagliflozin, an SGLT2 inhibitor, when started soon after a heart failure episode in type 2 diabetes patients. Participants received sotagliflozin or placebo around the time of hospital discharge, aiming to track cardiovascular deaths, hospitalizations, and urgent heart failure visits. Despite an early end due to funding, the study followed 1222 patients for nine months and found fewer cardiovascular events in the sotagliflozin group compared to placebo.

    The results indicated a significant drop in cardiovascular events for those on sotagliflozin, with 51.0 versus 76.3 events per 100 patient-years and a hazard ratio of 0.67. Although cardiovascular death rates were lower in the sotagliflozin group, they were not statistically significant. Overall, sotagliflozin initiated post-heart failure hospitalization led to better cardiovascular outcomes, showcasing its benefits for high-risk patients.

    Reference: Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16. PMID: 33200892.

  • Albuminuria: A Critical Predictor of Heart Failure Risk and Progression

    Albuminuria: A Critical Predictor of Heart Failure Risk and Progression

    Albuminuria, prevalent in heart failure (HF), independently predicts HF incidence and progression, yet its causes and mechanisms remain unclear. Despite being underutilized in cardiovascular trials, it emerges as a critical predictor of HF risk, especially when present alongside normal eGFR, suggesting its potential as an early indicator of cardiovascular and kidney disease. Incorporating albuminuria into HF risk prediction models may aid in forecasting HF development and targeting interventions to reduce albuminuria could potentially mitigate HF incidence and progression.

    Albuminuria independently forecasts HF risk, but its full prognostic potential and therapeutic implications are not fully understood. Despite its underutilization in cardiovascular trials, its inclusion in HF risk prediction models could enhance risk assessment. Future research should explore interventions targeting albuminuria reduction and clarify its prognostic significance in different HF subgroups like HFpEF and HFrEF.

    Reference: Khan MS, Shahid I, Anker SD, et al. Albuminuria and Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Jan 24;81(3):270-282. doi: 10.1016/j.jacc.2022.10.028. PMID: 36653095.

  • Finerenone Shows Promise in Reducing Heart Failure Risks in High-Risk T2D Patients With CKD

    Finerenone Shows Promise in Reducing Heart Failure Risks in High-Risk T2D Patients With CKD

    The FIDELITY trial examined finerenone’s impact on heart failure (HF) outcomes in 13,026 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Finerenone significantly decreased the risk of HF-related hospitalizations, cardiovascular death, and recurrent HF compared to placebo. Notably, patients with higher baseline estimated glomerular filtration rate (eGFR) and lower urine albumin-to-creatinine ratio (UACR) experienced the lowest incidence of adverse outcomes, yet finerenone consistently improved HF outcomes across all eGFR and/or UACR categories.

    These findings highlight finerenone’s potential to ameliorate HF-related outcomes in high-risk T2D patients with CKD, irrespective of their baseline kidney function and albuminuria levels. Further investigation is warranted to elucidate the underlying mechanisms of these benefits and assess the long-term impact of finerenone therapy on cardiovascular outcomes in this patient population.

    Reference: Filippatos G, Anker SD, Pitt B, et al. Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes. JACC Heart Fail. 2022 Nov;10(11):860-870. doi: 10.1016/j.jchf.2022.07.013. Epub 2022 Oct 12. Erratum in: JACC Heart Fail. 2023 Aug;11(8 Pt 1):1034-1035. PMID: 36328655.…

  • Finerenone Reduces Heart Failure Risks in CKD and T2D Patients

    Finerenone Reduces Heart Failure Risks in CKD and T2D Patients

    In patients with albuminuric chronic kidney disease and type 2 diabetes, finerenone, a nonsteroidal mineralocorticoid receptor antagonist, exhibited significant cardiovascular benefits, particularly in reducing heart failure (HF) risks. Analyses from the FIGARO-DKD trials revealed that finerenone lowered the incidence of new-onset HF, cardiovascular death, and hospitalizations for HF compared to placebo. These benefits extended across various HF outcomes, including a reduction in total HF hospitalizations by 30%, demonstrating finerenone’s efficacy in mitigating HF-related morbidity and mortality in this high-risk patient population, regardless of prior HF history.

    The findings underscore finerenone’s potential as a therapeutic option for HF prevention in patients with chronic kidney disease and type 2 diabetes. The observed benefits of finerenone were consistent across subgroups, suggesting its efficacy remains irrespective of patients’ baseline HF status. These results emphasize the significance of finerenone in improving cardiovascular outcomes in this vulnerable population and highlight the need for further exploration of its long-term impact on HF prevention and management.

    Reference: Filippatos G, Anker SD, Agarwal R, et al. Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses From the FIGARO-DKD Trial. Circulation. 2022 Feb 8;145(6):437-447. doi: 10.1161/CIRCULATIONAHA.121.057983. Epub 2021 Nov 13. PMID: 34775784; PMCID: PMC8812430.

  • Guidelines Align on Diabetes and CKD Management, Tackle Implementation Challenges

    Guidelines Align on Diabetes and CKD Management, Tackle Implementation Challenges

    The 2022 ADA Standards of Medical Care in Diabetes and the KDIGO 2022 Clinical Practice Guideline provide evidence-based recommendations for managing diabetes and chronic kidney disease (CKD). These jointly reviewed guidelines emphasize comprehensive care, integrating proven pharmacotherapy with healthy lifestyle practices. Specific consensus statements offer guidance on drug usage, including renin-angiotensin system inhibitors, metformin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist, with the goal of enhancing clinical outcomes for individuals with diabetes and CKD.

    Despite alignment between the 2022 ADA Standards of Care and KDIGO 2022 guideline, challenges like high costs and limited healthcare resources may hinder broad implementation of these recommendations, necessitating efforts to improve accessibility and address disparities. Ongoing research in diabetes, CKD, and cardiovascular disease is anticipated to provide further insights, driving continual evolution of clinical practice guidelines.

    Reference: de Boer IH, Khunti K, Sadusky T, et al. Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Diabetes Care. 2022 Dec 1;45(12):3075-3090. doi: 10.2337/dci22-0027. PMID: 36189689; PMCID: PMC9870667.