Introduction to Optimal Management of Patients With Cardio-Kidney-Metabolic Syndrome

Am J Manag Care. 2024;30(suppl 10):S179-S180. https://doi.org/10.37765/ajmc.2024.89669

The link between cardiovascular and kidney health has been known since Robert Bright first described significant changes to the structure of the heart in patients with advanced kidney disease nearly 200 years ago.¹ The French pathologist Frédéric Justin Collet similarly utilized autopsy-based anatomical findings to describe passive renal (kidney) congestion secondary to heart dysfunction in 1903.² Yet, the term cardiorenal syndrome (CRS) was only classified in more recent years to encompass the bidirectional relationship between primary cardiac and kidney disorders.^3-5

Originally, CRS was used to describe kidney injury that was secondary to heart failure (HF).⁶ In 2004, investigators at the National Heart, Lung, and Blood Institute formally defined CRS as a state in which therapy to relieve HF symptoms is limited by declining kidney function.⁷ In 2008, the definition of CRS was subsequently broadened by a consensus from the Acute Dialysis Quality Initiative, which established that cardiovascular and kidney diseases share similarities in pathophysiology and mutually aggravate worsening outcomes in the other organ class.^4,5 CRS was further classified into 5 subtypes according to whether the impairment of each organ was primary, secondary, or stemmed from coexisting cardiovascular and kidney dysfunction as a systemic disease.

Chronic kidney disease (CKD) induces a systemic, chronic, proinflammatory state that results in adverse vascular and myocardial remodeling processes including atherosclerosis, vascular calcification, valvular calcification, and myocardial fibrosis.⁸ In other words, CKD promotes an accelerated aging of the cardiovascular system. It should be noted that patients with CKD are more likely to die from cardiovascular disease (CVD) than they are from progression to end-stage kidney disease.⁹ Fortunately, therapies such as angiotensin receptor blockers, sodium glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide 1 receptor antagonists have demonstrated improvement in both cardiovascular and kidney outcomes.^10-13

Additionally, with the emergence of obesity as a driving force behind risk factors for cardiovascular and kidney disease, CRS was further expanded to cardio-renal-metabolic syndrome.¹⁴ Research has highlighted the strong association between obesity and the inflammatory, neurohormonal, vascular, and metabolic responses that converge in cardiovascular and renal impairment.¹⁵ Prolonged obesity was found to induce pathological changes in renal blood flow (RBF), vasodilation, and glomerular hyperfiltration, which are later followed by declines in RBF and glomerular filtration rate, which affect kidney function.^16,17 Furthermore, patients with obesity were affected by greater metabolic demands resulting in risk factors for metabolic syndrome, including insulin resistance, hypertension, and dyslipidemia, which contributed to obesity-related HF.^18,19

More recently, the American Heart Association (AHA) updated its classification and introduced the term cardio-kidney-metabolic syndrome (CKM) to reflect the multidirectional relationship between metabolic risk factors, CKD, and the cardiovascular system.²⁰ In a scientific statement from the AHA regarding the management of CKM syndrome, unique management considerations are recommended for individuals with established CVD, or who are at high risk for CVD with coexisting metabolic risk factors, CKD, or both.²¹

A disproportionate CKM burden exists in patients with adverse social determinants of health, family history, and concomitant inflammatory conditions.²⁰ Additionally, traditional risk factors for metabolic syndrome such as dyslipidemia, hypertension, obesity, insulin resistance, and hyperglycemia, as well as behavioral factors such as physical inactivity, smoking, and unhealthy eating patterns also increase the risk for worsened cardiovascular and kidney outcomes.^22,23 The current AHA advisory provides a holistic approach to prevention and care optimization within CKM syndrome, though it identifies an unmet need to move beyond subspecialty silos to collaborative interdisciplinary patient-centered care models to optimize CKM health outcomes.²⁰

This supplement will address some of the existing gaps and challenges to our understanding of CKM syndrome, including early screening and prevention measures, comprehensive management strategies to facilitate targeted interventions, and the translation of evidence-based guidelines to an integrated and interdisciplinary approach to care.²⁴

In the first article in this supplement,²⁵ Keith C. Ferdinand, MD, from the Tulane University School of Medicine, New Orleans, Louisiana, presents an overview of CKM syndrome and the recent AHA presidential statement on the classification and management of the CKM syndrome. Dr Ferdinand explores current evidence on the prevalence and pathophysiology of CKM syndrome, as well as considerations of comorbid conditions and social determinants of health.

Many treatment guidelines in this therapy area come from single specialty groups. Hence, in the second article,²⁶ Yehuda Handelsman, MD, from the Metabolic Institute of America, Tarzana, California summarizes the recommendations of a multispecialty group of experts in cardiology, endocrinology, diabetology, lipidology, coagulation, nephrology, hepatology, obesity, and primary care toward the management of diabetes, cardiorenal, and/or metabolic (DCRM) diseases. The recommendations are targeted toward nonspecialists and cover patient assessment and treatment, including lifestyle management and pharmacotherapy strategies.

Notably, both the AHA presidential statement and DCRM guidelines highlight the need for coordinated care for patients with CKM syndrome. In the final article,²⁷ Ian J. Neeland, MD, from Case Western Reserve University School of Medicine and Sanjay Rajagopalan, MD, from University Hospitals Cleveland Medical Center, both in Cleveland, Ohio, present an overview of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) program, which utilizes a coordinated framework approach to patients with CKM syndrome. They describe the key features of the CINEMA program and the key outcomes over the 2 years that the program has existed. The authors also discuss the scalability of such a program and some of the major barriers to implementation and potential strategies to overcome them.

In conclusion, this supplement explores the background, guidelines, and subsequent translation of data into clinical practice of CKM syndrome using evidence from existing literature, consensus statements from multidisciplinary experts, and existing programs for coordinated care.

Acknowledgments

The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors. The author did not receive payment related to the development of the manuscript. Writing support was provided by Jonathon Gibbs of Elevate Scientific Solutions, LLC, contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI) and Lilly USA, LLC. BIPI and Lilly were given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Author Affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD

Funding Source: This supplement was supported by Boehringer Ingelheim Pharmaceuticals, Inc and Lilly USA, LLC.

Author Disclosures: Dr Michos reports receiving consulting fees from Amgen; Arrowhead Pharmaceuticals; Boehringer Ingelheim; Edwards Lifesciences; Esperion; Ionis Pharmaceuticals, Inc; Medtronic; Merck; NewAmsterdam Pharma; Novartis; Novo Nordisk; and ZOLL.

Authorship Information: Concept and design; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.

Address Correspondence to: Erin D. Michos, MD, MHS. Johns Hopkins University School of Medicine, Blalock 524-B, 600 N Wolfe St, Baltimore, MD 21287. Email: edonnell@jhmi.edu

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