Perspective

Cardiovascular-Kidney-Metabolic Health Syndrome: What

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Does the American Heart Association Framework Mean for

Nephrology?
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Nisha Bansal ,1 Daniel Weiner ,2 and Mark Sarnak 2

JASN 00: 1–4, 2024. doi: https://doi.org/10.1681/ASN.0000000000000323

Overview of the American Heart Association’s Nephrologists have a substantial role in caring for indi-
Cardiovascular-Kidney-Metabolic Syndrome viduals across CKM stages. What does this new framework
Obesity, diabetes, and CKD are highly prevalent, com- mean for nephrology and care of kidney disease patients?
monly co-occur, and substantially increase cardiovascular
disease morbidity and mortality. The mechanisms of these Earlier Detection of CKD
four disease states also are closely intertwined, with mul- Cardiovascular disease risk factors, including CKD, are
tidirectional relationships, shared risk factors, and common often silent and undetected until clinically apparent dis-
therapeutic targets. Given the complex interactions among ease is present. This new staging system emphasizes
these diseases, the American Heart Association (AHA) re- early detection of cardiovascular disease risk factors,
cently proposed a new integrated health disorder, the including CKD. The CKM staging recommends assess-
cardiovascular-kidney-metabolic (CKM) syndrome, defined ment of both eGFR and the urine albumin-creatinine ratio
as a health disorder attributable to connections among in at-risk individuals, defined as those with obesity,
obesity, diabetes, CKD, and cardiovascular disease.1,2 hypertriglyceridemia.135 mg/dl, metabolic syndrome,
The CKM framework aims to move beyond individual diabetes, hypertension (stage 1 or higher), and those with
risk factor management, proposing a new integrated sys- clinical cardiovascular disease. Notably, this framework
temic staging system for those at risk for, and with, existing calls for albuminuria assessment in CKM stage 1, defined
cardiovascular disease (Figure 1). This staging system is by obesity or dysfunctional adiposity without CKD. We
designed to better reflect the pathophysiology, spectrum of hope that this AHA CKM framework raises awareness of
risk, and opportunities for prevention and care optimiza- kidney health and promotes screening for kidney disease
tion within the CKM syndrome. Stage 0 includes individ- among primary care and other subspecialty clinicians who
uals who are not overweight/obese and do not have are seeing these patients early in the course of disease, as
metabolic risk factors (e.g., hypertension, hypertriglyceride- measurement of urinary albumin-to-creatinine ratio (UACR)
mia), CKD, or subclinical/clinical cardiovascular disease. has remained dismally low despite previous guideline
Stage 1 includes individuals who have excess and/or dys- recommendations. 3 We also hope that this accelerates
functional adiposity, as manifested by high body mass index, implementation of CKD screening more broadly in the
waist circumference, or fasting blood sugar. Individuals in United States, including a more expansive recommen-
this stage do not have other metabolic risk factors or CKD. dation for kidney disease screening as currently being
Stage 2 includes individuals with metabolic risk factors (hy- considered by the US Preventative Services Task Force.
pertriglyceridemia, hypertension, diabetes) or CKD. Stage 3 Earlier detection and screening for CKD using both
includes individuals with subclinical atherosclerotic cardio- eGFR and UACR in individuals at even low or moderate
vascular disease (atherosclerosis or coronary artery calcium) risk may substantially delay or prevent progression of
or subclinical heart failure (elevated cardiac biomarkers or CKD, increase life-years and quality of life, and reduce
echocardiographic parameters) among individuals with health care costs.4,5
excess/dysfunctional adiposity, metabolic risk factors, or
CKD. Risk equivalents for subclinical cardiovascular disease
include stage G4 or G5 CKD. Finally, stage 4 CKM includes Kidney Disease across the Lifespan
individuals with clinical cardiovascular disease (coronary Kidney disease is not just a disease affecting older adults.
heart disease, heart failure, stroke, peripheral artery dis- As the incidence of metabolic diseases and obesity increases
ease, atrial fibrillation) among individuals with excess/ in younger individuals and children, greater guidance is
dysfunctional adiposity, metabolic risk factors, or CKD.1,2 needed on how and when to screen for complications such

1
Division of Nephrology, University of Washington, Seattle, Washington
2
Division of Nephrology, Tufts Medical Center, Boston, Massachusetts

Correspondence: Dr. Nisha Bansal, email: [email protected]

Published Online Ahead of Print: February 6, 2024

JASN ▪: 1–4, ▪▪▪, 2024 Copyright © 2024 by the American Society of Nephrology 1
 PERSPECTIVE www.jasn.org
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Figure 1. Stages of the American Heart Association CKM health syndrome. Reprinted from ref. 1 with permission. AFib, atrial fibrillation;
ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart disease; CKM, cardiovascular-kidney-metabolic; CVD, cardiovascular
disease; HF, heart failure; KDIGO, Kidney Disease Improving Global Outcomes; PAD, peripheral arterial disease.

as CKD. The CKM proposes screening for CKD in early life and slow the progression of CKD.7 There remain substan-
(age ,21 years) with risk factors such as obesity, hyper- tial barriers in initiation of these medications (in part due
triglyceridemia, diabetes, or hypertension. Earlier detection to social determinants of health [SDOH]), with patients
of CKD in younger individuals could have substantial who are most likely to benefit being less likely to receive
impact on lifetime survival and quality of life.6 these therapies.8 In addition, some of these therapies may
have short-term hemodynamic effects on kidney function
Focus on CKD Severity, Including Patients Treated with or have higher rates of adverse effects in individuals with
Dialysis CKD, which can lead to premature discontinuation of
Until now, outside of nephrology guidelines, CKD has these therapies. The CKM treatment approach encourages
largely been treated as a single entity, with less attention initiation and continuation of these important therapies in
to patients with kidney failure treated with dialysis. With patients with CKD, which is a current barrier in imple-
the CKM framework, individuals with CKD stage G4 and mentation and extends beyond nephrology. There is a
G5 by the Kidney Disease Improving Global Outcomes critical need for trials to evaluate implementation strate-
staging system are considered risk equivalents for subclin- gies to increase uptake of guideline-directed medical ther-
ical cardiovascular disease, resulting in a designation of at apy in patients with CKD, including the pace of initiation
least stage 3 CKM. In stage 4 CKM, patients with kidney and titration.
failure treated with dialysis are separated from those with-
out kidney failure because of the substantial cardiovascular New Risk Score for Cardiovascular Disease That Includes
risk and the unique approaches to risk factor management Kidney Function
and treatment (in the context of a lack of quality data to Previous cardiovascular disease risk scores have not typ-
guide treatment decisions). ically included eGFR and albuminuria as prediction var-
iables. The new CKM Predicting Risk of CVD EVENTs
Consideration of Kidney Function in Guideline-Directed (PREVENT) prediction model includes traditional cardio-
Medical Therapy vascular disease risk factors (age, total cholesterol, non-
Guideline-directed medical therapy therapies, such as HDL and HDL cholesterol, systolic BP, diabetes, current
renin-angiotensin-aldosterone inhibitors, mineralocorti- smoking, hypertension medications, and statins) and
coid receptor antagonists, sodium-glucose cotransporter- eGFR as predictors, with additional models tailored for
2 inhibitors, and glucagon-like peptide-1 receptor ago- high-risk individuals with inclusion of UACR when
nists, remain underutilized in patients with or at risk available.9,10 If this new model gets implemented into
for cardiovascular disease and CKD despite strong evi- practice, this would prompt earlier and wider measure-
dence that they improve cardiovascular disease outcomes ment of eGFR and UACR. In addition, the new PREVENT

2 JASN
 CKM and Nephrology, Bansal et al.

model predicts total cardiovascular disease, including risk implement broader screening for CKD, greater imple-
of heart failure in addition to atherosclerotic cardiovascu- mentation of newer kidney and cardiovascular disease
lar disease. This is an important addition for patients with protective therapies among patients with CKD, and mo-
CKD in whom the excess rates of heart failure are com- tivate greater propagation of collaborative care models.
parable with (or even exceed) that of atherosclerotic car- Furthermore, we hope that the CKM framework acceler-
diovascular disease. Furthermore, this new risk equation ates research in the field, including greater investigation
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does not include race as a variable, therefore aligning with of etiologies of CKD in patients with metabolic disease
the most recent race-free eGFR equations. and cardiovascular disease to guide disease-specific treat-
ments; research across the spectrum of CKD severity
Social Determinants of Health (including dialysis patients); and broader inclusion of
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SDOHs are highly prevalent in patients with CKD and are patients with CKD in cardiovascular disease clini-
strongly linked with higher risk of CKD and cardiovas- cal trials.
cular disease. However, there remain significant gaps in
identifying SDOHs in our patients. The CKM PREVENT
risk score proposes additional models that incorporate Disclosures
SDOHs and a social deprivation index. This is a step N. Bansal reports consultancy for AstraZeneca, advisory or
forward in recognizing the shared importance of SDOHs leadership role as an Kidney360 Associate Editor and an UpTo-
Date Section Editor, and advisory or leadership role for American
with biological risk factors; hopefully that will lead to
College of Physicians. M. Sarnak reports consultancy on the
more systematic interventions. Steering Committee of Trials Funded by Akebia, consultancy
for Boehringer Ingelheim (attended an Advisory Board), and
Patient Education research funding from NIH. M. Sarnak’s spouse reports employ-
Many people with kidney disease are unaware of their ment with and ownership interest in Eli Lilly. D. Weiner reports
diagnosis; this may be due to lack of symptoms or ineffec- employment with Tufts Medical Center Physicians Organization;
research funding from Bayer (site PI), Cara (site PI), and Vertex
tive communication and education. This new CKM frame-
(site PI), with all compensation paid to Tufts MC; advisory or
work may help start important conversations about kidney
leadership role as Co Editor-in-Chief of NKF Primer on Kidney
health (e.g., prevention and treatment) in individuals at risk Diseases 8th Edition, Editor-in-Chief of Kidney Medicine, Medical
or with CKD from health care professionals outside Director of Clinical Research for Dialysis Clinic Inc., Member of
of nephrology. ASN Quality and Policy Committees and ASN representative to
KCP, and Member of Scientific Advisory Board for National
Kidney Foundation; and other interests or relationships as Mem-
Interdisciplinary Care Models ber of Safety and Clinical Events Committee for “A Prospective,
The AHA CKM framework encourages value-based ap- Multi-Center, Open-Label Assessment of Efficacy and Safety of
proaches to interdisciplinary care to reduce the fragmen- Quanta SC1 for Home Hemodialysis” Trial (Avania CRO) and
tation and inequitable access to therapies that may occur in Member of Adjudications Committee for ProKidney REACT Trial
individuals with overlapping CKM conditions. The CKM (WCG Clinical CRO).
statement suggests that the interdisciplinary CKM team
would be supported by a coordinator and includes rep-
resentation from primary care, cardiology, nephrology, Funding
endocrinology, pharmacy, and nursing, as well as care None.
navigators, social workers, or community health workers.
In addition, targeted referrals to subspecialists to activate
additional expertise are recommended to higher-risk pa- Acknowledgments
tients with CKM syndrome. The principles espoused here The content of this article reflects the personal experience and
views of the author(s) and should not be considered medical advice
are appropriate; however, marked shifts in health care
or recommendation. The content does not reflect the views or
models, particularly in the United States where payers
opinions of the American Society of Nephrology (ASN) or JASN.
seldom take multiyear perspectives, would need to occur Responsibility for the information and views expressed herein lies
for the financial aspects of a CKM value-based care model entirely with the author(s).
to be implemented widely.

Next Steps: Putting the AHA CKM into Practice Author Contributions
Conceptualization: Nisha Bansal, Mark Sarnak, Daniel Weiner.
The AHA’s CKM framework places kidney health in the
Writing – original draft: Nisha Bansal.
center of this new syndrome, bringing attention to the
Writing – review & editing: Nisha Bansal, Mark Sarnak,
often-overlooked public health impact of kidney disease. Daniel Weiner.
This is an important advance for the nephrology com-
munity and provides a new opportunity to forge strong
partnerships with other clinicians to advance the care of References
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