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Albuminuria in Cardiovascular, Kidney, and Metabolic Disorders: A State-of-

the-Art Review

Article in Circulation · March 2025

DOI: 10.1161/CIRCULATIONAHA.124.071079

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 Circulation

IN DEPTH

Albuminuria in Cardiovascular, Kidney, and

Metabolic Disorders: A State-of-the-Art Review
Sophie E. Claudel , MD; Ashish Verma , MB, BS

ABSTRACT: Albuminuria—increased urine albumin excretion—is associated with cardiovascular mortality among patients with
diabetes, hypertension, chronic kidney disease, or heart failure, as well as among adults with few cardiovascular risk factors.
Many authors have hypothesized that albuminuria reflects widespread endothelial dysfunction, but additional work is needed
to uncover whether albuminuria is directly pathologic or causative of cardiovascular disease. Urinary albumin-to-creatinine
ratio is an attractive, unifying biomarker of cardiovascular, kidney, and metabolic conditions that may be useful for identifying
and monitoring disease trajectory. However, albuminuria may develop through unique mechanisms across these distinct
clinical phenotypes. This state-of-the-art review discusses the role of albuminuria in cardiovascular, kidney, and metabolic
conditions; identifies potential pathways linking albuminuria to adverse outcomes; and provides practical approaches to
screening and managing albuminuria for clinical cardiologists. Future research is needed to determine how broadly and how
frequently to screen patients for albuminuria, whether it is cost-effective to treat low-grade albuminuria (10–30 mg/g), and
how to equitably offer newer antiproteinuric therapies across the spectrum of cardiovascular-kidney-metabolic diseases.

Key Words: albuminuria ◼ cardiovascular diseases ◼ metabolic syndrome ◼ renal insufficiency, chronic

C
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ardiovascular disease (CVD) is the leading This narrative, state-of-the-art review discusses the
cause of death worldwide, and scalable, nonin- role of albuminuria in CKM conditions and identifies
vasive biomarkers for CVD are a growing area potential pathways linking albuminuria to adverse cardio-
of research interest.1 A CVD biomarker ideally would vascular outcomes. This review highlights the importance
accurately identify high-risk individuals, convey prog- of testing for albuminuria in cardiovascular practice and
nostic value, and allow early intervention in the disease provides suggestions for evidence-based treatment ini-
course. Increased urinary albumin excretion is a known tiation in patients with CKM disorders.
CVD risk factor among patients with diabetes, hyper-
tension, chronic kidney disease (CKD), coronary artery
disease, or heart failure,2 and may convey risk among MEASUREMENT, CLASSIFICATION, AND
those with few CVD risk factors.3–5 Albuminuria is also
a strong determinant of CKD progression in patients PATHOGENESIS OF ALBUMINURIA
with and without metabolic diseases.6 Therefore, urinary In clinical practice, spot urine albumin is quantified us-
albumin-to-creatinine ratio (UACR) is an attractive, uni- ing a fluorescent immunoassay or liquid chromatography,
fying biomarker of cardiovascular, kidney, and metabolic and spot urine creatinine is measured using a standard-
(CKM) conditions that may be useful for identifying and ized enzymatic method or the Jaffe reaction.10 Where-
monitoring disease trajectory. The dose–response rela- as 24-hour urine collection is preferred, spot UACR is
tionship between UACR and cardiovascular outcomes suitable for most clinical scenarios, so long as the as-
makes this biomarker particularly relevant to cardiology sumption that an individual excretes ≈1000 mg/day
clinical practice.7–9 of ­creatinine holds.11 These quantitative methods are

Correspondence to: Ashish Verma, MB, BS, 14 Evans Biomedical Research Center, X-521, 650 Albany St, Boston University Chobanian & Avedisian School of
Medicine, Boston, MA 02118. Email [email protected]
For Sources of Funding and Disclosures, see page 727.
© 2025 American Heart Association, Inc.
Circulation is available at www.ahajournals.org/journal/circ

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 Claudel and Verma Albuminuria in CKM Disorders

Under normal physiologic conditions, up to several

Nonstandard Abbreviations and Acronyms grams of albumin may be filtered and reabsorbed by the

STATE OF THE ART

early proximal tubule (either intact or after catabolism),
ACEI  angiotensin-converting enzyme although the precise glomerular sieving coefficient is
inhibitor debated (Figure 1).13–15 Protein that is excreted into the
ARB angiotensin receptor blocker urine can be benign or pathologic.11 Transient causes of
ARNI  angiotensin receptor-neprilysin proteinuria include fever, orthostatic proteinuria, urinary
inhibitor tract infection, pregnancy, or vigorous exercise. Tran-
CKD chronic kidney disease sient proteinuria can also be seen in patients with severe
CKM cardiovascular, kidney, and metabolic hypertension, poor glycemic control, or severe hyperlip-
CVD cardiovascular disease idemia.11 Persistent proteinuria is pathologic and may be
DKD diabetic kidney disease tubular (albumin and nonalbumin protein) or glomerular
eGFR estimated glomerular filtration rate (albumin-predominant) in pathogenesis.11,16–18 Glomeru-
ESKD end-stage kidney disease lar proteinuria results from foot process effacement,
FSGS focal segmental glomerulosclerosis glomerular basement membrane injury, or increased glo-
GBM glomerular basement membrane
merular hydrostatic pressure that disrupts selective glo-
merular ultrafiltration.16 Albuminuria may be detectable
glucagon-like peptide-1 receptor
GLP1-RA 
agonist
in kidney disease before a decline in glomerular filtration
rate.17
MASLD  metabolic associated steatotic liver
disease
Current clinical practice guidelines classify a UACR
measurement of <30 mg/g (<3.4 mg/mmol) as “nor-
MRA  mineralocorticoid receptor
antagonist
mal to minimally increased,” 30 to 300 mg/g (3.4–34
mg/mmol) as “moderately increased,” and ≥300 mg/g
Predicting Risk of Cardiovascular
PREVENT 
Events
(34 mg/mmol) as “severely increased.”18 Albuminuria
>3.0 to 3.5 g/d is considered “nephrotic range.” How-
SGLT2i sodium-glucose cotransporter-2
inhibitor
ever, it is well recognized that a continuous relationship
exists between increasing albuminuria and adverse
UACR urinary albumin-to-creatinine ratio
clinical outcomes that begins far below the traditional
“microalbuminuria” threshold (<30 mg/g).4–6,19,20 Pre-
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strongly ­preferred to urine dipstick analysis, which has vious authors have articulated issues with the current
low sensitivity and detects only advanced albuminuria albuminuria classification system, principally the over-
(typically ≥300 mg/g).12 The value of dipstick albuminuria emphasis on thresholds.21,22 The false dichotomiza-
analysis is in the widespread availability and affordabil- tion between “normal” and “abnormal” UACR at 30
ity that may increase screening in resource-constrained mg/g obscures risk and may predispose clinicians to
settings. However, where possible, quantitative methods overlook opportunities for cardiorenal risk reduction.
are preferred (Table 1). A new framework that incorporates the continuous

Table 1. Methods to Measure Albuminuria

Method Advantages Disadvantages

Dipstick Low cost Low sensitivity
Point-of-care testing Semiquantitative
Does not evaluate low levels of albuminuria well and thus only detects advanced
disease
Spot ASG, mg/L Lower cost due to reliance on urine specific gravity Specific gravity may be affected by external factors
and not creatinine concentration Lower accuracy with very dilute or very concentrated urine
Spot ACR, mg/g* Convenient for patients More costly than dipstick
High sensitivity May be affected by diurnal variation in albumin excretion
High specificity
First morning void High sensitivity Less convenient for patients than random spot ACR
ACR, mg/g* High specificity
May be more closely correlated to 24-h AER than spot
ACR
24-h AER, mg/h High specificity Time consuming
High sensitivity Cumbersome for patients
Not affected by diurnal variation in albumin excretion Incomplete collections have low utility

ACR indicates albumin-creatinine ratio; AER, albumin excretion rate; and ASG, albumin adjusted for specific gravity.
*Depending on the laboratory, the methods for quantifying urine creatinine may vary (eg, Jaffe versus enzymatic) and affect the reliability of results.

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 Claudel and Verma Albuminuria in CKM Disorders
STATE OF THE ART
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Figure 1. Pathophysiology of albuminuria.

Mechanisms of albuminuria include both loss of glomerular basement membrane (GBM) integrity and impaired proximal tubular albumin
reabsorption. Created in BioRender.com.

r­elationship may improve clinical management of albu- One of the pitfalls of measuring albuminuria is the day-
minuria, although multiple additional knowledge gaps to-day variability in an individual’s urinary albumin excre-
remain (Table 2). tion.23,24 Therefore, repeat quantitative ­ measurements

Table 2. Knowledge Gaps

Area Questions
Diagnosis Should the general population be screened for albuminuria?
Is 30 mg/g an appropriate threshold for diagnosing CKD given the associations between ACR <30 mg/g and adverse clinical outcomes?
Variability What are the causes of intraindividual variability in repeated measurements of albuminuria?
What degree of variability is seen between repeat albuminuria measurements among patients without diabetes?
Monitoring How frequently should albuminuria be reassessed? Should the frequency of reassessment be different according to different clinical
characteristics?
In patients with albuminuria, what degree of albuminuria reduction in response to treatment is sufficient?
Is there a percent reduction or absolute threshold that should be the treatment target?
What degree of fluctuation between repeat collections should prompt additional diagnostic evaluation?
Treatment At what threshold of albuminuria should antiproteinuric therapies be initiated?
Prognosis What is the relative contribution of albuminuria reduction to improved cardiovascular outcomes with antiproteinuric therapies (versus other
cardioprotective effects of these medications)?
Is initiation of antiproteinuric therapy at ACR <30 mg/g associated with improved cardiovascular or kidney outcomes?
Is albuminuria reduction associated with decreased incidence of ASCVD in patients without additional preexisting risk factors?
Is it cost-effective to treat ACR <30 mg/g?

ACR indicates albumin-creatinine ratio; ASCVD, atherosclerotic cardiovascular disease; and CKD, chronic kidney disease.

718 March 11, 2025 Circulation. 2025;151:716–732. DOI: 10.1161/CIRCULATIONAHA.124.071079

 Claudel and Verma Albuminuria in CKM Disorders

are required for confirmation.23 This is especially true in vascular health (such as nitric oxide and von Willebrand
diabetes-associated CKD, where a repeated measure- factor).53,54 In one study, the authors posit that increased

STATE OF THE ART

ment of UACR can vary from 25% to 375% of the initial lipid infiltration of vascular structures increases glomeru-
value,24 although this variation may also be seen in other lar transcapillary albumin leak.45 Other common distur-
forms of CKD.23 bances in atherosclerotic disease include reduced nitric
oxide bioavailability, which promotes arterial stiffness and
impaired vasodilation.55
CLINICAL PHENOTYPES AND In patients with diabetes, many of whom also have
MECHANISMS ASSOCIATED WITH metabolic syndrome, albuminuria may develop second-
ary to either alterations to glomerular charge selectiv-
ALBUMINURIA
ity or impaired proximal tubular albumin reabsorption.56
There are multiple mechanisms by which albuminuria Change in GBM size selectivity does not appear to be a
can develop. These phenotypes of albuminuria and pro- contributing factor.56 The Steno hypothesis argues that
posed mechanisms are summarized in Figure 2. In many albuminuria is a consequence of global intima damage
patients, however, there may be overlapping or concomi- due to alterations in the extracellular matrix.57,58 Serum
tant mechanisms by which albuminuria develops. albumin glycosylation is likely one mechanism by which
In patients with CKD, podocyte foot process efface- albumin is able bypass GBM charge selectivity in dia-
ment leads to insufficient counterpressure and relax- betes.59 Alterations to GBM proteoglycans also disrupt
ation of the glomerular basement membrane (GBM) charge selectivity.59,60 Insulin resistance can lead to
fiber matrix.25,26 This causes increased glomerular cap- endothelial dysfunction, and impaired vasodilation in the
illary wall permeability and results in albuminuria. As setting of reduced nitric oxide further impairs renal auto-
glomerular disease progresses, the subpodocyte space regulation.55,61 Global alterations to the endothelium, as
may widen to cover a greater proportion of the filtration measured by von Willebrand factor, may precede albu-
membrane and modulate filtration barrier permeability.27 minuria in diabetes.62
Expansion of the subpodocyte space and an increase in
hydraulic resistance can lead to further podocyte detach-
ment and worsening albuminuria.27 Alternatively, or con- ALBUMINURIA IS A RISK FACTOR FOR
currently, albuminuria can arise from impaired albumin
reabsorption in the proximal tubule.13,28 CVD
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In patients with hypertension, increased intraglo- Albuminuria is strongly associated with CVD mortal-
merular pressure causes glomerular hyperfiltration and ity7,20,63,64 and all-cause mortality in diverse populations.7–9
hyperpermeability, and ongoing intraglomerular capil- Similarly, albuminuria is longitudinally associated with
lary endothelial damage can result in capillary albumin major cardiovascular complications, such as nonfatal
leak.29,30 In one study, patients with albuminuria demon- myocardial infarction, nonfatal stroke, coronary revascu-
strated normal tubular albumin reabsorption, indicating larization, and peripheral artery revascularization.7,64–66 Al-
that hypertension increases glomerular albuminuria.31 buminuria has also been identified as an independent risk
In patients with heart failure, elevated central venous factor for stroke and other cerebrovascular diseases.67–69
pressure can cause low renal perfusion pressure,32,33 Multiple authors have described associations between
chronic tubulointerstitial damage,34–36 or renal conges- albuminuria and CVD risk factors. For example, albumin-
tion,35 any of which may precipitate albuminuria. Volume uria has been associated with left ventricular hypertro-
overload also increases release of natriuretic peptides, phy,49,70,71 vascular stiffness and remodeling,49,50,52,72,73
which may cause damage to the endothelial glycocalyx,37 and progression of coronary artery calcification.74 Each
although this is debated,38 and result in albuminuria.36 of these conditions confers a high risk of CVD events
Aldosterone escape in heart failure leads to sodium and demonstrates the likely systemic vascular pathology
and water retention, as well as kidney fibrosis.39 More associated with albuminuria.
broadly, increased aldosterone levels are associated with Perhaps the most well-described relationships
increased albuminuria.40–43 High intraglomerular pres- between albuminuria and CVD are in the context of heart
sure increases transcapillary flux of the ultrafiltrate and failure.44 Approximately 32% of US adults with heart
results in albuminuria.44 failure have albuminuria ≥30 mg/g.75 Albuminuria is not
In patients with atherosclerotic cardiovascular dis- only associated with greater risk of incident heart fail-
ease, albuminuria can develop secondary to endothelial ure76 and diastolic dysfunction,70 but also confers risk of
inflammation and endothelial dysfunction.45,46 Endothe- worsening CVD in patients with preexisting heart failure
lial disturbances are common in sustained atherogenic regardless of ejection fraction.77 Development of albu-
states and dyslipidemia. Albuminuria is associated with minuria is strongly associated with adverse outcomes,
loss of the endothelial glycocalyx,47 dynamic vascular such as increased hospitalizations for heart failure,64,78
elasticity,48–50 perfusion,51,52 and serologic markers of systemic vascular congestion,34 and progressive systolic

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 Claudel and Verma Albuminuria in CKM Disorders
STATE OF THE ART
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Figure 2. Clinical phenotypes and mechanisms of albuminuria.

Albuminuria may arise as a consequence of chronic kidney disease, heart failure, atherosclerotic cardiovascular disease (ASCVD), hypertension,
or metabolic syndrome. These mechanisms converge on a final common pathway of kidney dysfunction and increase risk for adverse cardiorenal
events. ACEI indicates angiotensin-converting enzyme inhibitor; ANP, atrial natriuretic peptide; ARB, angiotensin receptor blocker; CKM,
cardiovascular–kidney–metabolic disease; GBM, glomerular basement membrane; GLP1-RA, glucagon-like peptide-1 receptor agonist; MR,
mineralocorticoid receptor; NO, nitric oxide; nsMRA, nonsteroidal mineralocorticoid receptor antagonist; ROS, reactive oxygen species; and
SGLT2i, sodium-glucose cotransporter-2 inhibitor. Created in BioRender.com.

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 Claudel and Verma Albuminuria in CKM Disorders

dysfunction.77 Albuminuria is known to improve risk strat- glomerular hyperfiltration that accompanies longstand-
ification in heart failure, but current heart failure society ing diabetes.91 Early studies of diabetes, kidney function,

STATE OF THE ART

guidelines do not comment on the need for albuminuria and UACR were limited by small sample sizes and lack of
screening in this population.79 biopsy confirmation to determine whether changes con-
In general, studies of albuminuria and CVD are per- sistent with diabetic kidney disease (DKD) were present
formed in populations already at high cardiovascular risk histologically.92 The classic trajectory of DKD includes
and therefore offer limited insight into the mechanism progressive albuminuria and estimated glomerular filtra-
behind the association of albuminuria and CVD mortality. tion rate (eGFR) decline. Greater albuminuria in DKD
Associations between albuminuria and incident hyper- has been previously associated with increased risk of
tension80 and incident atrial fibrillation81,82 provide only progressing to ESKD91 and a higher risk of adverse car-
slightly more evidence that interim development of addi- diovascular outcomes.93,94 Rising UACR may precede a
tional CVD risk factors may contribute to the association decline in eGFR for patients with progressive DKD, mak-
with mortality; however, further work is needed.46 One ing it a useful prognostic marker for patients with the
hypothesis is that the presence of albuminuria repre- “classic” DKD phenotype.91 A subset of patients with dia-
sents a systemic microinflammatory state characterized betes exhibit non- or minimally albuminuric disease phe-
by diffuse endothelial dysfunction. This is supported by notypes and nonetheless experience progressive eGFR
an association between albuminuria and elevated car- decline.91,95 An even smaller proportion of patients expe-
diac troponin T in adults without known CVD.83 rience albuminuria regression and stabilization of kidney
function. However, in one study, the risk for adverse CVD
outcomes remained elevated in these patients.96 Pat-
Low Levels of Albuminuria and CVD terns of albuminuria prevalence and trajectories vary
Albuminuria does not need to be high grade to convey between type 1 and type 2 diabetes.91 A greater propor-
cardiovascular risk. One study found that increasing al- tion of patients with type 2 diabetes progress to diabetic
buminuria in the low grade range (UACR <30 mg/g) is nephropathy compared with those with type 1 diabetes.97
associated with CVD mortality among adults without ma- Whereas patients with type 2 diabetes can frequently
jor cardiovascular risk factors.20 In this and several other experience regression of albuminuria, patients with type
recent articles, cardiovascular risk appears to increase at 1 diabetes who develop CKD often exhibit progressive
UACR ≈7 to 10 mg/g.20,84,85 Low-grade albuminuria has albuminuria over time.91
been associated with adverse cardiovascular risk fac-
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tors, including incident hypertension,63 heart failure,76 and

coronary artery disease,19 as well as major adverse car- ALBUMINURIA AND METABOLIC-
diovascular events4,5,7,65 and mortality.4,19,20 Data from the ASSOCIATED DISORDERS
CKD Prognosis Consortium show that low levels of albu-
A major limitation of the existing literature on the
minuria are associated with major adverse cardiovascular
relationship between metabolic syndrome, metabolic
­
events in diverse populations with CKD.7
dysfunction-associated steatotic liver disease (MASLD),
dysglycemia, and albuminuria is the reliance on cross-
sectional studies.98,99 Here we briefly outline the work
ALBUMINURIA IS A RISK FACTOR FOR
examining albuminuria in the context of these metabolic-
PROGRESSIVE KIDNEY DISEASE associated conditions, acknowledging the limitations.
Not all patients with CKD have albuminuria, but increased
urinary albumin excretion >30 mg/g is a diagnostic cri-
terion for CKD, and albuminuria screening is a standard Albuminuria and Obesity
component of the clinical CKD workup.18 However, lower Multiple measures of adiposity have been associated
levels of albuminuria are also a risk factor for incident with albuminuria.100 Central obesity, specifically, may be
CKD.86,87 In patients with CKD, increasing albuminuria a crucial risk factor for incident albuminuria indepen-
within the low grade range (UACR <30 mg/g) is linearly dent of diabetes status.100–103 Obesity is an increasingly
associated with increased risk of CKD progression and common cause of secondary focal segmental glomeru-
incident ESKD.6 Risk for CKD progression appears to in- losclerosis (FSGS), which is characterized by substan-
crease at UACR ≈7 to 10 mg/g. Greater baseline albu- tial proteinuria.104 Obesity-associated FSGS typically
minuria and worsening of albuminuria are independently involves an indolent course followed by progression to
associated with CKD progression and end-stage kidney ESKD. It is hypothesized that increased oxidative stress,
disease (ESKD) in patients with and without diabetes.7,88–90 generalized inflammation, chronic glomerular hypoxia,
Diabetes is the most common cause of CKD world- and insulin resistance in obesity lead to the histologic
wide. Albuminuria is a common consequence of diabetes changes in obesity-associated FSGS.104 In patients
due to the sustained hyperglycemia, inflammation, and with obesity, elevated intrarenal resistance on Doppler

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 Claudel and Verma Albuminuria in CKM Disorders

ultrasound is associated with albuminuria, suggesting GLP1-RAs, and nonsteroidal MRAs demonstrate ben-
a possible mechanistic link between adiposity and the efit among patients already treated with maximal ACEI/
STATE OF THE ART

development of CKD and CVD events.105–107 However, ARBs. The additive benefit of these therapies has the
this cross-­sectional evidence precludes any conclusions potential to improve global cardiovascular outcomes, with
about causal pathways. the greatest evidence to date among patients with type 2
diabetes.117 Table 3 highlights recent cardiovascular tri-
als with enrollment based on albuminuria, similar to other
Albuminuria and MASLD risk factor–based enrollment criteria (eg, diabetes, previ-
MASLD is associated with albuminuria in epidemio- ous CVD).
logic studies and is a prominent CVD risk factor. Sev- The mechanisms by which cardio-kidney protective and
eral studies have found an association between MASLD antiproteinuric therapies provide CVD benefit are only par-
and albuminuria,108,109 with one study noting that the tially understood. ACEI/ARBs and angiotensin-­receptor/
association was independent of insulin resistance or neprilysin inhibitors (ARNIs) improve cardiac remodeling
obesity.110 Albuminuria <30 mg/g may also be a risk after myocardial infarction.118,119 Steroidal MRAs, which
factor for developing MASLD, as shown in one prospec- have antiproteinuric effects, have been used for decades
tive, ­population-based study of Chinese adults.111 In this to improve CVD outcomes in patients with heart failure
study, risk appeared to increase at UACR ≈2.5 mg/g. with reduced ejection fraction, and new data show ben-
The pathophysiology of how albuminuria may lead to efit of nonsteroidal MRAs in patients with heart failure
steatotic liver disease, and the reverse, is unclear, but with preserved ejection fraction.120 The CVD protective
the epidemiologic association may be driven by a gen- effects of SGLT2is may be driven primarily by a reduction
eralized state of endothelial inflammation or the incident in hospitalization for heart failure,121 whereas the benefits
development of obesity. of GLP1-RA appear to be more broadly cardioprotective
in the setting of obesity.122 Both SGLT2is and GLP1-RAs
may act on metabolic pathways and can be used for car-
Albuminuria and Insulin Resistance diovascular benefit across a range of metabolic and car-
Insulin resistance—a key risk factor for metabolic syn- diovascular conditions. None of these medications was
drome, diabetes, MASLD, and CVD—is closely associ- initially developed for their cardioprotective effects, and
ated with albuminuria in patients without diabetes,98,112 the precise mechanism by which they improve CVD out-
comes remains an active area of investigation.
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as well as those with prediabetes.99 In patients without

diabetes, insulin resistance and elevated glomerular Albuminuria reduction is also associated with a
hydrostatic pressure were cross-sectionally associated slower rate of CKD progression and a lower likelihood
with albuminuria.98 Longitudinally, elevated baseline ho- of progression to ESKD. Residual albuminuria after
meostatic model assessment of insulin resistance in antiproteinuric treatment is a strong risk factor for dis-
adults without diabetes was associated with subsequent ease progression.123 The initial clinical trials of ACEIs
development of albuminuria.112 Inflammatory or oxidative and ARBs made these therapies the cornerstone of
pathways may mediate the relationship between dysgly- CKD care for the next 20 years.124,125 Recent evidence
cemia and albuminuria, although this hypothesis has yet demonstrates improved kidney outcomes after treat-
to be explored. ment with SGLT2is,126 GLP1-RAs,127 and nonsteroidal
MRAs on a background of ACEI/ARBs.128 The data on
steroidal MRAs and clinical kidney outcomes are less
well established due to lack of randomized clinical trial
ALBUMINURIA REDUCTION AND
data, although epidemiologic literature suggests some
CARDIOVASCULAR–KIDNEY OUTCOMES benefit.128,129
It is well described that CKD increases the risk of in- The benefits of newer antiproteinuric medications in
cident CVD events and CVD events increase the risk slowing CKD progression are multifactorial and likely
of CKD progression.113,114 Cardio-kidney protective extend beyond albuminuria reduction alone, particularly
medications with antiproteinuric effects reduce incident because nonalbuminuric patients also derive benefit.130
CVD events and CVD mortality in high-risk populations, Whereas other authors have pointed to post hoc analyses
likely due to multifactorial pathways and mechanisms of recent cardiovascular and kidney trials as exhibiting
not directly related to albuminuria reduction.115,116 These effect modification by baseline UACR, the P values for
therapies include angiotensin-converting enzyme inhibi- interaction are nonsignificant in all but one trial (Table 4).
tors (ACEIs) and angiotensin receptor blockers (ARBs), Furthermore, these trials enrolled few patients with low
sodium-glucose cotransporter-2 inhibitors (SGLT2is), levels of albuminuria, and therefore subgroup analyses
glucagon-like peptide-1 receptor agonists (GLP1-RAs), were underpowered.
and mineralocorticoid receptor antagonists (MRAs). The Cardio-kidney protective medications have effects
more recent cardiovascular and kidney trials on SGLT2is, beyond their albuminuria reduction, which may be

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 Claudel and Verma Albuminuria in CKM Disorders

Table 3. Cardiovascular Outcomes Trials Enrolling on the Basis of Albuminuria

Trials Eligibility Intervention Outcomes

STATE OF THE ART

Specific ACR enrollment criteria
 CREDENCE eGFR 30–90 mL/min per 1.73 m2 and ACR 300–500 mg/g Canagliflozin Doubling of SCr
ESKD
Death from kidney disease or CVD
 DAPA-CKD eGFR 25–75 mL/min per 1.73 m2 and ACR 200–5000 mg/g Dapagliflozin eGFR decline >50%
ESKD
Death from kidney disease or CVD
 EMPA-KIDNEY eGFR 20–45 mL/min per 1.73 m2 Empagliflozin eGFR decline ≥40%
eGFR 45–90 mL/min per 1.73 m2 and ACR ≥200 mg/g ESKD
eGFR decline to <10
Death from CVD
 FIDELIO-DKD eGFR 25–60 mL/min per 1.73 m2 and retinopathy Finerenone eGFR decline ≥40%
eGFR 25–75 mL/min per 1.73 m2 and ACR 300–5000 mg/g ESKD
ACR 30–300 mg/g Death from kidney disease
 FIGARO-DKD eGFR 25–90 mL/min per 1.73 m2 and ACR 30–300 mg/g Finerenone Death from CVD, nonfatal MI, nonfatal
eGFR >60 mL/min per 1.73 m2 and ACR 300–5000 mg/g stroke, or hospitalization for heart failure
 FLOW eGFR 50–75 mL/min per 1.73 m2 and ACR 300–5000 mg/g Semaglutide eGFR decline >50%
eGFR 25–50 mL/min per 1.73 m2 and ACR 100–5000 mg/g ESKD
Death from kidney disease or CVD
Nonspecific proteinuria enrollment criteria
 CANVAS and CANVAS-R Age >40 y and previous CVD Canagliflozin Death from CVD, nonfatal MI, or nonfatal
Age >50 y and CVD risk factors (including microalbuminuria or stroke
proteinuria)
 SCORED eGFR 25–60 mL/min per 1.73 m2 Sotagliflozin Death from CVD, hospitalization for heart
Age >18 and at least 1 major CVD risk factor failure, urgent visits for heart failure
Age >55 and at least 2 minor CVD risk factors (including ACR
30–300 mg/g)
 LEADER Patients >50 y with CVD comorbidities Liraglutide Death from CVD, nonfatal MI, or nonfatal
Patients >60 y with CVD risk factors (including microalbuminuria or stroke
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proteinuria)
 PIONEER-6 Patients >50 y with major CVD risk factors Semaglutide Death from CVD, nonfatal MI, or nonfatal
Patients >60 y with minor CVD risk factors (including stroke
microalbuminuria or proteinuria)

ACR indicates albumin:creatinine ratio; CANVAS, Canagliflozin Cardiovascular Assessment Study; CANVAS-R, A Study of the Effects of Canagliflozin (JNJ-
28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus; CREDENCE, Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular
Outcomes in Participants With Diabetic Nephropathy; CVD, cardiovascular disease; DAPA-CKD, A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and
Cardiovascular Mortality in Patients With Chronic Kidney Disease; eGFR, estimated glomerular filtration rate; EMPA-KIDNEY, The Study of Heart and Kidney Protection
With Empagliflozin; ESKD, end-stage kidney disease; FIDELIO-DKD, Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney
Disease; FLOW, A Research Study to See How Semaglutide Works Compared to placebo in People With Type 2 Diabetes and Chronic Kidney Disease; LEADER, Li-
raglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; MI, myocardial infarction; PIONEER-6, A Trial Investigating the Cardiovascular
Safety of Oral Semaglutide in Subjects With Type 2 Diabetes; SCORED, Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and
Moderate Renal Impairment Who Are at Cardiovascular Risk; and SCr, serum creatinine.

i­mportant components of their effect on CKD outcomes. are also pursuing a related approach, aldosterone syn-
Both SGLT2is and GLP1-RAs improve blood pressure thase inhibition, to reduce CKD progression.137
control and induce weight loss, whereas MRAs pro- Given the diversity of mechanisms of action across
vide aldosterone antagonism. With SGLT2is specifically, cardio-kidney protective therapies with antiprotein-
there is ongoing investigation into mechanisms related uric effects, combination therapy using ACEI/ARBs,
to tubuloglomerular feedback in reducing intraglomeru- SGLT2is, GLP1-RAs, and MRAs is an emerging area of
lar pressure, as well as anti-inflammatory131 and meta- research interest. Whereas previous work of combina-
bolic132 effects. GLP1-RAs may offer renoprotection tion ACEI and ARB demonstrated reduced albuminuria
through reduced kidney inflammation and fibrosis,133 and without improving renal outcomes compared with mono-
results are awaited from the mechanistic REMODEL (A therapy,138 this does not appear to be the case for com-
Research Study to Find Out How Semaglutide Works in bination treatment across the newer medication classes
the Kidneys Compared to placebo, in People With Type for diabetic kidney disease.117 In FLOW (A Research
2 Diabetes and Chronic Kidney Disease).134 New data Study to See How Semaglutide Works Compared to pla-
have brought additional attention to the role of aldoste- cebo in People With Type 2 Diabetes and Chronic Kidney
rone antagonism in treating albuminuric CKD43,135 and Disease), there was no evidence of effect modification
preventing CVD events in these patients.136 Investigators for the composite kidney outcome based on background

Circulation. 2025;151:716–732. DOI: 10.1161/CIRCULATIONAHA.124.071079 March 11, 2025 723

 Claudel and Verma Albuminuria in CKM Disorders

Table 4. Post hoc Analyses of Cardiovascular and Kidney Trials, Stratified by Urinary Albumin-to-Creatinine Ratio
Event rates in control Event rates in treatment Effect estimates for study drug, HR (95% CI)
STATE OF THE ART

<30 30–300 ≥300 <30 30–300 ≥300

Trial Intervention Outcome Pinteraction mg/g mg/g mg/g mg/g mg/g mg/g <30 mg/g 30–300 mg/g ≥300 mg/g

FIGARO- Finerenone vs Cardiovascular 0.60 NA 4.42 4.49 per NA 3.88 per 3.94 per NA 0.87 0.90
DKD placebo death, nonfatal MI, per 100 100 py 100 py 100 py (0.73–1.04) (0.75–1.08)
nonfatal stroke, or py
HHF

Composite kidney 0.02 NA 2.30 5.02 per NA 2.63 per 3.83 per NA 1.16 0.74
outcome* per 100 100 py 100 py 100 py (0.91–1.47) (0.62–0.90)
py

FIDELIO- Finerenone vs Composite kidney NR 0/11 19/350 485/2470 2/12 20/335 578/2493 — 0.92 0.83
DKD placebo outcome† (0.49–1.72) (0.73–0.93)

FIDELITY‡ Finerenone vs Composite kidney 0.67 40/2023 424/4371 38/2076 321/4321 0.94 (0.60–1.47) 0.75
placebo outcome§ (0.65–0.87)

CAN- Canagliflozin Composite kidney 0.37 NR NR NR NR NR NR 0.50 0.64 (0.47–0.88)

VAS and vs placebo outcome* (0.33–0.77)
­CANVAS-R

EMPA-REG Empagliflozin Cardiovascular 0.40 134/1382 90/675 58/260 241/2789 158/ 86/509 0.89 0.89 0.69
vs placebo death, nonfatal MI, 1338 (0.72–1.10) (0.69–1.16) (0.49–0.96)
nonfatal stroke

EMPA- Empagliflozin Cardiovascular NR 42/663 78/937 438/1705 42/665 67/927 323/1712 1.01 0.91 0.67
KIDNEY vs placebo death or progres- (0.66–1.55) (0.65–1.26) (0.58–0.78)
sion of kidney
disease

EMPEROR- Empagliflozin Cardiovascular 0.71 8.2 per 16.2 22.2 per 6.6 per 11.8 per 18.3 per 0.80 0.74 0.78
Pooled∥ vs placebo death or HHF 100 py per 100 100 py 100 py 100 py 100 py (0.69–0.92) (0.63–0.86) (0.63–0.98)
py

DECLARE- Dapagliflozin Cardiovascular 0.47 10.2 per 21.8 37.2 per 9.2 per 16.8 per 28.5 per 0.90 0.76 0.77
TIMI 58 vs placebo death or HHF 1000 py per 1000 py 1000 py 1000 1000 py (0.75–1.08) (0.61–0.95) (0.55–1.06)
1000 py
py

SCORED Sotagliflozin Cardiovascular NR 4.2 per 9.4 per 100 py 4.4 per 6.3 per 100 py 1.05 0.67 (0.55–0.80)
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vs placebo death, HHF, urgent 100 py 100 py (0.76–1.46)

visits for HF

LEADER Liraglutide vs Cardiovascular 0.36 335/2821 338/1738 318/ 277/1684 0.92 0.83 (0.71–0.97)
placebo death, nonfatal MI, 2894 (0.79–1.07)
or nonfatal stroke

SUSTAIN 6 Semaglutide Cardiovascular 0.48 73/986 36/412 35/224 43/948 39/472 26/196 0.61 0.87 0.76
vs placebo death, nonfatal MI, (0.42–0.89) (0.55–1.37) (0.46–1.28)
or nonfatal stroke

FLOW Semaglutide Composite kidney NR 62/552 348/1214 55/561 276/1205 0.86 (0.60–1.23) 0.74
vs placebo outcome¶ (0.63–0.87)

SELECT Semaglutide Composite kidney 0.70 31/7471 67/941 95/166 24/7377 47/1027 80/159 0.78 0.63 0.77
vs placebo outcome# (0.46,1.33) (0.44,0.92) (0.57, 1.03)

PARADIGM- Sacubitril- Cardiovascular 0.35 158/697 70/215 133/734 68/226 0.77 0.94 (0.67–1.31)
HF Valsartan vs death or HHF (0.61–0.97)
Enalapril

CANVAS indicates Canagliflozin Cardiovascular Assessment Study; CANVAS-R, A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult
Participants With Type 2 Diabetes Mellitus; DECLARE–TIMI 58, Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58; EMPA-KIDNEY,
The Study of Heart and Kidney Protection With Empagliflozin; EMPA-REG, BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus
Patients; FLOW, A Research Study to See How Semaglutide Works Compared to placebo in People With Type 2 Diabetes and Chronic Kidney Disease; HF, heart failure;
HHF, hospitalization for heart failure; HR, hazard ratio; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; MI, myocardial
infarction; NA, not applicable; NR, not reported; PARADIGM-HF, Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in
Heart Failure; py, person years; SCORED, Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes and Moderate Renal Impairment
Who Are at Cardiovascular Risk; SELECT, Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity; and SUSTAIN-6, Trial to Evaluate
Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes.
*Includes ≥40% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease, or death from renal causes.
†Includes kidney failure, sustained decrease of at least 40% in eGFR over at least 4 weeks, or death from renal causes.
‡FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis) is a combined
analysis of FIGARO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease) and
FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease).
§Includes ≥57% reduction in eGFR, end-stage kidney disease, or death from renal causes.
∥EMPEROR Pooled is a combined analysis of EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection
Fraction) and EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
¶Includes kidney failure, sustained decrease of at least 50% in eGFR over at least 28 days, or death from renal or cardiovascular causes.
#Includes death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent eGFR<15 mL/min per 1.73 m2, persistent ≥50% reduction
in eGFR, or onset of persistent macroalbuminuria.

724 March 11, 2025 Circulation. 2025;151:716–732. DOI: 10.1161/CIRCULATIONAHA.124.071079

 Claudel and Verma Albuminuria in CKM Disorders

SGLT2i use,127 and in a meta-analysis of SGLT2i trials, Combination therapy is central to effective imple-
there is no evidence of effect modification based on mentation of cardio-kidney protective therapies. Early,

STATE OF THE ART

background GLP1-RA use.139 These findings provide rapid sequence initiation and uptitration of these medi-
preliminary evidence of independent effects of these 2 cations may prevent delays in care and limit therapeu-
classes. Additional work has demonstrated additive ben- tic inertia.147 Patients on multidrug therapy are most
efit of ACEI/ARBs and SGLT2is in nondiabetic kidney likely to achieve the greatest benefit, including longer
disease.140 Further work will be needed to assess any event-free survival.117 Although not well studied with
potential additive or synergistic benefits of ACEI/ARBs, the SGLT2is or oral GLP1-RAs, the hypertension lit-
SGLT2is, GLP1-RAs, and MRAs, and which patients erature demonstrates that multidrug combination pills
should be considered for combination therapy. decrease pill burden for patients and can improve
As discussed previously, none of the more recent medication adherence.148 Combination therapy may
cardio-kidney protective drug classes was designed also reduce the need for ACEI/ARB and MRA discon-
specifically for albuminuria reduction. Furthermore, tinuation due to hyperkalemia. Given new data demon-
current clinical trials do not assess whether improved strating that ACEI/ARBs should not be preemptively
outcomes are mediated by albuminuria reduction or stopped in advanced CKD due to worse cardiovascular
whether albuminuria is instead a convenient biomarker outcomes,149,150 managing hyperkalemia with SGLT2is,
of the yet undiscovered underlying mechanism. It is also loop diuretics, dietary modification, and potassium bind-
important to recognize the heterogeneity in recent tri- ers is essential to delivering high-quality cardio-kidney
als with respect to changes in albuminuria and clinical care.151,152
outcomes. This is especially true in the case of heart
failure trials, where patients continue to exhibit kidney
disease progression, or exhibit no renal benefit, despite ALBUMINURIA AS A BIOMARKER OF
improved CVD outcomes.141,142 This apparent therapeu-
CARDIOVASCULAR-KIDNEY-METABOLIC
tic disconnect has been described for ARBs, ARNIs,
SGLT2is, and nonsteroidal MRAs, and is largely attrib- HEALTH
uted to recruitment of patients with low background risk The American Heart Association report on CKM syn-
of CKD progression (eg, those with lower albuminuria drome highlights the importance of albuminuria in CKD
and less advanced CKD)141,143 or insufficient follow-up and heart failure. However, the authors defer recom-
time.141 Albuminuria data are also not routinely available mending albuminuria screening until the later stages of
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in many previous cardiovascular trials.143 For example, the CKM when impaired eGFR is already present.116 Given
PARADIGM-HF trial (Prospective Comparison of ARNI the evidence described in this review, it may be prudent
With ACEI to Determine Impact on Global Mortality and for clinicians to consider screening for albuminuria using
Morbidity in Heart Failure), comparing ARNIs versus a broader definition of risk than the CKM framework.153
ACEIs, demonstrated worsening albuminuria in the ARNI This could range from screening the general population
group despite improvement in heart failure outcomes.144 (a strategy currently under evaluation by the US Preven-
This would seem to challenge the association between tative Task Force Service for CKD surveillance)154 to a
albuminuria reduction and improved CVD outcomes risk-based approach incorporating obesity, liver disease,
and suggest that the effects of ARNI are mediated by insulin resistance, and behavioral features (eg, low physi-
improved blood pressure and other cardiovascular inter- cal activity, smoking).
mediaries. However, the subsequent UK HARP III trial Albuminuria screening is guideline recommended
(UK Heart and Renal Protection III) demonstrated no dif- for high-risk populations, such as those with diabetes,
ference in kidney outcomes (and no worsening in albu- CKD, hypertension, or at high risk of clinical CVD or CKD
minuria) among patients with CKD treated with ARNIs (Table 5). Rates of albuminuria screening among cur-
versus ARBs.145 Whether these differences are related rently indicated patient groups remain severely low.155–157
to the study population (ie, patients with heart failure In the face of burgeoning treatments for CKD and prelim-
in PARADIGM-HF versus patients without heart failure inary cost-effectiveness analyses showing the benefits
in UK HARP III) is an important unanswered question. of screening,158 strategies to promote screening across a
Other authors have hypothesized that physiologic dif- greater range of high-risk populations (eg, hypertension,
ferences in heart failure specifically underlie the diver- diabetes, CKD, atherosclerotic cardiovascular disease,
gence in renal outcomes in trials of patients with heart heart failure, metabolic syndrome) are urgently needed.
failure versus CKD.141 A pooled analysis of finerenone Most patients eligible for albuminuria screening cur-
trials demonstrates cardiovascular and kidney benefit rently are managed in primary care offices, where com-
with nonsteroidal MRA in a mixed heart failure and CKD peting demands, limited time, clinical complexity, and
population, suggesting that the limitations of heart failure clinician lack of awareness of evolving guidelines may
trial design may be responsible for reported lack of CKD be barriers to screening.159 A 2014 study identified
benefit in these participants.146 a major barrier to albuminuria screening for patients

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 Claudel and Verma Albuminuria in CKM Disorders

Table 5. Recent Guidelines for Albuminuria Screening

Society Year Patient populations Screening recommendation

STATE OF THE ART

Kidney Disease: Improving 2024 Adults at risk for CKD, including hypertension, First morning UACR is preferred; confirm positive
Global Outcomes diabetes, cardiovascular disease, or those with dipstick albuminuria with more accurate methods
genetic or environmental risk factors specific to region (such as UACR)
of residence
Patients with CKD UACR at least annually; assess albuminuria
more frequently in patients at higher risk for CKD
progression; a doubling of albuminuria warrants
evaluation
American Heart Association 2023 Stage 2 CKM syndrome: patients with metabolic risk UACR annually
Statement on Cardiovascular- factors or CKD
Kidney-Metabolic Health
Stage 3 CKM syndrome: patients with subclinical UACR at least annually, more frequently in those with
CVD in CKM syndrome CKD
Stage 4 CKM syndrome: patients with clinical CVD UACR at least annually, more frequently in those with
and excess or dysfunctional adiposity, other CKM risk higher Kidney Disease: Improving Global Outcomes
factors, or CKD risk
American Diabetes 2023 Patients without established diabetic kidney disease: Spot UACR annually
Association Type 1 diabetes duration of ≥5 years
All patients with type 2 diabetes
Patients with established diabetic kidney disease Spot UACR 1–4 times per y
National Institute for Health 2021 Patients at risk for CKD, including those with Spot UACR with frequency depending on underlying
and Care Excellence diabetes, hypertension, previous acute kidney injury, risk factors; monitor for progression of CKD for
cardiovascular disease, structural renal tract disease, at least 3 y after acute kidney injury even if eGFR
recurrent renal calculi, multisystem diseases with returned to baseline
potential kidney involvement, gout, family history of
kidney disease, or incidental detection of hematuria or
proteinuria
Patients with diabetes Annual UACR
European Society of 2021 Patients with hypertension, diabetes, or CKD Routine assessment of UACR (or dipstick urinary
Cardiology in collaboration protein if ACR not available)
with the European
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Association of Preventive
Cardiology
International Society of 2020 Patients with hypertension Routine assessment of spot UACR
Hypertension
Pregnant patients with hypertension Dipstick followed by ACR if positive, twice in
pregnancy (early and late)
European Society of 2019 Patients with diabetes or at risk of developing “Routine assessment of microalbuminuria should be
Cardiology in collaboration diabetes or cardiovascular disease carried out to identify patients at risk of developing
with the European renal dysfunction or CVD”
Association for the Study of
Diabetes
European Society of 2018 Patients with hypertension Annual UACR
Cardiology and the European
Pregnant patients with hypertension Dipstick followed by ACR if positive, twice in
Society of Hypertension
pregnancy (early and late)

CKD indicates chronic kidney disease; CKM, cardiovascular, kidney, and metabolic; CVD, cardiovascular disease; and UACR, urinary albumin-to-creatinine ratio.

with ­nondiabetic CKD: the perception that it would not Cardiovascular practices can improve the care of
change management.160 Whether clinician attitudes have patients with CVD and those at risk for worsening CKM
changed since introducing newer antiproteinuric medi- syndrome by incorporating routine albuminuria test-
cations is unknown. Implementation and improvement ing. Once identified, patients with albuminuria can be
scientists will be crucial to increasing real-world screen- monitored more closely (Figure 3). The 2023 American
ing rates by designing systematic, scalable, and adapt- Heart Association PREVENT (Predicting Risk of Cardio-
able interventions. Increased support for primary care vascular Events) cardiovascular risk calculator includes
clinicians and developing novel workflows may increase UACR for improved prediction of CVD events.162 Patients
guideline-directed albuminuria screening and treat- with elevated PREVENT scores are recommended for
ment implementation. As an alternative, some research- statin therapy, similar to the atherosclerotic cardiovascu-
ers have proposed that home-based, population-wide lar disease risk calculator. In addition to providing valu-
screening approaches may be more scalable, although able risk stratification, UACR can also guide treatment
potentially more costly to implement.161 intensification (Figure 3). There are ongoing efforts

726 March 11, 2025 Circulation. 2025;151:716–732. DOI: 10.1161/CIRCULATIONAHA.124.071079

 Claudel and Verma Albuminuria in CKM Disorders

STATE OF THE ART

Figure 3. Proposed algorithm for managing albuminuria in patients with known cardiovascular risk factors.
Simplified algorithm for evaluating and managing albuminuria in patients with known cardiovascular risk factors. Retesting for albuminuria is
crucial for modifying cardiovascular risk. ACEI indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ASCVD,
atherosclerotic cardiovascular disease; eGFR, estimated glomerular filtration rate; GLP1-RA, glucagon-like peptide-1 receptor agonist; HTN,
hypertension; MRA, mineralocorticoid receptor antagonist; nsMRA, nonsteroidal mineralocorticoid receptor antagonist; SGLT2i, sodium-glucose
cotransporter-2 inhibitor; and UACR, urinary albumin-to-creatinine ratio. Created in BioRender.com.
Downloaded from http://ahajournals.org by on March 10, 2025

within nephrology to implement rapid sequence uptitra- to determine how broadly and how frequently to screen
tion of guideline-directed medical therapy for diabetic patients for albuminuria, whether it is cost-effective to
kidney disease, including ACEI/ARBs, SGLT2is, GLP1- treat low-grade albuminuria (for example, 10–30 mg/g),
RAs, and nonsteroidal MRAs, similar to the cardiology and how to equitably offer newer cardio-kidney protec-
approach to heart failure therapies.147 These same prin- tive therapies across the spectrum of CKM syndrome.
ciples are directly applicable to cardiovascular clinical Answering these questions may shift the clinical practice
spaces for patients with CKM syndrome and CVD risk. of cardiovascular risk reduction and improve population
Through appropriate UACR testing, cardiovascular prac- health.
tices will be at the forefront of detecting otherwise undi-
agnosed CKD through this approach. Patients can then
be started on appropriate therapies based on their risk ARTICLE INFORMATION
factor profile or referred to nephrology, as appropriate. Affiliations
Department of Medicine, Boston Medical Center, MA (S.E.C., A.V.). Department
of Medicine, Section of Nephrology, Boston University Chobanian & Avedisian
School of Medicine, MA (S.E.C., A.V.).
CONCLUSION
Sources of Funding
Albuminuria is a marker of widespread vascular dysfunc- Supported by the National Heart, Lung, and Blood Institute, National Institutes
tion and subclinical cardiovascular risk that heralds evolv- of Health (award R38HL143584 to Dr Claudel). Dr Verma is supported by an
ing CKM dysfunction. As an inexpensive and noninvasive American Heart Association Career Development Award (24CDA1274501).

test, UACR provides a glimpse into the early develop- Disclosures

ment of CKM syndrome. Even low-grade albuminuria, None.
below the traditional threshold of 30 mg/g, likely rep-
resents smoldering endothelial or vascular disease and
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