Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease

Journal of the American Heart Association

Contemporary Review

 

Authors

Joshua I Barzilay , MD; Youssef M. K. Farag, MD, PhD, MPH; Jeffrey Durthaler ,
DPh

Doi:

doi: 10.1161/JAHA.123.030131

Citation:

Barzilay JI, Farag YM, Durthaler J. Albuminuria: An Underappreciated Risk
Factor for Cardiovascular Disease. Journal of the American Heart
Association. 2024 Jan 16;13(2):e030131.

Published:

Jan 12, 2024  

Abstract:

Albuminuria, an established biomarker of the progression of chronic

kidney disease,
 is also recognized as a biomarker for the
risk of

cardiovascular disease.
 Elevated
urinary albumin excretion
 indicates
kidney damage
 and
systemic vascular disease,
 including
myocardial

capillary
disease
and
arterial stiffness.
 Albuminuria is associated with an
increased risk of coronary artery disease, stroke, heart failure,

arrhythmias, and microvascular disease.
 There are now several
therapeutic agents that can lead to albuminuria lowering and a reduction
in cardiovascular risk. However, screening for albuminuria is still low.
Considering the importance of multidisciplinary management of patients
with cardiovascular disease, it is crucial that health care professionals
managing such patients are aware of the benefits of albuminuria
surveillance and management.

KEY POINTS

Key_points_img

Reciprocal mechanisms of cardiac and renal disease leading to albuminuria

Injury to the glomerulus resulting in albuminuria is seen in cardiovascular disease because of the shared pathological processes with chronic kidney disease and because of compensatory mechanisms in chronic cardiovascular disease.

Introduction

  • Biomarkers play a vital role in assessing CVD risk.
  • High-sensitivity CRP levels indicate increased risk of adverse cardiovascular events.
  • B-type natriuretic peptides and troponin serve as markers for heart failure and myocardial ischemia.
  • Albuminuria,
     often overlooked,
    strongly correlates with CVD risk
     and
    chronic kidney disease.
  • This review aims to highlight albuminuria's significance in cardiovascular health and available treatments for reducing CVD risk.

Albuminuria

  • In a study with 9198 patients in a primary care setting,
    highest prevalence of microalbuminuria was noted in combined cases of diabetes and hypertension
     - 58%
  • Hemodynamic alterations due to hyperglycemia and hypertension initiate processes damaging the glomerular filtration barrier, comprising the endothelial surface layer, fenestrated endothelial cells, glomerular basement membrane, and podocytes. This damage leads to mesangial expansion, basement membrane thickening, and podocyte injury, increasing albuminuria and ultimately causing glomerulosclerosis.
  • Elevated inflammatory markers associated with albuminuria suggest a connection with atherosclerosis development. Additionally, dysfunction in one system, such as chronic cardiac dysfunction, can induce compensatory mechanisms that impair renal function, contributing to albuminuria and cardiorenal syndromes.

Overview of Urine Albumin Measurement Methods in Clinical Practice

Test

Benefits

Drawbacks

Best use

24-h AER

Accurate measurement of albuminuria excretion

Cumbersome

When accurate albuminuria diagnosis is required

Random spot UACR

Convenient, good screening test for microalbuminuria, high sensitivity

Not a good estimate of 24-h AER,

 variability owing to 

excercise, posture, hydration 

level, extremes of diaet or

 muscle mass, requires re-testing

Screening (if first morning spot UACR is not convenient)

First morning spot UACR

Stronger correlation with

24-h AER than random spot

UACR

Affected by variability of

 albuminuria, requires re-testing

Screening

Urine dipstick

Immediate results, conveninent, low cost

Poor specificity and sensitivity to microalbuminuria

Screening (when UACR is unavailable), repeat if negative

Association of Albuminuria with Cardiovascular Disease

Cardiovascular Disease

Association with albuminuria

CAD

Increased severity of CAD
High coronary artery calcium score
Predictor of silent ischemia
Underdeveloped collateral vessels
in areas of CAD
Poor coronary artery bypass graft
outcomes
Risk predictor of CAD

Stroke

Stroke risk predictor

Arterial Stiffness

Predictor of arterial stiffness

Myocardial Capillary Disease

Reduced myocardial flow reserve

Heart Failure

Predictor of heart failure
Predictor of systolic dysfunction
Predictor of diastolic dysfunction
Prognosis of heart failure

Arrhythmia

Increased prevalence and risk of atrial fibrillation
Increased percentage of time in atrial fibrillation
Increased prevalence of non-sustained ventricular tachycardia

The impact of Albuminuria lowering on cardiovascular outcomes

  • The
    progression of albuminuria is closely linked to diabetes and blood pressure 

    management,
     with effective control crucial for meaningful reduction, while
    weight

     loss, lipid control, and smoking cessation also play roles in lowering albuminuria

     levels
     and mitigating renal deterioration.
  • Recent reports indicate that
    reducing albuminuria, particularly with RAAS inhibitors,

     is more effective in mitigating renal complications
     than cardiovascular risks.Though
    regardless of their effect on albuminuria, a meta-analysis on patients with CKD has shown
     
    reduced risk of MACE with ACEi/ARBs
  • Clinical trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, show significant
    reductions in albuminuria and cardiovascular events with the use of SGLT2 inhibitors,

    though it is unknown whether this is a casual relationship.
  • Steroidal and nonsteroidal mineralocorticoid receptor antagonists (MRAs) such as
    spironolactone, eplerenone, and Finerenone reduce albuminuria and cardiovascular
     risk by blocking overstimulation of MR in various cells.
  • Finerenone, a nonsteroidal MRA, exhibits higher selectivity for MR and lower incidence
    of adverse effects compared to steroidal MRAs like spironolactone and eplerenone.
  • Clinical trials and meta-analyses demonstrate significant reductions in albuminuria and
    cardiovascular events with Finerenone treatment, leading to its approval for reducing renal
    and cardiovascular events in patients with type 2 diabetes and chronic kidney disease

Guideline Recommendations in Relation to Albuminuria Screening

Guideline

Population

Preferred testing method

Timing

KDIGO

At risk for and with CKD to detect progression

First morning spot UACR

Annually, and 1-4 times per year depending on the stage of CKD

ACC/AHA

With hypertension to detect hypertension mediated organ

damage or screening for secondary hypertension

First morning spot UACR

Optional

ISH

With hypertension to detect hypertension mediated organ

damage or screening for secondary hypertension

First morning spot UACR

or urine dipstick

Routinely

ADA

Anyone with diabetic kidney disease or at risk of kidney

disease (type 1 diabetes with duration of >5y; type 2

diabetesregardless of treatment) to detect progression

of disease

Random spot UACR

Annually, or 1–4 times per year depending on the stage of CKD

Factors that may contribute to low albuminuria testing rates

  • Lack of awareness of the association of albuminuria with CVD
  • Lack of awareness of the guidelines
  • Lack of time/high workload
  • Fragmented healthcare
  • Patients have limited access to healthcare
  • Low disease awareness
  • Poor adherence
  • Inconsistent advice among the guidelines

Importance of Screening for Albuminuria : a graphical abstract

Increased_risk_img

Conclusion

Screening for albuminuria is important to identify patients at risk of CVD and CKD
and to
intervene early with cardiorenal-protective therapies that can help slow disease progression

and improve patient outcomes.

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Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease
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