Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease

Journal of the American Heart Association

Contemporary Review

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.

• 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.

• 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

• 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

• 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

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.