What are the implications of elevated Albumin to Creatinine Ratio (ACR) and proteinuria in the urine?

From the Guidelines

Elevated albumin-to-creatinine ratio (ACR) and protein in the urine indicate kidney damage and require prompt medical attention, with referral to a nephrologist for uncertainty about the etiology of kidney disease, difficult management issues, and rapidly progressing kidney disease 1. An elevated ACR and protein in the urine, known as proteinuria, are indicators of kidney damage. The normal ACR is less than 30 mg/g, with 30-300 mg/g indicating microalbuminuria and over 300 mg/g suggesting macroalbuminuria.

• Key points to consider:
  • Measurement of urinary ACR is recommended for evaluation of proteinuria in preference to urinary total protein for many reasons, including its greater sensitivity for detecting low-grade but clinically important albuminuria 1.
  • Reduction in ACR in intervention trials targeted at blood pressure reduction or renin–angiotensin blockade has shown benefit for progression of CKD 1.
  • Urine protein excretion has important prognostic implications not only for CKD progression but also for risk of other adverse clinical outcomes, including all-cause mortality and cardiovascular events, irrespective of baseline kidney function 1.
• Treatment typically includes medications like angiotensin-converting enzyme inhibitors (ACE inhibitors) such as lisinopril (10-40 mg daily) or angiotensin II receptor blockers (ARBs) such as losartan (50-100 mg daily), which reduce protein leakage and protect kidney function.
• Blood pressure control is essential, aiming for below 130/80 mmHg.
• Lifestyle modifications are also crucial, including:
  • Reducing sodium intake to less than 2,300 mg daily
  • Moderating protein consumption
  • Maintaining healthy blood glucose levels if diabetic
  • Regular exercise These interventions are important because persistent proteinuria can lead to progressive kidney damage, eventually resulting in chronic kidney disease or kidney failure, as noted in the most recent guidelines 1.
• The protein in urine occurs when the kidney's filtering units (glomeruli) become damaged, allowing proteins that should remain in the bloodstream to leak into the urine.
• It is also important to consider that two of three specimens of UACR collected within a 3- to 6-month period should be abnormal before considering a patient to have high or very high albuminuria, due to high biological variability of >20% between measurements in urinary albumin excretion 1.

From the Research

Elevated ACR and Protein in the Urine

• Elevated Albumin-to-Creatinine Ratio (ACR) and protein in the urine are indicators of kidney damage and disease progression 2.
• The relationship between ACR and protein-to-creatinine ratio (PCR) is nonlinear, with the albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria 2.
• Sex is an important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio 2.

Management of Proteinuria

• Blockade of the renin-angiotensin-aldosterone system is a recommended treatment for proteinuria, and can be achieved using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) 3, 4, 5.
• Combination therapy with an ACE inhibitor and an ARB can result in a significant decrease in proteinuria, but may also increase the risk of adverse events such as hyperkalaemia and progressive renal impairment 4, 5.
• The routine use of combined renin-angiotensin-aldosterone inhibition for albuminuria is not supported by current evidence, and the decision to use combination therapy should be made on a case-by-case basis 5.

Treatment Options

• ACEIs and ARBs are effective in reducing proteinuria in patients with chronic kidney disease (CKD) and proteinuria 3, 4, 6.
• The combination of olmesartan and temocapril has been shown to be effective in reducing proteinuria in normotensive CKD patients and IgA nephropathy 3.
• Enalapril has been shown to be effective in reducing albuminuria in diabetic nephropathy 3.
• Calcium channel blockers may be recommended for patients with stage G4-5 CKD aged ≥75 years 6.

Prescription Rates

• Despite guideline recommendations, ACEIs and ARBs are insufficiently prescribed for patients with hypertension associated with CKD and proteinuria 6.
• The prescription rate of ACEIs and ARBs is lower in patients aged <75 years with CKD stage G1-G5 compared to patients aged ≥75 years with CKD stage G1-G3 6.