What does an elevated Albumin-to-Creatinine Ratio (ACR) indicate when urine albumin and creatinine levels are normal?

From the Guidelines

A high albumin-to-creatinine ratio (ACR) with normal individual levels of urine albumin and creatinine suggests early kidney damage or dysfunction, particularly in the glomeruli, and is associated with increased risk for adverse outcomes, as indicated by the most recent study 1. This condition requires further investigation and monitoring to determine the underlying cause and to prevent progression of kidney disease.

Key Points

• An elevated ACR is a sensitive indicator of early kidney damage, even when individual levels of urine albumin and creatinine are normal 1.
• The ACR is a continuous measurement, and differences within the normal and abnormal ranges are associated with renal and cardiovascular outcomes 1.
• A sustained reduction in albuminuria of at least 30% to 50% is considered a surrogate marker of slowed progression of kidney disease 1.

Recommendations

Consult a nephrologist for a comprehensive evaluation and to establish a management plan. Additional steps include:

1. Repeat the urine test to confirm the results.
2. Undergo a complete metabolic panel and estimated glomerular filtration rate (eGFR) test.
3. Monitor blood pressure regularly.
4. Implement lifestyle changes: reduce salt intake, maintain a healthy weight, exercise regularly, and avoid smoking. If confirmed, your doctor may recommend:

• ACE inhibitors or ARBs to protect kidney function (e.g., lisinopril 10-40 mg daily or losartan 50-100 mg daily) 1.
• More frequent monitoring of kidney function (every 3-6 months) 1.
• Screening for other complications like anemia or bone disease.

Justification

The ACR is more sensitive than individual measurements for detecting early kidney damage, as it can indicate increased glomerular permeability to albumin before overt proteinuria develops 1. This early detection allows for timely intervention to slow the progression of kidney disease and prevent complications.

From the Research

Elevated Albumin-to-Creatinine Ratio (ACR) Indications

• An elevated ACR, even within the normal range, is associated with increased risk of all-cause and cardiovascular mortality 2.
• The severity of albuminuria, as indicated by ACR, can stratify the risk of progressive chronic kidney disease in patients undergoing radical or partial nephrectomy 3.
• Reclassification of albuminuria categories using ACR instead of 24-hour urinary albumin excretion (UAE) is generally indicative of the presence of cardiovascular risk factors and prognosis 4.
• In adolescents with Type 1 diabetes mellitus, hyperfiltration and elevated ACR are early indicators of diabetic nephropathy, and ACR is associated with greater odds of hyperfiltration and rapid GFR decline 5.
• However, an ACR at levels below the microalbuminuria range does not independently predict incident diabetes in adults at high risk of developing type 2 diabetes 6.

Implications of Elevated ACR

• Elevated ACR is associated with increased risk of cardiovascular and all-cause mortality, even in individuals without comorbidities 2.
• ACR can be used to stratify the risk of progressive chronic kidney disease in patients undergoing nephrectomy 3.
• The use of ACR instead of 24-hour UAE for staging albuminuria may result in reclassification of albuminuria categories, which can have implications for cardiovascular risk assessment and prognosis 4.
• In adolescents with Type 1 diabetes mellitus, monitoring ACR and hyperfiltration can help identify early indicators of diabetic nephropathy and inform strategies for reducing cardiorenal complications 5.