What are the normal albumin‑creatinine ratio (ACR) values, how are micro‑albuminuria and macro‑albuminuria defined, and how should an elevated ACR be confirmed and managed?

Albumin-Creatinine Ratio: Normal Values, Definitions, and Management

Normal Values and Classification

The albumin-creatinine ratio (ACR) is classified into three categories by KDIGO guidelines: A1 (normal to mildly increased) is <30 mg/g, A2 (moderately increased, formerly "microalbuminuria") is 30–299 mg/g, and A3 (severely increased, formerly "macroalbuminuria") is ≥300 mg/g. 1

• The term "microalbuminuria" should no longer be used by laboratories or clinicians; instead, use "moderately increased albuminuria" (ACR 30–299 mg/g) and "severely increased albuminuria" (ACR ≥300 mg/g). 2
• Normal ACR is defined as <30 mg/g creatinine in adults. 1
• These thresholds apply to both diabetic and non-diabetic populations for risk stratification of chronic kidney disease progression and cardiovascular events. 1

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Confirmation Requirements

An elevated ACR must be confirmed with repeat testing before establishing a diagnosis of persistent albuminuria—obtain at least 2 positive results out of 3 separate specimens collected within a 3–6 month period. 1

• Single ACR measurements can vary by 40–50% due to biological variability, making confirmation essential to avoid misdiagnosis. 1
• Use a first-morning void specimen for confirmatory testing to minimize variability and exclude orthostatic proteinuria, particularly in children and young adults. 2
• Confirm any ACR ≥30 mg/g on a random untimed urine with a subsequent early morning urine sample. 2

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Pre-Collection Precautions to Avoid False Elevations

Before collecting urine for ACR testing, exclude transient causes that can artificially elevate results:

• Vigorous exercise: Avoid within 24 hours of collection, as physical activity causes temporary protein elevation. 2, 1
• Acute illness: Defer testing during febrile illness, urinary tract infection, marked hyperglycemia, severe hypertension, or congestive heart failure. 1
• Menstrual contamination: Do not collect during menses. 1
• Hematuria: Blood in urine can falsely elevate ACR. 1

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Preferred Testing Method

Urine ACR is the preferred initial test for albuminuria screening, measured on a first-morning midstream urine sample. 2

• Clinical laboratories must report ACR as a ratio (mg albumin per g creatinine) in addition to albumin concentration alone, not concentration alone. 2
• If ACR is not available, reagent strip urinalysis for albumin with automated reading is an acceptable alternative, but positive results must be confirmed with quantitative ACR. 2
• Routine 24-hour urine collections are unnecessary for albuminuria screening or monitoring; spot ACR provides equivalent clinical information with better patient compliance. 1

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Management of Elevated ACR

For ACR 30–299 mg/g (Moderately Increased Albuminuria):

• Initiate an ACE inhibitor or ARB even if blood pressure is normal, as these agents reduce albuminuria independent of blood pressure lowering. 1
• Target blood pressure <130/80 mmHg in patients with albuminuria. 1
• Implement dietary sodium restriction (<2 g/day) and protein restriction (~0.8 g/kg/day). 1
• In patients with type 2 diabetes and eGFR ≥30 mL/min/1.73 m², add an SGLT2 inhibitor to reduce risk of CKD progression. 1
• Monitor serum creatinine and potassium 1–2 weeks after starting ACE inhibitor or ARB to detect hyperkalemia or acute kidney injury. 1

For ACR ≥300 mg/g (Severely Increased Albuminuria):

• Immediate nephrology referral is indicated, as this represents high risk for progressive kidney disease, cardiovascular events, and mortality. 1
• Kidney biopsy is typically required to determine underlying cause and guide immunosuppressive therapy. 1
• Aim for >30% sustained reduction in albuminuria as a treatment goal. 1

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Monitoring Frequency

• Assess eGFR and albuminuria at least annually in people with CKD. 2
• For higher-risk individuals (eGFR 30–60 mL/min/1.73 m² or albuminuria >300 mg/g), monitor every 3–6 months. 2
• In diabetic patients with moderately or severely increased albuminuria, perform biannual assessments to guide therapeutic adjustments. 1

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Common Pitfalls and Caveats

• Do not rely on albumin concentration alone without creatinine correction—urine concentration changes can cause false results. 1
• Do not diagnose CKD based on a single elevated ACR—biological variability is substantial and confirmation is mandatory. 3
• In patients with extreme muscle mass variations (cachexia, muscle atrophy, extreme obesity, amputations), ACR may systematically underestimate or overestimate albuminuria because creatinine excretion is abnormal; consider 24-hour collection in these specific cases. 1, 4
• Point-of-care ACR devices may be used where laboratory access is limited, but ensure external quality assessment and use the same preanalytical criteria as laboratory testing. 2
• False elevations occur with hematuria, febrile illness, or vigorous exercise within 24 hours—always exclude these before confirming persistent albuminuria. 1