What if the microalbumin to creatinine (MACR) ratio is elevated in the presence of normal creatinine levels and normal Glomerular Filtration Rate (GFR)?

Elevated Microalbumin to Creatinine Ratio with Normal Creatinine and GFR

An elevated microalbumin to creatinine ratio (MACR) with normal creatinine and GFR represents early kidney damage and requires intervention despite normal filtration markers, as it significantly increases cardiovascular and renal progression risk. 1

Clinical Significance

An elevated MACR (≥30 mg/g creatinine) with normal creatinine and GFR indicates:

• Early kidney damage before detectable decline in filtration function
• Increased risk for progression to overt nephropathy
• Significant cardiovascular risk marker
• Need for intervention despite normal filtration markers

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines emphasize that albuminuria is an independent risk factor for adverse outcomes at any level of GFR 1. This relationship exists on a continuum, with risk increasing as albuminuria rises, even when GFR remains normal.

Diagnostic Considerations

Confirming the Finding

• Persistent albuminuria requires confirmation with 2 out of 3 positive samples over a 3-6 month period 1
• Rule out transient causes of elevated MACR:
  • Exercise within 24 hours before collection
  • Fever or acute illness
  • Urinary tract infection
  • Marked hyperglycemia
  • Congestive heart failure
  • Marked hypertension

Terminology

• The term "microalbuminuria" (30-299 mg/g creatinine) is no longer recommended 1
• Current terminology uses albuminuria categories:
  • A1: <30 mg/g (normal to mildly increased)
  • A2: 30-299 mg/g (moderately increased)
  • A3: ≥300 mg/g (severely increased)

Management Algorithm

1. Confirm Persistent Albuminuria

• Repeat MACR testing 2-3 times over 3-6 months
• Use first morning urine when possible
• Avoid testing after exercise, during fever, or urinary tract infection

2. Risk Assessment

• Evaluate for other cardiovascular risk factors
• Screen for other diabetic complications if diabetes is present
• Assess for other causes of kidney damage if clinical picture is atypical

3. Blood Pressure Management

• For patients with MACR ≥30 mg/g and <300 mg/g:

  • Target BP <130/80 mmHg 1
  • Use ACE inhibitor or ARB as first-line therapy 1

• For patients with MACR ≥300 mg/g:

  • Target BP <130/80 mmHg
  • ACE inhibitor or ARB is strongly recommended 1

4. Metabolic Control (if diabetic)

• Optimize glycemic control (target HbA1c <7.0%)
• Manage dyslipidemia

5. Monitoring

• Monitor MACR every 6-12 months to assess response to treatment 1
• Monitor serum creatinine and potassium when using ACE inhibitors, ARBs, or diuretics 1
• Annual assessment of GFR

Clinical Implications

The presence of elevated MACR with normal creatinine and GFR represents a critical window for intervention. At this stage, kidney damage is potentially reversible with appropriate treatment. Without intervention, patients face increased risk of:

• Progressive decline in kidney function
• Cardiovascular events
• All-cause mortality

Common Pitfalls to Avoid

1. Dismissing elevated MACR when GFR is normal - This represents early kidney damage and requires intervention
2. Failing to confirm persistence - Transient elevations can occur; confirm with repeat testing
3. Not initiating ACE inhibitor/ARB therapy - These agents specifically reduce albuminuria beyond their blood pressure-lowering effects
4. Inadequate monitoring - Regular follow-up of MACR is needed to assess treatment response
5. Missing non-diabetic causes - Consider other etiologies, especially with atypical presentation

Early intervention in patients with elevated MACR but normal creatinine and GFR provides the best opportunity to prevent progression to more advanced kidney disease and reduce cardiovascular risk.