How to manage elevated Urine Albumin-to-Creatinine Ratio (UACR)?

Management of Elevated Urine Albumin-to-Creatinine Ratio (UACR)

For patients with elevated UACR, an ACE inhibitor or angiotensin receptor blocker (ARB) at the maximally tolerated dose is the recommended first-line treatment, especially for those with UACR ≥300 mg/g (Grade A recommendation) or 30-299 mg/g (Grade B recommendation). 1

Assessment and Diagnosis

• Elevated UACR is defined as ≥30 mg/g creatinine, with levels categorized as:

  • 30-299 mg/g: Moderately elevated (formerly microalbuminuria)
  • ≥300 mg/g: Severely elevated (formerly macroalbuminuria) 1

• Confirm elevated UACR with at least two of three urine samples collected over a 6-month interval to account for variability 1, 2

• Annual screening for albuminuria is recommended for:

  • All patients with type 2 diabetes
  • Patients with type 1 diabetes with duration ≥5 years 1

Treatment Algorithm

Step 1: Optimize Glycemic Control

• Tight glycemic control reduces the risk or slows progression of diabetic kidney disease 1

Step 2: Optimize Blood Pressure Control

• Target blood pressure <130/80 mmHg for most patients with diabetes 1
• For patients with UACR ≥30 mg/g, blood pressure control is particularly important 1

Step 3: Pharmacological Management Based on UACR Level

For UACR 30-299 mg/g:

• An ACE inhibitor or ARB is suggested as first-line therapy (Grade B recommendation) 1
• Titrate to maximum tolerated dose to normalize albumin excretion 1

For UACR ≥300 mg/g:

• An ACE inhibitor or ARB is strongly recommended (Grade A recommendation) 1
• If one class is not tolerated, the other should be substituted 1

For resistant hypertension with elevated UACR:

• Consider adding a mineralocorticoid receptor antagonist (MRA) if blood pressure targets are not met on three classes of antihypertensive medications including a diuretic 1

Step 4: Monitoring

• Monitor serum creatinine/eGFR and potassium levels:

  • At baseline before starting therapy
  • 7-14 days after initiation or dose change
  • At least annually thereafter 1

• Continue monitoring UACR to assess progression of kidney disease 1

Additional Interventions

Lifestyle Modifications

• Weight reduction (if indicated) through caloric restriction 1
• Physical activity (at least 150 minutes of moderate-intensity aerobic activity per week) 1, 3
• Sodium restriction (<2,300 mg/day) 1
• Increased consumption of fruits, vegetables, and low-fat dairy products 1
• Avoiding excessive alcohol consumption 1

Nutritional Considerations

• Protein intake should be maintained at the recommended daily allowance of 0.8 g/kg/day (based on ideal body weight) for adults 1
• For children and adolescents, protein intake should be at 0.85-1.2 g/kg/day (according to age) 1

Special Populations

Children and Adolescents with Diabetes

• Begin screening for albuminuria once the child has had diabetes for 5 years 1
• Treatment with an ACE inhibitor should be considered when elevated UACR (>30 mg/g) is documented with at least two of three urine samples 1
• For children with hypertension and elevated UACR, an ACE inhibitor is the preferred initial treatment 1

Important Considerations and Pitfalls

• Contraindications: ACE inhibitors, ARBs, MRAs, direct renin inhibitors, and neprilysin inhibitors should be avoided in sexually active individuals of childbearing potential who are not using reliable contraception and are contraindicated in pregnancy 1

• Avoid combination therapy: Combinations of ACE inhibitors and ARBs, or combinations of either with direct renin inhibitors, should not be used due to increased risk of adverse events 1

• Clinical significance of low-normal UACR: Recent evidence suggests that even UACR values >10 mg/g (though still within the "normal" range <30 mg/g) may predict progression to chronic kidney disease in patients with type 2 diabetes 4

• Variability in UACR measurements: UACR demonstrates high within-individual variability, with a coefficient of variation of approximately 49%, which may necessitate multiple measurements for accurate assessment 2

• Cardiovascular risk: Elevated UACR is associated with increased cardiovascular mortality, even at levels below the microalbuminuria threshold, highlighting the importance of early intervention 5, 6