Treatment for Elevated Albumin-to-Creatinine Ratio (ACR)
For patients with elevated ACR ≥30 mg/g creatinine, initiate an ACE inhibitor or angiotensin receptor blocker (ARB) at maximum tolerated dose, regardless of whether hypertension is present, as this is the cornerstone of therapy to reduce progression of kidney disease. 1, 2
Confirmation and Classification
Before initiating treatment, confirm the elevation with at least two of three urine samples collected over 3-6 months, as biological variability can exceed 20% between measurements. 3, 2
ACR Categories:
- Normal: <30 mg/g creatinine 3
- Moderately elevated (microalbuminuria): 30-299 mg/g creatinine 1, 3, 2
- Severely elevated (macroalbuminuria): ≥300 mg/g creatinine 1, 3, 2
Primary Pharmacologic Treatment
ACE Inhibitors or ARBs
For ACR 30-299 mg/g: ACE inhibitor or ARB is recommended as first-line therapy (Grade B recommendation). 1, 2
For ACR ≥300 mg/g: ACE inhibitor or ARB is strongly recommended as first-line therapy (Grade A recommendation). 1, 2
- Titrate to the maximum tolerated dose indicated for blood pressure treatment to normalize albumin excretion. 1, 2
- If one class is not tolerated, substitute with the other class. 1
- In the RENAAL study, losartan reduced proteinuria by 34% within 3 months and reduced progression to end-stage renal disease by 28.6% in patients with type 2 diabetes and ACR ≥300 mg/g. 4
Critical caveat: ACE inhibitors and ARBs are contraindicated in pregnancy and should be avoided in individuals of childbearing potential not using reliable contraception due to teratogenic effects. 1, 2
Do Not Discontinue for Minor Creatinine Increases
Continue ACE inhibitor or ARB therapy despite minor increases in serum creatinine (≤30%) in the absence of volume depletion. 1, 3 Continuation of these medications even as eGFR declines to <30 mL/min/1.73 m² may provide cardiovascular benefit without significantly increasing risk of end-stage kidney disease. 1
Blood Pressure Management
Target blood pressure <130/80 mmHg for most patients with diabetes and elevated ACR. 1, 2
- Blood pressure control is particularly important when ACR ≥30 mg/g. 2
- For patients with confirmed blood pressure ≥140/90 mmHg, promptly initiate and titrate pharmacologic therapy in addition to lifestyle modifications. 1
- For blood pressure ≥160/100 mmHg, initiate two antihypertensive medications or a single-pill combination. 1
Additional Antihypertensive Agents
If blood pressure targets are not met on three classes of antihypertensives (including a diuretic), consider adding a mineralocorticoid receptor antagonist (MRA). 1, 2 However, MRAs increase hyperkalemia risk when combined with ACE inhibitors or ARBs, requiring close monitoring. 1
Never combine: ACE inhibitors with ARBs, or either with direct renin inhibitors, as this increases adverse events without added cardiovascular benefit. 1, 2
Glycemic Control
Optimize glucose control to reduce risk or slow progression of diabetic kidney disease. 1, 2 Tight glycemic control is essential as a foundational intervention. 2
Dietary Modifications
For patients with CKD stage 3 or higher (eGFR <60 mL/min/1.73 m²) not on dialysis:
- Limit dietary protein intake to 0.8 g/kg body weight per day (the recommended daily allowance). 1, 3, 2
- For children and adolescents: 0.85-1.2 g/kg/day. 2
Lifestyle interventions:
- Weight reduction through caloric restriction if overweight 2
- Sodium restriction 2
- Increased consumption of fruits and vegetables 2
- Regular physical activity 2
- Avoid excessive alcohol consumption 2
Monitoring Requirements
At baseline and 7-14 days after initiation or dose change:
At least annually thereafter:
For patients with ACR >30 mg/g and/or eGFR <60 mL/min/1.73 m²: Monitor twice annually to guide therapy. 1
Nephrology Referral
Refer to nephrology in the following situations:
- eGFR <30 mL/min/1.73 m² 3
- Uncertainty about etiology of kidney disease 1, 3
- Worsening ACR despite treatment 1
- Decrease in eGFR 1
- Rapidly progressive kidney disease 3