What is the recommended workup and initial management for microalbuminuria?

Workup for Microalbuminuria

Confirm persistent microalbuminuria by obtaining at least two abnormal urine albumin-to-creatinine ratios (30–299 mg/g creatinine) from three separate specimens collected over 3–6 months, then immediately initiate an ACE inhibitor regardless of blood pressure status. 1

Initial Diagnostic Confirmation

Specimen Collection Protocol

• Obtain a spot urine albumin-to-creatinine ratio (UACR) on a random urine sample as the preferred screening method, which is more practical than 24-hour collections and provides accurate results. 2
• Use first-morning void specimens whenever possible to account for diurnal variation in albumin excretion and to rule out orthostatic proteinuria in adolescents and young adults. 2, 1
• Collect 2–3 additional specimens over a 3–6 month period because day-to-day variability in urinary albumin excretion is substantial; diagnosis requires 2 of 3 samples to be abnormal (30–299 mg/g creatinine). 2, 1

Pre-Collection Requirements

• Instruct patients to avoid vigorous exercise for 24 hours before each collection, as physical activity transiently elevates urinary albumin. 2, 1
• Do not collect specimens during acute illness, fever, urinary tract infection, marked hyperglycemia (>300 mg/dL), marked hypertension, congestive heart failure, menstruation, or in the presence of hematuria or pyuria, as all of these conditions cause false elevations. 2, 1

Diagnostic Thresholds

Category	UACR (mg/g creatinine)
Normal	<30
Microalbuminuria	30–299
Macroalbuminuria	≥300

2

Exclude Alternative Causes of Kidney Disease

Consider non-diabetic causes of chronic kidney disease if any of the following are present: 2

• Absence of diabetic retinopathy (especially in type 1 diabetes of >10 years duration)
• Rapidly declining GFR or rapidly increasing proteinuria
• Nephrotic syndrome
• Refractory hypertension despite multiple agents
• Active urinary sediment (red cell casts, dysmorphic RBCs)
• Signs or symptoms of systemic disease (rash, arthritis, constitutional symptoms)

• 30% reduction in GFR within 2–3 months after starting an ACE inhibitor or ARB

Baseline Laboratory Assessment

Once persistent microalbuminuria is confirmed, obtain the following baseline studies before initiating treatment:

• Serum creatinine and calculate estimated GFR to stage chronic kidney disease and establish baseline renal function. 1, 3
• Serum potassium to identify pre-existing hyperkalemia before starting ACE inhibitor or ARB therapy. 1, 3
• Hemoglobin A1c to assess glycemic control, with a target <7%. 1, 3
• Fasting lipid panel because microalbuminuria signals markedly increased cardiovascular risk and aggressive lipid management is indicated. 2, 1
• Dilated retinal examination to assess for diabetic retinopathy, which supports the diagnosis of diabetic kidney disease when present alongside microalbuminuria. 2

Cardiovascular Risk Screening

Screen all patients with microalbuminuria for cardiovascular disease because microalbuminuria is an independent marker of 2–4-fold increased cardiovascular mortality, not just a renal marker. 2, 1, 4

• Assess for symptoms of coronary artery disease, peripheral arterial disease, and cerebrovascular disease
• Consider stress testing or coronary calcium scoring in asymptomatic patients with multiple risk factors
• Aggressively manage all modifiable cardiovascular risk factors (smoking cessation, blood pressure control, lipid management, antiplatelet therapy if indicated)

Common Pitfalls to Avoid

• Do not treat based on a single elevated UACR result—day-to-day variability is high and confirmation with 2 of 3 abnormal specimens is mandatory. 2, 1
• Do not delay ACE inhibitor or ARB therapy until hypertension develops—renoprotective benefits exist independent of blood pressure lowering, even in normotensive patients. 1, 3
• Do not use standard urine dipsticks for protein—they lack sufficient sensitivity to detect microalbuminuria and only become positive at protein excretion >300–500 mg/day. 2, 4
• Do not forget to recheck serum creatinine and potassium within 1–2 weeks after initiating or titrating ACE inhibitor/ARB therapy to detect hyperkalemia or acute kidney injury. 1, 3
• In adolescents with a positive random UACR, always obtain a first-morning void specimen immediately upon arising to exclude benign orthostatic proteinuria, which requires no treatment. 1, 3

Initial Management After Confirmation

Pharmacologic Intervention

• Start an ACE inhibitor immediately in all patients with confirmed persistent microalbuminuria, regardless of blood pressure level. 1, 3
• If ACE inhibitor is not tolerated (typically due to cough), substitute an ARB—both have equivalent efficacy in delaying progression to macroalbuminuria. 1, 3
• Titrate the ACE inhibitor or ARB dose to achieve the lowest possible albumin excretion, not just to blood pressure targets. 1, 3
• Target blood pressure <130/80 mmHg using additional antihypertensive agents as needed (non-dihydropyridine calcium channel blockers, beta-blockers, or diuretics). 1, 3, 4

Glycemic Optimization

• Target HbA1c <7% to reduce risk and slow progression of diabetic nephropathy. 1, 3

Dietary Modification

• Limit dietary protein to approximately 0.8 g/kg body weight per day (≈10% of total calories) under supervision of a registered dietitian. 1, 3
• Consider further restriction to 0.6 g/kg/day if estimated GFR begins to decline, though this requires careful nutritional monitoring to prevent deficiencies. 1, 3

Lipid Management

• Aggressively treat dyslipidemia because lowering cholesterol may reduce proteinuria and microalbuminuria signals high cardiovascular risk. 2, 1

Ongoing Monitoring Strategy

• Measure UACR every 3–6 months to evaluate treatment response; a ≥30% reduction in albuminuria indicates positive response to therapy. 1, 3
• Monitor serum potassium regularly when patients are on ACE inhibitors or ARBs, especially in those with declining GFR. 1, 3
• Measure serum creatinine and calculate estimated GFR at least annually to stage chronic kidney disease and detect progression. 1, 3

Nephrology Referral Criteria

Refer to a nephrologist when: 1, 3

• Estimated GFR falls below 60 mL/min/1.73 m² (mandatory referral at GFR <30 mL/min/1.73 m²)
• Hypertension or hyperkalemia becomes difficult to control despite optimal therapy
• Uncertainty exists about the etiology of kidney disease (to exclude non-diabetic causes)
• Rapid progression of proteinuria or rapid decline in GFR occurs