Management and Treatment of Albuminuria
Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the first-line treatment for albuminuria, with the goal of reducing urinary albumin excretion and slowing progression of kidney disease. 1
Definition and Classification
Albuminuria refers to the presence of albumin in urine and is categorized based on the albumin-to-creatinine ratio (ACR):
- Normal: <30 mg/g creatinine
- Moderately increased (formerly microalbuminuria): 30-300 mg/g creatinine
- Severely increased (formerly macroalbuminuria): >300 mg/g creatinine 2
The term "microalbuminuria" is now discouraged in favor of more quantitative descriptions of albuminuria by category or specific value 2.
Diagnosis and Evaluation
Screening Method
- The preferred method for detecting albuminuria is the urine albumin-to-creatinine ratio (UACR) in a random spot urine collection 2, 1
- First morning void samples are optimal 1
- Due to variability in urinary albumin excretion, two of three specimens collected within a 3-6 month period should be abnormal before confirming diagnosis 2
Factors Affecting Measurement
Avoid collection during:
- Exercise within 24 hours
- Infection or fever
- Congestive heart failure
- Marked hyperglycemia
- Marked hypertension 2, 1
Treatment Approach
First-Line Therapy
ACE inhibitors or ARBs:
- Should be uptitrated to maximally tolerated dose 1
- Losartan has been shown to reduce proteinuria by an average of 34% within 3 months and significantly reduce the rate of decline in GFR by 13% 3
- In patients with type 2 diabetes with nephropathy, losartan reduced the risk of doubling of serum creatinine by 25% and end-stage renal disease by 29% 3
Blood Pressure Control:
Lifestyle Modifications
- Restrict dietary sodium to <2.0 g/day 1
- Weight normalization for overweight/obese patients 1, 4
- Regular exercise 1
- Smoking cessation 2, 1
- For diabetic patients, maintain HbA1c <7% 1
- Target LDL cholesterol <100 mg/dL 1
Special Considerations
- Combination therapy: Avoid combining different inhibitors of the renin-angiotensin system (e.g., ACEi plus ARB) as they provide no additional benefit on cardiovascular disease or diabetic kidney disease and have higher adverse event rates (hyperkalemia or acute kidney injury) 2
- Temporary discontinuation: ACEIs or ARBs should be temporarily suspended during acute illness with vomiting/diarrhea, volume depletion, or prior to procedures with contrast 1
Monitoring
Frequency
- For stable patients: Every 3-6 months with spot urine PCR/ACR 1
- Monitor serum creatinine and potassium regularly when on ACEIs or ARBs 1
- For diabetic patients: Annual screening, or every 6 months if eGFR <60 mL/min/1.73 m² or albuminuria >30 mg/g 1
Response Assessment
- A >30% sustained reduction in albuminuria is considered a marker of slowed kidney disease progression 1
- Goal is to achieve UACR <30 mg/g if possible 1
When to Refer to Nephrology
Consider referral when:
- Proteinuria >3.5 g/day (nephrotic range) 1
- Rapidly declining kidney function 2, 1
- eGFR <30 mL/min/1.73 m² 2, 1
- Active urinary sediment 2, 1
- Uncertainty about the etiology of kidney disease 2
Clinical Significance of Albuminuria
Albuminuria is not just a marker of kidney damage but also:
- An independent risk factor for cardiovascular disease 4, 5, 6
- A marker of endothelial dysfunction and systemic vascular disease 4, 6
- Associated with higher blood pressures, increased serum total cholesterol, and reduced HDL cholesterol in non-diabetic hypertensive patients 4
- May directly contribute to kidney disease progression through tubular damage from excessive albumin reabsorption, leading to inflammation and fibrosis 7, 8
Cautions and Pitfalls
- Dihydropyridine calcium channel blockers (amlodipine, nifedipine) may exacerbate edema and increase proteinuria 1
- In patients with massive proteinuria (>5 g/24h), consider thromboprophylaxis due to increased risk of venous thromboembolism 1
- Equations based on serum creatinine may overestimate GFR in nephrotic syndrome with hypoalbuminemia 1
- Unexplained albuminuria (>500 mg/24 hours) or azotemia in patients receiving pamidronate or zoledronic acid should prompt discontinuation of these drugs until renal abnormalities resolve 2
By following this comprehensive approach to managing albuminuria, clinicians can help reduce the risk of kidney disease progression and associated cardiovascular complications.