Treatment of Albuminuria in Diabetes and Hypertension
Initiate an ACE inhibitor or ARB and titrate to the maximum tolerated dose in all patients with diabetes, hypertension, and albuminuria. 1
First-Line Therapy: RAS Blockade
Start either an ACE inhibitor or ARB immediately in patients with diabetes, hypertension, and albuminuria, regardless of the degree of albuminuria. 1
- Titrate to maximum approved doses (e.g., lisinopril 40 mg daily, losartan 100 mg daily) rather than standard doses, as higher doses provide superior renoprotection. 1, 2
- The renoprotective effect extends beyond blood pressure reduction alone—these agents reduce albuminuria through direct effects on glomerular hemodynamics. 3
Monitoring Protocol After Initiation or Dose Adjustment
Check serum creatinine, eGFR, and potassium within 2-4 weeks of starting therapy or increasing the dose. 1, 2
- Continue therapy if creatinine rises ≤30% within 4 weeks—this is an expected hemodynamic effect and not a reason to stop. 1, 2
- If creatinine rises >30%, evaluate for acute kidney injury, volume depletion, renal artery stenosis, and nephrotoxic medications (NSAIDs, diuretics). 1
- For hyperkalemia, attempt management with dietary potassium restriction, diuretics, sodium bicarbonate, or GI cation exchangers before reducing or stopping the ACE inhibitor/ARB. 1, 2
- Reduce dose or discontinue only as a last resort for uncontrolled hyperkalemia or symptomatic hypotension despite medical management. 1
Additional Therapies Beyond RAS Blockade
SGLT2 Inhibitors
Add an SGLT2 inhibitor if eGFR ≥30 mL/min/1.73m² for additional cardiorenal protection in type 2 diabetes. 1, 2
Blood Pressure Control
Target blood pressure <130/80 mmHg using additional agents if needed after maximizing ACE inhibitor/ARB dose. 2
- Add a dihydropyridine calcium channel blocker (e.g., amlodipine) as the next agent if blood pressure remains above target. 2
- Consider a thiazide or thiazide-like diuretic for resistant hypertension. 3
- Consider a nonsteroidal mineralocorticoid receptor antagonist if albuminuria persists despite optimized ACE inhibitor/ARB and blood pressure control. 2
Comprehensive Risk Factor Management
All patients require simultaneous attention to: 1
- Glycemic control (HbA1c individualized to patient)
- Lipid management with statin therapy
- Smoking cessation
- Dietary sodium restriction (<2 g/day)
- Exercise and weight management
Special Populations and Contraindications
Normotensive Patients with Albuminuria
For macroalbuminuria (>300 mg/g) without hypertension, ACE inhibitor or ARB therapy may be considered even in normotensive patients. 4
- Evidence is weaker for microalbuminuria (30-299 mg/g) in normotensive patients, but therapy may be considered with additional risk factors for progression. 4
Women of Childbearing Potential
Advise contraception in all women receiving ACE inhibitor or ARB therapy. 1
- Discontinue immediately in women considering pregnancy or who become pregnant due to teratogenic effects. 1, 4
Critical Pitfalls to Avoid
Do not combine ACE inhibitors with ARBs—dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury, hypotension) without additional cardiovascular or renal benefit in most patients. 2, 4
- Historical studies showing additive albuminuria reduction with dual blockade 5, 6, 7 have been superseded by outcomes trials demonstrating harm.
Do not use suboptimal doses—approximately 45-67% of eligible patients with albuminuria ≥300 mg/g are not receiving ACE inhibitor/ARB therapy at all, representing a major gap in preventive care. 8
Do not discontinue prematurely for modest creatinine elevation—up to 30% increase is acceptable and expected. 1, 2
Evidence for Outcomes
In the RENAAL trial, losartan reduced the composite endpoint of doubling serum creatinine, ESRD, or death by 16% (p=0.022), reduced progression to ESRD by 29%, and reduced proteinuria by 34% in type 2 diabetic patients with nephropathy. 9