What is the recommended treatment for patients with macroalbuminuria?

Treatment of Macroalbuminuria

For patients with macroalbuminuria (≥300 mg/24h or ≥300 mg/g creatinine), initiate either an ACE inhibitor or ARB as first-line therapy regardless of blood pressure status. 1

Definition and Clinical Significance

• Macroalbuminuria is defined as urinary albumin excretion ≥300 mg/24h or albumin-to-creatinine ratio ≥300 mg/g 1
• Patients with macroalbuminuria are at high risk for progression to end-stage renal disease (ESRD), with significantly accelerated GFR loss compared to those with normal albumin excretion 2
• Macroalbuminuria also confers substantial cardiovascular risk, with increased rates of coronary heart disease, stroke, and cardiovascular mortality 3, 4

Primary Pharmacologic Treatment

ACE Inhibitors or ARBs

Either ACE inhibitors or ARBs should be used as first-line therapy in all nonpregnant patients with macroalbuminuria. 1

• If one class is not tolerated due to side effects (e.g., cough with ACE inhibitors), substitute the other class 1
• The FDA has specifically approved losartan for treatment of diabetic nephropathy with elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and hypertension 5
• In the RENAAL trial, losartan reduced the primary composite endpoint (doubling of serum creatinine, ESRD, or death) by 16% and reduced ESRD alone by 29% in patients with type 2 diabetes and macroalbuminuria 5
• Losartan also reduced proteinuria by an average of 34% and slowed the rate of decline in GFR by 13% 5

Dosing Strategy

• Start losartan at 50 mg once daily, then titrate to 100 mg once daily if blood pressure goals are not achieved 5
• In the RENAAL study, 72% of patients received the 100 mg daily dose more than 50% of the time 5
• For ACE inhibitors, titrate to maximum approved doses for optimal renoprotection, as the optimal dose for kidney protection may be higher than that required for blood pressure control alone 6

Essential Adjunctive Measures

Blood Pressure Optimization

Optimize blood pressure control to reduce risk and slow progression of nephropathy. 1

• Target blood pressure <130/80 mmHg in patients with diabetes and macroalbuminuria 7
• Additional antihypertensive agents (diuretics, calcium-channel blockers, alpha- or beta-blockers, centrally acting agents) can be added as needed to achieve blood pressure goals 5
• Avoid dual RAS blockade (combining ACE inhibitors with ARBs) as this increases risk of hyperkalemia and acute kidney injury without additional benefit 8, 7

Glycemic Control

Optimize glucose control to reduce risk and slow progression of nephropathy. 1

• Target glycosylated hemoglobin <7.0% to retard progression of renal disease 9
• Consider adding an SGLT2 inhibitor if eGFR ≥20 ml/min/1.73 m² for additional renoprotection 7

Dietary Protein Restriction

• Reduce protein intake to 0.8-1.0 g/kg body weight/day in patients with diabetes and earlier stages of CKD 1
• Further restriction to 0.8 g/kg body weight/day may be useful in later stages of CKD 1
• Protein-restricted meal plans should be designed by a registered dietitian to avoid nutritional deficiency 1

Monitoring Requirements

Laboratory Monitoring

Monitor serum creatinine and potassium levels within 2-4 weeks after initiating ACE inhibitor or ARB therapy, and regularly thereafter. 1, 7

• Check for development of hyperkalemia, particularly in patients with reduced kidney function 1, 8
• Monitor urinary albumin excretion to assess both response to therapy and disease progression 1, 6
• Assess estimated GFR at least annually 1, 6
• In patients with established kidney disease, monitor urinary albumin and eGFR 1-4 times per year depending on CKD stage 7

Common Pitfalls to Avoid

• Do not discontinue ACE inhibitor/ARB therapy for modest increases in serum creatinine (up to 30% increase is acceptable and reflects hemodynamic changes) 1
• Temporarily suspend ACE inhibitor/ARB during intercurrent illnesses or before IV radiocontrast administration to reduce risk of acute kidney injury 8
• Avoid combining ACE inhibitors with ARBs, as dual RAS blockade increases adverse events without improving outcomes 8, 7

Specialist Referral Indications

Consider referral to a nephrologist when eGFR falls below 60 ml/min/1.73 m². 1, 6

• Refer when there is uncertainty about the etiology of kidney disease 1
• Refer for difficulties in management of hypertension or hyperkalemia 1
• Early referral reduces cost and improves quality of care 6

Additional Cardiovascular Risk Management

• Patients with macroalbuminuria should receive aspirin and statin therapy (if not contraindicated) to reduce cardiovascular events 1
• Address all cardiovascular risk factors including dyslipidemia, smoking cessation, and lifestyle modifications 1