What is the treatment for diabetic proteinuria?

Treatment of Diabetic Proteinuria

ACE inhibitors or ARBs should be used as first-line therapy for diabetic proteinuria, titrated to maximally tolerated doses to reduce proteinuria to <1 g/day. 1, 2, 3

First-Line Treatment

Renin-Angiotensin System (RAS) Blockade

• ACE inhibitors or ARBs: These are the cornerstone of diabetic proteinuria treatment
  • Losartan is FDA-approved specifically for diabetic nephropathy with elevated serum creatinine and proteinuria 3
  • These medications reduce proteinuria through both BP-dependent and BP-independent mechanisms 2
  • Titrate to maximum tolerated dose 2, 1
  • Monitor serum creatinine and potassium within 1-2 weeks after initiation or dose increase 1
  • A modest increase in serum creatinine (up to 30%) is acceptable and expected 2, 1
  • Discontinue if kidney function continues to worsen or if refractory hyperkalemia develops 2

Blood Pressure Targets

• For proteinuria >1 g/day: Target BP <125/75 mmHg 1
• For proteinuria <1 g/day: Target BP <130/80 mmHg 1
• For pediatric patients: Target BP ≤50th percentile for age, sex, and height 1

Second-Line and Adjunctive Treatments

Additional Antihypertensive Agents

• If BP targets not achieved with ACE inhibitor/ARB alone:
  • Add a diuretic (preferably thiazide-like) 1
  • Consider non-dihydropyridine calcium channel blockers for additional antiproteinuric effect 1
  • For resistant edema, use loop diuretics in combination with other mechanistically different diuretics 2

Combination RAS Blockade

• Dual RAS blockade (ACE inhibitor + ARB) may provide additional proteinuria reduction 4
• However, use with caution due to increased risk of hyperkalemia and acute kidney injury 2

Monitoring and Follow-up

Laboratory Monitoring

• Check serum creatinine and potassium 1-2 weeks after starting or increasing dose of ACE inhibitor/ARB 1
• Monitor albumin:creatinine ratio every 3-6 months to assess treatment response 1
• Goal: Reduce proteinuria to <1 g/day or as low as possible 1

Adverse Effects Monitoring

• Watch for hypokalemia with thiazide and loop diuretics 2
• Monitor for hyperkalemia with ACE inhibitors, ARBs, and spironolactone 2
• Be alert for volume depletion, especially in elderly patients 2

Lifestyle Modifications

Dietary Recommendations

• Sodium restriction: <2 g/day 1
• Protein intake: 0.8 g/kg/day (avoid high protein intake >1.3 g/kg/day) 1
• Diet high in vegetables, fruits, whole grains, fiber, legumes, and plant-based proteins 1

Other Lifestyle Factors

• Moderate-intensity physical activity for at least 150 minutes per week 1
• Weight normalization if overweight or obese 1

Special Considerations

Medication Management During Illness

• Counsel patients to hold ACE inhibitors/ARBs and diuretics when at risk for volume depletion 2
• Consider temporarily stopping RAS blockers during "sick days" 2

Refractory Hyperkalemia

• Use potassium-wasting diuretics and/or potassium-binding agents to maintain normal potassium levels while continuing RAS blockade 2
• Treat metabolic acidosis (serum bicarbonate <22 mmol/L) 2

Clinical Pearls

• The antiproteinuric effect of ACE inhibitors/ARBs is often evident within 3 months of starting therapy 3
• Losartan has been shown to reduce proteinuria by an average of 34% within 3 months and significantly slow the decline in glomerular filtration rate 3
• The beneficial effects of RAS blockade are seen even in patients taking other antihypertensive medications, oral hypoglycemic agents, and lipid-lowering agents 3