What is the treatment for proteinuria?

Treatment of Proteinuria

The first-line treatment for proteinuria is an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) titrated to maximally tolerated dose, which should be used in all patients with persistent proteinuria regardless of the underlying cause. 1

First-Line Therapy: Renin-Angiotensin System Blockade

• Use ACEi or ARB to maximally tolerated or allowed dose as first-line therapy in treating patients with both hypertension and proteinuria 1
• Uptitrate an ACEi or ARB to maximally tolerated or allowed daily dose as first-line therapy in treating patients with glomerulonephritis and proteinuria alone 1
• For diabetic nephropathy with proteinuria, losartan has been shown to significantly reduce proteinuria by an average of 34%, with effects evident within 3 months of starting therapy 2
• Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%) as this is an expected effect 1

Blood Pressure Targets

• Target systolic blood pressure in most adult patients is <120 mm Hg using standardized office BP measurement 1
• In patients with glomerular disease, a practical target is SBP of 120-130 mm Hg in most patients 1
• For children, target 24-hour mean arterial pressure at the 50th percentile for age, sex, and height by ambulatory blood pressure monitoring 1

Management Based on Proteinuria Severity

For persistent proteinuria >1 g/day:

• Long-term ACEi or ARB treatment is strongly recommended 1
• Blood pressure target should be 125/75 mmHg 1
• For IgA nephropathy with persistent proteinuria >1 g/day despite 3-6 months of optimized supportive care and GFR >50 ml/min/1.73 m², a 6-month course of corticosteroid therapy should be considered 1

For proteinuria between 0.5-1 g/day:

• ACEi or ARB treatment is suggested 1
• Blood pressure target should be 130/80 mmHg 1
• Proteinuria goal is variable depending on primary disease process, but typically <1 g/day 1

Management of Treatment Resistance

• For patients who fail to achieve proteinuria reductions on maximally tolerated therapy, intensify dietary sodium restriction to <2.0 g/d (<90 mmol/d) 1
• Consider using mineralocorticoid receptor antagonists in refractory cases (monitor for hyperkalemia) 1
• Use potassium-wasting diuretics and/or potassium-binding agents to reduce serum potassium to normal, in order to continue RAS blocking medications 1
• Treat metabolic acidosis (serum bicarbonate <22 mmol/l) to optimize therapy 1

Lifestyle Modifications

• Employ lifestyle modifications in all patients as synergistic means for improving control of hypertension and proteinuria 1:
  • Restrict dietary sodium to <2.0 g/d (<90 mmol/d) 1
  • Normalize weight 1
  • Stop smoking 1
  • Exercise regularly 1

Disease-Specific Considerations

• For lupus nephritis, combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide) is recommended for nephrotic-range proteinuria 1
• For patients with podocytopathy (MCD, SSNS, FSGS) expected to be rapidly responsive to immunosuppression, it may be reasonable to delay initiation of ACEi or ARB if they don't have hypertension 1
• For diabetic nephropathy with proteinuria, losartan is indicated for treatment and has been shown to reduce the rate of progression of nephropathy 2

Monitoring and Follow-up

• Monitor labs frequently if on ACEi or ARB 1
• Counsel patients to hold ACEi or ARB and diuretics when at risk for volume depletion 1
• Consider transiently stopping RAS inhibitors during sick days 1
• Evidence of improvement in proteinuria should be noted by 3 months, and at least 50% reduction in proteinuria by 6 months 1

Common Pitfalls and Caveats

• Do not start ACEi/ARB in patients who present with abrupt onset of nephrotic syndrome as these drugs can cause acute kidney injury especially in patients with minimal change disease 1
• Stop ACEi or ARB if kidney function continues to worsen and/or refractory hyperkalemia develops 1
• For patients with nephrotic-range proteinuria at baseline, the time frames for improvement may be extended by 6–12 months due to slower proteinuria recovery 1
• Not accounting for the lag between treatment initiation and reduction in proteinuria can lead to premature treatment changes 3