Treatment of Persistent Proteinuria
For persistent proteinuria, first-line treatment should be an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) titrated to the maximally tolerated dose, with a target of reducing proteinuria to less than 1 g/day. 1
Initial Management Based on Proteinuria Severity
For Proteinuria >1 g/day:
- Long-term ACEi or ARB treatment is strongly recommended with uptitration of the drug depending on blood pressure response 1
- Target blood pressure should be <125/75 mmHg for optimal renal protection 1
- Titrate ACEi or ARB upward as far as tolerated to achieve proteinuria <1 g/day 1
- Monitor serum creatinine and potassium regularly; a modest increase in creatinine (up to 30%) is expected and should not prompt discontinuation 1, 2
For Proteinuria Between 0.5-1 g/day:
- ACEi or ARB treatment is still recommended but with less strong evidence 1
- Target blood pressure should be <130/80 mmHg 1, 2
- In children with proteinuria between 0.5-1 g/day/1.73m², ACEi or ARB is also recommended 1
Management of Persistent Proteinuria Despite Initial Therapy
If proteinuria persists ≥1 g/day despite 3-6 months of optimized supportive care (including maximally tolerated ACEi/ARB and blood pressure control):
- For patients with GFR >50 ml/min/1.73m², consider a 6-month course of corticosteroid therapy 1
- Consider adding fish oil as an adjunctive therapy 1
- Intensify dietary sodium restriction to <2.0 g/day to enhance antiproteinuric effects 1, 2
- For refractory cases, consider mineralocorticoid receptor antagonists (monitor closely for hyperkalemia) 1, 3
Special Considerations
For Patients with Reduced Renal Function:
- Avoid immunosuppressive therapy in patients with GFR <30 ml/min/1.73m² unless there is crescentic glomerulonephritis with rapidly deteriorating kidney function 1
- Adjust medication doses according to renal function 1
- Use potassium-wasting diuretics and/or potassium-binding agents to manage hyperkalemia when using RAS blockers 1, 2
For Specific Glomerular Diseases:
- In IgA nephropathy with persistent proteinuria ≥1 g/day despite optimal supportive care and GFR >50 ml/min/1.73m², a 6-month course of corticosteroids is suggested 1
- For crescentic IgA nephropathy (>50% crescents with rapidly progressive renal deterioration), steroids and cyclophosphamide are recommended 1
- For Henoch-Schönlein purpura nephritis, treatment approach should be similar to IgA nephropathy 1
Lifestyle Modifications
- Restrict dietary sodium to <2.0 g/day to enhance antiproteinuric effects of medications 1, 2
- Normalize weight through appropriate diet and exercise 1, 3
- Stop smoking 1
- Exercise regularly 1
Monitoring and Follow-up
- Monitor proteinuria, blood pressure, and eGFR regularly to assess response to therapy and risk of progression 1
- Monitor serum potassium and creatinine frequently when on ACEi or ARB therapy 1, 2
- Counsel patients to temporarily hold ACEi/ARB and diuretics during periods of volume depletion (illness with vomiting/diarrhea) 1, 3
- Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%) unless kidney function continues to worsen or refractory hyperkalemia develops 1, 2
Common Pitfalls and Caveats
- Failure to titrate ACEi/ARB to maximally tolerated doses before adding other therapies 1, 4
- Inadequate sodium restriction limiting the antiproteinuric effect of medications 1, 2
- Premature discontinuation of ACEi/ARB due to expected modest increases in serum creatinine 1, 2
- Inadequate monitoring of potassium levels when using RAS blockade, particularly in patients with reduced GFR 1, 5
- Failure to recognize and treat underlying causes of proteinuria before initiating symptomatic therapy 3, 6