Treatment of Proteinuria with Renin-Angiotensin System Blockade

First-Line Therapy

The American College of Cardiology recommends using ACEi or ARB to maximally tolerated or allowed dose as first-line therapy in treating patients with both hypertension and proteinuria 1
The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest uptitrating an ACEi or ARB to maximally tolerated or allowed daily dose as first-line therapy in treating patients with glomerulonephritis and proteinuria alone 3
Do not stop ACEi or ARB with modest and stable increase in serum creatinine (up to 30%) as this is an expected effect 1

The American Heart Association recommends targeting systolic blood pressure in most adult patients at <120 mm Hg using standardized office BP measurement 2
For patients with glomerular disease, a practical target is SBP of 120-130 mm Hg in most patients 2
For children, target 24-hour mean arterial pressure at the 50th percentile for age, sex, and height by ambulatory blood pressure monitoring 2

The National Kidney Foundation recommends long-term ACEi or ARB treatment for persistent proteinuria >1 g/day 4, 5
Blood pressure target should be 125/75 mmHg for patients with persistent proteinuria >1 g/day 5
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 4

Intensify dietary sodium restriction to <2.0 g/d (<90 mmol/d) for patients who fail to achieve proteinuria reductions on maximally tolerated therapy 1, 6
Consider using mineralocorticoid receptor antagonists in refractory cases (monitor for hyperkalemia) 6
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

Employ lifestyle modifications in all patients as synergistic means for improving control of hypertension and proteinuria, including restricting dietary sodium to <2.0 g/d (<90 mmol/d), normalizing weight, stopping smoking, and exercising regularly 1, 6

For lupus nephritis, combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide) is recommended for nephrotic-range proteinuria 7
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 6

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 8