What is the initial management for a patient with nephrotic syndrome, hypertension, and impaired renal function?

Initial Management of Nephrotic Syndrome with Hypertension and Renal Failure

Start an ACE inhibitor or ARB at maximally tolerated dose as first-line therapy, targeting systolic blood pressure <120 mmHg, while implementing strict sodium restriction to <2.0 g/day and managing edema with loop diuretics. 1

Blood Pressure Management

Target systolic blood pressure <120 mmHg using standardized office measurement. 1 In practice, achieving 120-130 mmHg is realistic in most patients with glomerular disease. 1

ACE Inhibitor/ARB Therapy

• Uptitrate to maximally tolerated or allowed daily dose as first-line therapy for both hypertension and proteinuria reduction 1
• Do not discontinue if serum creatinine rises modestly (up to 30%) and remains stable 1
• Stop ACE inhibitor/ARB only if kidney function continues to worsen or refractory hyperkalemia develops 1
• Critical caveat: Do not start ACE inhibitor/ARB in patients with abrupt onset nephrotic syndrome, as these drugs can cause acute kidney injury, especially in minimal change disease 1

Managing Hyperkalemia to Continue RAS Blockade

• Use potassium-wasting diuretics (loop or thiazide diuretics) to reduce serum potassium to normal range 1
• Consider potassium-binding agents (patiromer, sodium zirconium cyclosilicate) to allow continued use of ACE inhibitor/ARB 1
• Treat metabolic acidosis if serum bicarbonate <22 mmol/L, as acidosis worsens hyperkalemia 1

Edema Management

Start loop diuretics (furosemide or bumetanide) as first-line therapy for edema. 1

Diuretic Strategy

• Begin with loop diuretics alone (bolus or continuous infusion) 1
• If insufficient response, add thiazide diuretics for sequential nephron blockade 1
• Monitor closely for volume depletion, hyponatremia, hypokalemia, and GFR reduction 1

Diuretic-Resistant Edema

For patients not responding to standard diuretics: 1

• Add amiloride (reduces potassium loss and may improve diuresis)
• Add acetazolamide (treats metabolic alkalosis but weak diuretic effect)
• Consider loop diuretics combined with intravenous albumin
• Consider ultrafiltration or hemodialysis in severe cases

Lifestyle Modifications

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) as this is synergistic with pharmacologic therapy for controlling hypertension and proteinuria. 1

Additional measures: 1

• Normalize body weight
• Stop smoking
• Regular exercise

Intensify sodium restriction further in patients failing to achieve proteinuria reduction despite maximally tolerated medical therapy. 1

Patient Education on Medication Safety

Counsel patients to hold ACE inhibitor/ARB and diuretics during intercurrent illnesses when at risk for volume depletion (gastroenteritis, fever, reduced oral intake). 1 Consider transiently stopping RAS inhibitors during sick days. 1

Monitoring Requirements

Monitor labs frequently when on ACE inhibitor or ARB therapy: 1

• Serum creatinine
• Serum potassium
• Proteinuria levels

Additional Cardiovascular Risk Management

Hyperlipidemia Treatment

Consider starting a statin as first-line therapy for persistent hyperlipidemia, particularly in patients with additional cardiovascular risk factors including hypertension. 1 Reduced eGFR and albuminuria independently increase atherosclerotic cardiovascular disease risk. 1

Refractory Hypertension

Consider mineralocorticoid receptor antagonists (spironolactone or eplerenone) in refractory cases, with careful monitoring for hyperkalemia. 1

Common Pitfalls to Avoid

• Do not prematurely discontinue ACE inhibitor/ARB for modest creatinine increases up to 30% if stable 1
• Do not start ACE inhibitor/ARB in abrupt-onset nephrotic syndrome without first ruling out minimal change disease 1
• Do not neglect patient education about holding RAS inhibitors and diuretics during volume depletion risk 1
• Do not ignore hyperkalemia management, as this often limits optimal RAS blockade dosing 1