What is the initial management for a patient with nephrotic syndrome (NS) experiencing fluid overload?

Management of Fluid Overload in Nephrotic Syndrome

Loop diuretics are the cornerstone of initial management for fluid overload in nephrotic syndrome, but must be used cautiously and only when true intravascular volume overload is present (evidenced by good peripheral perfusion and hypertension), as aggressive diuresis can precipitate hypovolemia and thrombosis. 1

Critical Initial Assessment: Distinguish Intravascular Status

Before initiating diuretics, you must differentiate between:

• True intravascular overload (good peripheral perfusion, hypertension, adequate urine output) → Safe to use diuretics 1
• Hypovolemia with peripheral edema (prolonged capillary refill, tachycardia, hypotension, oliguria, abdominal discomfort) → Diuretics are contraindicated and may worsen outcomes 1

This distinction is critical because nephrotic syndrome causes paradoxical states where massive peripheral edema coexists with intravascular volume depletion. 1

First-Line Diuretic Management

Initial Therapy

Start with intravenous loop diuretics as first-line therapy for confirmed volume overload. 1

• Furosemide 0.5-2 mg/kg IV bolus initially 1
• For severe edema: escalate to 0.5-2 mg/kg per dose IV or oral, up to 6 times daily (maximum 10 mg/kg/day) 1
• Twice-daily dosing is preferred over once-daily for better efficacy 1
• Administer IV infusions over 5-30 minutes to prevent ototoxicity 1, 2

Critical Safety Threshold

High-dose furosemide (>6 mg/kg/day) should NOT be given for longer than 1 week due to permanent hearing loss risk 1, 3

Alternative Loop Diuretics

Consider switching to bumetanide or torsemide if furosemide fails, particularly when intestinal wall edema impairs oral bioavailability 1

Combination Diuretic Therapy for Resistant Edema

When loop diuretics alone are insufficient:

Add Thiazide-Type Diuretics

Combine loop diuretics with thiazide diuretics for synergistic distal tubule blockade 1

• All thiazide-like diuretics in high doses are equally effective; none is preferred 1
• Metolazone is commonly used in clinical practice 1

Potassium-Sparing Diuretics: Amiloride Over Spironolactone

If adding potassium-sparing agents, use amiloride rather than spironolactone 1

The rationale: Urinary proteases (plasmin) directly activate epithelial sodium channels (ENaC) independent of mineralocorticoid receptors in nephrotic syndrome, making ENaC blockers like amiloride mechanistically superior to spironolactone. 1

Acetazolamide for Refractory Cases

Consider adding acetazolamide for diuretic-resistant edema, especially with concurrent metabolic alkalosis or hypercapnia 1, 4

Albumin Infusion Strategy

When to Use Albumin

Albumin infusions should be based on clinical indicators of hypovolemia, NOT serum albumin levels 1

Indications for albumin:

• Oliguria with acute kidney injury 1
• Prolonged capillary refill time, tachycardia, hypotension 1
• Abdominal discomfort suggesting hypovolemia 1
• Failure to thrive (particularly in children) 1

Albumin Dosing

• Severe disease: 1-4 g/kg daily 1
• Marked hypoalbuminemia (<1.5-2 g/dL): Consider albumin to facilitate diuresis 1

Albumin-Furosemide Combination

When using albumin, administer furosemide 0.5-2 mg/kg IV bolus at the END of each albumin infusion (in absence of hypovolemia or hyponatremia) 1, 2

This timing maximizes intravascular oncotic pressure before promoting diuresis. 2

Adjunctive Measures

Sodium Restriction

Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1

ACE Inhibitors/ARBs

Uptitrate ACE inhibitors or ARBs to maximally tolerated doses for antiproteinuric effect 1

• Do not stop with modest stable creatinine increases (up to 30%) 1
• Avoid initiating in acute presentations with abrupt-onset nephrotic syndrome (risk of acute kidney injury, especially in minimal change disease) 1

Blood Pressure Targets

Target systolic blood pressure <120 mmHg in most adults 1

Essential Monitoring Requirements

Monitor closely during active diuresis: 1

• Fluid status and daily weights
• Electrolytes (hypokalemia, hyponatremia, hyperkalemia with amiloride)
• Blood pressure (supine and standing)
• Renal function (creatinine, estimated GFR)
• Urine output

Critical Contraindications and Pitfalls

Absolute Contraindications to Diuretics

Stop furosemide immediately in anuria 1

Common Pitfalls to Avoid

• Never use diuretics in hypovolemic states (prolonged capillary refill, hypotension, oliguria) as this promotes thrombosis 1
• Avoid intravenous fluids and saline in nephrotic syndrome; concentrate oral intake instead 1
• Do not combine ACE inhibitors with ARBs in older adults or those with diabetes/cardiovascular disease due to safety concerns 1
• Prophylactic anticoagulation is NOT routinely recommended for nephrotic syndrome alone (only for specific high-risk situations like membranous nephropathy with severe hypoalbuminemia) 5, 6

Refractory Volume Overload

For truly diuretic-resistant cases despite maximal medical therapy:

• Loop diuretics with IV albumin 1
• Continuous IV loop diuretic infusion rather than boluses 1
• Ultrafiltration or hemodialysis for severe refractory cases 1
• Consider tolvaptan (vasopressin V2 receptor antagonist) in diabetic nephropathy with preserved cardiac function unresponsive to furosemide 7