Clinical Manifestations
Primary Clinical Features
- Edema: Initially periorbital (especially in the morning) and dependent areas (ankles, feet) that progresses to generalized edema and anasarca in severe cases. Caused by decreased plasma oncotic pressure due to hypoalbuminemia.
- Proteinuria: Massive protein loss in urine (>3.5g/24hrs) leads to frothy or foamy urine. This is the hallmark diagnostic finding.
- Hypoalbuminemia: Serum albumin levels drop below 3.0 g/dL due to urinary losses, resulting in decreased oncotic pressure in the vascular space.
- Hyperlipidemia: Elevated cholesterol and triglycerides occur due to increased hepatic synthesis of lipoproteins and decreased catabolism.
Key Points
- Edema is typically pitting and may be severe enough to cause ascites, pleural effusions, or genital edema
- Frothy urine is a classic patient-reported symptom that should prompt evaluation
Complications
- Thromboembolism: Patients have increased risk of venous thrombosis and pulmonary embolism due to urinary loss of anticoagulant proteins and increased production of procoagulant factors.
- Infections: Increased susceptibility to infections, particularly pneumonia and cellulitis, due to urinary loss of immunoglobulins and complement proteins.
- Acute kidney injury: May develop from hypovolemia, nephrotoxic medications, or progression of the underlying disease.
- Malnutrition: Protein malnutrition can occur due to persistent protein losses.
Key Points
- Hypercoagulable state increases risk of deep vein thrombosis and renal vein thrombosis
- Immunocompromised state requires vigilant monitoring for signs of infection
Clinical Scenario
A 7-year-old boy presents with periorbital edema that is worse in the morning, and ankle swelling that worsens throughout the day. His mother reports his urine appears "foamy." Physical examination reveals generalized edema and mild hypertension. Urinalysis shows 4+ protein, but no hematuria. Serum albumin is 1.8 g/dL, and cholesterol is 320 mg/dL. This presentation is classic for minimal change disease, the most common cause of nephrotic syndrome in children.
Treatment and Management
General Management Principles
- Dietary modifications: Moderate sodium restriction (2-3g/day) to control edema; protein intake of 0.8-1.0 g/kg/day to replace urinary losses while avoiding excessive protein load on kidneys.
- Edema management: Judicious use of loop diuretics (furosemide) for symptomatic edema; severe cases may require combination diuretic therapy.
- Anticoagulation: Prophylactic anticoagulation may be considered in patients with severe hypoalbuminemia (<2.0 g/dL) or other risk factors for thrombosis.
- Hyperlipidemia management: Statins for persistent hyperlipidemia, especially in adults.
Key Points
- Diuretics should be used cautiously as patients may be intravascularly depleted despite edema
- Albumin infusions may be given before diuretics in severe hypoalbuminemia to enhance diuretic efficacy
Specific Treatments Based on Etiology
- Minimal Change Disease: Corticosteroids (prednisone) are first-line therapy with 80-90% response rate in children. Typical regimen is prednisone 2 mg/kg/day (max 60 mg) for 4-6 weeks, followed by alternate-day therapy.
- Focal Segmental Glomerulosclerosis: Corticosteroids for 3-6 months; calcineurin inhibitors (cyclosporine, tacrolimus) for steroid-resistant cases.
- Membranous Nephropathy: Cyclical therapy with corticosteroids and cytotoxic agents (cyclophosphamide); calcineurin inhibitors; rituximab for resistant cases.
- Secondary causes: Treatment directed at underlying disease (e.g., glycemic control for diabetic nephropathy, antivirals for viral hepatitis).
Key Points
- Steroid response in minimal change disease typically occurs within 1-2 weeks
- Steroid-resistant nephrotic syndrome requires kidney biopsy if not already performed
Supportive Care and Monitoring
- Monitor daily weights to assess fluid status
- Measure urine protein regularly to evaluate response to therapy
- Check serum albumin, electrolytes, and renal function periodically
- Administer pneumococcal vaccination due to increased infection risk
- Educate patient/family about medication adherence and signs of relapse
- Counsel on avoiding nephrotoxic medications (NSAIDs)
Key Points
- Daily weight is the most practical measure of fluid status changes
- Relapse is common (50-70% in minimal change disease) and indicated by recurrence of proteinuria
Important Nursing Considerations
Monitor for signs of thromboembolism (leg pain/swelling, chest pain, shortness of breath) due to hypercoagulable state. Assess for early signs of infection as immunosuppressive therapy increases infection risk. Evaluate for medication side effects, particularly cushingoid features with prolonged steroid use.