What is nephrotic syndrome?

Nephrotic Syndrome

Nephrotic syndrome is characterized by a triad of clinical features: severe proteinuria (>3.5g/24 hours), hypoalbuminemia (<30g/L), and peripheral edema, often accompanied by hyperlipidemia. 1, 2

Definition and Pathophysiology

• Nephrotic syndrome results from pathological injury to renal glomeruli, causing breakdown of the glomerular filtration barrier and allowing excessive protein leakage into urine 2
• The condition can be primary (idiopathic) or secondary to systemic disorders such as diabetes mellitus 3
• Evidence suggests that primary T-cell disorders may be responsible for some forms of nephrotic syndrome, with a proposed T-cell-driven circulating factor that interferes with glomerular permeability to albumin 1

Primary Histologic Variants

• Three major histologic variants cause primary nephrotic syndrome: minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy 1
• The relative frequency of these subtypes varies considerably according to age and ethnicity 4
• In children, minimal change disease is the most common cause 5
• In white adults, membranous nephropathy is most frequent, while in populations of African ancestry, focal segmental glomerulosclerosis predominates 6

Clinical Presentation

• Patients typically present with peripheral edema, particularly periorbital edema in the morning or dependent pitting edema later in the day 6
• Fatigue is common, without evidence of serious liver damage or cardiac failure 2
• Diagnosis is confirmed by finding:
  • Proteinuria >3.5g/24 hours or urine protein:creatinine ratio >300-350 mg/mmol 6
  • Hypoalbuminemia <30g/L 2
  • Peripheral edema 3
  • Often hyperlipidemia 1

Complications

• Venous thromboembolism is a significant risk, particularly affecting deep veins of lower extremities and renal veins 7
• Pulmonary embolism is the most dangerous complication of nephrotic syndrome 7
• Increased risk of infections, particularly cellulitis and spontaneous bacterial peritonitis 1
• Accelerated coronary heart disease risk due to hyperlipidemia, hypertension, and hypercoagulability 1
• Prolonged nephrotic proteinuria can lead to renal scarring and eventual renal failure 4
• Patients with proteinuria >3.8g/day have a 35% risk of end-stage renal disease within 2 years 1

Management Approach

• Core management focuses on maintaining intravascular euvolemia, adequate nutrition, preventing complications, and preserving kidney function 8
• Diuretics (primarily furosemide 0.5-2 mg/kg per dose) are indicated for patients with intravascular fluid overload and preserved kidney function 8
• Avoid diuretics in patients with evidence of intravascular hypovolemia 8
• Prednisone is indicated to induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome 9
• Sodium and fluid restriction are appropriate for most patients 3
• ACE inhibitors or ARBs are recommended to reduce proteinuria 3

Special Considerations

• Renal biopsy is often recommended to guide management and prognosis, especially in adults or in cases with atypical features 3
• Renal biopsy is usually not indicated in children aged 1-10 years with typical symptoms who achieve complete remission with corticosteroids 5
• Immunosuppressive treatment, including corticosteroids, is often used though evidence for some regimens is limited 3
• Routine prophylactic treatment to prevent infection or thrombosis is not generally recommended 3

Pitfalls to Avoid

• Do not use immunosuppressive agents for genetic forms of congenital nephrotic syndrome as they are unlikely to respond 8
• Be cautious with diuretic dosing; excessive doses should not be given for extended periods 8
• Avoid albumin infusions except in cases with specific complications 5
• Do not delay nephrology consultation (ideally within 2 weeks) for patients with newly diagnosed nephrotic syndrome 6