What is the difference between nephritic and nephrotic syndrome?

Nephritic vs. Nephrotic Syndrome: Key Differences

Nephrotic syndrome and nephritic syndrome are distinct clinical entities with different pathophysiological mechanisms, clinical presentations, and management approaches. 1

Definition and Clinical Features

Nephrotic Syndrome

• Definition: Characterized by heavy proteinuria (>3.5g/24h), hypoalbuminemia (<3.0g/dL), edema, and hyperlipidemia 2, 1
• Clinical presentation:
  • Periorbital edema (most noticeable in the morning)
  • Dependent pitting edema (more common later in the day)
  • Fatigue without evidence of heart failure or severe liver disease 3, 4

Nephritic Syndrome

• Definition: Characterized by hematuria, proteinuria (typically non-nephrotic range), hypertension, and often acute kidney injury 5, 6
• Clinical presentation:
  • Hematuria (microscopic or gross)
  • Hypertension (often more severe than in nephrotic syndrome)
  • Variable proteinuria (typically <3.5g/day)
  • Fluid retention and edema
  • Often presents with acute kidney injury 6

Pathophysiology

Nephrotic Syndrome

• Primary defect: Damage to podocytes and glomerular basement membrane leading to increased permeability
• Results in massive protein loss in urine
• Hypoalbuminemia leads to decreased oncotic pressure causing edema
• Liver increases production of lipoproteins leading to hyperlipidemia 7

Nephritic Syndrome

• Primary defect: Inflammation of the glomeruli
• Inflammatory process causes damage to glomerular capillaries
• Results in leakage of red blood cells into urine (hematuria)
• Inflammatory damage causes reduced glomerular filtration rate
• Sodium and water retention leads to hypertension 6

Common Causes

Nephrotic Syndrome

• Children: Minimal change disease (most common) 1
• Adults:
  • White adults: Membranous nephropathy (most common)
  • African ancestry: Focal segmental glomerulosclerosis (most common)
  • Secondary causes: Diabetes mellitus (most common systemic cause), lupus, amyloidosis, medications 3, 4

Nephritic Syndrome

• Post-infectious glomerulonephritis (especially post-streptococcal)
• IgA nephropathy
• Lupus nephritis
• Membranoproliferative glomerulonephritis
• ANCA-associated vasculitis 5, 6

Laboratory Findings

Nephrotic Syndrome

• Proteinuria >3.5g/24h or urine protein:creatinine ratio (PCR) >300-350 mg/mmol
• Serum albumin <3.0g/dL
• Elevated lipids (cholesterol and triglycerides)
• Normal or mildly elevated serum creatinine
• Urinalysis may show oval fat bodies and fatty casts 2, 3

Nephritic Syndrome

• Hematuria (dysmorphic RBCs, RBC casts)
• Proteinuria (typically <3.5g/day)
• Elevated serum creatinine
• Urinalysis showing RBCs and RBC casts
• Possible low complement levels (C3, C4) in certain causes 5, 6

Management Approach

Nephrotic Syndrome

1. Supportive care:

   • Edema management with diuretics (furosemide 0.5-2 mg/kg)
   • ACE inhibitors or ARBs for proteinuria
   • Statins for hyperlipidemia (target LDL <100 mg/dL)
   • Anticoagulation in high-risk patients 1

2. Disease-specific therapy:

   • Primary FSGS: High-dose oral glucocorticoids (1mg/kg/day) for 4-16 weeks
   • Steroid-resistant cases: Consider calcineurin inhibitors 2, 1
   • Minimal change disease: Corticosteroids as first-line 1

Nephritic Syndrome

1. Supportive care:

   • Blood pressure control
   • Management of fluid overload
   • Monitoring kidney function 6

2. Disease-specific therapy:

   • Post-infectious GN: Antimicrobial therapy for underlying infection
   • IgA nephropathy: ACE inhibitors/ARBs, consider corticosteroids for persistent proteinuria
   • Lupus nephritis: Mycophenolate mofetil or cyclophosphamide plus glucocorticoids 1
   • ANCA-associated vasculitis: Cyclophosphamide or rituximab plus corticosteroids 1

Complications

Nephrotic Syndrome

• Venous thromboembolism
• Infections
• Acute kidney injury
• Malnutrition
• Hyperlipidemia and accelerated atherosclerosis 4

Nephritic Syndrome

• Rapidly progressive glomerulonephritis
• Hypertensive crisis
• Acute kidney injury progressing to chronic kidney disease
• Pulmonary edema 6

Monitoring and Follow-up

Both Syndromes

• Regular monitoring of:
  • Renal function (serum creatinine, GFR)
  • Proteinuria
  • Blood pressure
  • Edema
  • In children: growth velocity, especially with prolonged corticosteroid treatment 1

Pitfalls to Avoid

• Treating based on serum albumin levels alone rather than clinical indicators
• Overreliance on immunosuppression for genetic forms of nephrotic syndrome
• Fluid overload due to excessive fluid administration
• Inadequate thromboprophylaxis in high-risk patients
• Failure to monitor for and prevent infections in immunosuppressed patients 1

The distinction between nephrotic and nephritic syndromes is crucial for appropriate diagnosis, management, and prognosis. While there may be overlap in some cases, understanding the fundamental differences guides therapeutic decisions and helps predict outcomes.