What are the differences between nephrotic syndrome and nephritic syndrome, including their causes and diagnostic approaches?

Differences Between Nephrotic and Nephritic Syndrome

Nephrotic syndrome and nephritic syndrome are distinct glomerular disorders with different clinical presentations, underlying causes, and management approaches.

Key Differences

Feature	Nephrotic Syndrome	Nephritic Syndrome
Definition	Heavy proteinuria (>3.5g/24h), hypoalbuminemia (<3.0g/dL), edema, hyperlipidemia	Hematuria, proteinuria (usually non-nephrotic), hypertension, abnormal kidney function
Pathophysiology	Damage to podocytes and glomerular filtration barrier	Inflammation of glomeruli
Clinical Presentation	Peripheral edema, foamy urine, fatigue	Hematuria (tea/cola-colored urine), hypertension, oliguria
Prognosis	Variable depending on cause	Generally poorer than nephrotic syndrome [1]

Causes of Nephrotic Syndrome

Primary Causes

• Minimal change disease (most common in children)
• Focal segmental glomerulosclerosis (FSGS)
• Membranous nephropathy
• Membranoproliferative glomerulonephritis

Secondary Causes

• Diabetes mellitus
• Systemic lupus erythematosus
• Amyloidosis
• HIV infection
• Medications (NSAIDs, gold, penicillamine)
• Malignancies

Causes of Nephritic Syndrome

Primary Causes

• Post-infectious glomerulonephritis
• IgA nephropathy (most common cause globally)
• Rapidly progressive glomerulonephritis

Secondary Causes

• Lupus nephritis
• ANCA-associated vasculitis
• Anti-glomerular basement membrane disease
• Cryoglobulinemia
• Henoch-Schönlein purpura

Diagnostic Approach

Nephrotic Syndrome

1. Laboratory evaluation:

   • Urinalysis: Proteinuria, oval fat bodies, fatty casts
   • 24-hour urine protein: >3.5g/24h
   • Serum albumin: <3.0g/dL
   • Lipid profile: Elevated cholesterol and triglycerides
   • Renal function tests

2. Additional testing:

   • Screen for secondary causes (diabetes, lupus, HIV)
   • Genetic testing in suspected hereditary forms 2

3. Kidney biopsy:

   • Indicated in adults with nephrotic syndrome without clear etiology
   • May show diffuse foot process effacement in primary FSGS 3

Nephritic Syndrome

1. Laboratory evaluation:

   • Urinalysis: Hematuria, red cell casts, proteinuria
   • Complement levels (often low in post-infectious GN, lupus nephritis)
   • ANCA, anti-GBM antibodies
   • Renal function tests

2. Additional testing:

   • Streptococcal antibody titers (ASO, anti-DNase B)
   • ANA, anti-dsDNA for lupus

3. Kidney biopsy:

   • Often necessary to determine specific cause and guide treatment

Management Approach

Nephrotic Syndrome

1. Supportive care:

   • Edema management with diuretics
   • ACE inhibitors or ARBs for proteinuria
   • Statins for hyperlipidemia
   • Anticoagulation in high-risk patients (albumin <20g/L) 2

2. Disease-specific therapy:

   • Primary FSGS: High-dose oral glucocorticoids (1mg/kg/day) for 4-16 weeks 3
   • Steroid-resistant cases: Consider calcineurin inhibitors 3
   • Genetic forms: Focus on supportive care rather than immunosuppression 2

Nephritic Syndrome

1. Supportive care:

   • Blood pressure control
   • Management of acute kidney injury if present

2. Disease-specific therapy:

   • Post-infectious GN: Antimicrobial therapy for underlying infection
   • IgA nephropathy: ACE inhibitors/ARBs, consider corticosteroids for persistent proteinuria
   • ANCA-associated vasculitis: Cyclophosphamide or rituximab plus corticosteroids 2
   • Lupus nephritis: Mycophenolate mofetil or cyclophosphamide plus glucocorticoids 2

Common Pitfalls to Avoid

1. Treating genetic forms of nephrotic syndrome with immunosuppression
2. Inadequate thromboprophylaxis in high-risk nephrotic patients
3. Overreliance on serum albumin levels alone for fluid management
4. Failure to monitor for infections in immunosuppressed patients
5. Delaying genetic testing in suspected congenital/infantile cases 2

Monitoring

Regular monitoring should include:

• Body weight and blood pressure
• Renal function (eGFR, serum creatinine)
• Proteinuria
• Serum albumin
• Urinary sediment
• Growth velocity in pediatric patients 2

Response assessment should evaluate for complete response (return of serum creatinine to baseline and decline in proteinuria) or partial response (stabilization of serum creatinine but persistent proteinuria) 2.