Nephotic vs Nephritic disease

Kidney diseases can present in a variety of ways, but two of the most commonly encountered syndromes in clinical practice are nephrotic syndrome and nephritic syndrome. Though they may sound similar, they are distinct entities with different causes, clinical features, and treatment approaches.

What Are Nephrotic and Nephritic Syndromes?

Nephrotic Syndrome

Nephrotic syndrome is a glomerular disease characterized by significant protein loss in the urine. It results from damage to the glomerular filtration barrier, especially the podocytes, which leads to increased permeability to proteins.

Key Features:

• Massive proteinuria (>3.5 g/day)
• Hypoalbuminemia
• Generalized edema (often starting in the face or lower limbs)
• Hyperlipidemia and lipiduria
  • Oval fat bodies

Nephrotic Syndrome - "O" for protein lOss

Nephritic Syndrome

Nephritic syndrome, on the other hand, is typically an inflammatory process affecting the glomeruli. It leads to reduced glomerular filtration and leakage of red blood cells into the urine.

Key Features:

• Hematuria (often with red blood cell casts)
• Mild to moderate proteinuria (<3.5 g/day)
• Hypertension
• Azotemia (elevated BUN/creatinine)
• Oliguria

Nephritic Syndrome - "I" for Inflammatory Injury

What Causes These Syndromes?

Nephrotic Syndrome:

• Minimal Change Disease (especially in children)
  • Most common cause in children
    • Peri-orbital edema
  • Etiology: T-cell cytokine-mediated podocyte injury → effacement of foot processes
  • Labs: Selective albuminuria
  • Electron microscopy: Effacement of podocyte foot processes; light microscopy is usually normal
  • Responds very well to corticosteroids
• Focal Segmental Glomerulosclerosis (FSGS)
  • Common in African American adults, HIV patients, and those with heroin use or obesity
  • Etiology: Segmental sclerosis in some glomeruli; podocyte injury is hallmark
  • Poor steroid response; may progress to end stage renal disease
• Membranous Glomerulonephritis
  • Most common cause in adults
  • Primary: Autoantibodies against PLA2R receptor on podocytes
  • Secondary: SLE (class V), hepatitis B/C, solid tumors, NSAIDs, syphilis
  • Histology: Thickened capillary walls, "spike and dome" on silver stain; subepithelial deposits
• Diabetic Nephropathy
  • Most common overall cause of nephrotic syndrome in adults
  • Pathology: Mesangial expansion, GBM thickening, Kimmelstiel-Wilson nodules
  • Microalbuminuria → overt proteinuria → End stage renal disease
• Amyloidosis
  • Amyloid deposits in glomeruli stain with Congo red (apple-green birefringence)
  • Associated with multiple myeloma, chronic inflammatory conditions

Nephritic Syndrome:

• Rapidly Progressive Glomerulonephritis (RPGN)
  • Medical emergency with rapid renal failure
  • Histology: Crescent formation on LM
  • Subtypes based on immunofluorescence:
    • Type I: Anti-GBM disease (e.g., Goodpasture’s) – anti-GBM antibodies + hemoptysis
    • Type II: Immune complex (e.g., PSGN, SLE, IgA nephropathy)
    • Type III: Pauci-immune (e.g., ANCA-associated vasculitis – GPA, MPA, EGPA)
• Post-streptococcal glomerulonephritis (PSGN)
  • Children, ~2-4 weeks after group A strep pharyngitis or skin infection
  • Pathogenesis: Immune complex deposition (IgG, IgM, C3) - type 3 hypersensitivity reaction
  • Clinical: Hematuria ("tea-colored urine"), periorbital edema, hypertension
  • Labs: ↓ C3, ↑ anti-streptolysin O (ASO) titers
  • Light microscopy: Hypercellular glomeruli
  • EM: Subepithelial humps
• IgA nephropathy (Berger’s disease)
  • Most common glomerulonephritis worldwide
  • Typically within days of URI or GI infection (vs. PSGN)
  • Pathogenesis: IgA immune complex deposition in mesangium - type 3 hypersensitivity reaction
  • Can progress to RPGN or chronic kidney disease
• Lupus nephritis
  • Class III: Focal proliferative GN (some glomeruli)
  • Class IV: Diffuse proliferative GN (most glomeruli)
  • Full-house IF: IgG, IgA, IgM, C3, C1q
  • Associated with low complement and positive anti-dsDNA
• Alport syndrome
  • Hereditary nephritis due to mutations in type IV collagen
  • X-linked most common
  • Clinical: Hematuria, sensorineural hearing loss, ocular abnormalities
  • EM: "Basket-weave" GBM appearance

Membranoproliferative Glomerulonephritis (MPGN)

• Can present with nephrotic, nephritic, or mixed features
• Type I: Subendothelial immune complex deposits, often associated with Hep C
• Type II (Dense Deposit Disease): Due to C3 nephritic factor, overactivation of the alternative complement pathway

Treatment

Nephrotic Syndrome:

• Steroids (especially in minimal change disease)
• Immunosuppressants (e.g., cyclophosphamide, cyclosporine)
• ACE inhibitors/ARBs to reduce proteinuria
• Diuretics for edema
• Statins for hyperlipidemia

Nephritic Syndrome:

• Antihypertensives
• Diuretics for fluid control
• Steroids or immunosuppressants, depending on the cause
• Antibiotics (e.g., for post-infectious causes)
• Plasmapheresis in severe cases like RPGN