Nephrotic Syndrome
Disease Minimal Change Disease Membranous Nephropathy Focal Segmental GS Membranoproliferative GN Ig
Epidemiology - Most common cause in - Most common cause in adults - Most common cause in black - MIXED nephritic & nephrotic - Men
children (90%) - 1-7 y.o. - Peak age → 30-40 adults - 10% of all GN cases - 80%
- Adolescents (50%) - Men > women - Most common cause of primary - In both children & adults - Mos
- Men > women ESRD - Most association w/ secondary causes
Etiology - Idiopathic (80%) - Idiopathic - Idiopathic - Immune complex-mediated IgA1 in
- Secondary: - Secondary: ● Mutations in black ● MPGN I → SLE, HCV, MGUS can't b
● Infection - HIV, vaccine ● Autoimmune diseases populations: APOL1 - Complement mediated
● Drugs & toxins ○ SLE - Secondary - Idiop
● MPGN II (C3 glomerulopathy)
● Tumor - Hodgkin ● Malignancy ● Sickle cell anemia - ↑ ris
→ C3 nephritic factor or FH/I mutation
● Infections ● Heroin use - HIV or HCV ●
● MPGN III
● Drugs ● Other forms of GN - MCD ●
● Nephron loss maladaptation ●
●
Pathophysiology - CD4 T cell disorder → cytokine - Antigens against podocyte - Can be linked to MCD history - Immune-complex mediated - Circu
proteins (PLA2R) → - Primary: Putative circulating factor ● Classical pathway activation
release → foot process injury → compl
toxic to podocyte ● Ig predominant staining
↓polyanions (-) Immunocomplex deposition in foreign
- Adaptive response to hyperfiltration - Complement-mediated
- Selective: albuminuria epimembranous space seen in nephron loss, obesity, ● C3 nephritic factor blocks C3 glycos
- IL-13 polymorphism → ↑↑↑ ● Membrane thickening diabetes, and hypertension
convertase degradation → Alternative pathw
● Complement activation - TGFβ → Macrophage infiltration &
- Other IL: 12 & 18 → vascular pathway - Asso
● GBM and slit diaphragm
permeability injury ECM accumulation = sclerosis ● C3 predominant staining or g.i.
- Foot process proteins genetic ● DDD→ Intramembranous deposits - Syste
- Altered T cell function → ↑IL-4 kidney
variants (nephrin, podocin) ● C3 GN → Mesangial, subendothelial, &
● ↑IgG4 - Usua
subepithelial deposits infecti
→ GBM & mesangium alterations → At
synph
Characteristic - Upper respiratory tract - Insidious onset - Acute onset if primary - BOTH hematuria and nephrotic proteinuria - Pers
clinical features infection, drugs or malignancies hemat
- Facial edema → first sign hemat
Light Microscopy - No glomerular changes - Diffuse thickening of capillary - Segmental areas of sclerosis in - Hypercellularity, mesangial expansion, - Mesa
- Lipid droplets in PCT SOME glomeruli thickening of capillary wall, GBM duplication - Seve
wall → "wire looping"
- Can use silver stain cresce
#
Disease Minimal Change Disease Membranous Nephropathy Focal Segmental GS Membranoproliferative GN Ig
Epidemiology - Most common cause in - Most common cause in adults - Most common cause in black - MIXED nephritic & nephrotic - Men
children (90%) - 1-7 y.o. - Peak age → 30-40 adults - 10% of all GN cases - 80%
- Adolescents (50%) - Men > women - Most common cause of primary - In both children & adults - Mos
- Men > women ESRD - Most association w/ secondary causes
Etiology - Idiopathic (80%) - Idiopathic - Idiopathic - Immune complex-mediated IgA1 in
- Secondary: - Secondary: ● Mutations in black ● MPGN I → SLE, HCV, MGUS can't b
● Infection - HIV, vaccine ● Autoimmune diseases populations: APOL1 - Complement mediated
● Drugs & toxins ○ SLE - Secondary - Idiop
● MPGN II (C3 glomerulopathy)
● Tumor - Hodgkin ● Malignancy ● Sickle cell anemia - ↑ ris
→ C3 nephritic factor or FH/I mutation
● Infections ● Heroin use - HIV or HCV ●
● MPGN III
● Drugs ● Other forms of GN - MCD ●
● Nephron loss maladaptation ●
●
Pathophysiology - CD4 T cell disorder → cytokine - Antigens against podocyte - Can be linked to MCD history - Immune-complex mediated - Circu
proteins (PLA2R) → - Primary: Putative circulating factor ● Classical pathway activation
release → foot process injury → compl
toxic to podocyte ● Ig predominant staining
↓polyanions (-) Immunocomplex deposition in foreign
- Adaptive response to hyperfiltration - Complement-mediated
- Selective: albuminuria epimembranous space seen in nephron loss, obesity, ● C3 nephritic factor blocks C3 glycos
- IL-13 polymorphism → ↑↑↑ ● Membrane thickening diabetes, and hypertension
convertase degradation → Alternative pathw
● Complement activation - TGFβ → Macrophage infiltration &
- Other IL: 12 & 18 → vascular pathway - Asso
● GBM and slit diaphragm
permeability injury ECM accumulation = sclerosis ● C3 predominant staining or g.i.
- Foot process proteins genetic ● DDD→ Intramembranous deposits - Syste
- Altered T cell function → ↑IL-4 kidney
variants (nephrin, podocin) ● C3 GN → Mesangial, subendothelial, &
● ↑IgG4 - Usua
subepithelial deposits infecti
→ GBM & mesangium alterations → At
synph
Characteristic - Upper respiratory tract - Insidious onset - Acute onset if primary - BOTH hematuria and nephrotic proteinuria - Pers
clinical features infection, drugs or malignancies hemat
- Facial edema → first sign hemat
Light Microscopy - No glomerular changes - Diffuse thickening of capillary - Segmental areas of sclerosis in - Hypercellularity, mesangial expansion, - Mesa
- Lipid droplets in PCT SOME glomeruli thickening of capillary wall, GBM duplication - Seve
wall → "wire looping"
- Can use silver stain cresce
#
