Nephrotic Syndrome
Dr. Raid Jastania
Causes
• Minimal Change disease (lipoid nephrosis)
• Membranous glomerulonephritis
• Focal segmental glomerulosclerosis
• Membranoproliferative glomerulonephritis
Minimal Change GN
Focal Segmental
GN
Membranous GN
Membrano-proliferative GN
Good Prognosis
Bad Prognosis
Minimal Change Disease
• Clinical presentation
Minimal Change Disease
• Most common cause of nephrotic syndrome in children 2-3 years
Minimal Change Disease
• Pathogenesis
Minimal Change Disease
• Pathogenesis:
• Disorder of T-cells
• Suspected mediators of epithelial cell injury:– IL-8, TNF
• Nephrin gene mutation
Minimal Change Disease
• Light Microscopy
Minimal Change Disease
• Light Microscopy
–Normal
–Lipoid Nephrosis
Minimal Change Disease
• Immuno Fluorescence:
Minimal Change Disease
• Immuno Fluorescence:
–Negative
Minimal Change Disease
• Electron Microscopy:
Minimal Change Disease
• Electron Microscopy:
–Loss of Foot Processes of epithelial cells
–Uniform and Diffuse
Minimal Change Disease
• Prognosis
Minimal Change Disease
• The changes are reversible
• 90% respond to steroid
• May recur
• 5% progress to CRF
Membranous Glomerulonephritis
• Clinical Presentation
Membranous Glomerulonephritis
• Nephrotic syndrome
• Non-selective proteinuria
• 30-50 years of age
Membranous Glomerulonephritis
• Primary or Secondary
Membranous Glomerulonephritis
• Primary or Secondary– 85% 15%
» 1. Infections (HepB, malaria)» 2. Cancer (Lung ca, colon ca)» 3. SLE» 4. Gold, mercury» 5. Drugs (penicillamine, capropril,
NSAID’s)
Membranous Glomerulonephritis
• Pathogenesis
Membranous Glomerulonephritis
• Pathogenesis
• Immune complex
–Mostly: In-situ
–Few: Circulating
• Complement activation (MAC)
Membranous Glomerulonephritis
• Light microscopy:
Membranous Glomerulonephritis
• Light microscopy:
• Thick GBM (diffuse)
• Spikes
Membranous Glomerulonephritis• Electron microscopy:
Membranous Glomerulonephritis
• Electron microscopy:
• Sub-epithelial deposits
Membranous Glomerulonephritis
• Immuno Fluorescence:
Membranous Glomerulonephritis
• Immuno Fluorescence:
• Ig, comp. deposits
Membranous Glomerulonephritis
• Prognosis
Membranous Glomerulonephritis
• Less response to steroid
• 40% progress to CRF
Minimal Change GN
Focal Segmental
GN
Membranous GN
Membrano-proliferative GN
Good Prognosis
Bad Prognosis
Focal Segmental Glomerulosclerosis
• Primary or Secondary
Focal Segmental Glomerulosclerosis
• Primary or Secondary
»1. Infections (HIV)
»2. Drugs/Toxins (Heroin)
»3. Inherited
»4. Progress from other GN
Focal Segmental Glomerulosclerosis
• Pathogenesis
Focal Segmental Glomerulosclerosis
• Pathogenesis:
• Relation to Minimal change GN
• Progression from other GN
• Ablation nephropathy
Focal Segmental Glomerulosclerosis
• Light microscopy
Focal Segmental Glomerulosclerosis
• Light microscopy:
• Hyalinosis/Sclerosis
Focal Segmental Glomerulosclerosis
• Immuno Fluorescence:
Focal Segmental Glomerulosclerosis
• Immuno Fluorescence:
• IgM, Comp.
Focal Segmental Glomerulosclerosis
• Electron Microscopy:
Focal Segmental Glomerulosclerosis
• Electron Microscopy:
• Not specific
• Deposits in areas of hyalinosis
• Epithelial cell detachment
Focal Segmental Glomerulosclerosis
• Prognosis
Focal Segmental Glomerulosclerosis
• 50% progress to CRF
• Recurrence in transplant
• Collapsing FSGS
Membranoproliferative Glomerulonephritis
• Clinical presentation
Membranoproliferative Glomerulonephritis
• Nephrotic, Nephritic-Nephrotic
Membranoproliferative Glomerulonephritis
• Light Microscopy:
Membranoproliferative Glomerulonephritis
• Light Microscopy:
• Thick GBM
• Tram-Track
• Large Glomeruli
• Mesangial proliferation
Membranoproliferative Glomerulonephritis
• Electron Microscopy:
Membranoproliferative Glomerulonephritis
• Electron Microscopy:
• Type I: sub-endothelial deposits
• Type II: dense-deposit disease (within GBM)
Membranoproliferative Glomerulonephritis
• Immuno Fluorescence:
Membranoproliferative Glomerulonephritis
• Immuno Fluorescence:
• Type I: Ig, Comp.
• Type II: C3 only, may be Ig
Membranoproliferative Glomerulonephritis
• Prognosis:
Membranoproliferative Glomerulonephritis
• Prognosis:
• Disease persists or progress to CRF
Minimal Change GN
Focal Segmental
GN
Membranous GN
Membrano-proliferative GN
Good Prognosis
Bad Prognosis