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