R10 Glomerular Diseases II

• Goodpasture's Disease
• -crescentic GN (anti-GBM+)

• Systemic Vasculitis
• -MP, WG, CS syndrome
• -Proliferative GN (ANCA+)
• -±crescents, ±vasculitis

• SLE
• -ANA+

• Henoch-Schonlein disease
• -proliferative GN (IgA)

• 
• -destruction of elastin
• -heavy lymphocytic infiltrate

• WHO class
• 1. Minimal (no tx)
• 2. Mesangial (no tx)
• 3. Focal Proliferative (steroids or none)
• 4. Diffuse Proliferative (steroids/ mycophenolate/ cyclophosphamide/ plasmapheresis)
• -crescentic
• -membranoproliferative
• 5. Membranous (steroids or none)

• 
• 

• Pathophysiology:
• 1. Mucosal antigen presentation
• 2. Abnormal IgA response
• 3. Circulating Ag:Ab complexes (IgA)
• 4. Mesangial IgA deposition/involvement of skin, joints, GI tract etc

• HIV Nephropathy
• -HIV infects renal cells (?)
• -infection leads to disregulated cytokine production (?)
• -common pathophysiology

• Heroin Nephropathy
• -mesangial deposition of foreign material from blood stream (?)
• -Mesangial reaction (?)
• -common pathophysiology

• Common Pathophysiology:
• -abnormal accumulation of hyaline material focally and segmentally within glomeruli
• -histology similar to idiopathic focal glomerulosclerosis
• -nephrotic syndrome and progressive renal failure

• 1. Alport Syndrome
• 2. Thin Basement Membrane Disease (benign familial hematuria syndrome)
• 3. Genetic Podocythopathies
• -Congenic nephrotic syndrome
• -steroid-resistant nephrotic syndrome
• -FSG1
• -FSG2

-genetic defects of alpha chains of type IV collagen (2 alpha chains on X chromosome, 4 on autosomes)

-mixed picture of autosomal dominant with greater penetrance in males

-defective structure of GBM

-sclerosing glomerular lesions with foam cells, interstitial lesions

• Sx:
• -hematuria
• -proteinuria
• -progressive renal failure

• Associated congenital sx:
• -nerve deafness
• -ocular abnormalities

"Benign Familial Hematuria Syndrome"

• -autosomal dominant inheritance
• -seen in siblings

• Presentation:
• -congenitally thin GBM
• -minor histological abnormalities
• -recurrent episodes of hematuria

*doesn't usually cause a decline in renal function

• 

• -cause FSGS-like lesions
• 

• Congenic nephrotic syndrome:
• -nephrin

• Steroid-Resistant:
• -Podocin

• FSG 1:
• -α actinin 4

• FSG 2:
• -TRP C6

-Diabetic Nephropathy

• Epidemiology:
• -fastest growing cause of ESRD
• -> 1/3 of ESRD cases
• -10% DM1, 90% DM2
• -40-50% DM1, 10-20% DM2 develop diabetic nephropathy

• Diabetic Nephropathy
• -progressive azotemia
• -proteinuria
• -edema
• -HTN

• Pathology:
• 
• -diffuse (mesangial thickening)

• 
• -Nodular (Kimmelstein-Wilson lesions)
• 

• Natural History:
• -starts out early with an increased GFR (hyperfiltration) and episodic albuminuria
• -later on GFR decreases and patient has hyperalbuminuria
• 

• Pathophysiology:
• -advanced Glycation End-Products (AGE)
• -non-enzymatically glycated products --> ROS etc --> TGFb, VEGF etc.

• Pathophysiology:
• -amyloid fibrils are indigestible protein in a crystalline "beta-pleated sheet" configuration
• -arises from various serum proteins (Ig's, beta-2 microglobulin, amyloid A protein etc)
• -amyloid accumulates in glomerular mesangial regions

• Histology:
• -congo red stain
• -apple green birefringence under polarized light
• -fibrillar periodicity on EM
• 
• 
• Causes nephrotic syndrome and chronic renal failure