Which nephrotic syndromes are the following diseases associated with?

1. HIV/heroine nephropathy
2. Hepatitis B
3. Hepatitis C

1. Focal segmental glomerular sclerosis
2. Membranous nephropathy
3. Membranoproliferative nephritis

• Characterized by immune deposits in the subendothelial areas (sometimes subepithelial).
• The basement membrane is split by interposition of cells (mesangial, endothelial, and WBCs) in glomerular capillary basement membrane.

A patient comes in post-upper respiratory infection with hematuria. Renal pathology shows focal and segmental mesangial proliferation with deposits of IgA and complements. What is the most likely diagnosis?

How would your diagnosis change if the patient had purpuric skin lesions?

• IgA nephropathy (aka Berger's disease)

• Henoch-Schonlein purpura

• Crescent formation
• Proliferation of epithelial cells, infiltration of inflammatory cells into Bowman's space
• Three subtypes
  1. Anti-GBM (glomerular basement membrane)
  2. Subendothelial immune complexes
  3. Pauci-immune, ANCA

• Goodpasture's disease
• Collagen antigen is also found in lung capillaries
• Patients with Alport disease receiving a renal transplant
• Immunofluorescence will be linear staining pattern instead of clumping (as in the case of post-infectious nephritis)

• AL (immunoglobulin light chain) and AA (serum amyloid A)
• Mesangium, GBM, tubular basement membranes, interstitium, blood vessel walls
• Enlarged kidney

Idiopathic membranous nephropathy

Class 5 lupus, hepatitis B, cancer

Subendothelial deposits can be seen on EM, with granular deposition seen on immunofluorescence. Further subclassified into active (proliferative) lesions and chronic (scarring) lesions.

Class III is focal (<50% of glomeruli) while IV is diffuse (>50%)

• Clear cell carcinoma
• VHL 
• VHL syndrome predisposes patient to hemangioblastomas and multiple benign renal cysts, as well as multiple renal cell carcinomas

Nephroblastoma (Wilm's tumor) a tumor arising from embryonic cells (blastemal, epithelial, stromal cell lines)

Prognosis is very good.

Bacterial toxins (verocytotoxins from E coli and Shiga toxins), cause endothelial injury, leading to intravascular thrombosis and platelet aggregation. Vasoconstriction and vascular obstruction ensues.

Disease mimics TTP

• Thickened glomerular and tubular basement membranes. Mesangial sclerosis, sometimes nodular (Kimmelstiel-Wilson's disease).
• Sclerosis seen in both afferent and efferent arterioles (hypertensive just afferent)

Note: Diabetic Nephropathy #1 cause of ESRD in USA

1. Fibrinoid necrosis of glomerular capillaries and afferent arterioles.
2. Hyperplastic arteriolitis (onion skinning lesions)

• Phenacetin
• Mixtures of aspirin, caffeine and acetaminophen

Presents as chronic tubulo-interstitial disease

Acute

Generally, chronic rejection induce intimal fibroplasia of medium sized arteria, with interstitial fibrosis and tubular atrophy

1. Seminomatous
   • Seminoma (ages 30-50)
   • Spermatocytic seminoma (ages >65)
2. Non-seminomatous
   • Embryonal
   • Yolk sac
   • Choriocarcinoma
   • Teratomas

• Placental alkaline phosphatase (PLAP) seen in seminomatous tumors
• Alpha-fetoprotein (AFP) seen in yolk sac or embryonal sinus tumors
• ß-human chorionic gonadotropin (hCG) for embryonal carcinomas and choriocarcinomas

• High NC ratio
• Increased nucleoli
• Increased number of cell layers
• Dark pink staining of cytoplasm
• Absent basal layer

Peripheral = prostate cancer

Transition = BPH

• Cigarette smoking, cyclophosphamide, schistosomiasis
• p53 and p16 deletions/mutations

The following are associated with what nephrotic syndrome?

1. Malignancy
2. Diabetes
3. Anti-phospholipase A2

1. Membranous nephropathy
2. Nodular and diffuse glomerular sclerosis
3. Idiopathic membranous nephropathy