Nephrotic Syndromes

Question 1

A conformational change in what chain of the type IV collagen of GBM results in Anti-GBM Glomerulonephritis?

Answer 1

The α3 chain

Question 2

Sometimes Anti-GBM antibodies cross-react with basement membranes of the lung alveoli. This can result in a systemic Anti-GBM syndrome called. . . ?

Answer 2

Goodpasture Syndrome

Question 3

Anti-GBM is associated with what type of inflammation?

Answer 3

Activation of complement via the CLASSICAL pathway primarily. However, alternative and mannose-binding lectin pathways can also be activated.

Question 4

What are five additional (i.e. excluding complement activation) mediators of glomerular damage in Anti-GBM Nephritis?

Answer 4

1. Monocytes/macrophages
2. Sensitized T cells
3. Platelets
4. Resident Glomerular Cells
5. Thrombin

Question 5

Name two proteins associated with the integrity of slit diaphragms.

Answer 5

Nephrin and Podocin (mutations in these structural proteins can result in rare hereditary forms of nephrotic syndrome)

Question 6

Name 4 distinguishing characteristics of nephrotic syndrome.

Answer 6

1. Massive proteinuria
2. Hypoalbuminemia
3. Generalized Edema
4. Hyperlipidemia and lipiduria

Question 7

Anasarca is commonly associated with what class of kidney disorders?

Answer 7

Nephrotic syndrome

Question 8

BUZZ WORD: “Foot Process Effacement” is associated with. . .

Answer 8

Minimal Change Disease

Question 9

BUZZ WORD: “Spike and Dome” is associated with. . .

Answer 9

Membranous Nephropathy

Question 10

BUZZ WORD: “Subepithelial Humps” is associated with. . .

Answer 10

Post-Infectious Glomerulonephritis (PIGN)

Question 11

BUZZ WORD: “Tram Tracks” is associated with. . .

Answer 11

Membranoproliferative Glomerulonephritis (MPGN)

Question 12

BUZZ WORD: “Basket Weave” is associated with. . .

Answer 12

Alport Syndrome

Question 13

BUZZ WORD: “Wire Loops” is associated with. . .

Answer 13

Lupus Nephritis

Question 14

BUZZ WORD: “Onion-skin” is associated with. . .

Answer 14

Hypertensive Nephropathy or Scleroderma

Question 15

Minimal-Change Disease is a disorder most common in what population?

Answer 15

Children

Question 16

What is diagnostic for a Minimal-Change Disease in electron microscopy?

Answer 16

Podocyte Effacement

Question 17

What is the prognosis for children with Minimal-Change Disease?

Answer 17

Good. More than 90% respond to a short course of corticosteriod therapy.

Question 18

Focal Segmental Glomerulosclerosis (FSGS) can be primary or secondary. What are the etiologies?

Answer 18

1. Primary - idiopathic
2. Secondary to:
   - HIV
   - Heroin abuse
   - Other nephropathies (e.g. IgA nephropathy)
   - Inherited

Question 19

Inherited or Congenital FSGS is associated with a mutation in what gene?

Answer 19

APOL1 - primarily affects African-Americans

Question 20

FSGS is associated with what circulating factor?

Answer 20

suPAR - activates B3 integrin (anchor for podocytes in GBM)

Question 21

What do the affected glomeruli of FSGS exhibit?

Answer 21

1. Increased mesangial matrix
2. Obliterated capillary lumina
3. Deposition of hyaline masses and lipid droplets

Question 22

What is a morphologic variant of FSGS?

Answer 22

Collapsing Glomerulopathy - Characterized by collapse of the glomerular tuft and podocyte hyperplasia. Carries a particularly poor prognosis.

Question 23

What characterizes membranous nephropathy morphologically?

Answer 23

Subepithelial immunoglobulin-containing deposits (thick GBM), as well as thickening of the capillaries and mesangial matrix. “Spike and Dome”

Question 24

Membranous nephropathy occurs secondarily to what disorders:

Answer 24

1. Infections (Hep B, Syphilis, Schistosomiasis, Malaria)
2. Malignancies (esp. carcinoma of the lung)
3. SLE
4. Exposure to gold/mercury
5. Drugs (penicillamine, captopril, NSAIDs)

Question 25

What antigen is most often recognized in cases of membranous nephropathy?

Answer 25

Phospholipase A2 Receptor - an endogenous podocyte antigen.

Question 26

What is unique/peculiar about membranous nephropathy as a renal disorder?

Answer 26

It is a disorder in which complement is recruited and there is MAC formation, however it is not considered a nephritis because there are no inflammatory cells involved in the process.

Question 27

What are the morphologic characteristics of Membranoproliferative Glomerulonephritis (MPGN type I)?

Answer 27

1. Hypercellularity in the glomerular tuft.
2. Expanded mesangium
3. Capillary wall changes - double contour (“Tram Tracks”)

Question 28

Dense Deposit Disease (formerly MPGN type II) is associated with what protein?

Answer 28

C3 Nephritic Factor (also less commonly mutations in factor H)