PATH: Nephrotic Syndrome II

Question 1

What is podocytopathy?

Answer 1

nephrotic syndromes of visceral epithelial injury that are divided into minimal change disease and FSGS

Question 2

What is suPAR?

Answer 2

circulating factor that may be responsible for primary FSGS–binds to and activates beta3 integrin which anchors podocytes the the GBM.

Question 3

Compare treatment of minimal change disease to FSGS.

Answer 3

90% of minimal change disease patients respond to steroid therapy; 50% of FSGS patients do not respond to steroid/calcineurin inhibitor therapy and will progress to ESRF in 10 years

Question 4

Why might some believe that FSGS is not one disease but rather many different diseases with a shared mechanism?

Answer 4

Because there are 4 different subtypes:

1) Cellular subtype (most common)
2) Perihilar subtype (vascular pole)
3) Glomerular tip (urinary pole; white adults)
4) Collapsing (HIV, drugs, blacks, worst prognosis)

Question 5

If you transplant a patient with FSGS, what is a poor prognostic factor you must watch out for?

Answer 5

elevated suPAR levels are predictive of recurrence in transplanted kidneys

Question 6

What factors favor FSGS over minimal change disease?

Answer 6

Older age
Hematuria
HTN
Non-selective proteinuria
Poor response to steroids

Question 7

What is the target antigen in congenital MN?

Answer 7

neutral endopeptidase (NEP)

Question 8

What is the target anion in idiopathic MN?

Answer 8

PLA2R (co-localized in situ with IgG4)

Question 9

What is membranous nephropathy associated with?

Answer 9

Caucasian adults; SLE, solid tumors, Hepatitis, drugs (penacillinamine/NSAIDs/captopril)

Question 10

What is the EM of MN?

Answer 10

“spikes” (subepithelial deposits) and “domes” (new GBM being laid down over it!)

Question 11

What is found in the subendoethelial desposits on IF with MN?

Answer 11

IgG and C3

Question 12

True or false: inflammatory cells are commonly seen in MN.

Answer 12

FALSE: no inflammation because the complement is not activated in a site that comes into contact with circulating inflammatory cells

Question 13

True or false: MN can spontaneously remit, lead to ESRF, or lead to persistent proteinuria.

Answer 13

TRUE!
40% spontaneously remit
30% ESRF
30% Persistent proteinuria

Question 14

How do “spikes and domes” form in idiopathic MN?

Answer 14

Antibodies against conformational epitope of M-type PLA2R forms a complex and starts a complement dependent process mediated by MAC (C3a and C5a are washed into urinary space and there is damage of podocytes with production of new GBM)

Question 15

What bugs lead to post-infectious GN?

Answer 15

Beta-hemolytic strep (strep pyogenes) from a throat or skin infection

Question 16

What antibody titers would you find in someone with a past strep throat infection?

Answer 16

Anti-streptolysin-O

Question 17

What antibody titers would you find in someone with a past strep skin infection?

Answer 17

Antihyaluronidase

Anti-DNAase B

Question 18

When would you see symptoms of post-infectious GN in someone?

Answer 18

1-6 weeks AFTER a throat or skin infection

Question 19

What are the s/s of post-infectious GN?

Answer 19

Nephritic syndrome (hematuria, HTN)
Edema
Proteinuria

Question 20

What is the complement like in post-infectious GN? What does it suggest?

Answer 20

Low C3 with normal C4

Suggests alternative complement pathway

Question 21

What does an EM of post-infectious GN look like?

Answer 21

subepithelial humps

Question 22

What does an IF of post-infectious GN look like?

Answer 22

IgG and C3 in glomerular capillary walls and mesangium (granular)

Question 23

What does an LM of post-infectious GN look like?

Answer 23

diffuse, proliferative GN