Nephrotic Syndrome Pathology

Question 1

5 clinical manifestations of nephrotic syndrome

Answer 1

• edema
• proteinuria (over 3g per 24hrs)
• hypoproteinemia
• hyperlipidemia
• lipiduria (oval fat bodies)

can have some overlap w/ nephritis- hematuria, azotemia, HTN (quantitative difference)

Question 2

why renal biopsy?

Answer 2

clinical and lab data not enough to narrow treatment regimen, tx can be personalized w/ enough info

Question 3

6 main diseases on DDx for nephrotic syndrome

Answer 3

• amyloidosis
• diabetic glomerulosclerosis
• MCD
• membranous nephropathy
• FSGS (focal segmental glomerulosclerosis)
• MPGN (membranoproliferative)

Question 4

age range for amyloid nephrotic syndrome

Answer 4

50s-70s

Question 5

renal mainfestation of amyloid

Answer 5

proteinuria and nephrotic syndrome (NS)

Question 6

most common peptides causing amyloid NS

Answer 6

AL amyloid (Ig light chians) and AA amyloid (A protein)

Question 7

LM appearance of amyloid

Answer 7

pink depositions in glomerulus, destroys normal structure

Question 8

IF and other stains for amyloid

Answer 8

congo red- pinkish stain in glomerulus
congo red polarized- apple green deposits

IF: anti lambda light chains

EM: fibrils

Question 9

why is prevalence likely underestimated for older pts w/ diabetic GS (glomerulosclerosis)

Answer 9

this is the presumed Dx w/ older pts w/ NS, often not biopsied w/o other findings

Question 10

most common cause of end stage renal disease

Answer 10

diabetic nephropathy- underlied by diabetic GS (proteinuria, progressive loss of GFR, HTN)

Question 11

histo LM appearance of diabetic GS

Answer 11

progressive thickening of GBM, increas in mesangial matrix eventually into Kimmelstiel-wilson nodules

Question 12

most common cause of childhood NS

Answer 12

MCD- over 90% but it is rarely biopsied, often treated w/ steroids

Question 13

LM and IF of MCD

Answer 13

often normal (minimal change)

Question 14

pathologic change in MCD

Answer 14

foot processes of podocytes are effaced, become one continuous sheet of cytoplasm (visible by EM)

not specific! can happen w/ other diseases, for Dx needs to be w/o other changes

Question 15

population risk for FSGS

Answer 15

african americans

Question 16

define “focal segmental” for FSGS

Answer 16

focal= some not all glomeruli (contrast to diffuse)

segmental= some but not all of a glomerulus (contrast to global)

Question 17

list some causes of FSGS

Answer 17

• idopathic (unkown, primary)
• secondary: viruses (HIV, parvovirus B19), podocyte mutations, drugs (heroin, interferon alpha, pamidronate), adaptive structural changes (Sickle cell, obesity)

Question 18

population for membranous nephropathy (MN)

Answer 18

caucaisians

Question 19

describe LM for MN (or MG, membranous glomerulapathy)

Answer 19

thick cap walls but no hypercellularity

Question 20

IF and EM for MN

Answer 20

granular capillary wall via IgG staining w/ IF

subepithelial dense deposits via EM (think about thickening the capillary wall)

Question 21

pathogenesis for MN

Answer 21

• IgG capable of crossing BM into interstitium
• bind to protein antigens from podocytes, form lattices and can fix complement
• accumulate under podocyte (subepithelial), podocytes lay down collagen around deposits

Question 22

primary/secondary MN causes

Answer 22

primary: anti phospholipase A2 receptor, other podocyte antigen autoAb

secondary:
- SLE
- infections (hep B, syphilis)
- exposure (metals, penicillamine)
- malignancy (carcinoma, sarcoma, lymphoma, leukemia)