Nephrotic Syndrome Pathology

Question 1

Check out this sweet flow chart

Question 2

What vein in the body is most likely to have thrombosis in nephrotic syndrome?

Answer 2

Renal vein.

Because at no place in the body would the ATIII level be lowest than that leaving the kidney.

Question 3

Nephrotic syndromes cause protein deficiencies

• Antithrombin III
• HD lipoprotein
• Immunoglobulin and complement
• Albumin
• General

What is the consequence for having low levels of each of these?

Answer 3

• Antithrombin III
  
  • Clotting tendency (especially in renal vein)
• HD lipoprotein
  
  • accelerated atherogenesis
• Immunoglobulin and complement
  
  • Susceptibility to infections
• Albumin
  
  • edema, hypotension, and drug toxicity (many drugs need to complex to albumin to maneuver through the body)
• General
  
  • protein malnutrition and growth retardation in kids

Question 4

Does nephrotic syndrome progress to chronic renal failure?

Answer 4

Yes, and vice versa

Question 5

Is nephrotic pathology typically inflammatory or non-inflammatory?

Answer 5

Non-inflammatory

Question 6

What are the two general mechanisms for nephrotic syndromes? Give examples of each.

Answer 6

• Circulating factors/Ig’s bind to glomerular epithelial cell membranes (podocytes) and/or glomerular basement membrane without fixing complement (e.g. minimal change disease and FSGS)
  
  • Loss of polyanion (charge selective) - albumin can freely go through if negative charge is lost
  • GEC detachment from GBM (size selective)
• Complement-fixing anti-glomerular epithelial cell antibodies (e.g. membranous nephropathy)
  
  • Alternative pathway
  • C5b-9 which increases permeability of GBM (size selective)
  • May involve oxidants/proteases from GEC

Question 7

What are the 3 major diseases that comprise of the majority of all nephrotic disease? Which of these is more common in children vs adults?

Answer 7

Membranous glomerulonephropathy (more common in adults)

Minimal change disease (more common in children)

Focal segmental glomerulosclerosis (more common in adults)

Question 8

What’s this?

Answer 8

Minimal change disease (entirely normal by LM, foot process effacement on EM, negative on IF)

Not hypercellular

Open capillary loops

No inflammatory cells

No basement membrane thickening

No scarring

Pedicels look connected

Question 9

How do you treat minimal change disease? What’s the prognosis?

Answer 9

Treat with steroids.

Prognosis is good.

Question 10

What’s this?

Answer 10

Focal segmental glomerulosclerosis

Focal - only some glomeruli involved

Segmental - only a portion of the glomeruli involved

Sclerosis - scarring

See how some glomeruli have too much pink. On the right picture, you can see that the sclerosis attaches to the bowman’s capsule.

Question 11

What are the 4 major categories of causes for FSGS?

Answer 11

1. Idiopathic/hereditary (primary) FSGS
2. HIV-associated nephropathy
3. Heroin nephropathy
4. Secondary FSGS (hyperfiltration injury)

Question 12

What is this?

Answer 12

Membranous nephropathy

Thicker and fuzzier. Rigid openings. Membranes have thickened.

Question 13

What’s this?

Answer 13

Membranous nephropathy.

Silver stain shows “strings of pearls”.

Question 14

What’s this?

Answer 14

Membranous nephropathy.

IF shows finely granular deposits (IgG and C3) circling around capillary loops.

EM shows deposits (dark spots) along the BM. These are subepithelial deposits.

If there are complement deposits, how come there isn’t an inflammatory process with membranous nephropathy? Because of where the deposits are. They are in bowman’s capsule, not the vasculature.

Injured podocytes are filled in with basement membrane material.

Question 15

How do you treat membranous nephropathy? What’s the prognosis?

Answer 15

Treat with steroids.

Some progress to ESRD.

Question 16

What are the stages of membranous nephropathy (including treatment) to lead to this?

Answer 16

Subepithelial deposits, more basement membrane material is formed eventually encasing the deposits, deposits dissolve if treated successfully.

Question 17

Membranous glomerulonephropathy/nephropathy occurs most often in adults and can be often associated with other diseases (in 15% of cases). Diagnosis requires further workup. What should you rule out?

Answer 17

“Bugs, drugs, tumors, and rheum”

Infections

Drugs (rheumatoid meds)

Malignant tumors (lung, colon, melanoma)

Systemic lupus erythematosus

Question 18

What is this? Is it nephritic, nephrotic, or mixed?

45 y/o female

Fine until 2-3 weeks ago

Flu like symptoms

Edema

Dark urine

Lethargic

Creatinine 2.3

UA shows RBCs, RBC casts, 4+ protein

Albumin 1.8

Answer 18

Membranoproliferative glomerulonephritis

Mixed (nephritic bc hematuria, RBC casts, and functional loss; nephrotic bc proteinuria, edema, hypoalbuminemia)

Diffuse

Double contour membranous change seen in silver stain

Question 19

What’s this?

Answer 19

Membranoproliferative glomerulonephritis

Bright prominent immune complex deposits by IF.

Subendothelial deposits cause damage to the endothelial cell. The endothelial cells retract and a new layer of basement membrane between the deposit and itself as a form of protection. This is why you get a double contour membranous change known as “tram tracking”

Question 20

How does membranoproliferative glomerulonephritis look morphologically?

Answer 20

Cell proliferation and thickening of glomerular basement membrane with double contours.

Question 21

In membranoproliferative glomerulonephritis, are deposits subepithelial or subendothelial?

Answer 21

Subendothelial

Question 22

How do you treat membranoproliferative glomerulonephritis? What’s the prognosis?

Answer 22

Treat with steroids and maybe interferons.

Some progress to ESRD

Question 23

What is this?

Answer 23

Renal amyloidosis.

Amorphous fluffy pink material in glomeruli and vessels.

Positive on congo red stain with apple green birefrigencence

Question 24

How does renal amyloidosis present?

Answer 24

Initially with proteinuria, develops to nephrotic syndrome, and eventually ESRD

Question 25

What’s this?

Answer 25

Renal emyloidosis.

Classic “spilled spaghetti” look.

Question 26

What are the top 3 causes of ESRD?

Answer 26

1. Diabetes
2. HTN/vascular disease
3. Glomerulonephritis

Question 27

Diabetes mellitus causes kidney lesions. Explain

Answer 27

• Hyaline arteriolar disease
  
  • microvascular is effected. Hyaline deposition causes narrowing of arterioles
  • If a patient has retinopathy, there is likely damage to the kidneys as well.
• Diabetic glomerulosclerosis
  
  • Glomerulus scars from within
  • Mesangium hyperproduce mesangial matrix and strangles itself out causing mesangial “lysis”.
  • Consequence of altered glucose and insulin metabolism.

Question 28

What is this?

Answer 28

Diabetes mellitus kidney lesions

Histology: hypocellular mesangium with big nodules of fibrosis.

EM: thickening of basement membrane

Question 29

True or False: Diabetes increases risk of pyelonephritis

Answer 29

True (acute and chronic)

This can cause renal scarring and renal papillary necrosis.

Question 30

What causes this?

Answer 30

Diabetes and HTN

Question 31

What causes this?

Answer 31

Malignant (accelerated) hypertensive renal disease.

Very little blood can get through vessels so prognosis is poor.