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Flashcards in Glomerulonephritis Deck (60):
1

What is glomerulonephritis?

A group of diseases associated with inflammatory injury of the glomeruli.

This means that the immune system is causing injury to tissue.

-Infiltration of leukocytes

-Deposition of immune proteins

-Disturbed function of the affected tissue

2

True or False: The glomerulus is a common target of inflammation

True

3

True or False: Glomerulonephritis progresses slowly

False. It progresses very rapidly

4

True or False: Glomerulonephritis responds poorly to treatment

False. It often responds well to treatment.

5

True or False: Glomerulonephritis is not a very common disease but it's important to keep it in mind since it can go badly very quickly but is very treatable

True

6

What are clinical findings most commonly found in patients with glomerulonephritis? (4)

  • Hematuria
    • dysmorphic RBCs
    • RBC casts
  • Proteinuria
  • Elevated creatinine
  • Elevated BP

7

What is the workup for patients with suspected glomerulonephritis?

  • H&P
    • Systemic symptoms (rash, fever, joint pain, pulmonary symptoms)
    • Recent infections
  • UA
    • Microscopic exam
    • Urine protein measurement
  • Labs and serologic tests
  • Renal biopsy

8

What is pulmonary-renal syndrome and how does it present?

It is glomerulonephritis with pulmonary capillaritis. It presents with nephritic syndrome and hemoptysis.

9

What typically causes pulmonary-renal syndrome?

Anti-GBM disease

ANCA associated vasculitis

Lupus

10

How do you treat pulmonary-renal syndrome?

Requires aggressive therapy

  • cytotoxic drugs
  • plasma exchange

11

What is rapidly progressive glomerulonephritis?

Nephritic syndrome where serum creatinine doubles or GFR falls by 50% within a day to 3 months.

12

What is rapidly progressive glomerulonephritis (RPGN) typically associated with? (3)

  1. Anti-GBM disease
  2. ANCA associated vasculitis
  3. Lupus

13

How do you treat rapidly progressive glomerulonephritis?

You have to treat aggressively

  • cytotoxic drugs
  • plasma exchange

14

What is pathognomonic of glomerulonephritis?

RBC cast

15

In UA, how can you tell if an RBC is from the glomerulus or elsewhere?

RBCs from the glomerulus can have a "mickey mouse ears" appearance. Also, if the RBCs are trapped in a cast then it's for sure from the nephron.

16

What blood test is used to detect lupus?

ANA, Anti-DS DNA

17

What blood test is used to detect pauci-immune vasculitis?

Anti-neutrophil cytoplasmic antibodies (ANCA)

18

What blood test is used to detect anti-GMB disease or goodpasture's syndrome?

Anti-GBM antibodies

19

If the patient with glomerulonephritis has low serum complement, what can you narrow your ddx to?

  • Systemic disease
    • Systemic Lupus Erythematosus
    • Subacute bacterial endocarditis
    • Cryoglobulinemia
    • Atypical hemolytic uremic syndrome
  • Renal limited
    • Acute post-streptococcal GN
    • Membranoproliferative GN

20

A definitive diagnosis of glomerulonephritis requires a _____

kidney biopsy

21

What are crescents?

It is a finding seen on renal biopsy that signifies severe disease. It is caused by the rupture of the capillary wall.

22

"crescentic" glomerulonephritis is typically associated with? (3)

  1. SLE
  2. Anti-GBM disease
  3. ANCA associated vasculitis

23

How do you treat a "crescentic" glomerulonephritis?

Aggressive therapy

  • cytotoxic drugs
  • plasma exchange

24

How do crescents form?

If you have very severe inflammation in the glomular capillary loops, it causes rupture and things drain into the urinary space. This causes the cells of bowman's capsule to proliferate and you get a growth around the glomerulus that looks like a crescent. The crescent kind of compresses the glomerulus into a little ball.

 

A image thumb
25

Pathophysiology of glomerulonephritis can be simplified into 3 categories. What are they?

  • Deposited immune-complexes
    • Lupus, MPGN
  • Antibodies specific for renal antigens
    • Anti-GBM disease, Lupus(?)
  • Other causes of inflammation within glomeruli
    • Vasculitis (ANCA associated disease)
    • Hemolytic uremic syndrome
    • C3 glomerulopathy

26

What are the 4 locations of immuno-complex deposition within glomeruli?

  • Mesangial deposition
  • Subendothelial deposition
  • Subepithelial deposition
    • E.g. Membranous nephropathy
  • Intra-membranous deposition

A image thumb
27

What are glomerular immune complexes caused by?

  • Antibodies to glomerular antigens
  • Antibodies to extra-glomerular antigens
    • Infections
    • Cancer
    • Drugs, foreign substances
  • Idiopathic (i.e. antibodies to unknown antigens)

28

What happens when immune complexes form and deposit in the kidney?

Complement is activated, cause inflammation, and basically act like there is an infection. Macrophages and neutrophils infiltrate and there is oxidative stresswhich cause capillary wall damage, fibrin formation, and then crescent formation if very severe.

29

Are diseases that deposit immune complexes in subendothelial space more or less inflammatory than those that deposit in the subepithelial space? What about mesangial deposits?

Immune complexes in the subendothelial space have ready access to circulation so if they activate complement, C5a (chemotactic factor) can enter the circulation and recruit inflammatory mediators.

Immune complexes in the subepithelial space have less access to circulation so C5a that is generated from activated complement system is typically swept out in the urine.

Mesangial deposits are somewhere in betwene because they have access to the circulation but are not as close to the filtration barrier.

So, inflammation from greater to less

Subendothelial, mesangial, subepithelial

30

What are two histologic findings that show rapidly progressive renal failure?

  • necrotizing lesions
  • crescents

31

What class of drugs are used to treat glomerulonephritis?

Immunosuppressants.

(cytotoxic drugs are typically immunosuppressants and anti-cancer)

32

Name 8 immunosuppressant drugs that are used to treat glomerulonephritis

  1. Prednisone
  2. Cyclophosphamide
  3. Mycophenolate mofetil (MMF)
  4. Azathioprine
  5. Chlorambucil
  6. Rituximab
  7. Eculizumab
  8. Intravenous immunoglobulin (IVIG)

33

What is plasma exchange?

Analogous to dialysis.

You take the patient's blood, remove the plasma, put a fluid back to replace the plasma.

 

These are anti-body driven diseases so the plasma removed from the patient is removing antibodies from the patient.

34

When is plasma exchange used?

  1. Anti-GBM disease
  2. Severe ANCA associated vasculitis
  3. Severe cryoglobulinemia

This is a pretty drastic procedure so it is only used in severe diseases.

35

What are 4 causes of glomerulonephritis?

  • IgA nephropathy
    • Mesangial immune-complexes containing IgA
  • Lupus nephritis
    • Immune-complex deposition
  • Anti-GBM disease
    • antibody to glomerular antigen
  • ANCA associated vasculitis
    • small vessel vasculitis
    • "Pauci-Immune" (ANCA has little to no evidence of immuno fluorescence)

36

What is the most common cause of glomerulonephritis world wide?

IgA nephropathy

37

How is IgA nephropathy thought to happen?

Abnormal sugars are formed on IgA1 and antibodies are formed against the abnormal sugar. Immune complexes form from this and often end up in the kidney. These end up specifically in the mesangium.

38

What's this?

Q image thumb

IgA Nephropathy.

 

Stained for IgA and deposits found in the mesangium.

39

True or False: IgA nephropathy is a kidney-limited disease

True

40

True or False: IgA nephropathy sometimes presents with a rash on the skin

False.

"Henoch schonlein purpura" is a skin disease where the same IgA can go to the skin to create palpable purpura. If biopsied they look the same as IgA nephropathy. Think of IgA nephropathy as the kidney-limited version of this disease.

A image thumb
41

What is the prognosis for IgA nephropathy?

30% have spontaneous remission and 30% progress to ESRD within 10-20 years.

40% chronic kidney disease

42

How do you treat IgA nephropathy?

Treatment is non-specific (blood pressure, and ACE inhibitors).

Also treat with prednisone although the benefit is uncertain

43

What is lupus nephritis and how many lupus patients have this?

Kidney disease associated with lupus. A little more than half of patients with lupus have this.

44

True or False: Lupus nephritis has variable presentaiton between patients and within the same patient over time.

True

45

How do you screen lupus patients for lupus nephritis?

UA with dipstick to check for protein and blood in urine

46

In lupus nephritis, where are the immune-complexes deposited?

Lupus is a very variable disease so the immune complexes can deposit in any of the places we discussed.

Mesangium

Subendothelial

Subepithelial

47

True or False: Generally, subendothelial immune complex deposits are classic for nephritic syndromes while subepithelial immune complex deposits are classic for nephrotic syndromes.

True

48

Explain the lupus classes

  • Class 1
    • Mesangial deposits presenting with hematuria.
      • Not treated with immunosuppression
  • Class 2
    • Mesangial deposits presenting with hematuria
      • Not treated with immunosuppression
  • Class 3
    • Subendothelial deposits presenting with hematuria, nephritic syndrome
      • Treated with immunosuppression
  • Class 4
    • Subendothelial deposits presenting with hematuria, nephritic syndrome
      • Treated with immunosuppression
  • Class 5
    • Subepithelial deposits presenting with proteinuria
      • Treated with immunosuppression
  • Class 6
    • Scarring of greater than 90% of the glomeruli, presenting with nephritic syndrome and progressive renal failure.
      • Not treated with immunosuppression

49

What causes anti-glomerular basement membrane disease?

It is caused by auto-antibodies to the NC1 domain of the alpha-3 chain of type IV collagen.

50

Is AntiGBM disease renal limited?

It can be renal limited or present with pulmonary-renal syndrome

51

True or False: Anti-GBM disease causes crescentic, necrotizing glomerulonephritis, and rapidly progressing glomerulonephritis and could kill a patient within days if left unrecognized and untreated.

True

52

Does Anti-GBM have linear or lumpy bumpy immunofluorescence?

Linear

53

Patients with nephritic syndrome, rapidly progressing glomerulonephritis, and/or pulmonary renal syndrome should be suspected for?

Anti-GBM disease or ANCA associated vasculitis

54

How do you diagnose anti-GBM disease?

Biopsy and detection of anti-GBM antibody

55

How do you treat anti-gbm disease?

Cytotoxic drugs (cyclophosphamide)

Corticosteroids

Plasma exchange to remove pathogenic autoantibodies

56

True or False: Anti-GBM disease rapidly progresses to end stage renal disease if left untreated

True

57

What is ANCA associated vasculitis?

It is a group of diseases (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, renal limited vasculitis) associated with autoantibody ANCA that targets small vessels causing inflammation.

ANCA stands for anti-neutrophil cytoplasmic antibodies. If you look at them in the lab they seem to bind to neutrophils. We don't know if that's their only function but that's what's onticed. It appears that the ANCA antibodies actually cause the disease because if you inject them into mice the mice get vasculitis.

However, when you stain the biopsies for IgG, nothing is shown. So it is called "pauci-immune" disease.

58

How do you diagnose ANCA associated vasculitis?

The lab takes neutrophils on a slide and add the patient's serum. The antibodies will bind the the neutrophils in one of two patterns. C-ANCA for cytoplasmic or P-ANCA for perinuclear.

The biopsy will have few or no immune complexes (pauci-immune).

 

 

59

What's the prognosis for ANCA associated vasculitis?

80% 1 year mortality without treatment

60

How do you treat ANCA associated vasculitis?

  • Cytotoxic drugs
    • Cyclophosphamide
  • Corticosteroids
  • B cell targeted therapies
    • Rituximab
  • Plasma exchange