Glomerulonephritis

Question 1

What is glomerulonephritis?

Answer 1

• Glomerulonephritis: A group of diseases associated with inflammatory injury of the glomeruli
• Sources of Inflammation
  
  • Infiltration of leukocytes
  • Deposition of immune proteins
  • Disturbed function of the affected tissue

Question 2

Is glomerulonephritis nephritic or nephrotic?

Answer 2

• Nephritic
  
  • Can be rapidly progressive and include pulmonary renal syndrome

Question 3

What 4 cell types may be affected in glomerulonephritis?

Answer 3

1. Mesangium
2. Podocytes
3. Capillaries
4. Parietal epithelial cells

Question 4

T/F: Anti-GBM disease leads to a nephrotic disease process

Answer 4

• False, Anti-GBM leads to Glomerulonephritis which is nephritic

Question 5

What are the two most common causes of glomerulonephritis with a renal etiology?

Answer 5

Most common renal etiology of glomerulonephritis

1. IgA nephropathy
   
   • Mesangial immune complexes containing IgA
2. Anti-GBM disease
   
   • Antibody to glomerular antigen

Note: there are many other etiologies but these were in red as the most common

Question 6

What are the two most common systemic etiologies of glomerulonephritis?

Answer 6

Most common systemic etiologies of glomerulonephritis

• Lupus nephritis
  
  • Immune complex deposition
• ANCA asscoiated vasculitis
  
  • “Pauci-Immune”
  • Small vessel vasculitis

Note: there are many other etiologies but these were in red as the most common

Question 7

What are the clinical findings c/w (consistent with) nephritic syndrome

Answer 7

Nephritic Syndrome Clinical Findings

• Hematuria
  
  • Dysmorphic RBC’s
  • RBC casts
• Proteinuria
  
  • 200mg - 10gm
• Elevated Cr
• Elevated BP

Question 8

What 3 diseases can cause pulmonary renal syndrome?

Answer 8

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

pulmonary-renal syndrome requires aggressive therapy like cytotoxic drugs and plasma exchange

Question 9

What are the criteria for calling a glomerulonephritis “rapidly progressive?”

Answer 9

• Serum Cr doubles or GFR falls by 50% within a few days to 3 months

Question 10

What 3 diseases are usually associated with Rapidly Progressive Glomerular Nephritis?

Answer 10

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

Note: these are the same 3 diseases that are associated with pulmomary renal syndrome

Question 11

What is pulmomnary renal syndrome?

Answer 11

Pulmomonary renal syndrome: Glomerulonephritis w/ pulmonary capillaritis

• Presents with nephritic syndrome and hemoptysis
• Capillaries of the kidney are involved and capillaries of the lung are invovled

Question 12

For the following labs name what diseases they test for:

1. ANA, Anti-DS DNA
2. C3,C4 - if they come back low
3. Blood cultures
4. ASO
5. Hepatitis C
6. Hepatitis B
7. Anti-neutrophil cytoplasmic antibodies (ANCA)
8. Anti-GBM antibodies

Answer 12

1. Lupus
2. Several diseases including glomerulonephritis, vasculitis, autoimmune, infection
3. Infection: Bacterial endocarditis specifically listed
4. Streptococcus
5. Cryoglobulinemia
6. Membranoproliferative glomerulonephritis
7. Pauci-immune vasculitis
8. Anti-GBM disease, good pasture’s syndrome

Question 13

Alex’s Made Up Vignette: 56 y/o female presents to the ED coughing up blood snd complaining of dark colored urine. A urine analysis reveals proteinuria and hematuria with RBC casts.

Question:

1. What tests should you order
2. Why?

Answer 13

1. ANA, ANCA, Anti-GBM
2. This is pulmonary renal syndrome:
   
   • The 3 main causes are Lupus, ANCA assoc Vasculitis, and Anti-GBM disease

Question 14

T/F: You do not need a kidney biopsy to definitively diagnose glomerulonephritis.

Answer 14

• False: Kidney biopsy is required for definitive diagnosis of glomerulonephritis

Question 15

1. A kidney biopsy is performed and cresencents are seen, what disease is this c/w?
2. What other diseases are usually associated with this disease?
3. What kind of treatment does this disease require?

Answer 15

1. “Crescentic” glomerulonephritis
   
   • associated with severe disease, caused by rupture of the capillary wall
2. The trifecta as I call them
   
   • Anti-GBM
   • ANCA associated vasculitis
   • Lupus
3. Aggressive therapy
   
   • Cytotoxic drugs
   • Plasma exchange (plasmaphoresis)

Question 16

• What disease is associated with subepithelial immune complex deposition?

Answer 16

• Membrounous disease

Question 17

What are the 8 main drugs used to treat glomerulonephritis?

Answer 17

1. Prednisone
2. Cyclophophamide
3. Mycophenolate mofetil (MMF)
4. Azathioprine
5. Chlorambucil
6. Rituximab
7. Eculizumab
8. Intravenous Immunoglobulin (IVIg)

Question 18

What is the most common cause of glomerulonephritis world wide?

Answer 18

• IgA nephropathy
  
  • Usually presents with hematurea +/- subnephrotic proteinuria

Question 19

What disease is c/w this IF slide?

Answer 19

• IgA nephropathy

Question 20

What are treatments availablefor IgA nephropathy?

Answer 20

• Symptom management: Blood pressure, ACE inhibitors)
• Prednisone (new studies show uncertain benefit though)

Question 21

Lupis nephritis can cause hematuria, nephritic disease, or nephrotic disease depending on where the immune complexes end up getting deposited.

Question: Immune complex depositions in what cell layers cause

1. Hematuria
2. Nephritic syndrome
3. Nephrotic syndrome

Answer 21

1. Hematuria - IC deposits in Mesangium
2. Nephritic - IC deposits in Subendothelial
3. Nephrotic - IC depotis in Subepithelial

Question 22

What disease is this based only on these IHC (immunohistochemistry) slides

Answer 22

• Anti-GBM
  
  • Notice in the slide on the left, how the capillaries have formed a “crescent” around the glomerulus
    
    • This should at least tell you its severe disease
  • Notice on the right slide the linear deposition of antibodies
    
    • This is deposition into the basement membrane structure
  • If untreated can lead to ESRD (end stage renal disease) quickly

Question 23

ANCA associated vasculitis is actually a group of diseases.

Question: What 4 vasculitis diseases make up ANCA associated vasculitis?

Answer 23

1. Granulomatosis with Polyangiitis (Wegener’s disease)
2. Microscropic polyangiitis
3. Eosinophilic granulomatosis with polyangiitis
4. Renal limited vasculitis

Question 24

• Is Granulomatosis with polyangiitis associated with C-ANCAor P-ANCA?
  
  • What are the clinical findings?

Answer 24

• Granulomatosis with polyangiitis:
  
  • C-ANCA (PR3)
    
    • Clinical findings: Nephritic syndrome often with extra-renal involvement (airways)

Question 25

* Is **Microscopic polyangiitis** associated with C-ANCA or P-ANCA? * What are the clinical findings?

Answer 25

* Microscopic polyangiitis * **P**-ANCA (MPO) * Clinical findings: Nephritic syndrome, often with extra-renal involvement (airways)

Question 26

* Is **Eosinophilic granulomatosis with polyangiitis** (Churg-Strauss) associated with associated with C-ANCA or P-ANCA? * What are the clinical findings?

Answer 26

* Eosinophilic granulomatosis with polyangiitis * **P**-ANCA (MPO) **\>** **C-**ANCA (PR3) * Clinical findings: Lung and skin vasculitis, asthma, eosinophilia

Question 27

T/F: Renal limited vasculitis is usually associated with C-ANCA (PR3)

Answer 27

* False, its usually associated with P-ANCA (MPO)

Question 28

What are the treatment guidelines for ANCA associated vasculitis?

Answer 28

* Cytotoxic drugs * Cyclophosphamide * Corticosteroids * B-cell targeted therapies * Rituximab * Plasma exchange (plasmaphoresis) * Removes pathogenic autoantibodies