glomerulonephritis

Question 1

Define glomerulonephritis

Answer 1

A group of diseases associated with inflammatory injury of the glomeruli indicated by Infiltration of leukocytes, Deposition of immune proteins and Disturbed function of the affected tissue

Question 2

Which cell types can be involved in glomerulonephritis

Answer 2

Mesangium, podocytes, capillaries/endothelium, parietal epithelial cells

Question 3

Nephritic syndrome definition

Answer 3

• Reduction in GFR (an elevated serum creatinine)
• Active urine sediment (RBC’s, WBC’s, and RBC casts)
• Proteinuria (usually sub-nephrotic)
• Edema
• Hypertension
• Reduction in GFR (an elevated serum creatinine)
• Active urine sediment (RBC’s, WBC’s, and RBC casts)
• Proteinuria (usually sub-nephrotic)
• Edema
• Hypertension
• Reduction in GFR (an elevated serum creatinine)
• Active urine sediment (RBC’s, WBC’s, and RBC casts)
• Proteinuria (usually sub-nephrotic)
• Edema
• Hypertension

Question 4

What causes proteinuria in nephritic syndrome

Answer 4

direct damage to the glomerular capillary wall induced by immunologic mechanisms leading to an increase in protein filtration. <3g/day b/c damage is focal (as opposed to nephrotic syndrome where entire capillary is affected)

Question 5

What causes reduced GFR in nephritic syndrome

Answer 5

acute, inflammatory process within the glomerulus resulting in glomerular vasoconstriction and/or occlusion or thrombosis of some glomerular capillary loops

Question 6

What causes active urine sediment in nephritic syndrome

Answer 6

The excretion of red cells, white cells and red cell casts reflects glomerular inflammation and disruption of the GBM

Question 7

What causes hypertension in nephritic syndrome

Answer 7

consequence of salt and water retention.

Question 8

What causes edema in nephritic syndrome

Answer 8

increase in tubular reabsorption of salt and water due to reduced, glomerular perfusion with well preserved tubular function leading to expansion of extracellular fluid volume

Question 9

Does glomerulonephritis require a kidney biopsy for diagnosis?

Answer 9

YES

Question 10

Syndromes associated with aggressive disease

Answer 10

Rapidly progressive glomerulonephritis (RPGN), Crescentic glomerulonephritis, Pulmonary-Renal syndrome

Question 11

Rapidly Progressive Glomerulonephritis (RPGN) description, associations and therapy

Answer 11

Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange

Question 12

Crescentic Glomerulonephritis description, associations and therapy

Answer 12

Crescents seen on biopsy. Caused by rupture of capillary wall. Usually associated with Anti-GBM disease, ANCA associated vasculitis and Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange

Question 13

Pulmonary-renal syndrome description, associations and therapy

Answer 13

Glomerulonephritis with pulmonary capillaritis. Presents with nephritic syndrome and hemoptysis. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange

Question 14

List mechanisms for glomerulonephritis pathophysiology and associated diseases

Answer 14

1) Deposited immune-complexes: Lupus, MPGN 2) Antibodies specific for renal antigens: Anti-GBM disease, lupus? 3) Other causes of inflammation within glomeruli: Vasculitis (ANCA associated disease), Hemolytic uremic syndrome, C3 glomerulopathy

Question 15

Describe locations of immune complex deposition within glomeruli

Answer 15

Mesangial, subendothelial, subepithelial, intra-membranous

Question 16

Describe causes of immune complex formation

Answer 16

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

Question 17

How do immune complexes cause damage to glomerulus?

Answer 17

Complement is activated which activates PMNs that release proteases/oxidants causing capillary wall damage, which then leads to fibrin and crescent development. Also, macrophages can be directly activated by deposits.

Question 18

Drugs used to treat glomerulonephritis

Answer 18

Immunosuppresives: Prednisone, cyclophosphamide, rituximab, IVIg

Question 19

Which diseases is plasma exchange used and what does it do

Answer 19

Removes large plasma proteins such as auto-antibodies. Used in anti-GBM disease, severe ANCA associated vasculitis, and severe cryoglobulinemia

Question 20

Post infectious glomerulonephritis etiology, pathology,

Answer 20

Abs + streptococcal Ags lodge in glomeruli and activate complement. Light microscopy: proliferative and exudative glomerulonephritis with infiltration of neutrophils and monocytes. Immunofluorescence (IF): granular deposits of IgG and C3 in the subendothelial, mesangial and subepithelial locations. EM: subendothelial and mesangial deposits, as well as the classic “subepithelial humps”.

Question 21

Post infectious glomerulonephritis presentation, diagnosis, treatment

Answer 21

Edema, weight gain, hematuria, subnephrotic proteinuria, GFR decreased, severe hypertension. Elevated anti-streptolysin O, decreased C3. Usually get better without treatment

Question 22

IgA nephropathy description/ presentation, associations, timeline and treatment

Answer 22

Mesangial IgA and mesangial expansion. Usually presents with hematuria +/- subnephrotic proteinuria. Associated with aberrant glycosylation of IgA1. Slowly progressive. Treated with prednisone, BP meds and ACEI
Mesangial IgA and mesangial expansion. Usually presents with hematuria +/- subnephrotic proteinuria. Associated with aberrant glycosylation of IgA1. Slowly progressive. Treated with prednisone, BP meds and ACEI

Question 23

MPGN

Answer 23

Mesangial proliferation and thickening of GBM. C3 and IgG deposits in capillary walls and mesangium. Presents as nephritic syndrome, with hypertension. Many have Hep C. Poor prognosis.

Question 24

Lupus nephritis causes

Answer 24

immune complex deposits: Mesangium (hematuria), subendothelial (nephritic syndrome and hematuria), and/or subepithelial (nephrotic)

Question 25

Classifications of lupus nephritis

Answer 25

I-II: mesangial. III-IV: subendothelial. V: subepithelial. VI: scarring of >90% of glomeruli leading to renal failure.

Question 26

lupus nephritis pathology and presentation

Answer 26

Immunofluorescence may demonstrate C3, IgG, IgM, IgA, and C1q all within the same kidney. These deposits appear as “lumps and bumps” Can present as nephritic or nephrotic

Question 27

Anti-glomerular basement membrane disease causes and result

Answer 27

Caused by auto-antibodies to the NC1 domain of the alpha-3 chain of type IV collagen. Can be renal or pulmonary-renal. Often causes crescentic, necrotizing glomerulonephritis and RPGN

Question 28

Goodpastures triad

Answer 28

pulmonary hemorrhage, iron deficiency anemia and GN associated with circulating antibody to GBM

Question 29

Anti-glomerular basement membrane disease diagnosis and treatment

Answer 29

Check patients with nephritic syndrome, RPGN, or pulm-renal syndrome. Diagnosed by biopsy(linear IgG deposits) and detection of anti-GBM antibodies. Can see crescent formation. If untreated, progresses to end stage renal disease. Treated with cytotoxic drugs, corticosteroids and plasma exchange

Question 30

ANCA associated vasculitis diagnosis

Answer 30

Check patients with nephritic syndrome, RPGN, or pulm-renal syndrome. Diagnosed by detection of ANCA (anti-neutrophil cytoplasmic antibodies) and biopsy

Question 31

ANCA associated vasculitis disease examples, clinical findings and type of ANCA

Answer 31

Granulomatosis with polyangiitis (formerly called Wegener’s disease) causes nephritic syndrome with airway involvement- C-ANCA. Microscopic polyangiitis causes nephritic syndrome with airway involvement- P-ANCA. Eosinophilic granulomatosis with polyangiitis causes lung and skin vasculitis, asthma and eosinophilia- P-ANCA/C_ANCA. Renal limited vasculitis is P-ANCA
Granulomatosis with polyangiitis (formerly called Wegener’s disease) causes nephritic syndrome with airway involvement- C-ANCA. Microscopic polyangiitis causes nephritic syndrome with airway involvement- P-ANCA. Eosinophilic granulomatosis with polyangiitis causes lung and skin vasculitis, asthma and eosinophilia- P-ANCA/C_ANCA. Renal limited vasculitis is P-ANCA

Question 32

Treatment of ANCA associated vasculitis

Answer 32

High mortality w/out treatment. Cytotoxic drugs, corticosteroids, Rituximab, plasma exchange

Question 33

Cryoglobulinemia description, pathology, presentation

Answer 33

Cryoglobulins are antibodies that precipitate in the cold. In vivo they can form immune-complexes that precipitate in small vessels, causing vasculitis. Membrano-proliferative pattern of injury with subendothelial immune deposits. Associated with Hepatitis C and presents with proteinuria, hematuria, purpura

Question 34

Henoch-Schonlein purpura description

Answer 34

in kids: (palpable purpura), arthritis, GI involvement (colic and bleeding) and glomerulonephritis. In adults: renal more severe, systemic less obvious. focal proliferative necrotizing glomerulonephritis, often with crescent formation, accompanied by mesangial and capillary wall deposits of IgA. Similar to IgA nephropathy