B73 Systemic diseases associated with glomerular damage

Question 1

List the systemic diseases that damage the kidneys

Answer 1

Diabetic nephropathy, aka diabetic glomerular sclerosis

Amyloidosis

Goodpasture syndrome

Polyartheritis nodosa

Wegener granulomatosis

SLE

Question 2

Breif bulletpoints for diabetic nephropathy

Answer 2

Basement membrane thickening related to non enzymatic glycosylation and subsequent hyaline arteriolosclerosis

Diffuse glomerulosclerosis mesangial proliferation and hyaline deposits.

Nodular glomerulosclerosis in the form of Kimmelstiel-Wilson nodules

Chronic pyelonephritis

Eventual renal failure

Progression is microalbuminuria, nephrosis syndrome, sclerosis and end stage renal disease

Question 3

How does amyloidosis cause glomerular damage?

Answer 3

• Subendothelial amyloid deposition
• Initially mesangial deposits of amyloid cause initial nephrosis syndrome.
• Then eventual diffuse thickenings of the capillary basement membranes and compression and occlusion of capillaries.
• There is also amyloidosis around the tubular epithelium.
• Progression eventually to end stage renal disease
• Early stage kidney is abnormally large, pale, gray. earlier
• On eventual end stage renal failure, it may be small contracted
• Most common types of amyloidosis that cause renal disease: are multiple myeloma and AL light chain amyloidosis and SAA associated amyloidosis.
• Beta2-microglobulin is most associated to occur secondary to renal failure due to inpaired excretion, and inneficient removal by dialysis.

Question 4

What are the most frequent systemic causes of nephrosis?

Answer 4

Diabetes, amyloidosis, and SLE

Question 5

How does goodpasture syndrome cause kidney damage?

Answer 5

Autoantibodies produced against the glomerular basement membrane (and also alveolar basement membrane)

Causes linear IF staining.

Causes nephritis syndrome that progresses to RPGN and lung hemorrhage

GBM antigen is against the alpha 3 chain of collagen 4.

Question 6

What are the major causes of RPGN?

Answer 6

anti-GBM crescentic glomeruonephritis

• Goodpasture syndrome,

Immune complex mediated crescentic glomerulonephritis

• IC-mediated Cresecentic glomerulonephritis. :crescents can be a complication of any of the IC mediated nephritises.
• Post strep GN
• SLE
• IgA nephropathy
• Henoch Shonlein purpura - similar to IgA nephropathy, involves IgA-immune complex deposition and C3 complement deposition in the kidney and in the walls of small vessels.

Pauci-immune crescentic glomerulonephritis

• Microscopic polyangitis
• Wegener granulomatosis
  
  • both of these two have anti-neutrophil cytoplasmic antibodies in the serum, ANCAs
• Idiopathic with no ANCA antibodies

Question 7

Describe Wegener’s granulomatosis

Answer 7

ii. Wegener’s granulomatosis is an ANCA positive, necrotizing vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end‐organ damage, it is life threatening and requires longterm immunosuppression.

triad of:
1. Acute necrotizing granulomas of the upper and/or lower respiratory tract (ear, nose, sinuses,
throat, or lungs)
2. Necrotizing or granulomatous vasculitis affecting small to medium‐sized vessels
(capillaries, venules, arterioles and arteries), most prominent in the lungs and
upper airways.
3. Renal disease in the form of focal, segmental, necrotizing, often crescentic,
glomerulonephritis.

_______

Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and
kidneys
2. Classic presentation is a middle-aged male with sinusitis or nasopharyngeal
ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria due
to rapidly progressive glomerulonephritis.
3. Serum c-ANCA levels correlate with disease activity,
4. Biopsy reveals large necrotizing granulomas with adjacent necrotizing vasculitis
(Fig. 7.4).
5. Treatment is cyclophosphamide and steroids; relapses are common,

Question 8

Describe polyarteritis nodosa

Answer 8

Causes segmental, transmural, necrotizing inflammation of small and medium arteries.

Fibrinoid necrosis is seen in active inflammation areas.

Old lesions have fibrous thickening extending through all layers.

Often cause thrombosis

Kidney, heart, liver, and GI vessels are most affected, in that order. Note the lungs are not involved.

about 1/3rd of cases have chronic hepatitis B and HBsAg immune complexes deposit in the vessels. The remaining cases are idiopathic.

Classically presents in young adults as hypertension (renal artery involvement), abdominal pain with melena (mesenteric artery involvement), neurologic disturbances, and skin lesions.

Lesions of varying stages are present. Early lesion consists of transmural
inflammation with fibrinoid necrosis (Fig. 7.3); eventually heals with fibrosis,
producing a ‘string-of-pearls’ appearance on imaging
4. Treatment is corticosteroids and cyclophosphamide; fatal if not treated

Question 9

What are the 6 classes of kidney disease seen in SLE?

Answer 9

According to WHO morphologic classification there are five patterns of glomerular disease in SLE:

Class I: Normal by LM, EM and IF microscope (< 5% of SLE patients).

Class II (mesangial lupus GN): 10‐25% of patients.
Mild clinical symptoms. Immune complexes deposits in the mesangium
with a slight increase in the mesangial matrix and cellularity

Class III (focal proliferative GN): 25‐30%
Lesions are present in portions of fewer than 50% of the glomeruli.
Typically, one or two foci show swelling and proliferation of endothelial
and mesangial cells, infiltration by neutrophils and/or fibrinoid deposits
with capillary thrombi.
Clinically associated with mild nephritis synd, microscopic hematuria and proteinuria,

Class IV (diffuse proliferative GN): 35-60%
Most serious form of renal SLE lesion, and also the most common
Most glomeruli show endothelial and mesangial proliferation affecting
the entire glomerulus, leading to diffuse hypercellularity of the
glomeruli.
c. EM / IF shows electron‐dense subendothelial immune‐complexes causing nephritis and potentially RPGN
d. In the course of time, glomerular injuries give rise to scarring
(glomerulosclerosis). Most of these patients have hematuria with
moderate to severe proteinuria, hypertension and renal insufficiency.

Class V (membranous GN) 10‐15%
b. Widespread thickening of capillary wall caused by subepithelial deposition immune complexes. Increased deposition of basement‐membrane.
c. Patients with this histological change almost always have severe
proteinuria, nephrosis

Class VI: Advanced sclerosing lupus nephritis: End stage renal deisease and comploete sclerosis of the glomeruli.