Isolated Glomerular Abnormalities - 923- 927

Question 1

What is Berger disease characterized by?

Answer 1

AKA IgA nephropathy…

Characterized by the presence of prominent IgA deposits in the mesangial regions and recurrent hematuria.

*the most common type of glomerulonephritis in the world.

Question 2

If I told you this was Berger’s disease, what would you say is lighting up in the image?

Answer 2

IgA

Question 3

The pathogenesis of Burgers disease seems to indicate a multi-hit etiology. What is the fundamental defect that leads to this condition?

Answer 3

Abberent glycosylation of IgA molecules, with attachment of O-linked glycans to the hinge region of the IgA molecule, particularly of the IgA1 subclass.

Question 4

On histologic examination Burger’s disease lesions vary considerably. What is the characteristic that is the key give-away?

Answer 4

Immunofluorescence reveals mesangial deposition of IgA, often with C3, properdin and lesser amounts of IgG or IgM.

Question 5

IgA nephropathy occurs with increased frequency in individuals with what?

Answer 5

• celiac disease (gluten enteropathy)
• people with intestinal mucosal defects
• liver disease

Question 6

Hereditary nephritis refers to a group of heterogeneous familial renal diseases associated with mutations in what?

Answer 6

Collagen genes that manifest primarily with glomerular injury.

Question 7

What are the two types of hereditary nephritis that Robbin’s judged worthy of consideration?

Answer 7

Alport syndrome

Thin basement membrane lesion

Question 8

Alport syndrome when fully developed is manifest by what?

Answer 8

1. hematuria with progression to renal failure
2. nerve deafness
3. lens dislocation
4. posterior cataracts
5. corneal dystrophy

Question 9

Is Alport syndrome worse in males or females?

Answer 9

Males, since it is most often X linked. ~90% of males progress to ESRD before 40 years of age.

Autosomal dominant pedigrees exist, where both men and women are susceptible to the full syndrome.

Question 10

What is the fundamental dysfunction in Alport’s syndrome?

Answer 10

Mutation leading to the defective assembly of the type collagen IV molecule.

Question 11

If you took a skin biopsy from an Alports patient, what would you see… or rather, not see?

Answer 11

Alpha-5 staining.

Question 12

What is the most common presenting sign of Alports?

Answer 12

Gross or microscopic hematuria, frequently accompanied by red cell casts.

Question 13

Thin basement membrane lesion (benign familial hematuria) is a fairly common hereditary entity manifested clinically by familial asymptomatic hematuria, usually uncovered on routine urinalysis. What do we see morphologically?

Answer 13

Diffuse thinning of the GBM to widths between 150 and 225 nm.

Question 14

The anomaly in thin basement membrane lesion has also been traced to mutations in genes encoding α3 or α4 chains of type IV collagen. Does this condition present with hearing loss or ocular abnormalities?

Answer 14

No

Question 15

What do homozygous individuals with thin basement membrane lesion disease face prognosis wise?

Answer 15

The disease in homozygotes resembles autosomal recessive Alports, and may progress to renal failure.

Question 16

Chronic glomerulonephritis refers to what?

Answer 16

End-stage glomerular disease that may result from specific types of glomerulonephritis of may develop without antecedent history of any of the well recognized forms of acute glomerulonephritis.

Question 17

What are some patients that may progress to chronic glomerulonephritis?

Answer 17

Patients with…

1. crescentic glomerulonephritis if they survive the acute episode typicall progress to this.
2. membranous nephropathy
3. IgA nephropathy
4. FSGS

Question 18

The kidneys are symmetrically contracted and have diffusely granular cortical surfaces. On section, the cortex is thinned, and there is an increase in peripelvic fat. The glomerular histology depends on the stage of the disease. In early cases, the glomeruli may still show evidence of the primary disease (e.g., membranous nephropathy or MPGN). However, there eventually ensues… what?

Answer 18

Obliteration of glomeruli, transforming them into acellular eosinophilic masses, consisting of a combination of trapped plasma proteins, increased mesangial matrix, basement membrane like material and collagen.

Question 19

What disease is this?

Answer 19

Chronic glomerulonephritis - the masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen.

Question 20

What is the prognosis for chronic glomerulonephritis?

Answer 20

If patients with this do not recieve a renal transplant or dialysis, they invariably die from the illness.

Question 21

What does Henoch-Schonlein Purpura consist of?

Answer 21

This childhood syndrome consists of purpuric skin lesions, abdominal pain and intestinal bleeding, and arthralgias along with renal abnormalities.

Question 22

The skin lesions in Henoch-Schönlein Purpura characteristically involve the extensor surfaces of arms and legs as well as buttocks; abdominal manifestations include pain, vomiting, and intestinal bleeding. Renal manifestations occur in 1/3 of patients and include?

Answer 22

1. gross or microscopic hematuria
2. nephritic syndrome
3. nephrotic syndrome
4. a small number of adults will develop a rapidly progressive form of glomerulonephritis with many crescents.

Question 23

What does onset of Henoch-Schönlein Purpura often follow?

Answer 23

Upper respiratory infection

Question 24

How is Henoch-Schönlein Purpura similar to IgA nephropathy?

Answer 24

It also involves deposition of IgA in the glomerular mesangium. This has led to the concept that these are manifestations of the same disease.

Question 25

Whatever the histologic lesions, the pathognomonic feature of Henoch-Schönlein purpura by fluorescence microscopy is…?

Answer 25

the deposition of IgA, sometimes with IgG and C3, in the mesangial region, sometimes with deposits extending to the capillary loops.

Question 26

The skin lesions in Henoch-Schönlein purpura consist of?

Answer 26

Subepidermal hemorrhages and a necrotizing vasculitis involving the small vessels of the dermis. (vasculitis also occurs in other organs such as the GI tract, but is rare in the kidney)

Question 27

What is the leading cause of kidney failure in the united states?

Answer 27

Question 28

In what percentage of diabetics does advanced or end stage kidney disease occur?

Answer 28

Up to 40% of both type I and type 2 diabetics.

Question 29

Fibrillary glomerulonephritis is a morphologic variant of glomerulonephritis associated with characteristic fibrillar deposits in the mesangium and glomerular capillary walls that resemble amyloid fibrils. What happens if you stain a sample with Congo red?

Answer 29

They will not stain with congo red. Though the deposits resemble amyloid fibrils superficially, the ultrastructure differs.

Question 30

What do fibrillary glomerulonephritis lesion usually show by light microscopy?

Answer 30

membranoproliferative or mesangioproliferative patterns