Histo: Renal Disease Pt.3

Question 1

What is membranous glomerulonephritis?

Answer 1

• Common cause of nephrotic syndrome in adults
• Characterised by immune deposits outside the glomerular basement membrane (subepithelial - ‘spikey’)
• Primary disease is autoimmune
• It can occur secondary to epithelial malignancy, SLE, drugs and infections

Question 2

Which antibodies are often found in primary membranous glomerulonephritis?

Answer 2

Antibodies against phospholipase A2 type M receptor (PLA2R)

Question 3

Describe the typical progression of diabetic nephropathy.

Answer 3

• Occurs in 30-40% diabetics
• Typically begins with microalbuminuria
• Progresses to proteinuria and, eventually, nephrotic syndrome

Question 4

List and describe the stages of diabetic nephropathy.

Answer 4

• Stage 1: thickening of the basement membrane on electron microscopy
• Stage 2: increase in mesangial matrix, without nodules
• Stage 3: nodular lesions/Kimmelstein-Wilson nodules
• Stage 4: advanced glomerulosclerosis

Question 5

What is amyloidosis?

Answer 5

Deposition of extracellular proteinaceous material exhibiting beta-pleated sheet structure

Question 6

What are the two types of amyloidosis?

Answer 6

• AA - derived from serum amyloid associated protein (SAA), an acute phase protein, and associated with chronic inflammatory disease
• AL - derived from immunoglobulin light chains usually as a result of multiple myeloma (80%)

Question 7

Describe the histological appearance of amyloidosis

Answer 7

Apple green birefringence with Congo red stain

Question 8

Name two causes of isolated / asymptomatic microscopic haematuria.

Answer 8

• Thin basement membrane disease
• IgA nephropathy

Question 9

How can the cause of asymptomatic proteinuria be confirmed?

Answer 9

Renal biopsy for histology, IHC, and electron microscopy (could be caused by several abnormalities)

Question 10

What is thin basement membrane disease and what causes it?

Answer 10

• Basement membrane <250 nm thickness
• Caused by a hereditary defect in type IV collagen synthesis
• Microscopic haematuria is the only consequence in most cases

Question 11

What is Alport syndrome?
What is its inheritance pattern?

Answer 11

• X-linked dominant condition caused by a mutation in the alpha-5 subunit of type IV collagen (some forms affect alpha-3 and alpha-4)
• Leads to progressive damage resulting in renal failure in middle-age
• Often accompanied by deafness and ocular disease

Question 12

What is IgA nephropathy?

Answer 12

• Most common cause of glomerulonephritis
• Caused by mesangial IgA immune complex deposition
• 30% will progress to end-stage renal failure
• Presents 1-2 days after an URTI with frank haematuria (earlier than acute post-infectious GN)
• Immunofluorescence shows granular deposition of IgA and C3 in mesangium

NOTE: Henoch-Schonlein purpura is a type of IgA nephropathy

Question 13

What is acute post-infectious (post-streptococcal) GN?

Answer 13

• Occurs 1-3 weeks after streptococcal throat infection or impetigo (usually Lancefield Group A α-haemolytic strep = Strep. pyogenes)
• Glomerular damage thought to be due to immune complex deposition

Question 14

What will a biopsy show in post-infectious GN?

Answer 14

• Light microscope: ↑cellularity of glomeruli
• Fluorescence Microscope: granular deposits of IgG and C3 in GBM
• Electron Microscope: Subendothelial humps

Question 15

List some causes of chronic kidney disease and state which is most common.

Answer 15

• Diabetes mellitus (most common) - 27.5%
• Glomerulonephritis - 14.1%
• Polycystic kidney disease - 7.4%
• Pyelonephritis - 6.5%
• Hypertension - 6.8%
• Renal vascular disease - 5.9%

Question 16

What are some diseases associated with chronic kidney disease?

Answer 16

• Ischaemic heart disease
• Calcium and phosphate derangement (due to resulting hyperparathyroidism, osteomalacia and osteoporosis)

Question 17

What is the pathophysiology of hypertensive nephropathy?

Answer 17

• Narrowing of arteries and arterioles leading to scarring and ischaemia of glomeruli
• Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring

Question 18

What are consequences of hypertensive nephropathy?

Answer 18

• Shrunken kidneys with granular cortices
• Nephrosclerosis on histology - arterial hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis

Question 19

What system is used to classify lupus nephritis?

Answer 19

ISN/RPS classification

Question 20

Describe the histological appearance of lupus nephritis

Answer 20

• Immune complex deposition in capillaries > ‘wire loop capillaries’ (thickened)
• Deposition of immune complexes & complement in the GBM in a lumpy-bumpy granular fashion.

Question 21

What are the outcomes of lupus nephritis?

Answer 21

Highly variable

• Acute renal failure
• Nephrotic syndrome
• Isolated urinary abnormality
• CKD

Six stages:
• 1: Minimal mesangial disease, almost normal
• 2: Mesangial disease
• 3: Focal deposits
• 4: Diffuse deposits
• 5: Subepithelial membranous disease
• 6: Advanced sclerosis (>90%)