Glomerular Disease

Question 1

What is the glomerular filtration barrier composed of?

Answer 1

1. fenestrated glomerular capillary endothelium
2. glomerular basement membrane
3. slit membrane between pedicels

Question 2

What is the function of the mesangium?

Answer 2

• contractile properties

- removal of trapped residues and aggregate protein from the basement membrane

Question 3

1. What is glomerular disease?
2. What is the term given to causes of glomerular disease driven by inflammatory processes?
3. Name 2 causes of non-inflammatory causes of glomerular disease

Answer 3

1. damage/disease affecting the glomerulus which consequently disrupts filtration, leading to nephritic or nephrotic syndrome
2. glomerulonephritis
3. diabetic nephropathy and amyloidosis

Question 4

Describe what the following terms mean relating to glomerular disease:

1. diffuse
2. focal
3. global
4. segmental
5. proliferative
6. sclerosing
7. necrotising
8. primary
9. secondary

Answer 4

1. all glomeruli are affected
2. only one/a few glomeruli are affected
3. whole glomerulus is affected
4. only part of the glomerulus is affected
5. increased number of cells within the glomerulus
6. scarring of the glomerulus
7. cell death within the glomerulus
8. glomerular inflammation intrinsic to the kidney
9. associated with disease extrinsic to the kidney - certain infections, systemic disorders or diabetes

Question 5

Describe the following mechanisms of glomerular injury, and examples of diseases:

1. immune complex trapping
2. in situ antigens
3. antigen deposition
4. endothelial cell injury

Answer 5

1. antigen-antibody complexes present in the blood get stuck in the basement membrane, triggering complement activation in the glomerulus
   - e.g. SLE
2. antigen present in the basement membrane
   - e.g. goodpastures
3. bacterial antigen becomes implanted in the basement membrane as a result of bacteraemia
   - e.g. post infectious glomerulonephritis
4. endotoxins activate both classical and alternate complement pathways. leading to endothelial damage
   - e.g. ANCA associated vasculitis; haemolytic uraemic syndrome

Question 6

name the 5 possible presentations of glomerulonephritis

Answer 6

1. isolated haematuria and/or proteinuria
2. nephrotic syndrome
3. nephritic syndrome
4. AKI
5. CKD

Question 7

What are the characteristic hallmarks of NEPHROTIC Syndrome

Answer 7

1. proteinuria (++++; >3.5g in 24 hours)
2. hypoalbuminaemia
3. hyperlipidaemia (liver compensates for hypoalbuminaemia which also increases lipid production)
4. oedema (loss of intravascular oncotic pressure)

Question 8

Name 4 causes of nephrotic syndrome

Answer 8

1. minimal change disease
2. focal, segmental, glomerulosclerosis
3. membranous glomerulonephritis
4. diabetic nephropathy

Question 9

How is nephrotic syndrome managed?

Answer 9

1. dietary sodium restriction
2. thiazide diuretic
3. albumin infusion
4. prophylactic anticoagulation
5. pneumococcal vaccine
6. statins
7. ACEi

Question 10

What are the 4 characteristics of NEPHRITIC syndrome?

Answer 10

1. Haematuria
2. proteinuria (++)
3. mild hypertension
4. oliguria

Question 11

Name 5 causes of nephritic syndrome

Answer 11

1. IgA nephropathy
2. post-strep glomerulonephritis
3. goodpastures syndrome
4. vasculitis
5. membranoproliferative glomerulonephritis

Question 12

does non proliferative glomerulonephritis generally cause nephritic or nephrotic syndrome?

Answer 12

Nephrotic syndrome

Question 13

1. what is the main investigation for minimal change disease?
2. in what patients is minimal change disease the most common cause of nephrotic syndrome?
3. how is minimal change disease managed?

Answer 13

1. renal biopsy - electron microscopy reveals abnormal podocytes
2. children
3. supportive care and prednisolone

Question 14

1. Name 2 secondary causes of FSGS
2. how is FSGS managed?
3. What is the prognosis of FSGS?

Answer 14

1. HIV infection; reflux nephropathy
2. general management of nephrotic syndrome
3. poor - 50% progress to ESKD

Question 15

1. What is the pathological mechanism underlying membranous glomerulonephritis?
2. is it a proloferative or non-proliferative glomerulonephritis?
3. Name 5 causes of membranous glomerulonephritis
4. What is useful in the management of the disease?
5. How does prognosis follow the rule of 1/3?

Answer 15

1.immune complex deposition within the glomerular basement membrane

2. non-proliferative
3. idiopathic; Hep B, SLE, malaria, penicillamine
4. steroids if the disease begins to progress
5. 1/3 have chronic membranous glomerulonephritis
   1/3 go into remission
   1/3 progress to ESKD

Question 16

does proliferative glomerulonephritis generally cause nephritic or nephrotic syndrome?

Answer 16

nephritic syndrome

Question 17

What is the most common type of glomerulonephritis in adults?

Answer 17

IgA nephropathy

Question 18

1. What is the main presentation of IgA nephropathy?
2. When does this symptom occur?
3. What is the diagnostic investigation?
4. How is the disease managed?
5. what is its prognosis?

Answer 18

1. macroscopic haematuria
2. 24-48 hours following upper respiratory tract infection
3. renal biopsy (IgA deposits; increased mesangial cells and ECM)
4. steroids and cyclophosphamide
5. can be relatively benign or lead to ESKD

Question 19

1. When does post-streptococcal glomerulonephritis occur?
2. What is found on renal biopsy?
3. What is the management and prognosis of the condition?

Answer 19

1. 2-4 weeks after strep pyrogenes infection
2. proliferation of mesangial cells; neutrophils and monocytes; compression of bowman’s space
3. supportive treatment; usually resolves within 2-4 weeks

Question 20

1. What autoantibodies are responsible for goodpastures syndrome
2. what is the clinical presentation of goodpastures syndrome and why?
3. How is the disease managed?
4. What is the disease prognosis?

Answer 20

1. anti-glomerular basement membrane antigens
2. nephritic syndrome and haemoptysis
   - GMB antigens present in glomeruli and lung alveoli
3. high dose immunosuppression with IV pred and cyclophosphamide; plasmapheresis to remove autoantibodies
4. results in CKD

Question 21

1. What is membranoproliferative glomerulonephritis caused by?
2. How does it differ from membranous glomerulonephritis?
3. How is it managed?

Answer 21

1. sub endothelial deposition of immune complexes. Can be primary or secondary to SLE/Hep B/C
2. mesangium and basement membrane is thickened.
3. steroids and cytotoxic drugs; treat underlying cause

Question 22

1. What is Wegener’s Granulomatosis?
2. What is it caused by?
3. How is it managed?

Answer 22

1. vasculitis affecting the lungs, kidneys and other organs
2. c-ANCA antibodies
3. IV steroids and cyclophosphamide

Question 23

1. What is microscopic polyangiitis?
2. What is it caused by?
3. How is it managed?

Answer 23

1. small vessel vasculitis affecting almost any organ system
2. p-ANCA antibodies
3. prednisolone and cyclophosphamide; plasmapheresis to remove antibodies

Question 24

1. What is Henoch-Schönlein Purpura?

2. Which patient group does this more commonly affect?

Answer 24

1. systemic IgA vasculitis - IgA and complement C3 are deposited in blood vessels
2. children

Question 25

Name another type of vasculitis that can cause proliferative glomerulonephritis

Answer 25

Haemolytic uraemic syndrome