Glomerular disease

Question 1

What is the most common cause of nephrotic syndrome in children?

Answer 1

Minimal change glomerulonephritis

Question 2

Describe the pathophysiology of minimal change glomerulonephritis

Answer 2

Biopsy appears normal under visible light microscopy
Electron microscopy show fusion of podocyte pedicles - this impairs selectivity of GBM, allowing protein to pass into the urine

Question 3

What problems can occur if the glomerular basement membrane fails and proteins are allowed to leak into the urine?

Answer 3

Albumin - oedema, hyperlipidaemia
Immunoglobulin - increased risk of infection
Anticoagulation factors - hypercoagulability, risk of thromboembolism

Question 4

How is membranous nephropathy diagnosed?

Answer 4

Biopsy and silver-stain microscopy

- biopsy shows diffuse thickening of the glomerular basement membrane

Question 5

What is the most common cause of nephrotic syndrome in adults?

Answer 5

Membranous nephropathy (diffusely thickened glomerular basement membrane)

Question 6

What is meant by “proliferative” glomerulonephritis?

Answer 6

Glomerular disease characterised by excess numbers of cells in glomeruli, including white blood cell infiltration.

Question 7

What is the major difference between nephritic and nephrotic syndrome?

Answer 7

Nephritic syndrome involves blood loss (haematuria)
Nephrotic syndrome involves protein loss (proteinuria) but not haematuria
(small amount of proteinuria may be seen in nephritic syndrome)

Question 8

What is the most common cause of nephritic syndrome in children?

Answer 8

Post-infective glomerulonephritis

- diffuse proliferative GN (>50% glomeruli affected)

Question 9

Describe the pathophysiology of post-infectious glomerulonephritis. Which organism is the most common cause?

Answer 9

Most commonly caused by group A strep (e.g. Strep pyogenes).
Infiltration of inflammatory cells (initially neutrophils) and overproliferation of the endothelial and mesangial cells lead to enlargement of the glomerulus.
Ig and complement are also deposited in the glomerulus (usually IgG.

Question 10

For which type of glomerular disease is a biopsy usually unnecessary?

Answer 10

Post-infective GN

Question 11

What is Wegener’s granulomatosis? What type of renal disease is it most associated with?

Answer 11

Granulomatosis with polyangiitis (GPA).
A form of vasculitis that affects small- and medium-size vessels in many organs.
(polyangiitis means inflammation of multiple blood vessels involving more than one type of vessel)
Associated with crescentic glomerulonephritis

Question 12

What is Churg-Strauss syndrome?

Answer 12

Eosinophilic granulomatosis with polyangiitis (EGPA).
A rare autoimmune condition that causes inflammation of small and medium-sized blood vessels in individuals with a history of airway allergic hypersensitivity.

Question 13

What is Goodpasture syndrome? Which antibodies are indicative of this disease?

Answer 13

A rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure.
Can cause Crescentic GN. Often also presents with a cough.
Anti-GMB autoantibodies

Question 14

Which type of glomerulonephritis is associated with the presence of ANCA antibodies in the serum/kidney

Answer 14

Crescentic GN (may present with rapidly progressive GN - RPGN)
May be a vasculitic cause, e.g. Wegener's granulomatosis or Churg-Strauss syndrome.

Question 15

In a patient with crescentic glomerulonephritis, what would a biopsy show?

Answer 15

Endothelial damage and fibrin deposits
Necrotic capillary loops
Cellular proliferation and macrophage infiltration within the Bowman’s space

Question 16

How is Crescentic glomerulonephritis treated?

Answer 16

Plasma exchange

Immunosuppression (prednisolone, cytotoxic agents)

Question 17

How is Crescentic glomerulonephritis diagnosed?

Answer 17

Biopsy - bowman’s space infiltration
Serology
- ANCA autoantibodies (vasculitis)
- anti-GBM autoantibodies (Goodpasture’s)

Question 18

Describe the pathophysiology of IgA nephropathy

Answer 18

IgA deposits are not removed
Mesangium (not the filtration membrane) becomes clogged with IgA
IgA irritates the mesangial cells and causes overproliferation
Glomerular capillaries remain clear and healthy

Question 19

What is IgA nephropathy?

Answer 19

IgA deposition causes increased proliferation of mesangial cells and over-production and accumulation of mesangial matrix. May be provoked by infection by actual cause is unknown.

Question 20

Describe the clinical features of nephritic syndrome

Answer 20

Proteinuria (mild)
Haematuria
Azotaemia (elevated blood nitrogen levels)
Red cell casts
Oliguria (urine < 300ml/day)
Antibodies
Hypertension

Question 21

Describe the clinical features of nephrotic syndrome

Answer 21

Na+ decrease (hyponatraemia)
Albumin decrease (hypoalbuminaemia)
Proteinuria
Hyperlipidaemia
Renal vein thrombosis
Oedema (orbital)
Thromboembolisms
Infection risk
Coagulability (due to loss of anticoagulation factors)

Question 22

Which conditions can cause secondary nephrotic syndrome?

Answer 22

Systemic Lupus Erythemus
HIV
Hepatitis B/C
Diabetes mellitus
Malignancy

Question 23

How would you investigate a patient presenting with features of nephritic syndrome?

Answer 23

Urine dipstick
Blood pressure measurement
Assess for oedema
FBC, U&E, ESR, CRP
eGFR (GFR if possible), renal function tests, LFTs
Serology for autoantibodies: ANCA, anti-GBM
Renal biopsy

Question 24

How would you investigate a patient presenting with features of nephrotic syndrome?

Answer 24

Urine dipstick
 - followed by urinalysis to quantify proteinuria
FBC, U&E, LFTs
Bone profile
Tests for underlying cause:
 - ESR, CRP
 - fasting glucose
 - immunoglobulins, serum/urine electrophoresis
 - serology: autoantibodies, hep B/C

Question 25

How is nephrotic syndrome managed?

Answer 25

Sodium/fluid restriction
High dose diuretic treatment
Treat underlying cause
Prophylaxis against complications (e.g. heparin, penicillin)

Question 26

Which antibodies are associated with post-infective GN?

Answer 26

Anti-streptolysin O titres (ASOT) if post-streptococcal infection

Question 27

What are the requirements to ensure a safe renal biopsy?

Answer 27

Blood pressure < 150/90
Platelets > 100x10^9/L
Normal clotting
No low molecular weight heparin in the last 24 hours