Glomerulonephritis

Question 1

What are the targets for pathology in the glomerulus?

Answer 1

• parietal epithelial cell
• podocyte
• mesangial cell
• endothelial cell

Question 2

List the mechanisms for glomerulonephritis

Answer 2

• antibodies, immune complexes, complement
• cell-mediated (eg. growth factors, cytokines, proteinuria)
• metabolic, genetic, vascular
• acute/chronic

Question 3

What investigation would you want to carry out if suspecting glomerulonephritis?

Answer 3

• kidney biopsy (US guided):
• light microscopy (look at tubules and interstitium - architecture)
• immunofluorescence (IgG/IgA/IgM etc. lighting up capillary wall)
• electron microscopy (look at ultrastructure for any deposits within glomerulus)

Question 4

List the spectrum of presentations of renal disease

Answer 4

• incidental finding +/- impaired kidney function
• visible haematuria
• synpharyngitic (sore throat + visible haematuria)
• nephritic syndrome
• nephrotic syndrome
• acutely unwell with rapid glomerulonephritis

Question 5

Define nephrotic syndrome

Answer 5

• 3.5g proteinuria per 24hr (PCR >300)
• serum albumin <30
• oedema (Na+ retention, decreased oncotic pressure etc.)
• hyperlipidaemia
• risk of venous thromboembolism + infection

Question 6

Define nephritic syndrome

Answer 6

• hypertension
• blood and protein in urine
• declining kidney function

Question 7

Describe the mechanisms of nephrotic syndrome

Answer 7

• high levels of proteinuria and lower levels of haematuria
• injury to podocytes

Results in:
- scarring
- deposition of matrix and other elements in glomeruli

Question 8

Describe the mechanism of nephritic syndrome

Answer 8

• high levels of haematuria and lower levels of proteinuria (need both for diagnosis tho)
• inflammation and reactive cell proliferation
• breaks in basement membrane
• crescent formation

Question 9

List some causes of nephritic and nephrotic syndrome

Answer 9

Nephritic (damage to glomeruli):
- IgA nephropathy
- small vessel vasculitis
- post-strep glomerulonephritis

Nephrotic (damage to podocytes):
- minimal change nephrotpathy
- membranous nephropathy
- diabetic nephropathy
- amyloidosis

Question 10

Describe the progression of IgA nephropathy

Answer 10

• starts with minor urinary abnormalities
• hypertension
• renal impairment and heavy proteinuria
• rapidly progressive glomerulonephritis

Question 11

Describe the features of IgA nephropathy

Answer 11

• can be precipitated by infection = synpharyngitic
• can be secondary to HSP, cirrhosis and coeliacs
• most common primary glomerular disease
• results in abnormal/over-production of IgA1, IgA I/C
• mesangial IgA, C3 deposition
• mesangial cell proliferation

Question 12

Describe the clinical presentation and management of IgA nephropathy

Answer 12

• haematuria
• hypertension
• proteinuria (varying its prognosis)
• no specific treatment
• anti-hypertensives (ACEi)
• risk of progression to ESRF

Question 13

Describe the features of membranous glomerulonephritis

Answer 13

• can occur secondary to malignancy, CTD or drugs (10%)
• contains anti-phospholipase A2 receptor antibody in primary cases (70%)
• commonest primary cause of nephrotic syndrome
• immune complex deposition in BM/sub-epithelial space
• risk of recurrence and progression to ESRF (1-2y)

Question 14

Describe the approach to treatment of membranous nephropathy

Answer 14

• treat underlying disease if secondary
• supportive non-immunological treatment (ACEi, statin, diuretics, salt restriction)
• specific immunotherapy (steroids, alkylating agents - cyclophosphamide, alternative agents - rituximab, cyclosporin

Question 15

Describe the features of minimal change disease

Answer 15

• commonest form of glomerulonephritis in children
• can cause nephrotic syndrome
• can be secondary to malignancy
• caused by T cell, cytokine mediated fusion of podocytes

Question 16

Describe the clinical presentation and management of minimal change disease

Answer 16

• can be acute (following URTI)
• oedema
• normal or reduced GFR
• can relapse
  (no biopsy needed, rarely causes RF)

Treatment: high dose steroids, prednisolone 1mg/kg for up to 8 weeks

Question 17

Describe the features of crescent GN (crescentic disease)/ rapidly progressing GN

Answer 17

• group of conditions that demonstrate glomerular crescents on kidney biopsy
• aggressive and risk of ESFR
• causes: ANCA vasculitis (MPO/PR3), Good-pastures (anti-GBM), lupus nephritis, infection, HSP