Glomerulonephritis

Question 1

Define

Answer 1

Immunologically mediated inflammation of renal glomeruli

• Damage to the glomerulus restricts blood flow, leading to compensatory ↑BP
• Damage to the filtration mechanism allows protein and blood to enter the urine
• Loss of the usual filtration capacity leads to acute kidney injury
• Includes a range of immune-mediated disorders

Question 2

Causes

Answer 2

Primary or secondary (when glomerular involvement is part of a systemic disease - e.g. SLE, polyarteritis nodosa)

Glomerulonephritides may be:

• Minimal change.
• Diffuse: affecting all glomeruli.
• Focal: affecting only some of the glomeruli.
• Segmental: only affecting parts of an affected glomerulus

There are loads of different types of glomerulonephritis with different aetiologies

• Some types are caused by the deposition of antigen-antibody complexes in the glomeruli
• This leads to inflammation and activation of complement and coagulation cascades
• The immune complexes may form within the glomerulus (more common) or be deposited from the circulation
• The antigens to which the antibodies are produced are UNKNOWN but may be associated with:

1. Bacteria (e.g. Streptococcus viridans, Staphylococci)
2. Viruses (e.g. HBV, HCB, measles, mumps, EBV)
3. Protozoal (e.g. Plasmodium malariae, schistosomiasis)
4. Inflammatory/Systemic diseases (e.g. SLE, vasculitis, cryoglobulinaemia)
5. Drugs (e.g. gold, penicillinamine)
6. Tumour

Classification is based on the site of nephron pathology and its distribution

Minimal-change Glomerulonephritis

• Light microscopy - minimal change
• Electron microscopy - loss of epithelial foot process

Membranous Glomerulonephritis

• Thickening of glomerular basement membrane (GBM) from immune complex deposition
• Associated with Goodpasture’s Syndrome

Membranoproliferative Glomerulonephritis (MPGN)

• Thickening of GBM
• Mesangial cell proliferation and interdeposition

Focal segmental glomerulosclerosis

• Glomerular scarring
• Associated with HIV

Focal segmental proliferative glomerulonephritis

• Mesangial and endothelial cell proliferation
• Focal = involvement of some glomeruli
• Segmental = involvement of parts of individual glomeruli

Diffuse proliferative glomerulonephritis

• Same as above but affects ALL glomeruli
• IgA Nephropathy
• Mesangial cell proliferation
• Mesangial IgA and C3 deposits

Crescentic Glomerulonephritis

• Crescent formation by macrophages and epithelial cells, which fills up Bowman’s space
• Focal Segmental Necrotising Glomerulonephritis
• Peripheral capillary loop necrosis (occurs in granulomatosis with polyangiitis, microscopy polyarteritis and other vasculitides)
• Often evolves into crescentic glomerulonephritis

Question 3

Epidemiology

Answer 3

Accounts for 25% of the cases of chronic renal failure

Question 4

Symptoms

Answer 4

• Haematuria
• Subcutaneous oedema
• Polyuria or oliguria
• History of recent infection
• Symptoms of uraemia or renal failure (acute and chronic)

Question 5

Signs

Answer 5

Hypertension

Proteinuria

Haematuria (especially in IgA nephropathy)

Renal failure

Nephrotic syndrome - consists of a TRIAD of:

• Proteinuria > 3.5 g/24 hrs
• Low serum albumin < 24 g/L
• Oedema
• NOTE: due to the hypoalbuminaema, the liver tries to compensate and increases production of lipids, causing hyperlipidaemia

Nephritic syndrome (TRIAD: hypertension + proteinuria + haematuria)

• Syndrome comprising of signs of nephritis
• Pores in the podocytes are large enough to allow protein AND red blood cells to pass into the urine

MAIN FEATURE: Haematuria

• This is in contrast to nephrotic syndrome, which is mainly concerned with proteinuria
• There may also be red cell casts in the urine - indicative of glomerular damage

Other features:

• Proteinuria
• Hypertension
• Low urine output (due to decreased renal function)
• NOTE: in nephrotic syndrome, only PROTEINS are moving into the urine

Question 6

Investigations

Answer 6

Bloods

• FBC
• U&Es + creatinine
• LFTs (check albumin)
• Lipid profile
• Complement studies
• Antibodies:
  
  • ANA
  • Anti-dsDNA
  • ANCA
  • Anti-GBM antibody
  • Cryoglobulins

Urine

• Microscopy - check for red cell casts
• 24 hr collection: creatinine clearance and protein

Imaging

• Renal tract ultrasound to exclude other pathology (e.g. obstruction)

Renal Biopsy

For microscopy

• Investigations for associated conditions (e.g. HBV, HCV and HIV serology)