Glomerulonephritis

21.5.07

Definition
• Disease affecting kidneys - classified according to changes seen in glomerulus on light, immunofluorescence and electron microscopy.

Clinical presentation
• Persistent microscopic haemuturia.
• Persistent proteinuria.
• Nephrotic syndrome.
• Recurrent macroscopic haemuturia.
• Acute nephritic syndrome.
• Acute/subacute renal failure.
• Chronic renal failure.

Proteinuria
• Normal range <0.2g/24 hours.
• Nephrotic syndrome.
• Definition: proteinuria >5g/24 hours.
• Oedema.
• Hypoalbuminaemia.
• Hypercholesterolaemia.
• Persistent proteinuria: above normal range, but not nephritic and usually asymptomatic.

Types of glomerulonephritis
• Based on histology.
• Although patients may share same histological type, clinical presentation may be variable.
• Some clinical presentations more characteristic of certain types.

Minimal change glomerulonephritis
• Usually presents as nephritic syndrome.
• Commonest cause of nephritic syndrome in children.
• Usually responds to oral steroids, if not cyclophosphamide/cyclosporin may be used.

Focal segmental glomerulonephritis
• Usually presents as nephritic syndrome.
• Responds less well to immunosuppression than minimal change glomerulonephritis.
• May be found in association with AIDS and with IVDU.
• ~50% will progress to ESRF.
• Focal segmental changes may be found late in course of patients whose initial biopsy showed minimal change glomerulonephritis.

Membranous glomerulonephritis
• Accounts for 20-30% adult nephritic syndrome and up to 5% children.
• May also present as asymptomatic proteinuria/chronic renal failure.
• In 20-30% cases, secondary to another cause.
• Up to 30% may develop ESRF.
• Up to 30% will resolve spontaneously.
• Immunosuppression reserved for those with intractable nephritic syndrome/progressive renal failure.
• Regimes include:
-Prednisolone.
-Cyclophosphamide.
-Azathioprine.
-Chlorambucil.
-Cyclosporin A.
-Mycophenolate.

Causes of secondary membranous glomerulonephritis
• Cancer: bronchus, breast, GI tract, prostate.
• Infection: hep B, syphilis, leprosy, filiriasis.
• Drugs: gold, penicillamine, captopril.
• Multisystem: SLE, sarcoidosis, RA.

IgA nephropathy
Presentation
• Often with recurrent episodes of macrohaematuria occurring within 12-24 hours of onset of URTI.
• Frequently accompanied by muscle and loin pain and fever out of proportion to severity of URTI.
• Commonest form of idiopathic GN worldwide.
• Typically affects young males M:F = 3:1.

Diagnosis
• Serum polyclonal IgA sometimes increases, but not of prognostic significance.
• On renal biopsy, mesangial deposits of IgA and C3.

Outcome
• Up to 50% adults: slowly progressive renal failure of 15-20 years of often asymptomatic progression.

Treatment
• Depends on presentation and progression.
• Immunosuppression often tried in severe nephritic syndrome/rapid progression of renal failure.

Membranoproliferative glomerulonephritis
• Usually presents as persistent proteinuria/nephritic syndrome/chronic renal failure.
• 3 histological types.
• May be secondary to systemic disease.
• Immunological abnormalities.
• Low serum, C3 complement found in 60-100% type I and 30-40% type II.
• Complement abnormalities indicate activation of alternative pathway.
• Treatment:
-If secondary to another disease, treat underlying disease.
-In idiopathic forms, no specific treatment of consistently proven benefit.

Rapidly progressive glomerulonephritis
• Form of glomerulonephritis causing renal damage - may progress from onset to ESRF within weeks/months.
• Characteristic lesion: focal necrotising glomerulonephritis with crescent formation.
• 3 main causes:
1. Antiglomerular basement membrane disease.
2. Vasculitis.
3. SLE.
• However, many other causes, including systemic disease, drugs, infections, neoplasia.
• Clinical presentation:
-Often dependent on presence/absence of systemic disease.
-If absent, patients may present with non-specific features of renal failure:
§Oliguria.
§Oedema.
§Dyspnoea/uraemic symptoms.
-Macroscopic haemuturia and loin pain sometimes reported.

Antiglomerular basement membrane disease
• Rare: affects M>F.
• May be associated with pulmonary haemorrhage.
• Characterised by presence of circulating antiglomerular basement membrane antibodies and deposition of IgG in basement membrane.

Vasculitis
• Rapidly progressive renal lesion may be seen in variety of systemic diseases, notably polyarteritis nodosa and Wegener's granulomatosis.
• Often associated with circulating anti-neutrophil cytoplasmic antibodies.

Post-streptococcal glomerulonephritis
• Occurs usually between 7 and 21 days after group A streptococcus infection.
• During epidemic, clinically detectable glomerulonephritis occurs in 5-10% after pharyngitis and ~25% after skin infections.
• Young children at highest risk.
• Presentation can vary from microhaematuria to full-blown nephritic syndrome.
• Investigations:
-Throat/skin swab.
-ASO titre.
-C3 and C4 complement may be decreased.

Alport's syndrome
• Inherited as x-linked trait.
• In males, usually progressive form of renal disease causing ESRF commonly between 16-35 years.
• Associated with sensorineural deafness and anterior lenticomus.