26th June 2023

Glomerulonephritides associated with nephritic syndrome

IgA Nephropathy (Berger’s disease)

IgA nephropathy, also known as Berger’s disease, is a type III hypersensitivity disorder caused by IgA immune complexes which deposit in the mesangium of the glomerulus. The mesangium is a matrix of cells that helps support the capillary loops, therefore, when this is damaged, it results in leakage of red blood cells leading to haematuria. It is the most common nephropathy worldwide and develops during infection of the mucosal lining, either of the respiratory tract or the gastrointestinal tract.

Associated Conditions:

• Coeliac disease
• Dermatitis herpetiformis
• Henoch-Schoenlein purpura (HSP) (there is significant pathological overlap with HSP and IgA)
• Alcoholic cirrhosis

Histology:

• Light microscopy – mesangial proliferation
• Electron microscopy – immune deposits in the mesangium
• Immunofluorescence – IgA immune complexes

Management:

• Control blood pressure – ACE inhibitors commonly used, which also reduce proteinuria
• Steroids – prevent immune complex formation.
• If isolated haematuria with no significant proteinuria, often no treatment is required, and renal function just needs to be monitored.

Prognosis:

• Approximately twenty-five percent of patients develop end stage renal failure.
• Frank haematuria with little or no proteinuria is a good prognostic factor
• Poor prognostic factors include
  • Male gender
  • Proteinuria (particularly >2 grams/day)
  • Hypertension
  • Smoking
  • Hyperlipidaemia

Rapidly progressive glomerulonephritis

Rapidly progressive glomerulonephritis (RPGN), also known as crescenteric glomerulonephritis, is caused by cell proliferation due to inflammation of the glomerulus, which leads to splitting or breaking of the glomerular basement membrane. This damage to the glomerular basement membrane allows larger molecules, such as inflammatory mediators, plasma proteins and fibrin, to pass into Bowman’s space. This leads to increased recruitment of monocytes and macrophages and increased proliferation of parietal epithelial cells, causing thickening. This results in the characteristic crescent-moon shaped glomeruli seen in RPGN, which can be visualised on electron microscopy. The glomeruli become significantly damaged, causing a decrease in renal function, and this can quickly progress to renal failure.
There are three types of RPGN categorised by what causes the original damage to the glomerular basement membrane and can be differentiated using immunofluorescence.

Type I

• Anti-glomerular basement membrane (Anti-GBM) antibodies cause damage to the glomerular basement membrane.
• Associated with Goodpasture’s syndrome
• Immunofluorescence shows linear IgG deposits along the basement membrane

Type II

• Caused by immune complexes
• Associated with post-streptococcal glomerulonephritis, systemic lupus erythematosus, IgA nephropathy, Henoch-Schoenlein purpura.
• Immunofluorescence – granular appearance of immune complexes

Type III

• Anti-neutrophil cytoplasmic antibody (ANCA) cause damage to the glomerular basement membrane
• Associated with
  • Granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) – cANCA
  • Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome)
  • Microscopic polyangiitis – pANCA
• Immunofluorescence – no changes (pauci-immune disease process, therefore no anti-GBM antibodies and no immune complexes).

Management:

Treatment options are the same for all three types and treatment should be initiated early to prevent a poor prognosis and development of renal failure.

• Anticoagulants – to protect against thromboembolism due to loss of fibrin
• Plasmapheresis
• Immunosuppressants
• Dialysis
• Transplant