What is glomerulonephritis?

Glomerulonephritis (GN) is a renal disease characterised by inflammation and damage to the glomeruli.  This allows protein (+/- blood) to leak out into the urine.

 

It may present with…

  • Isolated haematuria and/or proteinuria
  • Nephrotic syndrome
  • Nephritic syndrome
  • Acute renal failure
  • Chronic renal failure
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Glomerulonephritis (GN) is generally categorised into either proliferative or non-proliferative.

Diagnosing the pattern of GN is important because outcome and treatment depend upon the specific subtype.

Below each of the types of GN is discussed ,if you get lost use the diagram below to re-orientate yourself!

 
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Non-proliferative glomerulonephritis

Characterised by a lack of proliferation of cells in the glomeruli.

Generally, cause nephrotic syndrome.

 

Minimal change glomerulonephritis

Presents as nephrotic syndrome.

Accounts for 80% of all nephrotic syndrome in children and 20% in adults.

The cause of the disease is currently unknown.

 

Investigations

No abnormalities can be seen on light microscopy.

However, electron microscopy reveals abnormal podocytes (fused).

 

Treatment

Supportive caree.g. reducing oedema

Prednisolone can halt the disease process

90% of children and 80% of adults respond well often cured after 3 months

Focal segmental glomerulosclerosis (FSGS)

Presents as nephrotic syndrome.

Several genetic causes have been established.

Can be either primary (genetic mutations) or secondary (HIV / reflux nephropathy).

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Investigations

Specific segments of certain glomeruli develop sclerosed lesions.

Antibody tests are all negative.

 

Treatment

Salt restriction and diuretics – reduce oedema

Antihypertensives 

Statins – to treat hyperlipidaemia

Steroids often have no effect on the disease.

Cytotoxics drugs are sometimes useful.

Transplant is often required – 50% progress to renal failure

 

Membranous glomerulonephritis

Presents with nephrotic syndrome.

Slowly progressive.

Mainly affects people between the ages of 30-50.

Usually idiopathic but can be associated with – Hepatitis B / Malaria / Penicillamine / SLE

 

Caused by…

Immune complex deposition, which results in complement activation against glomerular basement membrane proteins.

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Investigations

Microscopic analysis shows thickened glomerular basement membrane.

Immunofluorescence shows diffuse uptake of IgG.

 

Treatment

Steroids can be used if disease begins to progress.

Prognosis follows the rule of thirds:

  • 1/3 have chronic membranous glomerulonephritis
  • 1/3 go into remission
  • 1/3 progress to end-stage renal failure

Proliferative glomerulonephritis

Characterised by ↑ numbers of cells in the glomerulus.

Usually presents with nephritic syndrome.

Dangerous! can progress to end-stage-renal-failure over weeks to years

IgA nephropathy

Most common type of GN in adults worldwide.

Presents as nephritic syndrome – macroscopic haematuria

Often appears 24-48hrs after an upper respiratory tract infection.

Episodes occur randomly for a few months and usually stop.

The disease can be relatively benign or can lead to end-stage renal failure.

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Investigations

A biopsy is needed to confirm the diagnosis.

Microscopically the disease is characterised by:

  • ↑ numbers of mesangial cells
  • ↑ matrix (cement that holds everything together)

Immunohistochemistry is +ve for IgA deposits in the matrix.

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Treatment

Difficult due to the wide spectrum of disease outcomes.

Evidence for therapy is still conflicting.

Steroids and cyclophosphamide have been used with varying results.

Prognosis is variable20% progress to end stage renal failure

 

Post-infectious glomerulonephritis

Can occur after virtually any infection.

Tends to occur after strep pyogenes infection.

Typically presents 2 weeks after the infection.

 
Investigations

Light microscopy shows:

  • Proliferation of mesangial cells
  • Neutrophils and monocytes
  • Bowman space is compressed – seen as classical crescentic glomerulonephritis

 

Diagnosis

Diagnosis based on:

  • Symptoms and signs of GN
  • History of recent strep infection
  • Streptococcal titres – may support the diagnosis
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Treatment
Supportive (disease usually resolves in 2-4 weeks).

 

Membranoproliferative glomerulonephritis

Presents with combined nephrotic and nephritic syndrome.

Caused by subendothelial deposition of immune complexes.

Different from membranous GN as mesangium is thickened as well as basement membrane.

Can be primary or secondary to a number of causes – SLE / Hepatitis B/C

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Investigations

Microscopy shows:

  • Thickened basement membrane
  • Thickened mesangium

 

Immunofluorescence shows:

  • Subendothelial deposition of IgG
  • Linear pattern

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Treatment

Optimal treatment for primary disease is not well defined.

Specific therapies should be reserved for severe disease steroids / cytotoxic drugs

Treat the underlying cause in secondary disease.

Poor prognosis most progress to end stage renal failure

 

Rapidly progressive glomerulonephritis (crescentic)

Also known as crescentic glomerulonephritis.

Carries poor prognosis – rapid progression to kidney failure over weeks

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Any type of glomerulonephritis can progress to rapidly progressive glomerulonephritis (RPGN).

However, some types only ever present as RPGN, as shown below.

 

Goodpasture’s syndrome 

Immune-mediated disease.

Antibodies directed against glomerular basement membrane antigens (anti-GBM antibodies).

These antigens are located in the glomeruli and in the alveoli of the lungs.

Patients’ therefore present with renal failure (nephritic syndrome) and haemoptysis.

Progression to renal failure is rapid without treatment.

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Investigations

Immunohistochemistry – IgG deposits along basement membrane of glomerulus

Antibodies – anti-GBM antibodies

 

Treatment

High dose immunosuppression is required:

  • IV Prednisolone
  • Cyclophosphamide
  • Plasmapheresis

Kidney damage that has already occurred is non-reversible.

 

Vasculitic disorders.

Wegener’s granulomatosis

A vasculitis affecting the lungs, kidney and other organs.

Life-threatening due to end-organ damage.

The disease is caused by anti-neutrophil cytoplasmic antibodies (c-ANCA).

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Diagnosis

c-ANCA is positive in almost all cases.

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Treatment

IV steroids – high dose initially, then tapered down.

Cyclophosphamide – used as a steroid-sparing agent.

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Microscopic polyangiitis

A small vessel vasculitis affecting almost any organ system.

The disease is caused by anti-neutrophil cytoplasmic antibodies (p-ANCA).

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Diagnosis

p-ANCA is positive in almost all cases.

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Treatment

Long-term prednisolone and cyclophosphamide.

Plasmapheresis can be helpful acutely to remove p-ANCA antibodies.

 


 

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