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
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!.
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.
No abnormalities can be seen on light microscopy.
However, electron microscopy reveals abnormal podocytes (fused).
Supportive care – e.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).
Specific segments of certain glomeruli develop sclerosed lesions.
Antibody tests are all negative.
Salt restriction and diuretics – reduce oedema
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
Presents with nephrotic syndrome.
Mainly affects people between the ages of 30-50.
Usually idiopathic but can be associated with – Hepatitis B / Malaria / Penicillamine / SLE
Immune complex deposition, which results in complement activation against glomerular basement membrane proteins..
Microscopic analysis shows thickened glomerular basement membrane.
Immunofluorescence shows diffuse uptake of IgG.
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
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
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.
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.
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 variable – 20% progress to end stage renal failure
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 based on:
- Symptoms and signs of GN
- History of recent strep infection
- Streptococcal titres – may support the diagnosis
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.
- Thickened basement membrane
- Thickened mesangium
- Subendothelial deposition of IgG
- Linear pattern
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
Any type of glomerulonephritis can progress to rapidly progressive glomerulonephritis (RPGN).
However, some types only ever present as RPGN, as shown below.
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.
Immunohistochemistry – IgG deposits along basement membrane of glomerulus
Antibodies – anti-GBM antibodies
High dose immunosuppression is required:
- IV Prednisolone
Kidney damage that has already occurred is non-reversible.
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).
c-ANCA is positive in almost all cases.
IV steroids – high dose initially, then tapered down.
Cyclophosphamide – used as a steroid-sparing agent.
A small vessel vasculitis affecting almost any organ system.
The disease is caused by anti-neutrophil cytoplasmic antibodies (p-ANCA).
p-ANCA is positive in almost all cases.
Long-term prednisolone and cyclophosphamide.
Plasmapheresis can be helpful acutely to remove p-ANCA antibodies.