Glomerulonephritis (GN) is a term often used to describe all pathological conditions of the glomerulus; however, strictly speaking, it refers to “inflammation of the glomerulus”. Glomerulonephritis represents a number of conditions where there is damage to the glomerular apparatus, causing the appearance of blood and protein in the urine.
The typical presentation of glomerulonephritis is oedema, hypertension and the presence of blood in the urine (often on microscopic). However, in practice, many cases are asymptomatic, or symptoms are mild and vague, which can make the diagnosis difficult.
There are many causes of glomerulonephritis, including infective, autoimmune and genetic disorders. Glomerulonephritis can be acute or chronic. Infective causes are the most common, and the vast majority of these cases will resolve. Chronic cases are more likely to have an underly immunological cause, and can be more difficult to recognise and treat.
Glomerular disease is a common cause of end-stage renal failure (ESRF). Early diagnosis is important because it can prevent progression to ESRF.
Treatment is often aimed at treating the underlying disorder, to prevent further glomerular damage.
These are not specific diagnoses in themselves, but help to categorise the presentation to narrow down the diagnosis.
Basic physiological principles
The glomerulus is the basic “filtration unit” of the kidney. It is a collection of small blood vessels surrounded by a semi-permeable membrane, through which the process of filtration occurs. The glomerulus is surrounded by Bowman’s capsule into which the filtrate flows, which then flows onto the proximal convoluted tubule as it goes through the process of reabsorption.
As such, conditions that case glomerulonephritis can result in large molecules and cells ending up in the urine that would not otherwise be present.
Glomerular physiology. This file is taken from wikimedia commons and is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.
Up to 50% of patients with glomerulonephritis have no symptoms
Reduced urine output
In severe cases:
Ask about any preceding illness – e.g. recent infections or flu-like symptoms
Urine microscopy for “red cell casts”
Clumps of red blood cells seen in the urine
May be performed in cases of severe disease to help confirm the cause of the glomerulonephritis
Serology for evidence of recent streptococcal infection – e.g. ASOT
Many cases initially present after positive urine dip for protein or haematuria.
Haematuria occurs in about 5% of the population
Most cases of haematuria are due to menstruation or from lower down the urinary tract – such as UTI. It is also important to rule out cancer in patients with haematuria.
Proteinuria in about 2.5% of the population
Proteinuria is more significant for glomerular disease and warrants further investigation. However, most cases are due to diabetes or hypertension, and not due to an underlying primary glomerular disorder.
The more severe the proteinuria, the more likely it is to lead to ESRF
Assessment of haematuria
Microscopic Haematuria assessment pathway. Adapted from [Source]
Acute glomerulonephritis most commonly occurs as a result of recent infection (post-streptococcal glomerulonephritis)- usually with streptococcus (e.g. tonsillitis), but can also sometimes be due to staphylococcus or pneumococcus.
Antigen-antibody complexes become trapped within the glomerulus. The disease classically presents in children and young adults as sore throat followed a couple of weeks later by oliguria, haematuria, hypertension, and slightly abnormal renal function.
The disease is self-limiting, and 90% of patients will spontaneously recover. Treatment generally involves the control of blood pressure, reduced fluid and salt intake, and in some cases the use of antibiotics and diuretics.
Rapidly progressive glomerulonephritis is a particularly aggressive form of glomerulonephritis which can cause acute renal failure (see below)
Chronic glomerulonephritis can be caused by the same things as acute glomerulonephritis. It can develop slowly, or it can result from a case of acute glomerulonephritis that doesn’t resolve.
The two main presenting features are haematuria and proteinuria. Chronic glomerulonephritis may also present as acute orchronic renal failure, or nephritic or nephritic syndromes.
There are numerous sub-types of the condition, and they are categorised according to histology.
Along with diabetes and hypertension, it is one of the most common causes of ESRF in the UK.
Minimal change glomerulonephritis
This accounts for 80% of cases of glomerulonephritis in children and 20% in adults. It is a T-cell mediated condition in which about 1/3 of cases will remit spontaneously, 1/3 will continue in a nephrotic state, and 1/3 will show progressive loss of renal function.
Minimal change glomerulonephritis presents with proteinuria, although haematuria and increased BP may also be present. The majority of cases present with nephrotic syndrome.
A biopsy will normally be performed, and under microscopy, this will appear normal – hence the name of the condition. However, under electron microscope, the condition will show damaged podocytes.
Steroids, i.e. prednisolone, are the main treatment, and this will cause remission in 95% of children and 70% of adults. However, relapse is common once treatment is stopped. If treatment with steroids is unsuccessful, or if relapse occurs, then the patient may be treated with ciclosporin.
About 1% of cases will progress to ESRF.
IgA nephropathy,aka Berger’s disease
This is the most common type of glomerulonephritis in the developed world. It nearly always presents with micro- or macroscopic haematuria, and proteinuria and hypertension are very common symptoms. Nephrotic syndrome may also be present.
A typical patient will be a young male who presents with haematuria a few days after a UTI or bout of pharyngitis.
ESRF is much more common in this disease, i.e. as it a long-term condition; 20% of patients will develop ESRF over a period of 20 years.
There is deposition of IgA in mesangial cells – which are found in the basement membrane of the glomerulus and are phagocytotic – probably as a result of over-production of IgA related to the preceding infection. The condition can rapidly disappear and then re-appear at a later stage. Often when it reappears it is associated with respiratory infection. Once again, renal biopsy is necessary to determine if the disease is present. Biopsy will show mesangial proliferation and IgA deposits.
Anti-inflammatories such as ciclosporin may be used, but the benefit they confer is not certain.
The prognosis is made worse by…
Proteinuria or renal failure at presentation
Rapidly Progressive GN (RPGN)
This is the most aggressive type of GN, and can progress to ESRF within days. There are different causes, but they all result in the same histological effects – proliferation of macrophages and parietal epithelial cells in Bowmann’s capsule, leading to a crescent-like appearance of the glomeruli.
The cause is often microscopic polyangitis – which is an autoimmune disease causing vasculitis, without signs of inflammation. RPGN can involve many other organs other than the kidneys, and it is seen alongside SLE and infections such as endocarditis.
RPGN presents with signs of renal failure. There may also be signs of systemic disease, e.g. SLE, if one is present. Signs might include:
Progressing to oliguria (no urine output)
Treat RPGN with aggressive immunosupression, e.g ciclosporin, clycophosphamide, and corticosteroids.
The prognosis is poor if the initial presentation has a serum creatinine of over 600μmol/L; if the level is below this, then 80% of patients will show signs of improvement without treatment.
There are many other types of glomerulonephritis that have not been mentioned here!
U+E – checking for filtration problems
ESR/CRP – checking for levels of inflammation
Autoantibodies, particularly anti-GMB, glomerular basement membrane, ANA, ANCA
Dr Tom Leach MBChB DCH EMCert(ACEM) currently works as a GP Registrar and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009.
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