- Glomerulonephritis is a general term describing inflammation in the renal glomeruli and may lead to renal failure.
- The inflammation is related to problems in the immune system.
- This condition is not directly caused by infections and should not be confused with pyelonephritis (an infection of the kidney substance).
- Glomeronephritis can have many causes and associations.
- The term primary glomeronephritis is used when the kidneys are the main site of pathology, whereas the term secondary glomerulonephritis is reserved for diseases in which the kidneys are one of many affected organ systems afflicted by a systemic disease.
- The glomerulonephritides are divided into many subtypes by means of clinical presentation and histology.
- The glomerulonephritides give rise to a range of kidney (renal) syndromes, including a nephritic syndrome, nephrotic syndrome, asymptomatic abnormalities, rapidly progressive renal failure and chronic renal failure.
- The diagnosis of a glomerulonephritis is suspected on the basis of the renal syndromes, combined with urinary investigations and some basic blood tests.
- A renal biopsy (for histology) and advanced blood tests are usually required for an accurate aetiological diagnosis.
- The treatment of glomerulonephritis depends on the specific renal syndrome and the underlying subtype of glomerulonephritis encountered.
- Treatment usually involves general supportive measures, the treatment of suspected complications and also specific therapy for the inflammation in the kidney.
- Many factors, including the renal function at presentation, the degree of proteinuria (amount of protein leaking into the urine) and the level of hypertension, predict the eventual renal outcome.
Glomerulonephritis is a general term used to describe inflammation in the kidneys’ glomeruli (i.e. part of the kidneys’ functional units) and its clinical consequences. This inflammatory condition is not caused by infections (as a direct consequence), but is mediated by the body’s own immune system.
Glomerulonephritis (plural: ‘glomerulonephritides’) may have many causes and should not be confused with pyelonephritis, a term used to describe infections (mostly bacterial) of the renal substance. Pyelonephritis is often localised to the ductile systems and the surrounding tissue of the kidneys.
In patients with glomerulonephritis, both kidneys are involved symmetrically, initially with immunologically mediated injury, later progressively affected by secondary mechanisms.
The renal lesions may be part of a generalised systemic disease, such as systemic vasculitis (inflammation of blood vessels) or be the primary (and only) site of pathology.
The classification of the glomerulonephritides is based on the causes (aetiology) or histology and is complex and complicated – even most doctors struggle with this.
The so-called ‘primary glomerulonephritides’ are diseases where most (if not all) of the pathology is localised to the kidneys. There can be systemic complications of the disease process, but the kidneys remain the main organ system involved. Dysfunction of the immune system is the underlying cause in most of these conditions. If no specific underlying cause for this can be identified, as is often the case, ‘idiopathic’ (primary) glomerulonephritis is diagnosed. (An example would then be ‘idiopathic membranous glomerulonephritis’). The primary glomerulonephritides are subdivided by clinical and pathological means into various subtypes. For an accurate diagnoses a renal biopsy (to attain a histological specimen) is usually necessary.
Histologically (by looking at cell types) the primary (and secondary) glomerulonephritides can be subdivided into:
- Minimal Change Nephropathy
- Membranous Nephropathy
- Focal Segmental Glomerulosclerosis
- Proliferate glomerulonephritides
- Diffuse glomerulonephritides
- Diffuse post-infective proliferate glomerulonephritis
- Mesangiocapillary/Membranoproliferative glomerulonephritis
- Crescentic nephritides
- Mesangial proliferative glomerulonephritis
- Focal glomerulonephritides
- Focal (segmental) proliferate glomerulonephritides
- IgA – nephropathy
- Other, e.g. Alport’s Syndrome
- Chronic (endstage) glomerulonephritis
Many other diseases can secondarily affect the kidneys, giving rise to most of the histological subtypes (or combinations thereof) listed above. In these diseases the renal pathology may be an incidental finding, being overshadowed by the other manifestations of the systemic diseases, or it may the main manifestation and even cause of death. (An example would be ‘membranous nephropathy secondary to Hepatitis B infection’.)
An abbreviated aetiological classification of the secondary glomerulonephritides:
- Hepatitis B
- Anti-inflammatory agents
- Pregnancy (pre-eclampsia)
Main symptoms and signs
Despite its many causes, glomerulonephritis has a fairly limited spectrum of presentations, ranging from no symptoms at all to life-threatening.
It is important to note that the above classifications do not equate to specific symptoms and signs. Different diseases and histological subtypes can have similar presentations and conversely the same pathology (both aetiological and histological) can present in different ways in different patients. Even in one particular patient, different presentations are sometimes observed at different times in their life.
It is therefore easier to divide the presentation of glomerulonephritis into ‘renal syndromes’ (groups of symptoms and signs), than to comprehend the different histological and aetiological subtypes.
The five main renal syndromes are:
- The nephritic syndrome is characterised by blood in the urine (haematuria) and a high blood pressure. The urine of is often described as ‘smoky’ or even ‘coke coloured’. Sometimes blood is only detectable by looking at the urine under the microscope. Patients may also complain of a decreased volume of urine (oliguria), oedema (swelling) and they may be feeling generally unwell and weak. A limited amount of protein can be detected in the urine. Patients may rarely present with symptoms similar to those of renal failure.
- The nephrotic syndrome is defined by heavy proteinuria (the detection of protein in abnormally high concentrations in the urine), a low concentration of the main form of protein in the blood, namely albumin (hypoalbuminaemia), and oedema (swelling). Patients usually first notice swelling of the feet, the lower legs and later around the eyes. The nephrotic syndrome can occur with or without renal failure, hypertension (high blood pressure) and haematuria (blood in the urine). Sometimes the complications of this syndrome dominate the picture. Examples are a predisposition to infections, a raised level of blood cholesterol leading to premature atherosclerosis (with strokes and heart attacks) and venous thrombosis (‘blood clots’).
- Asymptomatic proteinuria (protein in the urine), haematuria (blood in the urine) or both are found quite frequently when healthy individuals are screened for insurance or other routine purposes. These patients may remain asymptomatic for many years and recover spontaneously, or may progress to the other renal syndromes.
- Rapidly progressive renal failure is an aggressive form of glomerulonephritis sometimes associated with acute renal failure. Patients may have oedema, shortness of breath, convulsions and cardiac arrhythmias or many other complaints.
- Chronic renal failure can be the end result of many forms of glomerulonephritis that went unnoticed by the patient or doctor. Patients are usually hypertensive, have varying degrees of proteinuria and complain of symptoms of chronic renal failure, such as a decreased effort tolerance, loss of energy and libido (sexual drive), a dry pale skin or many other non-specific complaints.
A glomerulonephritis is suspected when one of the renal syndromes is encountered. Although some urinary investigations and basic blood tests strengthen the suspicion, a combination of a renal biopsy (for histology) and more advanced blood tests is usually required for an accurate aetiological diagnosis. If definite therapy is considered, such a diagnosis is usually required.
- Urinary dipstick (tests for blood and protein in the urine)
- Midstream collection for microscopy & culture (to exclude infection)
- 24 hour collection for creatinine clearance & protein excretion
Basic blood tests:
- Renal functions
- Serum albumin & cholesterol
Renal biopsies are not routinely performed on all patients. The basic principle is to reserve this invasive procedure for situations where the result is likely to affect the patient’s management, or if there is diagnostic uncertainty regarding the renal pathology and the histology is likely to be of paramount importance in the diagnostic work up. It is, for example, completely acceptable to diagnose diabetic nephropathy (a very common diagnosis worldwide) in the absence of histology.
Accepted indications for renal biopsies in patients with suspected glomerulonephritis are:
- Nephrotic syndrome
- Nephritic syndrome
- Isolated proteinuria > 2 g / day
- Isolated persistent haematuria
- Associated systemic disease
- Acute renal failure of uncertain aetiology
- Failure of acute renal failure to reverse in six weeks
Advanced blood tests:
These tests are usually requested and interpreted in association with the renal syndrome, histology and other special investigations.
- HIV test
- Hepatitis B test
- Anti-nuclear factor (ANF)
- Anti-neutrophilic cytoplasmic antibodies (ANCA)
- Serum complement levels
- Syphilis test
The treatment of a patient with a glomerulonephritis is not only dependent on the specific underlying pathology (i.e. the cause) but also on the renal syndrome encountered. The treatment is a specialised field and usually involves general supportive measures, the treatment of suspected complications as well as specific therapy.
The principles of the therapy can be summarised as follows:
General and supportive measures
The precise suggestions vary with the different renal syndromes, but generally the help of a dietician is called for. Attention is given to the limitation of salt, potassium and protein intake (dietary advice usually takes the patient’s weight and protein loss in the urine into account). Supplemental water-soluble vitamins (vitamins C and B-complex) are usually prescribed.
Treatment of blood pressure
In most patients aggressive (but not precipitous) lowering of blood pressure is indicated.
Reduction of proteinuria
A group of drugs called ACE-inhibitors have been shown to lower the amount of protein in the urine and to decrease the rate of deterioration of renal function. Unless contra-indicated, an ACE-inhibitor should be prescribed to most patients. Other measures include the treatment of hypertension and the reductions of dietary protein.
Treatment of oedema
Diuretics (“water pills”, such as Lasix®) are usually prescribed, but care should be taken not to overdo this modality, as it can be harmful.
The management of complications
Pulmonary oedema (presenting as severe shortness of breath) can occur both in the nephritic syndrome and in patients with rapidly progressive renal failure. This means there is fluid accumulating on the lungs. Aggressive diuretic therapy, oxygen and other measures are required.
If significantly elevated, dietary measures and drugs should be employed to lower blood cholesterol.
In patients who previously suffered a thrombotic incident (‘blood clot’), special measures like warfarin therapy are usually required. Warfarin is a drug which helps to prevent blood clots.
Prophylactic antibiotics are not used. Constant surveillance and treatment for any indication are however important.
The specific treatment of the many subtypes of glomerulonephritis is generally under specialist supervision and requires an accurate diagnosis and vigilant follow-up. Therapeutic options include steroid therapy, sometimes combined with other immunosuppressive drugs, such as cyclophosphamide or azathioprine. These measures can be life saving, but can be extremely hazardous when used inappropriately.
Patients with renal failure may require dialysis therapy, either by circulating the patient’s blood through a dialysis machine, which is called heamodialysis, or by infusing fluid into the patients abdominal cavity (peritoneum) and removing this fluid at a later stage, a process called peritoneal dialysis.
As the single most common cause of the primary glomerulonephritides is ‘idiopathic’ (unknown), little can be done to prevent these afflictions. Among the secondary glomerulonephritides, the prevention of hepatitis B and HIV infections, as well as the development of type 2 diabetes, are possibilities for intervention.
The best hope for the preservation of renal function and the prevention of complications is early detection and appropriate therapy (which usually implies a proper diagnostic work-up in search of an accurate diagnosis).
Many factors have been shown to predict the outcome in a patient with a glomerulonephritis as the primary diagnosis. These factors differ slightly for the various renal syndromes, but certain general guidelines hold true.
The following factors are important in prognosis:
- The renal function at presentation: The worse the degree of renal failure, the worse the final outcome tends to be.
- High blood pressure: Lowering blood pressure in hypertensive patients has been shown to decrease the rate of decline of renal function. Aggressive blood pressure control is a very important aspect in the management of these patients.
- The degree of proteinuria: The higher the degree of protein loss in the urine, the faster renal functions tend to deteriorate.
- The specific histopathological subtype: Some types (e.g. focal segmental glomerulosclerosis) fare worse than others (e.g. minimal change nephropathy).
- The renal syndrome: Uncomplicated nephritic syndrome rarely leads to long-term problems, whereas severe nephrotic syndrome, rapidly progressive renal failure and chronic renal failure often do.
When to see your doctor
Renal diseases and especially glomerulonephritides often present with vague and non-specific symptoms.
The following symptoms definitely require medical attention:
- Swelling of the legs or around the eyes
- Abnormal shortness of breath
- Very high (more than three litres) or low (less than 400ml) volumes of urine per day
- Blood in the urine
Written by Prof Helmuth Reuter - MBChB (US), FRCP (Edinburgh), FCP (SA), MMed (US), Department of Internal Medicine, University of Stellenbosch