Glomerulonephropathies are diseases which cause inflammation in the glomeruli. These can be divided into nephrotic and nephritic syndrome, and this article will cover the causes and management of a patient with suspected glomerular disease.
Nephrotic syndrome and nephritic syndrome are terms describing a group of symptoms caused by different diseases. Nephrotic syndrome is an important clinical entity and a well-defined group of symptoms. Nephritic syndrome is less commonly used and typically refers to severe and acute presentations of glomerulonephritis with hypertension and reduced urine output. However, many glomerulopathies can present with both nephrotic and nephritic features or mild proteinuria and haematuria not meeting the definition of either syndrome.
Glomerulopathies can further be classified as primary or secondary, with primary diseases directly affecting the kidneys and secondary diseases caused by another disease or process.
When describing diseases of the glomerulus, terminology can be confusing. Terms are used when describing histological patterns on kidney biopsy and usually are not specific diagnoses. The only exception is focal segmental glomerulosclerosis (FSGS), a type of nephrotic syndrome defined by focal and segmental glomerulosclerosis on histology.
Nephrotic syndrome is typically caused by diseases which damage the filtration barrier at the glomerular basement membrane and is defined by a triad of proteinuria, hypoalbuminemia and oedema. Proteinuria is defined as a loss of 3.5g of protein per 24 hours, which equates to a urine protein:creatinine ratio of approximately 300mg/mmol. It is caused by increased basement membrane permeability, causing increased urinary loss of protein (including albumin). Hypoalbuminemia is caused by loss of albumin in the urine, usually compensated by the liver in healthy individuals, but unable to do so in nephrotic syndrome. Oedema is thought to be related to either hypoalbuminemia or excess salt and water retention in the kidney triggered by nephrotic syndrome, presenting with peripheral oedema.
Nephritic syndrome occurs due to inflammation and damage to endothelial cells of glomerular capillaries and can be triggered by several disease processes.
Clinical features of nephritic syndrome include:
Treatment varies depending on the cause of nephrotic syndrome. However, treatment can be divided into general/supportive measures and immunosuppression.
General/supportive measures for nephrotic syndrome include:
Unless the patient is deemed high-risk, supportive measures may be tried to see if remission occurs without the need for immunosuppression.
Immunosuppression regimens vary depending on the cause of nephrotic syndrome:
Other agents that may be used (particular if treating resistant or relapsing diseases) include calcineurin inhibitors (e.g. tacrolimus), mycophenolate mofetil, azathioprine and rituximab.
Rapidly progressive glomerulonephritis (also known as crescentic glomerulonephritis) is a classification of acute glomerulonephritis that is associated with the presence of crescents on renal biopsy.
RPGN is characterized by a 50% decline in kidney function over a period of 3 months, or even faster, in a matter of days or weeks. It is not a single disease process, but rather a form of glomerulonephritis that presents very acutely, resulting in a rapid decline in kidney function and the presence of crescents (inflammation and proliferation of cells in the Bowman's space that compress the glomerulus).
The pathology of acute glomerulonephritis can be divided into three main categories: immune complex disease, vasculitis (often pauci-immune) and anti-GBM associated diseases.
Immune complex diseases are caused by an activation of the complement system, where immune complexes deposit on the glomerular capillaries and lead to inflammation and damage. They can be identified by low levels of C3 and/or C4, depending on which arm of the complement system is activated. Examples include post-infectious glomerulonephritis (usually post-streptococcal infection), IgA nephropathy, and membranoproliferative glomerulonephritis (MPGN).
Chronicity of disease is important in nephritic syndrome. If symptoms occur and renal function declines over days or weeks, it can be classified as acute glomerulonephritis. If the symptoms occur over months to years with little reduction in kidney function, then it is chronic glomerulonephritis.
Nephritic syndrome is a histological finding which can be caused by a variety of underlying diseases. These include paraprotein-producing malignancies, autoimmune diseases, chronic viral infections (e.g. hepatitis C), small vessel, medium vessel or large vessel vasculitis, as well as diseases with ANCA antibodies and anti-GBM antibodies.
Vasculitis can also cause nephritic syndrome. It is a systemic disease which affects other organs, or can be renal-specific. Complement levels will be normal. Vasculitis is classified by the size of the vessels involved or their immunofluorescence pattern on histology. Diseases associated with renal vasculitis include granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (eGPA) and microscopic polyangiitis (MPA). These are pauci-immune diseases as there is a relative lack of immune deposits on immunofluorescence. The associated ANCA antibodies (cANCA or pANCA) can be useful in monitoring treatment response.
Anti-GBM disease can also cause nephritic syndrome, typically an RPGN. The complement levels will be normal. This is caused by anti-GBM antibodies against the type IV collagen present in the kidneys and the lungs. If the disease is associated with pulmonary and renal features it is called Goodpasture's disease. Lung involvement may present as massive haemoptysis. Linear GBM staining can be seen on immunofluorescence.
Conditions which predominantly cause nephritic syndrome include immune complex diseases such as post-streptococcal GN and IgA GN (previously Berger's disease), as well as membranoproliferative glomerulonephritis, systemic lupus erythematosus (SLE), shunt nephritis from infected ventricular peritoneal shunts.
Glomerulonephropathies are a set of diseases which affect the glomeruli. Two of the most common manifestations are nephrotic syndrome and nephritic syndrome.
Nephrotic syndrome typically presents with proteinuria, hypoalbuminemia and oedema. Common causes include:
Nephritic syndrome typically presents with proteinuria, haematuria, hypertension and oliguria (in severe cases). Common causes include:
Like nephrotic syndrome, treatment varies depending on the underlying cause and severity. For example, many patients with IgA nephropathy have a slowly progressive course where the only treatment is supportive (e.g. ACE inhibitors for control of blood pressure and proteinuria). Conversely, anti-GBM disease typically presents as an RPGN requiring immediate and intensive immunosuppression and plasma exchange.
If severe renal impairment then dialysis may be required. Transplantation may be considered later as long as the disease process is controlled.
Glomerulonephritis is a type of kidney disease that affects the glomeruli, which are the tiny filters located in the kidneys. Injured or damaged glomeruli can no longer filter waste products, electrolytes and fluid from the bodies blood. This type of kidney disease is caused by the immune system attacking the glomeruli, usually as a reaction to an infection, or by deposits of immune complexes.
Glomerulonephritis can be classified into four main categories:
IgA nephropathy is the most common type of glomerulonephritis. It is caused by an accumulation of a certain type of antibody, IgA. IgA nephropathy has been linked to certain infections and immune disorders. FSGS is a type of glomerulonephritis that affects the glomerular basement membranes. It is caused by a defect in the filtration process, and it is the leading cause of chronic kidney disease in adults. MN is a type of glomerulonephritis that affects the glomeruli and is caused by deposits of antibodies in the kidney's basement membrane. MPGN affects the immune cells in the glomeruli, leading to excessive inflammation and damage to the kidneys.
Glomerulonephritis can lead to a number of serious health complications. These complications can include hypertension (high blood pressure), proteinuria (increased protein in the urine), fluid overload, and electrolyte problems. Treatment for glomerulonephritis typically includes medications that help reduce inflammation, protect the kidneys, and control blood pressure levels.
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