Rapidly progressive glomerulonephritis
Encyclopedia
Rapidly progressive glomerulonephritis (RPGN) is a syndrome
of the kidney
that is characterized by a rapid loss of renal function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute renal failure
and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus
, or Wegener granulomatosis; the remaining cases are idiopathic
. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent
-shaped scar
s). Because of this microscopic feature, RPGN is also called crescentic glomerulonephritis.
), urinary protein (proteinuria
), and occasionally high blood pressure (hypertension
) and edema
. The clinical picture is consistent with nephritic syndrome
, although the degree of proteinuria may occasionally exceed 3 g
/24 h, a range associated with nephrotic syndrome
. Untreated disease may progress to decreased urinary volume (oliguria
), which is associated with poor kidney function.
, corticosteroid
s, and cytotoxic drugs may promote recovery in Goodpasture syndrome, a cause of type I RPGN. Despite even early treatment, however, many patients with RPGN may ultimately require dialysis
and possibly renal transplant.
patterns.
(GBM). It is also called anti-GBM glomerulonephritis. The antibodies are directed against a particular protein found in the GBM, type IV collagen, specifically the noncollagenous region of its α3 chain.
In addition to the anti-GBM antibodies, some cases of type I RPGN are also associated with antibodies directed against the basement membrane
of lung alveoli, producing Goodpasture syndrome. The majority of type I disease, however, features anti-GBM antibodies alone; these cases are considered idiopathic.
es accounts for 25% of RPGN and is classified as type II. Thus any immune complex disease that involves the glomerulus may progress to RPGN if severe enough. These diseases include systemic lupus erythematosus
, acute proliferative glomerulonephritis, Henoch-Schönlein purpura
, and IgA nephropathy
. While polyarteritis nodosa
also involves vasculitis
associated immune complex deposition that can lead to renal failure, it is not considered part of type-II RPGN because it mainly affects medium sized vessels and does not necessarily involve the kidneys.
RPGN, type III RPGN accounts for 55% of RPGN and features neither immune complex deposition nor anti-GBM antibodies. Instead, the glomeruli are damaged in an undefined manner, perhaps through the activation of neutrophils in response to anti-neutrophil cytoplasmic antibodies (ANCA). Type III RPGN may be isolated to the glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most cases of the latter, the systemic disease is an ANCA-associated vasculitis
such as Wegener granulomatosis, microscopic polyangiitis
, or Churg-Strauss syndrome
.
Classification of type III RPGN into primary or secondary may be unnecessary, as primary type III RPGN and secondary type III RPGN may represent a spectrum of the same disease process.
The ANCA form may have a more favorable response to treatment than other forms.
(blood in the urine), red blood cell casts in the urine, and proteinuria
(protein in the urine), sometimes exceeding 3 g protein/24 h, a range associated with nephrotic syndrome
. Some patients also experience hypertension
(high blood pressure) and edema
. Severe disease is characterized by pronounced oliguria
or anuria
, which portends a poor prognosis.
Serum analysis
often aids in the diagnosis of a specific underlying disease. The presence of anti-GBM antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus
and type II RPGN; and type III and idiopathic RPGN are frequently associated with ANCA-positive serum.
is thought to contribute most strongly to crescent formation. Epithelial cells lining the Bowman capsule respond to the leaked fibrin and proliferate. Infiltrating white blood cell
s such as monocyte
s and macrophage
s may also proliferate. These proliferating cells surround and compress the glomerulus, forming a crescent-shaped scar that is readily visible on light microscopy of a renal biopsy
.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
that is characterized by a rapid loss of renal function, (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, or Wegener granulomatosis; the remaining cases are idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent
Crescent
In art and symbolism, a crescent is generally the shape produced when a circular disk has a segment of another circle removed from its edge, so that what remains is a shape enclosed by two circular arcs of different diameters which intersect at two points .In astronomy, a crescent...
-shaped scar
Scar
Scars are areas of fibrous tissue that replace normal skin after injury. A scar results from the biological process of wound repair in the skin and other tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound results in...
s). Because of this microscopic feature, RPGN is also called crescentic glomerulonephritis.
Presentation
Patients with RPGN have blood in the urine (hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
), urinary protein (proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
), and occasionally high blood pressure (hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
) and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
. The clinical picture is consistent with nephritic syndrome
Nephritic syndrome
Nephritic syndrome is a collection of signs associated with disorders affecting the kidneys, more specifically glomerular disorders. It is characterized by having small pores in the podocytes of the glomerulus, large enough to permit proteins and red blood cells to pass into the urine...
, although the degree of proteinuria may occasionally exceed 3 g
Gram
The gram is a metric system unit of mass....
/24 h, a range associated with nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. Untreated disease may progress to decreased urinary volume (oliguria
Oliguria
Oliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
), which is associated with poor kidney function.
Treatment
Treatment depends on the underlying disease process. For example, plasmapheresisPlasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s, and cytotoxic drugs may promote recovery in Goodpasture syndrome, a cause of type I RPGN. Despite even early treatment, however, many patients with RPGN may ultimately require dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
and possibly renal transplant.
Classification
RPGN can be classified into three types, based upon the immunofluorescenceImmunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
patterns.
- In type I RPGN, which accounts for approximately 20% of RPGN cases, injury is caused by antibodies directed against the glomerular basement membraneGlomerular basement membraneThe glomerular basement membrane is the basal laminal portion of the glomerulus. The Glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that...
. - Type II RPGN accounts for roughly 25% of RPGN cases and is characterized by the deposition of immune complexImmune complexAn immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
es in the glomerulus. - The remainder of RPGN cases are type III, or pauci-immunePauci-immunePauci-immune is a general term used to refer to a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescence.They can be associated with antineutrophil cytoplasmic antibodies ....
RPGN, which features antibodies directed against neutrophils (anti-neutrophil cytoplasmic antibodies, ANCA).
Type I
Accounting for approximately 20% of RPGN, type I RPGN is characterized by the presence of autoantibodies directed against the glomerular basement membraneGlomerular basement membrane
The glomerular basement membrane is the basal laminal portion of the glomerulus. The Glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that...
(GBM). It is also called anti-GBM glomerulonephritis. The antibodies are directed against a particular protein found in the GBM, type IV collagen, specifically the noncollagenous region of its α3 chain.
In addition to the anti-GBM antibodies, some cases of type I RPGN are also associated with antibodies directed against the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
of lung alveoli, producing Goodpasture syndrome. The majority of type I disease, however, features anti-GBM antibodies alone; these cases are considered idiopathic.
Type II
RPGN caused by the deposition of immune complexImmune complex
An immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
es accounts for 25% of RPGN and is classified as type II. Thus any immune complex disease that involves the glomerulus may progress to RPGN if severe enough. These diseases include systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, acute proliferative glomerulonephritis, Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
, and IgA nephropathy
IgA nephropathy
IgA nephropathy is a form of glomerulonephritis...
. While polyarteritis nodosa
Polyarteritis nodosa
Polyarteritis nodosa is a vasculitis of medium & small-sized arteries, which become swollen and damaged from attack by rogue immune cells. Polyarteritis nodosa is also called Kussmaul disease or Kussmaul-Maier disease...
also involves vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
associated immune complex deposition that can lead to renal failure, it is not considered part of type-II RPGN because it mainly affects medium sized vessels and does not necessarily involve the kidneys.
Type III
Also known as pauci-immunePauci-immune
Pauci-immune is a general term used to refer to a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescence.They can be associated with antineutrophil cytoplasmic antibodies ....
RPGN, type III RPGN accounts for 55% of RPGN and features neither immune complex deposition nor anti-GBM antibodies. Instead, the glomeruli are damaged in an undefined manner, perhaps through the activation of neutrophils in response to anti-neutrophil cytoplasmic antibodies (ANCA). Type III RPGN may be isolated to the glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most cases of the latter, the systemic disease is an ANCA-associated vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
such as Wegener granulomatosis, microscopic polyangiitis
Microscopic polyangiitis
Microscopic polyangiitis is an ill-defined autoimmune disease characterized by pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation.-Presentation:Because many different organ systems may be involved, a wide range of...
, or Churg-Strauss syndrome
Churg-Strauss syndrome
Churg–Strauss syndrome is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and...
.
Classification of type III RPGN into primary or secondary may be unnecessary, as primary type III RPGN and secondary type III RPGN may represent a spectrum of the same disease process.
The ANCA form may have a more favorable response to treatment than other forms.
Type IV
Type 4 has features of both types 1 and 3. This is also called "double-antibody" positive disease.Signs and symptoms
Most types of RPGN are characterized by severe and rapid loss of kidney function featuring severe hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
(blood in the urine), red blood cell casts in the urine, and proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(protein in the urine), sometimes exceeding 3 g protein/24 h, a range associated with nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
. Some patients also experience hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
(high blood pressure) and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
. Severe disease is characterized by pronounced oliguria
Oliguria
Oliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
or anuria
Anuria
Anuria means nonpassage of urine, in practice is defined as passage of less than 50 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage renal...
, which portends a poor prognosis.
Serum analysis
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
often aids in the diagnosis of a specific underlying disease. The presence of anti-GBM antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
and type II RPGN; and type III and idiopathic RPGN are frequently associated with ANCA-positive serum.
Crescent formation
Despite the wide variety of diseases that cause RPGN, all types of RPGN are characterized by glomeruluar injury and the formation of crescents. Severe injury and GBM rupture leads to the leakage of plasma proteins through the GBM. Of these proteins, fibrinFibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
is thought to contribute most strongly to crescent formation. Epithelial cells lining the Bowman capsule respond to the leaked fibrin and proliferate. Infiltrating white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s such as monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s may also proliferate. These proliferating cells surround and compress the glomerulus, forming a crescent-shaped scar that is readily visible on light microscopy of a renal biopsy
Renal biopsy
A renal biopsy is a procedure in which a sample of kidney tissue is obtained. Microscopic examination of the tissue can provide information needed to diagnose, monitor or treat a renal disorder.-Indications:...
.