Glomerulonephritis
Encyclopedia
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal
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...

 disease (usually of both kidneys) characterized by inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 of the glomeruli
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...

, or small blood vessels in the kidneys. It may present with isolated hematuria
Hematuria
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...

 and/or 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...

 (blood or protein in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

); or as a 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....

, a 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...

, acute renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...

, or chronic renal failure. They are categorised into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types. Diagnosing the pattern of GN is important because the outcome and treatment differs in different types. Primary causes are ones which are intrinsic to the kidney, whilst secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE
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...

, vasculitis) or diabetes.

Thin Basement Membrane Disease

Thin basement membrane disease
Thin basement membrane disease
Thin basement membrane disease is, along with IgA nephropathy, the most common cause of asymptomatic hematuria. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys...

 is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic hematuria
Hematuria
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...

.

Non Proliferative

This is characterised by the numbers of cells (lack of hypercellularity) in the glomeruli. They usually cause nephrotic syndrome. This includes the following types:

Minimal change GN (also known as Minimal Change Disease)

This form of GN causes 78.4% of nephrotic syndrome in children, but only 20% in adults. As the name indicates, there are no changes visible on simple light microscopy, but on electron microscopy there is fusion of podocytes (supportive cells in the glomerulus). Immunohistochemistry staining is negative. Treatment consists of supportive care for the massive fluid accumulation in the patients body (= oedema) and as well as steroids to halt the disease process (typically Prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

 1 mg/kg). Over 90% of children respond well to steroids, being essentially cured after 3 months of treatment. Adults have a lower response rate (80%). Failure to respond to steroids ('steroid resistant') or return of the disease when steroids are stopped ('steroid dependent') may require cytotoxic therapy (such as cyclosporin) which is associated with many side-effects.

Focal Segmental Glomerulosclerosis (FSGS)

FSGS may be primary or secondary to reflux nephropathy
Reflux nephropathy
Reflux nephropathy, RN is a term applied when small and scarred kidneys are associated with vesico-ureteric reflux . CPN being the most common cause, there are other causes including analgesic nephropathy and obstructive injury. Scarring is essential in developing RN and occurs almost during the...

, Alport syndrome
Alport syndrome
Alport syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome can also affect the eyes . The presence of blood in the urine is almost always found in this condition.It was first identified in a British...

, heroin abuse or HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

. FSGS presents as a 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....

 with varying degrees of impaired renal function (seen as a rising serum creatinine, hypertension). As the name suggests, only certain foci of glomeruli within the kidney are affected, and then only a segment of an individual glomerulus. The pathological lesion is sclerosis (fibrosis) within the glomerulus and hyalinisation of the feeding arterioles, but no increase in the number of cells (hence non-proliferative). The hyaline is an amorphous material, pink, homogeneous, resulting from combination of plasma proteins, increased mesangial matrix and collagen. Staining for antibodies and complement is essentially negative. Steroids are often tried but not shown to be effective. 50% of people with FSGS continue to have progressive deterioration of kidney function, ending in renal failure.

Membranous glomerulonephritis

Membranous glomerulonephritis (MGN), a relatively common type of glomerulonephritis in adults, frequently produces a mixed nephrotic
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....

 and nephritic picture. Its cause is usually unknown, but may be associated with cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s of the lung and bowel, infection such as hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

 and malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

, drugs including penicillamine
Penicillamine
Penicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...

, and connective tissue diseases such as 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...

. Individuals with cerebral shunt
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...

s are at risk of developing shunt nephritis
Shunt nephritis
Shunt nephritis is a rare disease of the kidney that can occur in patients being treated for hydrocephalus with a cerebral shunt. It usually results from an infected shunt that produces a long-standing blood infection, particularly by the bacterium Staphylococcus epidermidis. Kidney disease results...

, which frequently produces MGN.

Microscopically, MGN is characterized by a thickened glomerular basement membrane
Glomerular 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...

 without a hypercellular glomerulus. Immunofluorescence
Immunofluorescence
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...

 demonstrates diffuse granular uptake of IgG. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.

Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to end-stage renal failure. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with 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 is attempted if the disease progresses.

In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.

Proliferative

This type is characterised by increased number of cells in the glomerulus (hypercellular). Usually present as a 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...

 and usually progress to end-stage renal failure (ESRF) over weeks to years (depending on type).

General Information

IgA nephropathy
IgA nephropathy
IgA nephropathy is a form of glomerulonephritis...

 is the most common type of glomerulonephritis in adults worldwide. It usually presents as macroscopic haematuria (visibly bloody urine). It occasionally presents as a nephrotic syndrome. It often affects young males within days (24-48hrs) after an upper respiratory tract or gastrointestinal infection. Microscopic examination of biopsy specimens shows increased number of mesangial cells with increased matrix (the 'cement' which holds everything together). Immuno-staining is positive for immunoglobulin A deposits within the matrix. Prognosis is variable, 20% progress to ESRF. ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...

s are the mainstay of treatment.

Summary

This is a form of GN characterised by IgA deposits in the mesangeial regions and immunocytochemistry is required for definitive diagnosis of the disease.

Presentation

  1. Recurrent gross or microscopic hematuria
    • gross hematuria occurs post-infection of the respiratory (more common), gastrointestinal, or urinary tract
  2. mild proteinuria
  3. occasionally nephrotic syndrome (although it usually has a nephritic presentation)
  4. rarely, presents with crescentic Rapidly progressive GN

Causes

The disease can be primary or secondary to liver and intestinal diseases. It also overlaps with Henoch-Schonlein purpura, a systemic renal disease in children in which similar IgA deposits occur.

Pathology

plasma polymeric IgA is increased in IgA Nephropathy, and circulating IgA-containing immune complexes can be found in the blood of some patients. Plasma IgA is usually monomeric and polymeric plasma IgA is broken down in the liver. IgA is normally found in mucus.

There are two forms of IgA and only IgA1 causes nephrogenicity.

Histology

Characteristic finding:
  1. IgA deposition in the mesangium seen by immunofloresence
  2. Electron dense deposits in electron microscopy
  3. Absence of early complement components

May find:
  1. normal glomeruli
  2. mesangioproliferative GN
  3. focal proliferative GN (healing may cause focal segmental sclerosis)
  4. overt cresentic glomerulonephritis
  5. leukocytes in glomerular capillaries

Post-infectious

Post-infectious glomerulonephritis
Post-infectious glomerulonephritis
Acute proliferative glomerulonephritis is a disorder of the glomeruli , or small blood vessels in the kidneys. It is a common complication of infections, typically streptococcal skin infection rather than streptococcal pharyngitis, for which it is also known as postinfectious or poststreptococcal...

 can occur after essentially any infection, but classically occurs after infection with Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

. It typically occurs 10–14 days after a skin or pharyngeal
Pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...

 infection with this bacterium.

Patients present with signs and symptoms of glomerulonephritis. Diagnosis is made based on these findings in an individual with a history of recent streptococcal infection. Streptococcal titers in the blood (antistreptolysin O titers) may support the diagnosis.

Light microscopy demonstrates diffuse endocapillary hypercellularity due to proliferation of endothelial and mesangial cell
Mesangial cell
Mesangial cells are specialized cells around blood vessels in the kidneys, at the mesangium. They are specialized smooth muscle cells that function to regulate blood flow through the capillaries, usually divided into two types, each having a very distinct function and location:* Extraglomerular...

s, as well as an influx of neutrophils and 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. The Bowman space is compressed, in some cases to the extent that this produces a crescent formation characteristic of crescentic glomerulonephritis.

Biopsy is seldom done as the disease usually regresses without complications. Treatment is supportive, and the disease generally resolves in 2–4 weeks.

Membranoproliferative/mesangiocapillary GN

This may be primary, or secondary to SLE
SLE
-Medicine:* Systemic lupus erythematosus, an autoimmune disease affecting multiple systems in the body* Slit lamp examination, as used to examine the eye during an eye examination* St...

, viral hepatitis
Viral hepatitis
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute or chronic forms. The most common causes of viral hepatitis are the five unrelated hepatotropic viruses Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D, and Hepatitis E...

, or hypocomplementemia. One sees 'hypercellular and hyperlobular' glomeruli due to proliferation of both cells and the matrix within the mesangium. Usually presents with a combined nephritic-nephrotic picture, with inevitable progression to end stage renal failure.
The primary form consists of two types:
  • Type 1 (Classical and Alternative Complement
    Complement
    In many different fields, the complement of X is something that together with X makes a complete whole—something that supplies what X lacks.Complement may refer to:...

     activation)
  • Type 2 (also known as Dense Deposit Disease) Alternative Complement activation only. C3 Nephritic Factor stabilizes C3 convertase, leading to Hypocomplementemia. Unlike Type 1, no IgG is detected.

In both types, the basement membrane may develop a 'tram-track' appearance, due to duplication and splitting.

Rapidly progressive glomerulonephritis

Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis is a syndrome of the kidney that is characterized by a rapid loss of renal function, with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies...

(Crescentic GN) has a poor prognosis, with rapid progression to kidney failure over weeks. Steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

 therapy is sometimes used. Any of the above types of GN can be rapidly progressive. Additionally two further causes present as solely RPGN.
  • One is Goodpasture's syndrome
    Goodpasture's syndrome
    Goodpasture’s syndrome is a rare disease characterized by glomerulonephritis and hemorrhaging of the lungs...

    , an autoimmune disease whereby antibodies are directed against basal membrane antigens found in the kidney and lungs. As well as kidney failure, patient have hemoptysis (cough up blood). High dose immunosuppression is required (intravenous Methylprednisolone
    Methylprednisolone
    Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....

    ) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.

  • The second cause is vasculitic disorders such as Wegener's granulomatosis
    Wegener's granulomatosis
    Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...

     and polyarteritis. There is a lack of immune deposits on staining, but blood tests are positive for ANCA
    ANCA
    ANCA Pty Ltd is an Australia company which designs and manufactures CNC grinding machines. The company was founded in 1974 by Pat Boland and Pat McCluskey in Melbourne, Australia....

    antibody.


Histopathology: The majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of parietal cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space which leads to renal failure within weeks or months.
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