Glomerulonephritis

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Glomerulonephritis

Classification and external resources

Photomicrograph of a kidney biopsy from a patient with crescentic glomerulonephritisshowing prominent fibrocellular crescent formation and moderate mesangial proliferation in a glomerulus. Hematoxylin and eosin stain.

ICD-10

N00, N01, N03, N18

ICD-9

580-582

DiseasesDB

5245

MeSH

D005921

Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease (usually of both kidneys) characterized by inflammation of the glomeruli, or small blood vessels in the kidneys.[1] It may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as anephrotic syndrome, a nephritic syndrome, acute renal failure, 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, vasculitis) or diabetes.
Contents
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1 Thin Basement Membrane Disease 2 Non Proliferative

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2.1 Minimal change GN (also known as Minimal Change Disease) 2.2 Focal Segmental Glomerulosclerosis (FSGS) 2.3 Membranous glomerulonephritis

3 Proliferative

3.1 IgA nephropathy (Berger's disease)

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3.1.1 General Information 3.1.2 Summary 3.1.3 Presentation 3.1.4 Causes 3.1.5 Pathology 3.1.6 Histology

3.2 Post-infectious 3.3 Membranoproliferative/mesangiocapillary GN 3.4 Rapidly progressive glomerulonephritis

4 See also 5 References

Thin Basement Membrane Disease

Thin basement membrane disease 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.

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 79.4% 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 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, Alport syndrome, heroin abuse or HIV. FSGS presents as a nephrotic syndrome 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 nonproliferative). 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 and nephritic picture. Its cause is usually unknown, but may be associated with cancers of the lung and bowel, infection such as hepatitis and malaria, drugs including penicillamine, and connective tissue diseases such as systemic lupus erythematosus. Individuals with cerebral shunts are at risk of developing shunt nephritis, which frequently produces MGN. Microscopically, MGN is characterized by a thickened glomerular basement membrane without a hypercellular glomerulus. Immunofluorescence 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.[2][3] 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 corticosteroids 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 and usually progress to end-stage renal failure (ESRF) over weeks to years (depending on type).

IgA nephropathy (Berger's disease)

[4]

General Information
IgA nephropathy 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 inhibitors 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

1. 2. 3.

mild proteinuria occasionally nephrotic syndrome (although it usually has a nephritic presentation) rarely, presents with crescentic Rapidly progressive GN

Causes
The disease can be primary or secondary to liver and intestinal diseases. It also overlaps with HenochSchonlein 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. 2. 3. IgA deposition in the mesangium seen by immunofloresence Electron dense deposits in electron microscopy Absence of early complement components

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

Post-infectious
Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with Streptococcus pyogenes. It typically occurs 1014 days after a skin or pharyngealinfection 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 cells, as well as an influx of neutrophils and monocytes. 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 24 weeks.

Membranoproliferative/mesangiocapillary GN

This may be primary, or secondary to SLE, viral hepatitis, 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 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

Crescentic glomerulonephritis induced by infective endocarditis on PAS staining andimmunofluorescence. PAS staining (left) demonstrated circumferential and cellular crescent formation with interstitial nephritis. Immunofluorescence (right) demonstratedC3 positive staining in mesangial area.

Photomicrograph of renal biopsy showing crescent formation and tuft narrowing.Periodic acid silver methenamine stain.

Rapidly progressive glomerulonephritis (Crescentic GN) has a poor prognosis, with rapid progression to kidney failure over weeks. Steroid therapy is sometimes used.[5] Any of the above types of GN can be rapidly progressive. Additionally two further causes present as solely RPGN.

One is Goodpasture's syndrome, 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) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.

The second cause is vasculitic disorders such as Wegener's granulomatosis and polyarteritis. There is a lack of immune deposits on staining, but blood tests are positive for ANCA 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.

rulonephritis
Glomerulonephritis is a type of kidney disease in which the part of your kidneys that helps filter waste and fluids from the blood is damaged. Causes Glomerulonephritis may be caused by specific problems with the body's immune system. Often, the precise cause of glomerulonephritis is unknown. Damage to the glomeruli causes blood and protein to be lost in the urine. The condition may develop quickly, with loss of kidney function occurring over weeks and months (called rapidly progressive glomerulonephritis). In about a quarter of people with chronic glomerulonephritis there is no history of kidney disease and the disorder first appears as chronic renal failure. The following increase your risk of developing this condition: History of cancer Blood or lymphatic system disorders Exposure to hydrocarbon solvents Infections such as strep infections, viruses, heart infections,or abscesses Diabetes

Many conditions are known to cause or increase the risk for glomerulonephritis, including: Focal segmental glomerulosclerosis Goodpasture syndrome Membranoproliferative GN IgA nephropathy Lupus nephritis or Henoch-Schonlein purpura Anti-glomerular basement membrane antibody disease Blood vessel diseases such as vasculitis or polyarteritis Amyloidosis

Symptoms Common symptoms of glomerulonephritis are: Blood in the urine (dark, rust-colored, or brown urine) Foamy urine Swelling (edema) of the face, eyes, ankles, feet, legs, or abdomen

Symptoms that may also appear include the following: Abdominal pain Cough Diarrhea General ill feeling Fever Joint aches Muscle aches Loss of appetite Shortness of breath

Chronic renal failure symptoms may gradually develop. Other symptoms that may occur with this disease: Excessive urination Nosebleed Blood in the vomit or in stools

Exams and Tests Because symptoms develop gradually, the disorder may be discovered when there is an abnormal urinalysisduring a routine physical or examination for unrelated disorders. Glomerulonephritis can cause high blood pressure. It may only be discovered as a cause of high blood pressure that is difficult to control.

Laboratory tests may reveal anemia or show signs of reduced kidney functioning. A kidney biopsy confirms the diagnosis. Later, signs of chronic kidney failure may be seen, including swelling (edema), polyneuropathy, and signs of fluid overload, including abnormal heart and lung sounds. Imaging tests that may be done include: Abdominal CT scan Abdominal ultrasound Chest x-ray IVP

Urinalysis and other urine tests include: Examination of the urine under a microscope Creatinine clearance Total protein Uric acid, urine Urine concentration test Urine creatinine Urine protein Urine RBC Urine specific gravity

This disease may also affect the results of the following blood tests: Albumin Anti-glomerular basement membrane antibody test Anti-neutrophil cytoplasmic antibodies (ANCAs) BUN and creatinine Complement component 3 Complement levels

Treatment Treatment varies depending on the cause of the disorder, and the type and severity of symptoms. High blood pressure may be difficult to control, and it is generally the most important aspect of treatment. Medicines that may be prescribed include: Blood pressure medications are often needed to control high blood pressure. Angiotensinconverting enzyme inhibitors and angiotensin receptor blockers are most commonly prescribed. Corticosteroids may relieve symptoms in some cases. Medications that suppress the immune system may also be prescribed, depending on the cause of the condition.

A procedure called plasmapheresis may be used for some cases of glomerulonephritis due to immunerelated causes. The fluid part of the blood containing antibodies is removed and replaced with intravenous fluids or donated plasma (without antibodies). Removing antibodies may reduce inflammation in the kidney tissues. Dietary restrictions on salt, fluids, protein, and other substances may be recommended. Persons with this condition should be closely watched for signs that they are developing kidney failure. Dialysis or a kidney transplant may eventually be necessary. Support Groups You can often ease the stress of illness by joining support groups where members share common experiences and problems. See: Kidney disease - support group Outlook (Prognosis) Glomerulonephritis may be a temporary and reversible condition, or it may get worse. Progressive glomerulonephritis may lead to chronic kidney failure and end-stage kidney disease. If you have nephrotic syndrome and it can be controlled, other symptoms may also be controlled. If it can't be controlled, end-stage kidney disease may result. Possible Complications Nephrotic syndrome Acute nephritic syndrome Chronic kidney failure End-stage kidney disease Hypertension Malignant hypertension Fluid overload -- congestive heart failure, pulmonary edema Chronic or recurrent urinary tract infection Increased susceptibility to other infections Hyperkalemia

When to Contact a Medical Professional Call your health care provider if: You have disorders that are associated with an increased risk of glomerulonephritis You develop symptoms of glomerulonephritis

Prevention

There is no specific way to prevent most cases of glomerulonephritis. Some cases may be prevented by avoiding or limiting exposure to organic solvents, mercury, and nonsteroidal anti-inflammatory drugs (NSAIDs). Alternative Names Glomerulonephritis - chronic; Chronic nephritis; Glomerular disease; Necrotizing glomerulonephritis; Glomerulonephritis - crescentic; Crescentic glomerulonephritis; Rapidly progressive glomerulonephritis

What is glomerulonephritis?
Glomerulonephritis is an inflammatory disease of the kidneys, specifically the glomeruli. The glomeruli are the part of the kidneys in charge of filtering waste from the bloodstream. Glomeruli can become inflamed for a variety of reasons. Once inflamed, the glomeruli cannot filter waste properly and become leaky, which allows protein and blood to pass into the urine. Symptoms of glomerulonephritis include blood in the urine, foamy urine, and edema (swelling) of the legs, abdomen and body. As the disease progresses and the kidneys become more damaged, additional symptoms may appear, including abdominal pain, diarrhea, fever, aches, loss of appetite, and shortness of breath. Toward the end stages of the disease, more serious symptoms can occur, such as excessive urination, nosebleeds, bloody stool, and vomiting blood. Glomerulonephritis can even progress to kidney (renal) failure. While glomerulonephritis can happen to anyone, it most frequently occurs in people who have diabetes, autoimmune disorders, or certain genetic disorders. It can occur rapidly or it may develop very slowly over the course of years. Glomerulonephritis can cause high blood pressure, which often leads to its diagnosis. Treatment for glomerulonephritis includes blood pressure medication, steroids, and immunosuppressant drugs. Plasmapheresis (to remove antibodies against glomeruli from the blood), dialysis, or a kidney transplant may also become necessary depending upon the cause and severity of the condition. Changes in diet may also help to alleviate symptoms. In some cases, glomerulonephritis may reverse spontaneously; in others, it may become life threatening. Seek immediate medical care (call 911) for serious symptoms of glomerulonephritis, such as difficulty breathing, uncontrollable nosebleed, bloody stool, or vomiting blood. Seek prompt medical care if you have persistent or bothersome symptoms of glomerulonephritis.