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Definition
Glomerulonephritis is an inflammation of the renal glomeruli that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to hematuria, proteinuria, hypertension, and renal insufficiency.
Etiology
Glomerulonephritis may be caused by a lot of factors, but in many cases the exact cause of glomerulonephritis is unknown. It is thought that the condition is often caused by the immune system.
- Antigens and antibodies
Antigens are foreign substances in the body, such as proteins and toxins. The body also produces antibodies that are infection-fighting proteins. Antibodies circulate in the blood and help to get rid of antigens. If antigens and antibodies build up in your kidneys, they can become inflamed (swell). This reaction can affect the kidneys or it may cause problems in other parts of your body as well.
If you have a chronic (long-term) autoimmune condition, such as lupus (a condition that causes inflammation in the body’s tissues), your risk of developing glomerulonephritis is increased. An autoimmune condition is where the body’s own cells are attacked by mistake.
- Streptococci bacteria
Acute (short-term) glomerulonephritis is sometimes linked to streptococci bacteria. This is often referred to as acute post streptococcal glomerulonephritis, and it can follow a throat or skin infection. Streptococcus bacteria has a lot of surface antigens, which they use to attach host cells and to defend from immune system (M-protein, Streptolysin, Streptococcal pyrogenic exotoxin). The M-protein(Streptococcus) generates antibodies that cross-react with autoantigens on interstitial connective tissue, especially heart muscle, glomeruli, blood-vessel and synovium.
- Complication of other infections
It is also possible to develop glomerulonephritis as a serious complication of other infections including:
- HIV;
- hepatitis B;
- hepatitis C;
- tuberculosis;
- syphilis.
- Genetic factors
Most people with glomerulonephritis do not have a family member who also has the condition. However, certain types of glomerulonephritis can be inherited.
If you are diagnosed with a primary (genetical) glomerulonephritis , the health care professional who is treating you will be able to advise you about the chances of someone else in your family being affected, and they may recommended screening.
- Long-term medication use
Glomerulonephritis can sometimes occur as a side effect of the long-term use of certain drugs. Examples of medication that are often associated with the condition include:
- non-steroidal anti-inflammatory drugs;
- gold injections (used to treat rheumatoid arthritis);
- lithium (used to treat depression);
- penicillamine (used to treat arthritis).
People who take medicines that affect kidney function, should monitor this using renal tests.
- Other causes of glomerulonephritis
Glomerulonephritis can sometimes occur if the glomeruli are damaged as a result of a number of other conditions including:
- cancer and leukaemia;
- Hodgkin’s disease: detection of tumor antigens in glomeruli suggests the role of antigen-antibody complexes in pathogenesis;
- diabetes: because it generates a progressive angiopathy of capillaries in the kidney glomeruli and glomeruloscerosis;
- hypertension: as a result of hypertension, hyaline accumulates in the wall of small arteries and arterioles, producing the thickening of their walls and the narrowing of the lumens (hyaline arteriolosclerosis). Consequent ischemia will produce tubular atrophy, interstitial fibrosis, glomerular alterations and periglomerular fibrosis;
- Goodpasture’s syndrome (an autoimmune disorder that affects the lungs and kidneys, immune system attacks type IV collagen in basal lamina);
- liver disease;
- sickle cell disease: due to sickle cell nephropathy as a result of sickling of red blood cells in the microvasculature.
Symptoms
Inflammation of the kidneys may not be obvious at first. The symptoms can come on suddenly or appear up to three weeks after infection.
If your glomeruli have been damaged, small amounts of blood and/or protein may be filter into urine as the result of inflammation and podocytes alteration. This may only be apparent upon testing. In severe cases of glomerulonephritis, a greater amount of blood may be lost through the glomeruli, causing urine to turn red (haematuria). If a large amount of protein is lost through the damaged filters in kidneys, urine may also be cloudy or frothy.
As a result of kidney damage, glomerulonephritis may cause also:
- swelling of the face, eyes, ankles, feet, legs;
- vomit;
- fever;
- joint and muscle aches;
- a loss of appetite;
- breathing problems;
- abdominal and kidney pain.
Diagnosis
As the symptoms of glomerulonephritis are not always obvious, the condition is sometimes only diagnosed following a routine medical check-up or during tests related to having high blood pressure, feeling tired or being pregnant.
- Blood and urine tests
Blood tests check the level of antigens and antibodies in your blood. Particularly high readings of these proteins may indicate the disease.
A urine test may also be carried out to check whether you have any blood and/or protein in your urine.
Most common urine and blood tests:
- Examination of the urine under a microscope
- Creatinine clearance
- Total protein
- Uric acid, urine
- Urine concentration test
- Urine creatinine
- Urine protein
- Albumin
- Anti-glomerular basement membrane antibody test
- Anti-neutrophil cytoplasmic antibodies (ANCAs)
- Complement component 3
- Complement levels
- Renal function tests
Patients with glomerulonephritis may have a range of tests, known as renal function tests, to determine how well your kidneys are working. These tests will involve taking blood samples to determine the levels of sodium, chloride, potassium and urea.
- Kidney biopsy
A kidney biopsy is usually carried out using local anaesthetic and a small needle. Following the procedure, the tissue sample will be examined in a laboratory in order to find out how serious the condition is and to determine the most appropriate type of treatment.
Non Proliferative Glomerulonephritis
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
This form of GN causes 80% 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. Treatment consists of supportive care for the massive fluid accumulation in the patients body (edema) and as well as steroids to halt the disease process.
Fenestrated endothelium is present, and the basement membrane is normal. However, overlying epithelial cell foot processes are effaced (giving the appearance of fusion) and run together
- 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 within the glomerulus and hyalinisation of the feeding arterioles, but no increase in the number of cells (hence non-proliferative). Staining for antibodies and complement is essentially negative. 50% of people with FSGS continue to have progressive deterioration of kidney function, ending in renal failure.
Trichrome stain of a glomerulus in a patient with focal segmental glomerulosclerosis demonstrates blue collagen deposition
- Membranous glomerulonephritis
Membranous glomerulonephritis (MGN), a relatively common type of glomerulonephritis in adults, frequently produces a mixed nephrotic and nephritic picture. It is usually idiopathic, 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.
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.
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.
Membranous glomerulonephritis is an immunologically mediated disease in which deposts of mainly IgG and complement collect in the basement membrane and appear in a diffuse granular pattern by immunofluorescence, as seen here.
Proliferative Glomerulonephritis
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 over weeks to years.
- IgA nephropathy (Berger's disease)
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. 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.
The IgA is deposited mainly within the mesangium, which then increases mesangial cellularity as shown at the arrow.
- Post-infectious
Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with Streptococcus pyogenes. It typically occurs 10–14 days after a skin or pharyngeal 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 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 2–4 weeks.
The hypercellularity of post-infectious glomerulonephritis is due to increased numbers of epithelial, endothelial, and mesangial cells as well as neutrophils in and around the glomerular capillary loops.
- Membranoproliferative
This is primary, or secondary to SLE, viral hepatitis, hypocomplementemia. One sees 'hypercellular and hyperlobular' glomeruli due to proliferation of both cells and the matrix within the mesangium. Presents usually with as a nephrotic syndrome but can be nephritic, with inevitable progression to end stage renal failure.
As seen here, the glomerulus has increased overall cellularity, mainly increased mesangial cellularity.
- Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (Crescentic GN) has a poor prognosis, with rapid progression to kidney failure over weeks. Steroid therapy is sometimes used.
Within the glomeruli are crescents composed of proliferating epithelial cells. Note in the lower left glomerulus that the capillary loops are markedly thickened
Any of the above types of GN can be rapidly progressive.
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
Treatment
Treatment varies depending on the cause of the disorder, and the type and severity of symptoms. However high blood pressure is generally the most important aspect of treatment, and it could be difficult to control.
Medicines that may be prescribed include:
- Blood pressure medications are often needed to control high blood pressure. Angiotensin-converting 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 immune-related 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.
Complication
The possible complications of glomerulonephritis will vary according to the type and severity of the condition.
High blood pressure is a common complication of glomerulonephritis. This is because one of the glomerulus function is regulate blood pressure filtering blood. When glomeruli are damaged by inflammation, in some cases a glomerulosclerosi is found, they can't filter blood as they did before, so blood volume is increased and lead easily to hypertension.
If high blood pressure is left untreated, fluid overload can lead to heart failure, pulmonary edema, and malignant hypertension.
End-stage kidney disease and kidney failure are rare conditions, but glomerulonephritis damages the kidneys so that they can fail completely.
In most patients, glomerulonephritis only affects the kidneys. However, the immune system can also affect other parts of your body. For example, cutaneus rash or pain in your joints.
Other possible complications are:
- Chronic or recurrent urinary tract infection
- Increased susceptibility to other infections
- Hyperkalemia
Prognosis
Glomerulonephritis may be a temporary and reversible condition, or it may get worse, it depends on the type of GN and the seriousness of the condition. Rapidly progressive glomerulonephritis may lead to chronic kidney failure and end-stage kidney disease.
