Glomerulonephritis – Risk Factors, Complications, and Treatment

Glomerulonephritis – Overview

Glomerulonephritis refers to acute and chronic kidney diseases caused by injury to the glomerulus, a part of the kidney responsible for filtering blood. If the kidney is injured, it is unable to filter blood properly. Over time, the kidney’s efficiency decreases, affecting the removal of extra fluid and waste from the body. If the condition is left untreated, it can also cause kidney failure.  In this case, you will need dialysis, a procedure in which a machine filters your blood since your kidneys can’t do it for you. The last resort for kidney failure is a kidney transplant. Some other names for the diseases caused by glomerular injury are nephrotic syndrome and nephritis.

 

Pathophysiology

The underlying pathogenetic mechanism common to all of these different varieties of glomerulonephritis (GN) is immune-mediated, in which both humoral as well as cell-mediated pathways are active. The consequent inflammatory response, in many cases, paves the way for fibrotic events that follow.

The targets of immune-mediated damage vary according to the type of GN. For instance, glomerulonephritis associated with staphylococcus shows IgA and C3 complement deposits.

One of the targets is the glomerular basement membrane itself or some antigen trapped within it, as in post-streptococcal disease. Such antigen-antibody reactions can be systemic, with glomerulonephritis occurring as one of the components of the disease process, such as in systemic lupus erythematosus (SLE) or IgA nephropathy. On the other hand, in small vessel vasculitis, cell-mediated immune reactions are the main culprit instead of antigen-antibody reactions. Here, T lymphocytes and macrophages flood the glomeruli with resultant damage.

These initiating events activate common inflammatory pathways, i.e., the complement system and coagulation cascade. The generation of pro-inflammatory cytokines and complement products, in turn, results in the proliferation of glomerular cells. Cytokines such as platelet-derived growth factor (PDGF) are also released, ultimately causing glomerulosclerosis. This event is seen in those situations where the antigen is present for longer periods, for example, in hepatitis C viral infection. When the antigen is rapidly cleared, as in post-streptococcal GN, the resolution of inflammation is more likely.

Causes of Glomerulonephritis

Glomerulonephritis is often caused by a problem with your immune system. Sometimes it’s part of a condition such as systemic lupus erythematosus (SLE) or vasculitis.

In some cases, it can be caused by infections, such as:

• HIV
• Hepatitis B and hepatitis C
• Infection of the heart valves (endocarditis)

In most cases, glomerulonephritis does not run in families.

If you’re diagnosed with an inherited type of glomerulonephritis, a doctor can advise you about the chances of someone else in your family being affected.

They may recommend screening, which can identify people who may be at increased risk of developing the condition.

Risk factors

The cause is often unclear, but there are risk factors that can affect the likelihood of glomerulonephritis.

• Post-streptococcal glomerulonephritis can result from streptococcal infections of the throat or, in rarer cases, impetigo, a skin infection. Improved treatments for most streptococcal infections mean that this is now less common.
• Infectious diseases, such as tuberculosis (TB) and syphilis, can lead to glomerulonephritis. This is also true of bacterial endocarditis, an infection of the heart valves. Viral infections, such as HIV, hepatitis B, and hepatitis C also increase the risk.
• Acute glomerulonephritis may develop into chronic, or long-term, glomerulonephritis.
• Genetic factors can play a role, but people with glomerulonephritis do not normally have a family member who also has the condition.
• Long-term use of certain medications, including non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen or aspirin, can increase the risk.
• People with Hodgkin’s, sickle cell disease, and systemic diseases, especially diabetes are at higher risk.

What are the symptoms of Glomerulonephritis?

People with glomerulonephritis often don’t experience signs of the condition. But symptoms can include:

• Blood in the urine, which may make the pee look brown, pink or red.
• Fatigue, nausea or a rash.
• Hypertension (high blood pressure) or shortness of breath.
• Pain in the joints or abdomen (belly area).
• Peeing less often or more often than normal.
• Swelling in the legs or face.
• Urine that’s foamy.

If you have one or more of these symptoms, contact a healthcare provider.

Complications

Glomerulonephritis affects the ability of nephrons to filter the bloodstream efficiently. The breakdown in filtering results in:

• Accumulation of wastes or toxins in the bloodstream
• Poor regulation of essential minerals and nutrients
• Loss of red blood cells
• Loss of blood proteins

Possible complications of glomerulonephritis include:

• Acute kidney failure. Acute kidney failure is the sudden, rapid decline in kidney function, often associated with an infectious cause of glomerulonephritis. The accumulation of waste and fluids can be life-threatening if not treated promptly with an artificial filtering machine (dialysis). The kidneys often resume typical function after recovery.
• Chronic kidney disease. Persistent inflammation results in long-term damage and declining function of the kidneys. Chronic kidney disease is generally defined as kidney damage or decreased function for three or more months. Chronic kidney disease may advance to end-stage kidney disease, which requires either dialysis or a kidney transplant.
• High blood pressure. Damage to the glomeruli from inflammation or scarring can lead to increased blood pressure.
• Nephrotic syndrome. Nephrotic syndrome is a condition in which there is too much blood protein in urine and too little in the bloodstream. These proteins play a role in regulating fluids and cholesterol levels. A drop in blood proteins results in high cholesterol, high blood pressure and swelling (edema) of the face, hands, feet and abdomen. In rare instances, nephrotic syndrome may cause a blood clot in a kidney blood vessel.

How is Glomerulonephritis diagnosed?

The first step in diagnosis is a urinalysis test. Blood and protein in urine are important markers for the disease. A routine physical exam for another condition can also lead to the discovery of GN.

More urine testing may be necessary to check for important signs of kidney health, including:

• Creatinine clearance
• Total protein in the urine
• Urine concentration
• Urine specific gravity
• Urine red blood cells
• Urine osmolality

Blood tests may show:

• Anemia, which is a low level of red blood cells
• Abnormal albumin levels
• Abnormal blood urea nitrogen
• High creatinine levels

Your doctor may also order immunology testing to check for:

• Antiglomerular basement membrane antibodies
• Antineutrophil cytoplasmic antibodies
• Antinuclear antibodies
• Complement levels

Results of this testing may show your immune system is damaging your kidneys.

A biopsy of your kidneys may be necessary to confirm the diagnosis. This involves analyzing a small sample of kidney tissue taken by a needle.

To learn more about your condition, you may also have imaging tests such as the following:

• CT scan
• Kidney ultrasound
• Chest X-ray
• Intravenous pyelogram

Treatment of Glomerulonephritis

Treatment for glomerulonephritis depends on the cause of your condition and your symptoms. In mild cases, treatment is not always necessary. If treatment is needed, it’s usually carried out by a kidney specialist.

Dietary changes

In mild cases, a GP or dietitian will give you relevant advice about diet. You may be advised to reduce your intake of:

• foods that contain a high amount of salt
• foods or drinks that contain a high amount of potassium
• fluid

This should help control your blood pressure and ensure the amount of fluid in your body is regulated. You should have a regular review to ensure your blood contains the right levels of potassium, sodium chloride and other salts.

Cessation of smoking

Smoking may make kidney disease caused by glomerulonephritis worse.

It also increases the risk of complications like heart disease and stroke, which are more common in people with glomerulonephritis.

Immunosuppressants

Severe cases of glomerulonephritis, caused by problems with the immune system, are sometimes treated with types of medicine known as immunosuppressants. These medicines suppress your immune system.

Suppressing your immune system can be effective, but it also increases your risk of infections and can cause other side effects.

If you’re offered treatment with immunosuppressant medicines, they’ll be adjusted to the level needed to treat your condition and will be carefully monitored.

Steroids

You may be put on a course of medicines containing steroids such as prednisolone.

Steroids are used to reduce swelling and suppress your immune system.

Once your kidneys have started to recover, your dose of steroids will usually be lowered. You may continue to take a small dose, or this treatment may be stopped altogether.

Cyclophosphamide

Cyclophosphamide is an immunosuppressant used in very high doses to treat some cancers. It’s also an established treatment, in much lower doses, for glomerulonephritis.

Other immunosuppressants

Other medicines to help control your immune system include:

• Mycophenolate mofetil
• Azathioprine
• Rituximab
• Ciclosporin
• Tacrolimus

Other medicines

If your condition is thought to be linked to a viral infection, it may be treated with antiviral medication.

Individual symptoms can sometimes be treated. For example, swelling caused by a build-up of fluid may be treated with a type of medicine called a diuretic.

Treating high blood pressure

Glomerulonephritis often leads to high blood pressure, which can cause further kidney damage and other health problems.

Your blood pressure will be carefully monitored by the healthcare professionals treating you.

You may need to take medicines that lower blood pressure and help reduce the amount of protein that leaks into your urine, such as:

• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin receptor blockers (ARB)

Often, people who have high blood pressure and kidney disease need to take several medicines to control their blood pressure.

These medicines are commonly prescribed, even if your blood pressure is not particularly high, as they can help protect the kidneys.

Treating high cholesterol

High cholesterol levels are common in people with glomerulonephritis.

A doctor may recommend medicine to reduce cholesterol and help protect you against complications such as heart and vascular disease. Statins are the most frequently used medicine.

Plasma exchange

Plasma is a fluid that is part of the blood. It contains proteins that can make your kidneys inflamed.

Plasma exchange involves removing some of the plasma from your blood.

During the procedure, you’re connected to a machine that gradually removes some of your blood.

The plasma is separated from the blood cells and removed. A plasma substitute is then added to the blood before it’s put back into your body.

Plasma exchange may be used in certain circumstances if your condition is severe.

Treating chronic kidney disease or kidney failure

In severe cases that cannot be improved with other treatments, you may require:

• Kidney Dialysis – a treatment that takes over part of the kidney’s job and removes waste products from your body
• A Kidney Transplant – where a healthy kidney from a donor is surgically implanted to replace your own kidney

Vaccinations

People with glomerulonephritis can be more prone to infections, particularly if:

• You have nephrotic syndrome
• You develop chronic kidney disease

It’s a good idea to help protect yourself against infection by having a seasonal flu vaccine and a pneumonia vaccine.

Prevention of Glomerulonephritis

Most forms of glomerulonephritis cannot be prevented, but there are some ways to reduce the risk:

• Seek medical attention for a strep infection that causes a sore throat or impetigo.
• Keep diabetes and blood pressure under control.
• Practice safe sex using condoms.
• Avoid illegal intravenous drug use and sharing of needles.

Choosing a healthy lifestyle with plenty of exercise, quality sleep, and a well-rounded diet can reduce the risk of glomerulonephritis as well as the risk of other infections and hypertension.