Lupus Nephritis

What is lupus nephritis?

Lupus nephritis (LN) is a complication of an autoimmune disease called systemic lupus erythematosus (SLE). Normally, the body’s immune system makes proteins called antibodies that help to attack outside invaders like bacteria, viruses, and other germs to prevent or fight infection. In people with an autoimmune disease such as SLE, the immune system makes unwanted antibodies and attacks parts of the person’s own body. Most people with SLE have rashes and joint pain, but SLE can affect any organ of the body.

Approximately half of people with SLE also get LN [1,2], which is a serious and possibly life-threatening problem. Normally, the kidneys help clean the blood by removing waste and extra fluid, which are carried out of the body in urine. In people with LN, the immune system attacks the kidneys. This causes swelling inside the kidneys, which stops them from working properly and can cause permanent damage. In some people with LN, their kidneys continue to get worse and may eventually stop working completely [1,3]. If this happens, patients need either (1) dialysis, which uses a machine to clean the blood, or (2) a new kidney (kidney transplant).

What are the risk factors for lupus nephritis?

It is not known why some people get SLE. The reason that some people with SLE develop LN is also not clear. However, some things can increase the chance that a person will get LN. These are called risk factors. Having a risk factor does not mean that you will definitely get the disease. Risk factors for SLE and LN can include [1-3]:

• Gender – women are 8 to 15 times more likely than men to get SLE; however, among people with SLE, men are slightly more likely than women to get LN
• Race or ethnicity – people who are black, Hispanic, or Asian are 2 to 3 times more likely to get SLE and are more likely to die from LN than people who are white
• Genetic factors – people with variations in some genes are more likely to get SLE and LN
• Environmental factors – people are more likely to get SLE and LN if they smoke, are exposed to certain chemicals (including pesticides), or have had some types of infections

What are the symptoms of lupus nephritis?

The symptoms of LN in a person with SLE can be mild and aren’t the same in everyone. Many people do not have any obvious symptoms, so doctors use laboratory tests to monitor if a person with SLE has LN [1,3]. For all patients with SLE, doctors usually test for kidney problems at least yearly [3].

Here are some symptoms that a person with LN might have, but many people with LN do not have any of these symptoms:

• Swelling of the legs and feet
• Swelling of the face and hands
• Weight gain
• Fatigue
• High blood pressure
  
• Dark or foamy urine
• The need to urinate frequently

How is lupus nephritis diagnosed?

A person with SLE regularly has blood tests and urine tests performed to monitor if they might have kidney problems that could be LN. There are 3 things that doctors measure to check for LN [1,2]:

• Serum creatinine is a waste product from the muscles that can be found in the blood. Normally, the kidneys remove creatinine from the blood. If the kidneys are not working well, then there is more creatinine in the blood than normal
• Protein in the urine. More protein than normal in the urine is called proteinuria. Normally, the kidneys prevent too much protein from leaving the blood and going into the urine. If the kidneys are not working well, there is more protein in the urine than normal
• Blood in the urine. Blood in the urine is called hematuria. Normally, the kidneys prevent blood from moving into the urine. If the kidneys are not working well, some blood cells can move into the urine. Sometimes, hematuria can be seen by eye because the urine is darker than normal. Other times, a microscope is needed to see the blood cells

If the results of blood and urine tests suggest that a person with SLE has kidney problems, then a kidney biopsy can be used to diagnose LN. In a kidney biopsy, doctors remove a small amount of tissue from the kidney. The person is usually awake and given painkillers and numbing medication. Doctors then look at the tissue under a microscope to see if the person has LN [1,2].

How is lupus nephritis treated?

The main goal when treating LN is to stop the swelling inside the kidneys and prevent permanent damage to the kidneys. Reducing the amount of swelling helps the kidneys work better to clean the blood. LN is usually treated with drugs that reduce the activity of the immune system (called immunosuppressive drugs), including steroids and mycophenolate mofetil or cyclophosphamide [1,2]. These medicines can reduce the swelling inside the kidneys. After the kidneys are working better, the doctor may change the doses of these medicines. Most people with LN continue to take steroids and immunosuppressive drugs at a low dose to prevent the disease from becoming active again.

Many people have side effects from taking steroids for a long time. The doctor may give more medicines to treat or to lower the risk of these problems. Side effects from taking steroids for a long time include [4]:

• Weight gain
• Diabetes
• High blood pressure
• Higher risk of cataracts
• Higher risk of bone fracture
• Higher risk of infections

In about 10% of people with LN, the LN keeps getting worse despite treatment. This is called end-stage kidney disease, also known as kidney failure [3]. In people whose kidneys stop working completely, dialysis or a kidney transplant is needed.

A medicine called obinutuzumab is being studied to see how well it works to treat LN [6]. Obinutuzumab reduces the number of B cells in the body. B cells are part of the immune system that help activate the immune system and make antibodies. Reducing the number of B cells in the body might control LN by slowing the immune system attacks on the kidneys.

What is the outlook for a person with lupus nephritis?

LN is a serious kidney problem. People with LN are more likely to die at a younger age than people without LN.

• People with SLE have 2 to 3 times greater risk of death than people in the general population of their same age group [5]
• People with LN have 3 times greater risk of death than people with SLE but not LN [3]
• People with LN have 8 times greater risk of death than the people in the general population of their same age group [5]

People with LN whose kidneys work better after treatment will need to regularly see their doctor to check that LN has not become active again and to check for side effects from therapy.