Lupus Nephritis

Lupus nephritis (loo-pus neh-FRY-tis), also called LN, is kidney inflammation caused by systemic lupus erythematosus (SLE), often called lupus. Lupus is an autoimmune disease. This means the immune system attacks healthy parts of the body by mistake.

When lupus affects the kidneys, it can damage the tiny filters that clean the blood. This can cause protein or blood to leak into the urine and can make it harder for the kidneys to remove waste and extra fluid.

Lupus nephritis can be mild or severe. Some people have no symptoms at first. Regular kidney tests are important for anyone living with lupus because finding kidney changes early can help protect kidney function.

Lupus nephritis may not cause symptoms at first. Kidney changes can be found on urine or blood tests before you notice a problem. When symptoms happen, they may include:

• Foamy or bubbly urine, which can be a sign of protein in the urine
• Pink, red, or brown urine, which can be a sign of blood in the urine
• Swelling in the feet, ankles, legs, hands, face, or around the eyes
• Weight gain from extra fluid
• High blood pressure
• Peeing less than usual
• Feeling very tired

Call your doctor if you have lupus and notice new swelling, foamy or bloody urine, a major change in how much you pee, or other new symptoms. Do not wait for symptoms to get kidney tests if your doctor recommends regular screening.

Lupus nephritis happens when lupus causes the immune system to attack the kidneys. This leads to inflammation and can damage the kidney filters.

Doctors do not know exactly why some people with lupus develop kidney disease and others do not. Genes, immune system changes, hormones, infections, environmental exposures, and other factors may all play a role.

A kidney biopsy can show what lupus is doing inside the kidneys. The biopsy is grouped into six classes. The class numbers describe the pattern of kidney changes. They are not a simple scale from mild to severe, and more than one class can be present at the same time.

• Class I, minimal mesangial: Very small changes are seen under a microscope. Kidney tests may be normal.
• Class II, mesangial proliferative: More immune activity is seen in part of the kidney filter. Some people have blood or protein in the urine.
• Class III, focal: Inflammation affects fewer than half of the kidney filters. Treatment is usually needed when the disease is active.
• Class IV, diffuse: Inflammation affects at least half of the kidney filters. This is often an active form of lupus nephritis and usually needs treatment.
• Class V, membranous: The walls of the kidney filters are affected. This can cause a large amount of protein to leak into the urine.
• Class VI, advanced sclerosing: Most kidney filters have permanent scarring. Care focuses on protecting the kidney function that remains and planning treatment if kidney failure develops.

Your biopsy may also describe changes as active, chronic, or both. Active changes are caused by current inflammation and may improve with treatment. Chronic changes are scars that usually do not go away. Your doctor uses the class, the amount of activity and scarring, your urine protein level, and your kidney function to help choose treatment.

Lupus nephritis can cause lasting kidney damage, especially when it is not found or treated early. Possible complications include:

• Chronic kidney disease (CKD)
• Kidney failure that may require dialysis or a kidney transplant
• Nephrotic syndrome, which can cause heavy protein loss in the urine, swelling, and high cholesterol
• High blood pressure
• A higher risk of blood clots in some people
• A higher risk of heart and blood vessel disease
• Infections or other side effects related to medicines that lower immune system activity

Current U.S. kidney guidance notes that about 1 out of 10 people with lupus nephritis develop kidney failure. Individual risk can be higher or lower depending on the type of lupus nephritis, how much kidney damage is present, how well the disease responds to treatment, and other health factors.

People with lupus should have regular urine and blood tests to check for kidney involvement. Testing is also important when lupus is first diagnosed and when symptoms or a lupus flare suggest the kidneys may be affected.

If tests show signs of kidney damage, your doctor may recommend a kidney biopsy. A biopsy can confirm lupus nephritis, show the class of disease, and show how much inflammation and scarring are present. This information helps guide treatment.

Tests

Tests used to check for lupus nephritis may include:

• Urinalysis to look for protein, blood, and cells in the urine
• Urine protein-to-creatinine ratio (uPCR or UPCR) to measure how much protein is leaking into the urine
• Blood creatinine and estimated glomerular filtration rate (eGFR) to check how well the kidneys are filtering the blood
• Complement blood tests and anti-double-stranded DNA (anti-dsDNA) tests to look for signs of lupus activity
• Other lupus antibody tests when needed
• Kidney biopsy to examine a small sample of kidney tissue under a microscope

A kidney biopsy is often considered when urine protein is  500 mg a day or more, when urine tests show other signs of kidney inflammation, or when kidney function gets worse without another clear cause. Your doctor will decide whether a biopsy is needed based on your full health picture.

Overview

The goals of treatment are to calm kidney inflammation, lower the amount of protein in the urine, protect kidney function, prevent flares, and limit medicine side effects. Treatment should start promptly when active lupus nephritis is diagnosed.

Treatment is individualized. Your nephrologist and rheumatologist may work together to choose a plan based on your biopsy findings, urine protein level, kidney function, other lupus symptoms, other health conditions, pregnancy plans, and your treatment preferences.

Newer guidance emphasizes that treatment is often continuous over several years. Many people with active lupus nephritis receive a combination of medicines rather than one medicine alone. Steroid doses are usually lowered over time when the disease is responding.

Medicines

Medicines used for lupus nephritis may include:

• •Hydroxychloroquine, which is recommended for most people with lupus nephritis unless there is a reason it is not safe for them
• Glucocorticoids, also called steroids, such as prednisone or methylprednisolone, to quickly lower inflammation. Doctors now try to reduce the steroid dose as the disease comes under control
• Mycophenolate medicines, including mycophenolate mofetil (MMF) or mycophenolic acid (MPA)
• Cyclophosphamide
• Belimumab (Benlysta), a biologic medicine that can be added to other lupus nephritis medicines
• Calcineurin inhibitors, including voclosporin (Lupkynis), tacrolimus, or cyclosporine
• Obinutuzumab (Gazyva), a biologic medicine approved in the United States for adults with active lupus nephritis who are receiving standard therapy
• Azathioprine, which may be used for long-term treatment and in some people who are planning pregnancy
• Rituximab or other medicines in selected situations, such as when lupus nephritis does not improve enough with standard treatment

You may also need medicines to control blood pressure, lower protein in the urine, manage swelling or cholesterol, or prevent other complications. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are often used when they are appropriate for you.

Some lupus nephritis medicines can cause birth defects or may not be recommended during pregnancy. Talk with your doctor before trying to become pregnant and before stopping or changing any medicine.

Nutrition

There is no single lupus nephritis diet. What you need to eat may change based on your kidney function, blood pressure, swelling, urine protein, medicines, and blood test results.

A kidney dietitian can help you make a plan that fits your needs. You may be advised to:

• Limit sodium if you have high blood pressure or swelling
• Choose mostly fresh or minimally processed foods
• Eat an amount of protein that is right for your kidney health instead of automatically following a high-protein diet
• Ask whether you need to change potassium or phosphorus intake. Many people do not need to limit these unless blood tests or kidney function show a reason
• Talk with your doctor or dietitian before using herbal products or dietary supplements because some can affect the kidneys or interact with medicines

Exercise

Regular movement can support heart health, strength, sleep, mood, and energy. Walking, swimming, biking, stretching, and light strength exercises are options for many people.

Your activity may need to change during a lupus flare, with severe fatigue, or when swelling or other symptoms are worse. Ask your doctor what level of activity is safe for you, especially before starting a new exercise program.

Lupus nephritis care often involves both a kidney doctor, called a nephrologist, and a rheumatologist. Before your visit:

• Write down new symptoms or changes in swelling, urine, blood pressure, or energy
• Bring a list of all prescription medicines, over-the-counter medicines, vitamins, and other dietary supplements
• Bring recent home blood pressure readings if you check your blood pressure
• Ask whether you should have urine or blood tests before the appointment
• Write down your questions and treatment goals
• Tell your care team if you are pregnant, planning pregnancy, or want to discuss birth control because some medicines must be changed before pregnancy

Questions to ask

• What class of lupus nephritis do I have?
• Does my biopsy show active inflammation, scarring, or both?
• How much protein is in my urine, and is it getting better?
• What is my eGFR, and has my kidney function changed?
• What are the goals of my treatment?
• Why are you recommending these medicines together?
• What side effects should I watch for?
• How quickly should my steroid dose be lowered if treatment is working?
• How often will I need blood and urine tests?
• What would make you change my treatment plan?
• Are there vaccines or infection precautions I need because of my medicines?
• Should I meet with a kidney dietitian?
• How could lupus nephritis or my medicines affect pregnancy or birth control?
• Are there clinical trials that may be appropriate for me?

• Kidney Biopsy
• ACE Inhibitors and ARBs
• Vaccines and Kidney Disease
• Clinical Trials and Kidney Disease

Connect with NKF for answers, support, and free learning programs.

• NKF Cares: Patient Information Help Line
• NKF Kidney Learning Center
• NKF Peers

• Kidney Professionals
• Clinical Tools and Resources for Kidney Care