Lupus nephritis

Lupus nephritis is a serious kidney condition that develops when the body’s immune system mistakenly attacks the kidneys in people with lupus, potentially leading to kidney failure if left untreated.

What is lupus nephritis?
Who develops lupus nephritis?
What causes this condition?
Signs and symptoms
How is lupus nephritis diagnosed?
Classification of lupus nephritis
Treatment approaches
Dietary recommendations
Possible complications

Kidneys
Glomeruli
Nephrons

What is lupus nephritis?

Lupus nephritis is a problem that occurs often in people who have systemic lupus erythematosus, also called lupus. Lupus is a disease in which the body’s immune system attacks its own cells and organs, called autoimmune disease. Lupus causes the immune system to make proteins called autoantibodies. These proteins attack tissues and organs in the body, including the kidneys.^[1]

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. It occurs when the immune system mistakenly attacks the kidneys, leading to inflammation and possibly to organ damage. Inflammation of the kidneys can harm the ability of the overall kidney system to properly remove waste from blood, maintain the correct amount of body fluids, and regulate hormone levels for controlling blood pressure and blood volume.^[2]

The kidneys’ main job is to filter extra water and wastes out of the blood to make urine. To keep your body working properly, the kidneys balance the salts and minerals—such as calcium, phosphorus, sodium, and potassium—that circulate in the blood. Your kidneys also make hormones that help control blood pressure, make red blood cells, and keep your bones strong.^[9]

Lupus nephritis prevents your kidneys from controlling blood pressure and blood volume, filtering wastes out of your blood, maintaining the right levels of body fluids including salts, acids and minerals, and regulating hormone levels.^[3]

Who develops lupus nephritis?

Only adults and children with lupus can develop lupus nephritis. About 50% of adults with lupus will develop lupus nephritis. About 80% of children with lupus will develop this kidney condition.^[3] Studies have shown that over time up to 60% of lupus patients will develop lupus nephritis, including over half of children with lupus.^[2]

You’re more likely to get lupus if you are a woman—9 out of 10 people with lupus are women—between the ages of 15 and 44, though men are more likely to develop lupus nephritis. The condition is more common in women than in men, and there is an even higher prevalence and severity of the disease among African American, Asian and Hispanic women between 15 and 44, who tend to develop the disease earlier and experience more serious complications.^[2]^[3]

Additional risk factors include coming in contact with certain infections, viruses, toxic chemicals or pollutants in the environment, having a family history of the disease, and having another autoimmune disease.^[3]

What causes this condition?

In lupus nephritis, your body attacks your kidney, which leads to inflammation and abnormal kidney function. Long-term inflammation leads to scarring and permanent kidney damage.^[3]

Lupus nephritis develops through a mix of genetic, environmental, and immune system influences. It is mainly caused by a type of reaction where antibodies against double-stranded DNA form immune complexes with DNA. These complexes build up in areas of the kidney like the mesangium and around the glomerular basement membrane. This triggers the complement system, bringing in neutrophils and other immune cells, which cause inflammation and kidney damage.^[6]

Signs and symptoms

Lupus nephritis most often develops within five years from when lupus symptoms first appear. Symptoms include weight gain, swelling, increase in urination especially at night, blood and foamy appearance in the urine, and high blood pressure. In its early stages, however, the symptoms of lupus nephritis can go unnoticed.^[2]

Symptoms of lupus nephritis tend to develop about five years after lupus symptoms first appear. But lupus nephritis can be the first—and sometimes the only—manifestation of systemic lupus erythematosus.^[3]

Lupus nephritis can cause:

Edema, which is swelling due to fluid buildup in your lower body or around your eyes
Fever with no known cause
Hematuria, which is blood in the urine
High blood pressure
Increased urination, especially at night
Joint pain or swelling
Muscle pain
Proteinuria, which is protein in the urine and often causes your urine to look foamy
Red skin rash on the face
Weight gain due to excess fluid in your body^[1]^[3]

In lupus nephritis, common symptoms of lupus such as fever, joint pain, muscle pain, and a butterfly-shaped rash on the face may be seen. Early kidney involvement might not cause any noticeable symptoms. As the condition progresses, signs may include frequent urination, needing to pass urine at night, foamy urine, high blood pressure, and edema.^[6]

How is lupus nephritis diagnosed?

Your healthcare provider performs a physical examination, reviews your symptoms and evaluates your medical history.^[3] Getting tested and treated as soon as possible is extremely important. Testing used in evaluating and diagnosing kidney issues include a urine test or urinalysis, blood test, and kidney biopsy.^[2]

Blood and urine tests to detect lupus nephritis include:

Antibody blood tests check for high levels of proteins made by your immune system
Labs to assess kidney function
Urinalysis checks your urine for wastes and other abnormal substances
Urine protein test checks for protein in your urine^[3]

Your healthcare provider may also do a kidney biopsy. This is a procedure to examine a small piece of tissue or sample of cells from your kidneys. A biopsy can help your healthcare provider determine the severity of your kidney damage.^[3] A kidney biopsy should be considered in any patient with lupus who has clinical or laboratory evidence of active nephritis, especially upon the first episode of nephritis.^[7]

Laboratory tests for lupus disease activity include antibodies to double-stranded DNA, complement levels including C3, C4, and CH50, erythrocyte sedimentation rate, and C-reactive protein.^[7]

Classification of lupus nephritis

The World Health Organization and the International Society of Nephrology/Renal Pathology Society has divided lupus nephritis into six classes based on the biopsy. This classification was defined in 1982 and revised in 1995.^[6]

Lupus nephritis is staged according to the classification revised by the International Society of Nephrology and the Renal Pathology Society in 2003, as follows:

Class I – Minimal mesangial lupus nephritis
Class II – Mesangial proliferative lupus nephritis
Class III – Focal lupus nephritis (active and chronic; proliferative and sclerosing)
Class IV – Diffuse lupus nephritis (active and chronic; proliferative and sclerosing; segmental and global)
Class V – Membranous lupus nephritis
Class VI – Advanced sclerosis lupus nephritis^[7]

Class IV disease, which is diffuse proliferative nephritis, is both the most severe and the most common subtype.^[6]

Treatment approaches

There’s no cure for lupus nephritis. Treatment aims to reduce symptoms or make symptoms go away, called remission, keep the disease from getting worse, keep symptoms from coming back, and keep kidneys working well enough to not need a machine to filter waste from blood, called dialysis, or a kidney transplant.^[10]

The principal goal of therapy in lupus nephritis is to normalize kidney function or, at least, to prevent the progressive loss of kidney function. Therapy differs depending on the pathologic lesion. Patients should be on hydroxychloroquine if possible, as data suggest that this improves outcomes in patients who have lupus nephritis, in addition to reducing lupus-related flares and disease damage.^[12]

Medication and diet changes are the most common treatments for lupus nephritis. Your healthcare provider may recommend:

Blood pressure medication: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) help manage blood pressure and reduce protein loss.^[3]

Corticosteroids and immunosuppressive drugs: These medications prevent your immune system from attacking the blood vessels in your kidneys. Corticosteroid therapy should be instituted if the patient has clinically significant renal disease. Immunosuppressive agents, particularly cyclophosphamide, azathioprine, or mycophenolate mofetil, can be used if the patient has aggressive proliferative renal lesions, as they improve the renal outcome.^[3]^[12]

Calcineurin inhibitors: These medications, especially tacrolimus, have demonstrated benefit in lupus nephritis. Voclosporin is the first oral therapy approved by the US Food and Drug Administration for lupus nephritis in conjunction with immunosuppressive treatment.^[12]

Two drugs, Benlysta and Lupkynis, have been approved specifically to treat lupus nephritis.^[2]

Recent treatment guidelines from the American College of Rheumatology released in 2024 propose a triple therapy approach, which includes intravenous glucocorticoids followed by a combination of mycophenolic acid, belimumab, low dose cyclophosphamide or calcineurin inhibitors like tacrolimus or voclosporin. The guidelines also recommend implementing a reduced-dose glucocorticoid strategy to reduce toxicity, aiming for a prednisone target of less than or equal to 5 mg/day within six months of treatment, and ongoing treatment for 3 to 5 years to sustain kidney health and prevent relapses.^[15]

Dietary recommendations

If you have lupus nephritis, you may need to make some specific changes to your eating habits. Some of these changes depend on how well your kidneys are working. Your doctor can do blood tests to see if your kidneys are having trouble filtering out certain minerals in your blood. Your doctor can also refer you to a nutrition specialist called a registered dietitian to help with your eating plan.^[17]

Cut down on sodium: Most people, including those with lupus, need to cut down on sodium—but it’s even more important to limit sodium when you have kidney problems. Eating less sodium can help control swelling and high blood pressure caused by lupus nephritis. Try cooking more meals at home using fresh ingredients, as packaged foods and restaurant meals are often high in sodium. Check the Nutrition Facts label on packaged foods, and choose options with less sodium. Flavor your food with herbs and spices instead of salt.^[17]

Eat smaller portions of protein: Your kidneys get rid of waste from the protein you eat, so eating too much protein can be hard on your kidneys. Talk with your doctor or dietitian about the right amount of protein for you. If you have a protein-heavy meal like steak, pork, chicken or fish, eat a smaller portion and save the rest for the next day. Think of veggies and grains as the main part of your meals, and add smaller portions of protein foods.^[17]

Choose lower-potassium fruits and vegetables: Many fruits and vegetables contain potassium, a nutrient that helps keep cell fluid at the right level. However, too much potassium can be dangerous if your kidneys aren’t functioning at full capacity. Choosing lower-potassium fruits and vegetables will provide vitamins, minerals, antioxidants, and dietary fiber while protecting your kidneys.^[22]

Include heart-healthy unsaturated fats: Including heart-healthy unsaturated fats in your meals and snacks is a great way to maintain your calorie intake and support a healthy weight. Omega-3 fatty acids, known for their anti-inflammatory properties, are especially helpful if you have an autoimmune disease like lupus nephritis. Omega-3s can be found in plant-based sources, such as nuts and seeds, as well as in animal sources, including sardines, salmon, mackerel, and other fatty fish.^[22]

In addition to dietary changes, you can help protect your kidneys by controlling your blood pressure, diabetes and high cholesterol levels.^[2] Restrict fat intake or use lipid-lowering therapy such as statins for hyperlipidemia secondary to nephrotic syndrome. Administer calcium supplementation to prevent osteoporosis if you are on long-term corticosteroid therapy, and consider adding a bisphosphonate, depending on renal function. Avoid drugs that affect renal function, including nonsteroidal anti-inflammatory drugs (NSAIDs), especially in patients with elevated creatinine levels.^[12]

Possible complications

If lupus nephritis is not treated, symptoms can get worse and lead to kidney failure. People experiencing serious kidney complications like kidney failure may need either dialysis or a kidney transplant.^[2]

Lupus nephritis can lead to a variety of serious health problems, including kidney failure and end-stage renal disease.^[3] This condition often develops within 3 to 5 years of lupus onset and significantly increases the risk of end-stage renal disease. Ten to 22 percent of patients with the condition will develop end-stage kidney disease.^[4]^[13]

Patients with active lupus nephritis should avoid pregnancy, because it may worsen their renal disease and because certain medications used in the treatment may be teratogenic.^[12]