Lupus nephritis is a kidney condition caused by the autoimmune disease systemic lupus erythematosus (SLE).
“Although lupus nephritis can cause kidney damage, there are now effective treatments that can support kidney function and help prevent the more serious complications,” says Dr Rachel Jones, a consultant nephrologist at Addenbrooke’s Hospital, Cambridge, and chair of the Lupus Nephritis Rare Diseases Group.
“This means that the outlook for lupus nephritis patients is much brighter than in the past.”
What is lupus?
SLE or lupus affects the immune system, causing problems in the skin, joints, and other organs, including the kidneys.
Nine out of 10 cases are in women, most commonly in the 20 to 40 age group, although it can also affect children and older people, as well as men.
People from certain ethnic backgrounds are more likely to get lupus. Prevalence is four times higher in those with an Indo-Asian family background, 18 times higher if you have an African or Caribbean background and 19 times higher in Chinese families.
“In SLE the body produces a whole load of ‘sticky’ antibodies in the blood which get deposited around the body in various organ systems,” says Dr Jones.
“Classically SLE can cause symptoms such as skin rashes, joint problems, mouth ulcers, hair loss and kidney inflammation and damage known as lupus nephritis.”
What is lupus nephritis?
Around 60 per cent of lupus patients will develop lupus nephritis at some point during their illness.
In lupus nephritis the body’s immune system attacks the kidney, particularly the filtering structures in the kidney called glomeruli (there are around a million of these in the kidneys), causing inflammation.
If this is left untreated, the inflammation can progress to cause scarring and kidney failure, but drug treatments can help avoid this.
What are the symptoms of lupus nephritis?
Symptoms of lupus nephritis include:
- Frothy urine (a sign of protein in the urine)
- Brown urine (a sign of blood in the urine, although blood can also be present without being visible)
- swollen feet, ankles and hands
- puffiness around the eyes and tummy
- fatigue
- high blood pressure
“The goal is to detect lupus nephritis before kidney function becomes that bad and prescribe drugs that can support kidney function by switching off the inflammation and preventing further damage,” says Dr Jones.
How is lupus nephritis diagnosed?
“Lupus nephritis may be picked up in a kidney function test or by symptoms such as swollen ankles or high blood pressure,” says Dr Jones.
“There may be quite a bit of protein and/or blood in the urine and this won’t usually be visible. The amount present is an indication of how inflamed the kidneys are. However, there are other inflammatory kidney conditions that can cause the same symptoms, so sometimes a kidney biopsy might be done to confirm the diagnosis, and this can also tell your doctor what stage of lupus nephritis you have.”
Different types of lupus nephritis
“Lupus nephritis is very much a spectrum disease, ranging from mild to very severe kidney inflammation and damage, “explains Dr Jones.
“There are six different stages, with stage one being hardly any changes, through to six being significant scarring. Stages three, four and five are the most inflamed stages, requiring immunosuppressive treatments.
“The drugs you are prescribed will depend on your stage of disease.”
What are the treatment options for lupus nephritis?
When you have lupus nephritis, it is usual to be treated by a nephrologist (a doctor who specialises in the kidneys).
You may also be treated by your rheumatologist. “You may be given a referral to nephrology; if you aren’t, your rheumatologist should seek advice from a nephrologist as part of good multi-disciplinary care,” says Dr Jones.
There are a number of treatments available for lupus nephritis, which aim to preserve kidney function, prevent disease flare ups, and improve quality of life and survival. “What you are prescribed will depend on the stage of the disease and how well previous treatments have worked for you. Most of the treatments are immune suppressants.”
“Clinical guidelines are currently being updated for drug treatments for lupus nephritis as it is an increasingly complex area, but the good news is there are now more treatment options.”Dr Rachel Jones, consultant nephrologist at Addenbrooke’s Hospital, Cambridge, and chair of the Lupus Nephritis Rare Diseases Group
What drug treatments are available for lupus nephritis?
“This is a treatment for malaria but can also help with some SLE symptoms and prevent your lupus nephritis from relapsing,” says Dr Jones.
“Hydroxychloroquine is not an immunosuppressant.”
The standard immunosuppressant drugs for lupus nephritis include mycophenolate and cyclophosphamide (or sometimes azathioprine) and work by supressing the immune system to stop damage to the kidneys from antibodies.
“A downside of cyclophosphamide is that it can affect both male and female fertility if used in high doses, and of course lupus nephritis affects women in their childbearing years,” explains Dr Jones. “Mycophenolate, a tablet treatment, doesn’t affect fertility and therefore these days is a much more attractive treatment, although it is not safe during pregnancy.
“However, the response rate to both drugs is quite low. When there is active inflammation, getting people into full remission, where kidney function is stable or ideally improved, with significant reduction in urine protein, can be really hard. When these drugs are used with corticosteroids, probably only 20 to 30 per cent of patients will get into full remission by 6 to 12 months. Around 60 to 70 per cent will get into partial remission within a year, so to improve the response rate these drugs are often used with newer therapies including biologics.”
Steroids such as prednisone calm the immune system, suppressing inflammation, and are started in the majority of patients. However, they also have a lot of potential side effects including anxiety, mood swings, insomnia, irritation of the stomach lining, weight gain, diabetes, and osteoporosis.
“Because of side effects we usually start patients on a higher dose to calm the inflammation and then wean them down to a low maintenance dose. We try to stop steroids as quickly as possible, but patients may need to take low dose steroids for many months,” says Dr Jones.
“It can take a couple of years to get patients with lupus nephritis into full remission with immunosuppressant and steroid combinations, so these are not wonder drugs.
“If these combinations don’t work in the first few months, then we may try another class of drugs called biologics in combination with immunosuppressants.”
Biologic drugs are produced from large molecules from living cells and target different parts of the immune system that fuel inflammation. They include:
Rituximab: This a drug given by infusion which is long acting and acts on white blood cells called B cells, which are the cells that make the bad antibodies in lupus. “They also make good ones which does means that the drug can make patients liable to infections,” says Dr Jones. “Rituximab works, particularly if used in combination with mycophenolate or cyclophosphamide.”
Belimumab: This works by reducing the activity of a type of white blood cell, and is a treatment specifically developed for lupus. It is long acting, and it can take six months before it is fully effective. Again, belimumab is usually used in combination with mycophenolate or cyclophosphamide.
Voclosporin is a new type of immunosuppressant approved by NICE in 2023 to treat lupus nephritis in people with class 3 to class 5 disease, and is now being made available throughout the NHS, in combination with mycophenolate.
It is a calcineurin inhibitor drug acting on an enzyme that activates T-cells in the body’s immune system; by reducing the levels of the enzyme it reduces inflammation in the body.
“Voclosporin is the first oral drug specially developed for lupus nephritis and has been shown in clinical trials to improve the chances of achieving remission and allow lower doses of steroids to be used,” says Dr Jones.
Lifestyle advice for lupus nephritis
Having an autoimmune disease such as lupus can raise the risk of cardiovascular disease. Fatigue and depression are common complaints with lupus, so maintaining a healthy lifestyle is important, says Dr Jones.
“Eating a healthy diet and taking exercise is the standard advice. Specific types of exercise such as yoga and Pilates can help with joint problems by building muscle strength and flexibility.
“Taking a vitamin D supplement is also beneficial, as is avoiding triggers for flare ups such as stress or assessing your workload if full time work is proving too demanding.
“It’s also important to have regular blood and urine tests. Some people like to use test strips for detecting protein and blood in their urine that they can use at home, for instance. Also, if people feel unwell, they can request a blood test to check on their kidney function.
“You can also have access to your kidney function and other test results through hospital systems such as Patients Know Best (PKB) and MyChart."
Lupus nephritis: where to get support and advice
People with lupus can wait a long time to get a diagnosis, six years on average, and be acutely unwell by that stage, explains Debbie Kinsey, Health information Manager at Lupus UK.
“Lupus patients need regular monitoring to check their kidney function blood and urine tests at least once a year, so they can be diagnosed and treated as soon as possible if they do develop nephritis,” says Debbie.
“Many people with lupus nephritis have no specific symptoms until it is more severe. Damage to the kidneys will show on urine tests much earlier than in blood tests, so you should have regular urine tests as part of routine lupus check-ups so that it can be diagnosed and monitored as early as possible. Treating any kidney involvement early can help to prevent further damage, or the damage becoming more severe.”
Specialist lupus nurses are available to give advice at some hospitals on practical issues such as medication side effects.
Lupus UK offers information and opportunities to connect with other people with lupus, including regular events, regional support groups online and in person, an active online forum, and peer support from people with lupus who are happy to talk with you on the phone.