What Is the Treatment for Lupus Nephritis?

• What is lupus nephritis?
• Lupus nephritis treatment
• Controversial treatments for lupus nephritis
• New lupus nephritis treatments

Lupus nephritis is kidney disease that is caused by lupus. There are many forms of kidney disease that are referred to as lupus nephritis, and their patterns of abnormalities can be identified by a kidney biopsy. 

Other types of kidney diseases that are not caused by lupus can sometimes occur in a patient with lupus. While treatment for lupus nephritis can sometimes be initiated without a kidney biopsy, more often, a biopsy is done before starting treatment. The biopsy can define the cause of the kidney disease and guide treatment.

A variety of effective lupus nephritis treatments are available for any particular form of lupus nephritis. Treatment for lupus nephritis depends not only on the form of kidney disease, but also on the manner in which lupus is affecting other areas of the person's body, their overall health, and their personal wishes. Also, medical control of conditions that could further injure the kidneys, such as elevated blood pressure and medication-induced kidney toxicity, is essential.

In general, lupus nephritis is a result of inflammation in the kidneys that is associated with an overactive immune (defense) system. As a consequence, antibodies against the patient's own tissues (autoantibodies) form antibody-tissue (antibody-antigen) unions (complexes) that in turn deposit in the kidney and initiate a destructive inflammatory reaction.

The severity of the kidney disease often parallels the severity of the immune abnormalities that can be measured in the blood of patients with lupus (such as DNA antibody, complement levels, etc.). Accordingly, treatment usually involves medications that reduce inflammation and suppress the immune system. When lupus nephritis leads to kidney failure, however, kidney dialysis or transplantation is necessary to sustain life.

Corticosteroids

Corticosteroids, such as prednisone and prednisolone, are accepted as the initial treatment for lupus nephritis. The steroids may be given by mouth or intravenously. Also, high-dose corticosteroids (methylprednisolone) that are given in single, large doses (pulses) intravenously for three consecutive days are also a useful initial treatment for lupus nephritis, which is then followed by corticosteroids by mouth.

Immunosuppressants

The immune suppression medications that are used to treat lupus nephritis include azathioprine (Imuran) and cyclophosphamide (Cytoxan), both of which can be given by mouth. Cyclophosphamide is also given as an intravenous, single large dose (pulse) in certain situations. These pulses are continued monthly for six months and every three months thereafter. Recently, the immunosuppressant drug mycophenolate mofetil (Cellcept) has been used successfully to treat lupus kidney disease and seems to represent another option.

Lupkynis (voclosporin) is an immunosuppressant used with other drugs like steroids to treat lupus while protecting some kidney cells. Lupkynis should not be taken with a medicine termed cyclophosphamide (see above).

Other treatments that are used for lupus nephritis, but are still unproven or controversial, include:

• plasmapheresis,
• intravenous immunoglobulin infusions, and
• fish oils containing omega-3 fatty acids.

Plasmapheresis is a procedure in which the blood is filtered through a special machine to separate the plasma, which is the liquid portion of the blood, from the cells of the blood.

• The plasma is removed and replaced, typically with another solution such as saline or albumin.
• Intravenous immunoglobulin is a sterile solution of concentrated antibodies extracted from healthy people that is given straight into a vein.
• The immunoglobulin is used to treat disorders of the immune system or to boost the immune response to serious illness.
• Omega-3 fatty acids have been shown to reduce inflammation in the kidneys of mice with a lupus-like illness.

Pregnancy and fertility

In treating lupus nephritis, special considerations must be given to each individual's particular situation and lifestyle. For example, because cyclophosphamide can damage the ovaries, a woman who desires a future pregnancy might not be a candidate for this treatment. Furthermore, a woman who develops lupus nephritis during pregnancy faces risks of injury to the unborn baby as well as possible permanent kidney impairment from untreated lupus nephritis.

Pregnant women with lupus nephritis require intense fetal and maternal monitoring. It should also be noted that birth control pills containing synthetic estrogens are essentially contraindicated (forbidden or not recommended) in women with active lupus nephritis.

Novel approaches to the treatment of lupus nephritis, such as using adenosine analogues, and combinations of existing medications, are being studied. Indeed, many of these approaches are on their way to being put to use in the near future. Some of these treatments, involving the blocking of various molecules that stimulate the cells of inflammation, are being studied at the National Institutes of Health in Bethesda, Maryland.

Belimumab is a synthetic (man-made) injectable antibody that reduces the activity of immune cells called B-cells in patients with systemic lupus erythematosus (SLE) and it was is FDA approved in 2011 and in 2019 for use in children. Saphnelo (anifrolumab-fnia) dampens type 1 interferon effects on inflammation and has been FDA approved in 2021.

Finally, attempts are being made to completely reconstitute the immune system in patients with lupus by using bone marrow transplantation and stem cell transplantation. All of these approaches are in the very preliminary stages of development and are not yet accepted as useful. What is clear is that the treatment of lupus nephritis in decades to come will not be the same as it is today.

SLIDESHOW

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