What Is the Current Recommended Treatment for Lupus Nephritis?

Medical Author: William C. Shiel Jr., MD, FACP, FACR
Medical Editor: Leslie J. Schoenfield, MD, PhD

Lupus nephritis is kidney disease that is caused by lupus. To start, it must be understood that there are many forms of kidney disease that are referred to as lupus nephritis. Each form is distinguished by characteristic patterns of abnormalities as defined by a kidney biopsy. (A biopsy is the removal of a sample of tissue for microscopic examination.) Typically, the findings on a kidney biopsy of a lupus patient are classified according to the appearance of the tissue and immune abnormalities seen under the microscope.

In addition to the numerous unique forms of lupus kidney disease, other types of kidney diseases that are not from 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. Thus, when the blood tests and the overall state of the lupus disease so require, the biopsy can define the cause of the kidney disease when it is in question. The biopsy can also guide treatment when it demonstrates the presence of such severe kidney damage that a favorable response to potentially toxic medications is unlikely.

Any particular form of lupus nephritis has a variety of treatments available that are effective. Moreover, the treatment for individual patients with lupus nephritis depends not only on their own particular form of kidney disease, but also on the manner in which lupus is affecting other areas of their 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 (auto-antibodies) form antibody-tissue (antibody-antigen) unions (complexes) that in turn deposit in the kidney and initiate a destructive inflammatory reaction. In fact, very often, the severity of the kidney disease 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, 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. 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.

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.

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. Likewise, pregnancies in 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.

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.