Systemic Lupus Erythematosus

Lupus is a life-threatening, antibody-mediated disease in which disease-causing antibodies damage various tissues. According to recent statistics compiled by the Lupus Foundation of America, epidemiological studies and other sources, the number of lupus patients in the United States is estimated to be between 500,000 and 1,000,000, and approximately 16,000 new cases are diagnosed each year. Approximately nine out of 10 lupus patients are women, who usually develop the disease during their childbearing years. Lupus is characterized by a multitude of symptoms that may include chronic kidney inflammation, which may lead to kidney failure, serious episodes of cardiac and central-nervous-system inflammation, as well as extreme fatigue, arthritis and rashes. Approximately 80% of all lupus patients progress to serious symptoms. Approximately 40-45% of lupus patients will develop kidney disease which is a leading cause of death in lupus.

Anti-dsDNA Antibodies and Lupus Nephritis

Antibodies to double-stranded DNA (dsDNA) can be detected in up to 85% of lupus patients who are not receiving immunosuppressive therapy. Anti-dsDNA antibodies are widely believed to cause kidney disease (nephritis), often resulting in morbidity and mortality in lupus patients.

Lupus nephritis is characterized by periods of extreme, acute inflammation — called “renal flares” — which often require treatment with high-dose corticosteroids, immunosuppressive agents, and hospitalization. Patients who are not experiencing a renal flare often have chronic, lower levels of kidney inflammation which contribute to the morbidity and mortality of lupus nephritis. Over time, lupus nephritis can lead to deterioration of kidney function and to end-stage kidney disease, requiring long-term renal dialysis or kidney transplantation to sustain a patient’s life.

Current Treatments for Lupus Nephritis

Current treatments for lupus patients who have a renal flare often involve repeated administration of corticosteroids, often at high levels, that can lead to serious side effects when used long-term. Many patients with renal flares are also treated with immunosuppressive therapy, including anti-cancer or transplantation drugs, which can have a general suppressive effect on the immune system, may be carcinogenic and / or can cause birth defects. Treatment with immunosuppressive therapies can also leave patients vulnerable to serious infection, which is a significant cause of sickness and death in these patients.

Importantly, many patients fail to respond adequately to these treatments and fail to achieve full remission, or a return to the level of renal function prior to the flare. As a result, low to moderate levels of inflammation can continue as evidenced by elevated urine protein (proteinuria), elevated serum creatinine, and other markers of abnormal kidney function. This incomplete response to treatment with immunosuppressive therapies increases the risk of additional renal flares as well as the risk of end-stage kidney disease and death.