Lupus Nephritis (LN)

Systemic lupus erythematosus, or SLE, is a serious, potentially lethal autoimmune disorder characterized by multi-organ involvement and a chronic relapsing clinical course. Lupus Nephritis, or LN, refers to the specific involvement of the kidney that is seen in approximately 20% of SLE patients. It is estimated that approximately 63,000 individuals in the United States have LN. Although LN is a chronic disease, its course is characterized by intermittent periods of acute kidney inflammation and high disease activity, which are known as nephritic flares. The cumulative impact of these flares over time can cause irreversible damage to the kidneys. Although immunosuppressive therapy has improved prognosis for patients with LN, approximately 10% to 15% of these patients will develop end-stage renal disease, requiring a kidney transplant or initiation of dialysis. As such, LN is associated with an approximately six-fold increase in the rate of mortality compared with the general population.

The pathophysiology of LN involves the inappropriate production of autoantibodies which recognize self or ‘‘host’’ antigens, such as double-stranded DNA. The deposition of autoantibody-antigen complexes in the kidney activates the classical pathway of complement, resulting in generation of C5a, deposition of MAC, and subsequent tissue injury. Levels of the circulating complement components C3 and C4 are depleted in patients during LN flares, due to accelerated consumption of classical complement pathway proteins. Deposition of MAC has been observed in kidney biopsy samples from patients with LN. There have been several other case reports of improved kidney function in LN patients treated with eculizumab, suggesting inhibition of C5 may be disease modifying. Additionally, inhibition of C5a activity has been shown to improve renal function and histopathological features associated with LN in animal models of the disease.