The main goal of
therapy for
lupus nephritis is to achieve remission, as this has a major impact on patient and renal survival. Furthermore, early treatment success has been shown to improve long-term prognosis. This has traditionally been achieved with intravenous
cyclophosphamide, but recent data show that
mycophenolate mofetil is equally effective and causes fewer adverse effects. Research is ongoing to find new treatment targets. Possible future
therapies include
monoclonal antibodies against CD20 (
rituximab), CD22 (
epratuzumab) and CD40, and
therapies targeted at
cytokine secretion,
immunoglobulin secretion, B-cell maturation and T-cell proliferation and differentiation.
Rituximab has shown promise in patients with active proliferative
lupus nephritis, which suggests that B-cell depletion may be successful. Anti-
double-stranded DNA antibodies correlate with flares of
lupus nephritis and may represent another therapeutic target.
Therapy with LIP 394, which crosslinks anti-
double-stranded DNA antibodies in
solution or on the B-cell surface, has been shown to reduce flares.
Cardiovascular disease is a major cause of mortality in
systemic lupus erythematosus, and this must also be addressed if long-term outcomes are to be improved. Many patients with
systemic lupus erythematosus have subclinical
atherosclerosis quite early in the disease course, and the risk of
coronary artery disease at any level of traditional cardiovascular risk factors is higher than in the general population. Specific lupus-associated risk factors include the inflammatory process itself and
anticardiolipin antibodies. Possible strategies to reduce the risk include reduction of disease activity to improve endothelial function and reduction of
steroid dose whenever possible.
Therapy with
aspirin or
statins may be another possibility. Thus treatment of
lupus nephritis is evolving from standardised
therapy to individualised
therapy based on analysis of organ involvement, risk factors and
cytokine, antibody or cell profiles.