Lupus nephritis remains one of the most severe manifestations of
systemic lupus erythematosus associated with considerable morbidity and mortality. A better understanding of the pathogenesis of
lupus nephritis is an important step in identifying more targeted and less toxic therapeutic approaches. Substantial research has helped define the pathogenetic mechanisms of renal manifestations and, in particular, the complex role of
type I interferons is increasingly recognized; new insights have been gained into the contribution of
immune complexes containing endogenous
RNA and
DNA in triggering the production of
type I interferons by dendritic cells via activation of endosomal
toll-like receptors. At the same time, there have been considerable advances in the treatment of
lupus nephritis.
Corticosteroids have long been the cornerstone of
therapy, and the addition of
cyclophosphamide has contributed to renal function preservation in patients with severe proliferative
glomerulonephritis, though at the cost of serious adverse events. More recently, in an effort to minimize
drug toxicity and achieve equal effectiveness, other
immunosuppressive agents, including
mycophenolate mofetil, have been introduced. Herein, we provide a detailed review of the trials that established the equivalency of these agents in the induction and/or maintenance
therapy of
lupus nephritis, culminating in the recent publication of new treatment guidelines by the American College of Rheumatology. Although newer biologics have been approved and continue to be a focus of research, they have, for the most part, been relatively disappointing compared to the effectiveness of biologics in other
autoimmune diseases. Early diagnosis and treatment are essential for renal preservation.