Systemic lupus erythematosus (SLE) can be a devastating condition, striking young patients often in their prime reproductive years. Lupus nephritis is a common and serious complication occurring in roughly 50% of SLE cases, indicating a high likelihood of disease progression, morbidity, and mortality. As the early trials of steroid therapy, and later cyclophosphamide (CYC), therapeutic changes had been stagnant. Then came the introduction of mycophenolate mofetil (MMF) in the 2000s. After the Aspreva Lupus Management Study, there had been a dearth of trials showing positive therapy results. Since 2020, new studies have emerged for lupus nephritis involving the use of anti-BLYS agents, novel calcineurin inhibitors, CD20 blockade, and antiinterferon agents. Nephrology and rheumatology society guidelines in the United States and across the world are still catching up.

Although therapeutic guidelines are being developed, updates that have come through have focused on improved diagnostic and monitoring guidelines. One theme is the recommendation of increasingly tight proteinuria control and firmer guidelines for the rapid induction of remission. The reality of multitarget therapy and the expectation of rapid induction for a more complete remission are being widely recognized.

The need for more complete and more rapid induction and control of lupus nephritis is undisputed according to the evidence and guidelines, and the medications to achieve this are growing at a rate not seen over the prior two decades. What remains is a stepwise approach to recognize how to best optimize therapy. Based on available evidence, an algorithm for induction and maintenance treatment of lupus nephritis used by the University of California Irvine Lupus Nephritis clinic, is recommended.