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A pathophysiology-based approach to the diagnosis and treatment of lupus nephritis. Lupus is no longer an unknown chameleon of medicine. Significant progress has been made on unraveling the pathogenesis of lupus and lupus nephritis, and how to treat the disease. Here we provide an update on the pathophysiology of lupus and its related kidney disease, consider areas of controversy in disease management, and discuss the unmet needs of lupus nephritis and how to address these needs. We focus on rethinking how innovative therapies for lupus nephritis should be evaluated and evolving strategies to more efficiently mitigate irreversible nephron loss in patients with lupus nephritis.