title: Lupus nephritis: the evolving role of novel therapeutics.
abstract: Immune complex accumulation in the kidney is the hallmark of lupus nephritis and triggers a series of events that result in kidney inflammation and injury. Cytotoxic agents and corticosteroids are standard of care for lupus nephritis treatment, but are associated with considerable morbidity and suboptimal outcomes. Recently, there has been interest in using novel biologic agents and small molecules to treat lupus nephritis. These therapies can be broadly categorized as anti-inflammatory (laquinamod, anti-tumor necrosis factor-like weak inducer of apotosis, anti-C5, and retinoids), antiautoimmunity (anti-CD20, anti-interferon α, and costimulatory blockers), or both (anti-interleukin 6 and proteasome inhibitors). Recent lupus nephritis clinical trials applied biologics or small molecules of any category to induction treatment, seeking short-term end points of complete renal response. These trials in general have not succeeded. When lupus nephritis comes to clinical attention during the inflammatory stage of the disease, the autoimmune stage leading to kidney inflammation will have been active for some time. The optimal approach for using novel therapies may be to initially target kidney inflammation to preserve renal parenchyma, followed by suppression of autoimmunity. In this review, we discuss novel lupus nephritis therapies and how they fit into a combinatorial treatment strategy based on the pathogenic stage.
authors.affiliation: Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: rovin.1@osu.edu.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Division of Nephrology, Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Samir V
authors.initials: SV
authors.lastname: Parikh
mesh_terms: D000069594:Abatacept; D058186:Acute Kidney Injury / Q000209:etiology / Q000276:immunology; D000293:Adolescent; D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D017209:Apoptosis / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000074049:Cytokine TWEAK; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015363:Quinolones / Q000627:therapeutic use; D012074:Remission Induction; D000069283:Rituximab; D000079424:Tumor Necrosis Factor Inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D000069594:Abatacept; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D000074049:Cytokine TWEAK; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D015363:Quinolones; D000069283:Rituximab; D000079424:Tumor Necrosis Factor Inhibitors; D000093242:Interleukin-6 Inhibitors; C109743:TNFSF12 protein, human; C476223:laquinimod; C481642:eculizumab
keywords: Lupus nephritis; biologics; novel therapies; small molecules; systemic lupus erythematosus (SLE)