Anti-CD38 monoclonal antibodies in kidney disease: mechanistic rationale and emerging clinical evidence.

Over the past decades, the therapeutic landscape of nephrology has been transformed by the expanding use of immunosuppressive therapies, reflecting major advances in our understanding of the roles of the innate and adaptive immune systems in the pathogenesis of kidney diseases. While B-cell depletion via rituximab or obinutuzumab has improved immune-mediated kidney disease management, these agents remain insufficient. They spare long-lived plasma cells, memory B cells, and innate effectors, permitting persistent antibody production and ongoing tissue injury. Consequently, increasing attention has focused on anti-CD38 monoclonal antibodies, including daratumumab, isatuximab, and felzartamab, which target several of these pathogenic immune cell populations. Early clinical experience and emerging trial data in diseases such as IgA nephropathy, primary membranous nephropathy, and, most notably, kidney transplantation have suggested potential benefits in selected settings, further supporting their potential role in nephrology. In this narrative review, we summarize the current understanding of the pathophysiological role of CD38-expressing immune cells in kidney diseases and critically evaluate the available clinical evidence on the use of anti-CD38 monoclonal antibody therapies across a spectrum of renal disorders. The review also compares the roles of anti-CD38 monoclonal therapies in native kidney disease and antibody-mediated rejection, since they differ in mechanism, clinical evidence, and treatment options.