CD38-targeted therapies in kidney disease: evidence maturity, disease-stage dependence, and biomarker-guided retreatment

CD38 targeting can reach antibody-secreting cells that persist after B-cell depletion, along with selected natural killer-cell and other immune-cell subsets. This narrative review examines CD38-targeted antibodies in immune-mediated and monoclonal immunoglobulin-related kidney diseases and kidney transplantation. It asks what clinical studies establish, how disease stage may affect response durability, and whether biomarkers can guide retreatment. Evidence differs by agent, regimen, and outcome. The most mature randomized evidence with kidney-organ outcomes comes from daratumumab-based combination therapy in immunoglobulin light-chain (AL) amyloidosis, a plasma-cell disorder. In other kidney and transplant indications, early-phase randomized trials and uncontrolled studies show immunologic, tissue, or proteinuria responses, but long-term kidney or graft benefit remains unproven. Disease duration, previous treatment, and residual tissue injury may help explain variable responses, although treatment selection by disease stage has not been validated. Biomarkers measure distinct aspects of response and can support monitoring; changes alone do not establish pathogenic-cell depletion or justify retreatment. Biomarker-guided dosing was feasible in a selected transplant cohort and requires comparative validation. Clinical interpretation must remain specific to the studied antibody and regimen. Research priorities include trials with kidney and graft outcomes, prospective patient selection, comparisons of treatment strategies, validation of biomarker-guided retreatment, and cumulative safety during repeated therapy.