Open Access Stuart J. Perper, Susan V. Westmoreland, Jozsef Karman, Rachel Twomey, Jane Seagal, Rui Wang, Bradford L. McRae and Stephen H. Clarke J Immunol July 1, 2019, 203 (1) 58-75; DOI: https://doi.org/10.4049/jimmunol.1900043 Key Points CD40 antagonism reverses severe proteinuria and restores glomerular morphology. CD40 antagonism normalizes nephrotic and injury-associated gene expression. CD40 antagonism disrupts multiple disease-critical immunological mechanisms.