Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis often causes kidney failure via crescentic glomerulonephritis (ANCA-GN), and current treatments are non-specific, partially effective, and can have serious side effects. Here, spatial transcriptomics and single-cell RNA sequencing in kidney biopsies from 34 ANCA-GN patients reveal inflammatory glomerular and tubulointerstitial niches enriched for T cell activation pathways, especially Th1/Tc1 and Th17/Tc17-like effector cells. A digital pharmacology screen of approved immunomodulating drugs identifies ustekinumab (which blocks IL-12/IL-23) as the top candidate. In four patients with relapsing ANCA-GN treated with ustekinumab alongside steroids and low-dose cyclophosphamide, follow-ups over 26 weeks show the treatment is well tolerated and is associated with improved kidney function, reduced ANCA levels, lower inflammation, and improved disease activity scores.