Figure 2.

C5aR/CD88 small molecule antagonist CCX168 ameliorates anti-MPO–induced GN. Daily administration of 30 mg/kg CCX168, an orally active small molecule antagonist of human C5aR, markedly reduced the severity of anti-MPO–induced NCGN in hC5aR knock-in mice (7 days after anti-MPO injection). (A) Glomerular crescent formation induced by anti-MPO was reduced from 30.4% with vehicle alone to 3.3% with CCX168 (P<0.0001). (B) Urine hematuria, proteinuria, and leukocyturia were reduced in mice receiving CCX168 (dipstick scale, 0–4+). (C) Glomerular crescent and necrosis formation was reduced in animals receiving CCX168. Data were analyzed by Mann-Whitney t test; **P<0.01 and ***P<0.001. Data are presented as the median with SEM. BID, twice daily; QD, daily.