title: Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy.
abstract: The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.
authors.affiliation: Department of Nephrology and Dialysis, Ospedale A. Manzoni, Lecco, Italy. claudio.pozzi@icp.mi.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Pozzi
authors.forename: Simeone
authors.initials: S
authors.lastname: Andrulli
authors.forename: Antonello
authors.initials: A
authors.lastname: Pani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scaini
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Giambattista
authors.initials: G
authors.lastname: Fogazzi
authors.forename: Bruno
authors.initials: B
authors.lastname: Vogt
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Cristofaro
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Lino
authors.initials: L
authors.lastname: Cirami
authors.forename: Aldo Deni
authors.initials: AD
authors.lastname: Procaccini
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D001379:Azathioprine