Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy

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.