Steroid Treatment for Severe Childhood IgA Nephropathy

Abstract

A previous trial showed that treatment of children with severe IgA nephropathy (IgAN) using prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduced the severity of immunologic renal injury and prevented any increase in the percentage of sclerosed glomeruli. This study compared the effects of prednisolone, azathioprine, warfarin, and dipyridamole (combination) with those of prednisolone alone in 80 children with newly diagnosed IgAN that showed diffuse mesangial proliferation. Patients were randomly assigned to receive either the combination or prednisolone alone for 2 yr. The primary end point was the disappearance of proteinuria, defined as urinary protein excretion <0.1 g/m 2 per d, and the secondary end points were urinary protein excretion at the end of treatment, the change in the percentage of sclerosed glomeruli during the trial, and adverse effects. The two study groups were similar in terms of baseline characteristics. Thirty-nine of the 40 patients who received the combination and 39 of the 40 who received prednisolone completed the trial. Thirty-six (92.3%) of the 39 patients who received the combination and 29 (74.4%) of the 39 who received prednisolone reached the primary end point by the 2-yr follow-up point (P ‫؍‬ 0.007 log-rank). The percentage of sclerosed glomeruli was unchanged in the patients who received the combination but increased from 3.1 ؎ 4.8 to 14.6 ؎ 15.2% in the prednisolone group (P ‫؍‬ 0.0003). The frequency of adverse effects was similar in the two groups. It is concluded that combination treatment may be better for severe IgAN than treatment with prednisolone alone.

Long-Term Results of a Randomized Controlled Trial in Childhood IgA Nephropathy

“…Our previous two RCTs and clinical trial showed the short-term effectiveness of combination therapy in childhood IgA nephropathy (5,9,10). To the best of our knowledge, no well-designed RCTs of childhood IgA nephropathy have been performed with the exception of those that we conducted.…”

“…Goumenos et al (29) retrospectively reported that treatment with prednisolone and azathioprine appeared to be beneficial in slowing the progression of severe adult IgA nephropathy. We conducted another multicenter prospective RCT comparing combination therapy with prednisolone monotherapy for severe childhood IgA nephropathy (9). The results of this study showed that patients who received prednisolone monotherapy had more sclerosed glomeruli than did those who received combination therapy, although proteinuria was reduced in both groups.…”

Current Therapy for IgA Nephropathy

“…64 In the other trial, azathioprine plus corticosteroids plus anticoagulants were tested against steroids alone. 65 In both cases, the combination therapy led to higher rates of complete remission of proteinuria.…”

“…In two Japanese trials, both from the same group, 64,65 children with IgAN and severe histologic changes and/or significant proteinuria, yet normal GFR, received azathioprine plus corticosteroids plus anticoagulants versus anticoagulants alone. 64 In the other trial, azathioprine plus corticosteroids plus anticoagulants were tested against steroids alone.…”

Comparison of Glucocorticoids Alone and Combined with Cyclosporine A in Patients with IgA Nephropathy: A Prospective Randomized Controlled Trial

“…However, there is controversy over the efficacy of immunosuppressants. Some low-quality evidence has shown that treatment with glucocorticoids and cyclophosphamide (CTX) or azathioprine in progressive IgAN patients is significantly better than other treatment regimens (21)(22)(23)(24)(25). However, issues of case enrollment, observation bias and lack of better supportive care measures in these patients make these studies difficult to interpret (26).…”