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

Abstract

SummaryBackground and objectives Children with IgA nephropathy showing diffuse (Ͼ80%) mesangial proliferation are at high risk for end-stage renal failure (ESRF). A previous controlled trial showed that combination therapy consisting of prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease reduces immunologic renal injury and prevents the progression of sclerosed glomeruli. The objective of this study was to evaluate the long-term effectiveness of combination therapy in children with IgA nephropathy showing diffuse mesangial proliferation.Design, setting, participants, & measurements A secondary analysis of a multicenter, randomized, controlled trial involving 78 children with IgA nephropathy who received either 2-year combination therapy or heparin-warfarin and dipyridamole (control) therapy was conducted.Results The median duration of observation was 10 years (range, 0.5 to 18). Two of 40 patients (5%) who received combination therapy and five of 34 patients (14.7%) who received control therapy developed ESRF. A Kaplan-Meier plot of renal survival showed that the outcomes of patients in the combined therapy group were better than those in the control therapy group (log-rank P ϭ 0.03). The 10-year renal survival probability of each group was 97.1% (95% confidence interval, 81.4 to 99.6%) and 84.8% (95% confidence interval, 55.4 to 95.5%), respectively. The Cox proportional hazards model showed that the 2-year combination therapy was significantly associated with renal survival in both univariate and multivariate analyses.Conclusions Two-year combination therapy not only ameliorated the activity of the acute phase of nephritis but also improved the long-term outcome of severe childhood IgA nephropathy.

Successful therapy with tonsillectomy plus pulse therapy for the relapse of pediatric IgA nephropathy treated with multi-drugs combination therapy

“…As to long -term follow -up studies on multidrug combination therapy for severe pediatric IgAN, Kamei et al reported a marked improvement in renal survival in severe IgAN patients treated with combination therapy 7) . We also found that 89% of children with severe IgAN treated with combination therapy, consisting of prednisolone, mizoribine, warfarin, and dipyridamole, had no or only mild proteinuria, and reported that combination therapy had improved the long -term outcome of IgAN 10) .…”

“…In many centers, immunosuppression, particularly with combination therapy, for 2 years is reserved for severe cases categorized as crescentic nephritis 5 -10) . Recently, in Japan, Kamei et al reported that 90% of children with severe IgAN treated with combination therapy, consisting of prednisolone, heparin -warfarin, dipyridamole, and mizoribine or azathioprine, had no or only mild proteinuria, and mentioned that combination therapy had improved the long -term outcome of IgAN 7) . The prognosis of most severe cases of pediatric IgAN treated with multi -drugs combination therapy is good ; however, some patients with severe IgAN experience recurrence after combination therapy or resistance to treatment.…”

Pediatric IgA Nephropathy in Europe

“…In Japan, a RCT obtained good results treating children with severely proliferative IgAN over 2 years with CS/IS drugs in combination with antiplatelets and anticoagulants [25]. The results lasted for a decade after the end of treatment [26]; however, the side effects of this long-term heavy therapy were of some relevance. In Europe, much of the interest was focused on treating acute cases presenting with crescents and compromised renal function, with a few months of treatment obtaining encouraging results without side effects in some case series [18, 27, 28].…”

“…The severity and frequency of side effects is not reported to be severe, probably because prolonged treatment is avoided. The Japanese reports on an increase in T lesions in children in whom the decision for renal biopsy was delayed or when CS were not used [25, 26] have further stressed the attitude for Europe to treat progressive IgAN in children with aggressive therapy [18, 27, 28]. In Europe, the results of the long-term follow-up of the VALIGA study [13] clearly indicated that when T lesions develop, the disease enters a relentless phase of progression, and that M1, S1, and also C lesions in untreated cases can have an impact on disease outcome decades later in children as well as in adults.…”

IgA Nephropathy: A European Perspective in the Corticosteroid Treatment

“…The mesangial proliferation significantly decreased in children treated by corticosteroids. Ten years after the end of the treatment, the renal survival was significantly better in children previously treated with corticosteroids/immunosuppressors [19]. In Europe, the present tendency is to consider the presence of M1 as a possible marker of the need of corticosteroid therapy particularly in children and young subjects even with mild proteinuria, as suggested also from the collaborative study which pooled data from VALIGA, Chinese, Japanese, and North American cohorts [16].…”