Pathological sub-analysis of a multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy versus steroid pulse monotherapy in patients with immunoglobulin A nephropathy

Abstract

BackgroundThe IgA nephropathy (IgAN) Study Group in Japan conducted a multicenter, randomized, controlled trial of tonsillectomy with steroid pulse therapy (TSP) versus steroid pulse monotherapy in patients with IgAN (UMIN Clinical Trial Registry Number; C000000384). The effects of therapies in relation to pathological severity were analyzed in this study.MethodsThe patients with IgAN, urinary protein 1.0–3.5 g/day, serum creatinine of 1.5 mg/dl or less were randomly assigned to receiving TSP (Group A) or steroid pulses alone (Group B). The primary endpoint was the disappearance of proteinuria and/or hematuria. Twenty-six biopsies in Group A and 33 in Group B were available. The histological grades (HG) according to the percentage of glomeruli with crescent or sclerosis and the Oxford classification were analyzed.ResultsThe patients in Group A had a 4.32- to 12.1-fold greater benefit of disappearance of proteinuria and 3.61- to 8.17-fold greater benefit of clinical remission (disappearance of proteinuria and hematuria) than those in Group B in patients with HG2–3, acute lesions (cellular or fibrocellular crescent) affecting more than 5 % of glomeruli, chronic lesions (fibrous crescents or sclerosis) affecting more than 20 % and S1. In contrast, odds ratios for disappearance of proteinuria or clinical remission in Group A to Group B were not significant in patients with HG 1, acute lesion in 5 % or less of glomeruli, chronic lesion in 20 % or less and S0. The disappearance of hematuria showed no relation to pathological severity.ConclusionTSP might be better employed according to the pathological severity.Electronic supplementary materialThe online version of this article (doi:10.1007/s10157-015-1159-2) contains supplementary material, which is available to authorized users.

Validation of the revised Oxford classification for IgA nephropathy considering treatment with corticosteroids/immunosuppressors

“…However, chronic lesions can result from continuous inflammation in the glomeruli; therefore, some IgAN patients with chronic lesions also had active lesions, and immunosuppressors improved their renal outcomes. These results were also shown in a sub-analysis of the STOP-IgAN trial 31 and a sub-analysis 34 of the randomized controlled trial by the IgAN study group in Japan that compared tonsillectomy combined with steroid pulse therapy and steroid pulse monotherapy 33 . In the STOP-IgAN trial, the renal survival rate for IgAN patients with T scores with progression to ESRD was improved by corticosteroids/immunosuppressors (T1/2 vs. T0: 18% [3/17 patients] vs. 7% [1/15 patients]; p = 0.0603) but not supportive therapy (T1/2 vs. T0: 33% [4/12 patients] vs. 0% [0/25 patients]; p = 0.008) 31 .…”

“…In the STOP-IgAN trial, the renal survival rate for IgAN patients with T scores with progression to ESRD was improved by corticosteroids/immunosuppressors (T1/2 vs. T0: 18% [3/17 patients] vs. 7% [1/15 patients]; p = 0.0603) but not supportive therapy (T1/2 vs. T0: 33% [4/12 patients] vs. 0% [0/25 patients]; p = 0.008) 31 . A randomized controlled trial performed by the IgAN study group indicated that only the S score was an independent factor for the disappearance of both proteinuria and haematuiria by steroid pulse therapy combined with tonsillectomy; however, the M, E, and T scores were not 33,34 . These results were observed during the short-term (only 1 to 3 years); therefore, we propose that our long-term observation study shows clearer results.…”

The response of the Oxford classification to steroid in IgA nephropathy: a systematic review and meta-analysis

“…The characteristics of the included studies are summarized in the Table 1 . The inclusion criteria used in two trials [ 13 , 14 ] was IgAN patients with nephrotic syndrome, and the other one [ 15 ] was biopsy-proved IgAN and urinary protein excretion ranging from 1.0 to 3.5 g/24h. Another two studies [ 16 , 17 ] did not limit the scope of proteinuria, and the last study [ 16 ] used the immunosuppressive therapy and was only provided the data of M1, E1, S1, T0, and T1/2, without M0, E0, and S0.…”

“…A review of S lesions indicates there may be clinical utility in the subclassification of segmental sclerosis, which identified those cases with evidence of podocyte damage [ 23 ]. Katafuchi R et al suggested that only pathologic lesion S showed a significant heterogeneity between S0 and S1 to steroid treatment in the disappearance of proteinuria ( P = 0.045) [ 15 ]. Our meta-analysis suggested the difference in steroid resistance (OR 2.24, 95% CI 0.99 - 5.08, P = 0.05) when compared S1 with S0.…”

Successful treatment of recurrent immunoglobulin a nephropathy using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation: a case presentation

“…Additionally, recent randomized controlled study has examined the effect of steroid pulse therapy combined with tonsillectomy on clinical remission by pathological sub-analysis. This study has suggested that combined therapy has a greater benefit of clinical remission than steroid therapy alone in the moderate to severe pathological case that showed more than 25% of glomeruli exhibiting crescents, segmental sclerosis or global sclerosis (odds ratio 8.17) [ 19 ]. Our case also matched these criteria (42.1%: two crescents and 6 global sclerosis was observed in 19 glomeruli).…”