Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort
Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort
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DOI：
10.1093/ndt/gfy337
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发表时间：
2019-10-01
影响因子：
6.1
通讯作者：
Tardanico, Regina
中科院分区：
文献类型：
--
作者：
Bellur, Shubha S.;Roberts, Ian S. D.;Tardanico, Regina
背景伊加的验证（VALIGA）研究调查了来自13个欧洲国家的1147例患者中免疫球蛋白A肾病（IgAN）牛津分类的实用性。由当地病理学家对活检进行评分，然后在牛津进行中心审查。我们有两个不同的目标：评估病理学结果与给予皮质类固醇/免疫抑制剂（CS/IS）治疗的决定有多密切相关，并确定中心和当地病理学家之间MEST-C评分差异对牛津分类临床价值的影响。我们对每个病变的一致性类型（局部和中心病理学家评分缺失、局部存在和中心缺失、局部缺失和中心存在，两种评分均存在）与初始临床评估以及未接受CS/IS的患者的长期结局之间的相关性进行了测试。由当地病理学家评估的所有肾小球病变（M、E、C和S）与CS/IS治疗的决定独立相关，而肾小管间质病变的严重程度与决定无关。对于S（节段性硬化）和T（肾小管萎缩/间质纤维化），当地和中心病理学家之间的再现性为中度，对于M（系膜细胞过多）、E（毛细血管内细胞过多）和C（新月体），再现性较差。当地病理学家在统计学上发现每种病变更多，S病变除外，其在中心审查中更常见。当受影响的肾小球比例较低时，更有可能发生分歧。由中心病理学家评估的M病变与就诊时疾病的严重程度相关性更好，与结局的区别更好。相反，与中心审查相比，由当地病理学家评价的E病变与临床表现和结局的相关性更好。当当地和中心病理学家之间不一致时，C和S病变的临床表型介于双缺失病变（病情较轻）和双存在病变（病情较重）之间。我们的结论是，当地病理学家和中心审查员之间的MEST-C标准评分的差异对牛津分类的预后价值有显着影响。由于在该队列中提供免疫抑制治疗的决定与MEST-C评分密切相关，因此本研究表明需要为病理学家提供更详细的IgAN活检评分指导。
Background. The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries.Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS.Results. All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe).Conclusion. We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.