A Multicenter Application and Evaluation of the Oxford Classification of IgA Nephropathy in Adult Chinese Patients

Zeng, Caihong; Le, Weibo; Ni, Zhaohui; Zhang, Minfang; Miao, Lining; Luo, Ping; Wang, Rong; Lv, Zhimei; Chen, Jianghua; Tian, Jun-Ce; Chen, Nan; Pan, Xiaoxia; Fu, Ping; Hu, Zhangxue; Wang, Lining; Fan, Qiuling; Zheng, Hongliang; Zhang, Dewei; Wang, Yaping; Huo, Yanhong; Lin, Hongli; Chen, Shuni; Sun, Shan; Wang, Yanxia; Liu, Zhangsuo; Liu, Dong; Ma, Liang; Pan, Tao; Zhang, Aiping; Jiang, Xiaoyu; Xing, Changying; Sun, Bai Tao; Zhou, Qiaoling; Tang, Wenbing; Liu, Fuyou; Liu, Yanping; Liang, Shuang; Xu, Feng; Huang, Qian; Shen, Hongbing; Wang, Jianming; Shyr, Yu; Phillips, Sharon; Troyanov, Stéphan; Fogo, Agnes B.; Liu, Zhihong

doi:10.1053/j.ajkd.2012.06.011

Cited by 142 publications

(126 citation statements)

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“…The original Oxford study 1 and several subsequent validation studies [3][4][5][6]15 with similar entry criteria, excluding patients with eGFR,30 ml/min per 1.73 m 2 at the time of biopsy and/or rapid progression to ESRD, did not find crescents to be an independent predictor of poor renal outcomes in patients with IgA nephropathy. However, some other studies with less restrictive entry criteria 7-10 did find a significant association between crescents and a composite outcome including either ESRD or doubling of SCr/$50% reduction in eGFR (in one instance, also including death).…”

Section: Discussionmentioning

confidence: 97%

“…Endocapillary hypercellularity (E), although not predictive of poor outcome in the Oxford cohort, was associated with a significantly reduced rate of eGFR decline in patients treated with immunosuppressive therapy compared with those who were not. The Oxford Classification is, thus, composed of scores for M, E, S, and T. However, the presence or absence of cellular/fibrocellular crescents was not a significant predictor of these outcomes in the original Oxford cohort 1 or a number of validation studies [3][4][5][6] with similar entry criteria, which excluded patients with eGFR of ,30 ml/min per 1.73 m 2 at the time of biopsy and/or progression to ESRD within 12 months of the biopsy.…”

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confidence: 98%

“…In this study, we addressed active (cellular or fibrocellular) crescents as potential predictors of renal outcomes in IgA nephropathy in a large cohort pooled from four retrospective studies: Oxford, 1,2 the validation IgA (VALIGA) Study, 14 and two large Asian databases, 5,7 including both adults and children as well as patients with a low GFR (,30 ml/min per 1.73 m 2 ) and/or a rapidly progressive clinical course. We also studied how different fractions of crescents were associated with the rate of renal function decline and survival from a combined outcome defined as either a $50% decline in renal function or ESRD adjusting for covariates used in the original Oxford study and stratifying patients on the basis of whether they received immunosuppressive therapy.…”

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confidence: 99%

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A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

Haas

Verhave

Liu

et al. 2016

JASN

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The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a $50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean6SD eGFR of 78629 ml/min per 1.73 m 2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in over one fourth of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.

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Section: Discussionmentioning

confidence: 97%

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confidence: 98%

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confidence: 99%

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A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

Haas

Verhave

Liu

et al. 2016

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“…Of note, the present study did not show the independent association of renal outcomes with M or E lesion discrepant from previous validation studies of Oxford classification. 15,27,28 These observations might be partly arisen from the relatively low proportion of E1 lesion and the small number of corticosteroid users compared with previous studies. Most of the patients were treated with ACEi or ARBs during the follow-up regardless of pathological grade.…”

Section: Discussionmentioning

confidence: 73%

Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy

et al. 2016

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Glomerular IgG deposition is frequently observed in patients with IgA nephropathy. However, the association between glomerular IgG deposition and progression of IgA nephropathy is uncertain. Six hundred and twentyseven patients with biopsy-proven IgA nephropathy were recruited. Histological variables of the Oxford classification (Oxford-MEST) and the presence of glomerular IgG deposits were assessed. Renal progression defined as end-stage renal disease or 50% reduction in estimated glomerular filtration rate was analyzed using Kaplan-Meier methods and Cox regression analysis. Of the study population, 200 patients (31.9%) had glomerular IgG deposition on immunofluorescence staining. During a mean follow-up of 56.8 ± 37.5 months, the rate of renal progression was significantly higher in the IgA nephropathy patients with glomerular IgG deposition compared with the IgA nephropathy patients without glomerular IgG deposition (39.8 vs 12.3 per 1000 patientyears; Po 0.001). Of patients with IgG deposition, 178 (28.3%), 20 (3.2%), and 2 (0.3%) patients had mild, moderate, and marked glomerular IgG deposits, receptively. Kaplan-Meier analysis revealed that cumulative renal survival was significantly lower in IgA nephropathy patients with the higher intensity of glomerular IgG deposits (Po 0.001). In addition, Cox regression analysis revealed that moderate and marked glomerular IgG deposits significantly predicted renal outcome independent of Oxford-MEST and clinical variables (HR, 2.97; 95% CI, 1.01-8.77; P = 0.04). This study showed that that glomerular IgG deposition was independently associated with poor renal outcome in patient with IgA nephropathy.

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“…However, their score has not been verified in an independent validation cohort. Furthermore, none of these previously published risk scores used an internationally accepted pathologic grading system, such as the Oxford classification (12,14,31). To our knowledge, our study is the first investigation attempting to develop a risk score using the Oxford classification and to verify its external validity in an independent cohort.…”

Section: Variables Scoresmentioning

confidence: 97%

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

Tanaka

Ninomiya

Katafuchi

et al. 2013

Clinical Journal of the American Society of Nephrology

108

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SummaryBackground and objectives The risk assessment for developing ESRD remains limited in patients with IgA nephropathy (IgAN). The aim of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with IgAN.Design, setting, participants, & measurements A total of 698 patients with IgAN diagnosed by renal biopsy at Kyushu University Hospital (derivation cohort) between 1982 and 2010 were retrospectively followed. The Oxford classification was used to evaluate the pathologic lesions. The risk factors for developing ESRD were evaluated using a Cox proportional hazard model with a stepwise backward elimination method. The prediction rule was verified using data from 702 patients diagnosed at Japanese Red Cross Fukuoka Hospital (validation cohort) between 1979 and 2002.Results In the derivation cohort, 73 patients developed ESRD during the median 4.7-year follow-up. The final prediction model included proteinuria (hazard ratio [HR], 1.30; 95% confidence interval [95% CI], 1.16 to 1.45, every 1 g/24 hours), estimated GFR (HR, 0.84; 95% CI, 0.74 to 0.96, every 10 ml/min per 1.73 m 2 ), mesangial proliferation (HR, 1.85; 95% CI, 1.10 to 3.11), segmental sclerosis (HR, 3.21; 95% CI, 1.37 to 7.51), and interstitial fibrosis/tubular atrophy (T1: HR, 5.30; 95% CI, 2.63 to 10.7; T2: HR, 20.5; 95% CI, 9.05 to 46.5) as independent risk factors for developing ESRD. To create a prediction rule, the score for each variable was weighted by the regression coefficients calculated using the relevant Cox model. The incidence of ESRD increased linearly with increases in the total risk scores (P for trend ,0.001). Furthermore, the prediction rule demonstrated good discrimination (c-statistic=0.89) and calibration (Hosmer-Lemeshow test, P=0.78) in the validation cohort.Conclusions This study developed and validated a new prediction rule using clinical measures and the Oxford classification for developing ESRD in patients with IgAN.

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A Multicenter Application and Evaluation of the Oxford Classification of IgA Nephropathy in Adult Chinese Patients

Cited by 142 publications

References 28 publications

A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

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