Supplementary Material for: Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

背景：抗中性粒细胞胞浆抗体（anti-neutrophil cytoplasmic antibody, ANCA）相关性肾小球肾炎（glomerulonephritis, GN）的分型预后价值已在多项队列研究中得到证实，其中硬化性亚型的肾脏预后最差。目前关于硬化性ANCA相关性GN患者预后影响因素的已发表相关数据较为有限。
方法：本回顾性队列研究纳入了来自全球5个中心的硬化性ANCA相关性GN患者。本研究描述了该队列的临床特征，并评估了1年肾小球滤过率（glomerular filtration rate, GFR）与终末期肾病（end-stage renal disease, ESRD）的预测因素。采用肾脏病饮食改良研究（Modification of Diet in Renal Disease, MDRD）公式估算的肾小球滤过率（estimated GFR, eGFR）来衡量12个月时的肾功能，并通过简单线性回归与多元线性回归分析构建预测模型。此外，采用Cox比例风险回归模型评估无ESRD生存率。
结果：本研究共纳入50例患者，其中92%为白种人，60%为男性，平均年龄61岁。72%的患者为肾局限性病变，82%的患者MPO-ANCA呈阳性。肾活检标本的肾小球中位数为20个[四分位距（interquartile range, IQR）15~34]，96%的标本可见中至重度间质纤维化。总体而言，96%的患者接受了免疫抑制药物治疗，16%的患者接受了血浆置换治疗。除1例患者外，其余所有患者均获得了治疗应答。入组时的eGFR中位数（IQR）为14.5（9~19）mL/min/1.73m²。中位随访时间（IQR）为33.5（17~82）个月，其中26例患者进展为ESRD。共有10例患者死亡，其中6例发生在确诊后的第一年内。入组时GFR较低以及肾小管萎缩程度较高的患者，其进展为ESRD的风险显著更高（P=0.003；P=0.043）。
结论：对于入组时需透析的硬化性ANCA相关性GN患者而言，肾脏恢复极为罕见，且12%的患者在确诊后第一年内死亡。入组时的GFR水平与肾小管萎缩程度，可作为硬化性亚型ANCA相关性GN患者12个月时GFR水平及肾脏生存情况的显著预测因素。