Rheumatology, Montefiore Medical Center, Bronx, New York, USA
Rheumatology, Albert Einstein College of Medicine, Bronx, New York, USA.
Lupus Sci Med. 2022 Jan;9(1). doi: 10.1136/lupus-2021-000576.
Treatment failures for lupus nephritis (LN) are high with 10%-30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.
In this cross-sectional study, LN kidney biopsies were assessed for MAC deposition by staining for Complement C9, a component of the MAC. Chromogenic immunohistochemistry was performed on paraffin-embedded human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197). Tubular C9 staining intensity was analysed as present versus absent. IFTA was defined as minimal (<10%), mild (10%-24%), moderate (25%-50%) and severe (>50%).
Renal biopsies from 30 patients with LN were studied. There were 24 (80%) female sex, mean age (SD) was 33 (12) years old and 23 (77%) had pure/mixed proliferative LN. Tubular C9 staining was present in 7 (23%) biopsies. 27 patients had minimal-to-mild IFTA and 3 patients had moderate IFTA. Among the C9 + patients, 3 (43%) had moderate IFTA as compared with none in the C9- group, p=0.009. C9 + patients had higher median (IQR) proteinuria as compared with C9- patients: 6.2 g (3.3-13.1) vs 2.4 g (1.3-4.6), p=0.001 at the time of biopsy. There was no difference in estimated glomerular filtration rate (eGFR) between the C9 + and C9- groups.
This study demonstrated that tubular MAC deposition is associated with higher degree of IFTA and proteinuria, which are predictors of progression to ESRD. These results suggest that tubular MAC deposition may be useful in classification of LN. Understanding the role of complement in tubulointerstitial injury will also identify new avenues for LN treatment.
狼疮肾炎 (LN) 的治疗失败率较高，10%至 30%的患者在 10 年内进展为终末期肾病 (ESRD)。间质纤维化/肾小管萎缩 (IFTA) 是进展为 ESRD 的预测因素。先前的研究表明，LN 中蛋白尿引起的小管间质损伤是通过小管内补体激活介导的，特别是通过膜攻击复合物 (MAC)。本研究旨在探讨小管 MAC 沉积与 IFTA 和蛋白尿之间的关系。
在这项横断面研究中，通过染色补体 C9（MAC 的一个组成部分）来评估 LN 肾活检标本中的 MAC 沉积。使用未缀合的、鼠抗人补体 C9（Hycult Biotech，克隆 X197）对石蜡包埋的人肾活检切片进行显色免疫组织化学染色。分析肾小管 C9 染色强度为存在或不存在。IFTA 定义为最小（<10%）、轻度（10%-24%）、中度（25%-50%）和重度（>50%）。
研究了 30 例 LN 患者的肾活检标本。其中 24 例（80%）为女性，平均年龄（标准差）为 33（12）岁，23 例（77%）为纯/混合增生性 LN。7 例（23%）活检标本中存在肾小管 C9 染色。27 例患者的 IFTA 为最小至轻度，3 例患者的 IFTA 为中度。在 C9+患者中，3 例（43%）有中度 IFTA，而 C9-组无一例，p=0.009。与 C9-患者相比，C9+患者的中位（IQR）蛋白尿更高：6.2g（3.3-13.1）比 2.4g（1.3-4.6），p=0.001 在活检时。C9+和 C9-组之间的估计肾小球滤过率（eGFR）没有差异。
本研究表明，小管 MAC 沉积与更高程度的 IFTA 和蛋白尿相关，这是进展为 ESRD 的预测因素。这些结果表明，小管 MAC 沉积可能有助于 LN 的分类。了解补体在肾小管间质损伤中的作用也将为 LN 的治疗开辟新途径。
Zotero 插件