Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study

作者：Shudan Wang, Shudan Wang, Ming Wu, Luis Chiriboga, Briana Zeck, Béatrice Goilav, Shuwei Wang, Shuwei Wang, Alejandra Londoño Jimenez, Chaim Putterman, Daniel Schwartz, James Pullman, Anna Broder, H. Michael Belmont · 发表于：Lupus Science & Medicine · 年份：2022 · DOI：10.1136/lupus-2021-000576 · 被引用次数：21 · 研究领域：Systemic Lupus Erythematosus Research、Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes

INTRODUCTION: 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. METHODS: 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%). RESULTS: 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- patie...