Li Jingyi, Lv Jicheng, Wong Muh Goet, Shi Sufang, Zan Jincan, Monaghan Helen, Perkovic Vlado, Zhang Hong
Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
Kidney Int Rep. 2024 Aug 3;9(10):3016-3026. doi: 10.1016/j.ekir.2024.07.031. eCollection 2024 Oct.
The TESTING trial demonstrated that corticosteroids reduce the risk of kidney failure in patients with IgA nephropathy (IgAN) but increase the risk of serious adverse events. Reliable noninvasive biomarkers are needed to identify patients who would benefit most from corticosteroid therapy. Previous studies suggest glomerular macrophage infiltration is associated with response to immunosuppressive therapy in IgAN and urinary soluble CD163 ([u-sCD163], a marker of alternatively activated macrophages [M2]c macrophage) is correlated with clinical remission in vasculitis. This study aims to investigate the association between u-sCD163 and response of steroids therapy in IgAN.
We measured u-sCD163 in patients from a large IgAN cohort and Chinese participants of the TESTING trial. The correlation of baseline or serial u-sCD163 and their response of corticosteroids therapy or kidney outcomes were investigated.
In cross-sectional analysis, u-sCD163 levels correlated with kidney macrophage infiltration, especially in crescentic areas, and with active lesions. Subgroup analysis of the TESTING cohort showed higher levels u-sCD163 were associated with greater benefits from corticosteroids therapy in proteinuria remission (odds ratio, 35.56 [95% confidence interval, CI: 7.62-292.34] vs. 3.94 [95% CI: 1.39-12.93], for interaction: 0.036). Corticosteroids therapy significantly reduced u-sCD163 levels at 6 months compared to placebo group (79% [interquartile range: 58%-91%] vs. 37% [-11% to 58%], <0.001). There was no difference in the suppressive effects on u-sCD163 by either dosage of corticosteroids (full and reduced-dose). The suppression of u-sCD163 was significantly associated with a reduced risk of kidney progression events (adjusted hazard ratio: 0.52, 95% CI: 0.30-0.93, = 0.027).
u-sCD163 is a reliable noninvasive biomarker associated with active pathological lesions in IgAN and can guide glucocorticoid therapy.
TESTING试验表明，皮质类固醇可降低IgA肾病（IgAN）患者肾衰竭的风险，但会增加严重不良事件的风险。需要可靠的非侵入性生物标志物来识别最能从皮质类固醇治疗中获益的患者。先前的研究表明，肾小球巨噬细胞浸润与IgAN患者对免疫抑制治疗的反应相关，而尿可溶性CD163（[u-sCD163]，一种替代性活化巨噬细胞[M2]c巨噬细胞的标志物）与血管炎的临床缓解相关。本研究旨在探讨u-sCD163与IgAN患者类固醇治疗反应之间的关联。
我们测量了来自一个大型IgAN队列的患者以及TESTING试验的中国参与者的u-sCD163。研究了基线或连续u-sCD163与其对皮质类固醇治疗的反应或肾脏结局之间的相关性。
在横断面分析中，u-sCD163水平与肾脏巨噬细胞浸润相关，尤其是在新月体区域，并且与活动性病变相关。TESTING队列的亚组分析显示，较高水平的u-sCD163与皮质类固醇治疗在蛋白尿缓解方面的更大获益相关（优势比，35.56 [95%置信区间，CI：7.62 - 292.34] 对比 3.94 [95% CI：1.39 - 12.93]，交互作用：0.036）。与安慰剂组相比，皮质类固醇治疗在6个月时显著降低了u-sCD163水平（79% [四分位间距：58% - 91%] 对比 37% [-11%至58%]，<0.001）。两种剂量的皮质类固醇（全剂量和减量）对u-sCD-
