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  • Title: Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy.
    Author: Li J, Lv J, Wong MG, Shi S, Zan J, Monaghan H, Perkovic V, Zhang H, TESTING Study Biomarker Group.
    Journal: Kidney Int Rep; 2024 Oct; 9(10):3016-3026. PubMed ID: 39430181.
    Abstract:
    INTRODUCTION: 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. METHODS: 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. RESULTS: 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], P 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%], P <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, P = 0.027). CONCLUSION: u-sCD163 is a reliable noninvasive biomarker associated with active pathological lesions in IgAN and can guide glucocorticoid therapy.
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