Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy

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 ther...

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Main Authors: Jingyi Li, Jicheng Lv, Muh Goet Wong, Sufang Shi, Jincan Zan, Helen Monaghan, Vlado Perkovic, Hong Zhang, Rajiv Agarwal, Sean Barbour, Daniel Cattran, Alan Cass, Tak Mao Chan, John Feehally, Richard Glassock, Michelle A. Hladunewich, Lai Seong Hooi, Meg J. Jardine, Vivekanand Jha, David W. Johnson, Adeera Levin, Zhi-Hong Liu, Heather Reich, Giuseppe Remuzzi, David C. Wheeler, Muh Geot Wong, Mark Woodward, Yangfeng Wu, Minghui Zhao
Format: Article
Language:English
Published: Elsevier 2024-10-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924018618
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author Jingyi Li
Jicheng Lv
Muh Goet Wong
Sufang Shi
Jincan Zan
Helen Monaghan
Vlado Perkovic
Hong Zhang
Hong Zhang
Vlado Perkovic
Rajiv Agarwal
Sean Barbour
Daniel Cattran
Alan Cass
Tak Mao Chan
John Feehally
Richard Glassock
Michelle A. Hladunewich
Lai Seong Hooi
Meg J. Jardine
Vivekanand Jha
David W. Johnson
Adeera Levin
Zhi-Hong Liu
Jicheng Lv
Helen Monaghan
Heather Reich
Giuseppe Remuzzi
David C. Wheeler
Muh Geot Wong
Mark Woodward
Yangfeng Wu
Minghui Zhao
author_facet Jingyi Li
Jicheng Lv
Muh Goet Wong
Sufang Shi
Jincan Zan
Helen Monaghan
Vlado Perkovic
Hong Zhang
Hong Zhang
Vlado Perkovic
Rajiv Agarwal
Sean Barbour
Daniel Cattran
Alan Cass
Tak Mao Chan
John Feehally
Richard Glassock
Michelle A. Hladunewich
Lai Seong Hooi
Meg J. Jardine
Vivekanand Jha
David W. Johnson
Adeera Levin
Zhi-Hong Liu
Jicheng Lv
Helen Monaghan
Heather Reich
Giuseppe Remuzzi
David C. Wheeler
Muh Geot Wong
Mark Woodward
Yangfeng Wu
Minghui Zhao
author_sort Jingyi Li
collection DOAJ
description 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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spelling doaj-art-7f9f3a004a3e4c5bbb24ec6c565687032025-08-20T02:33:36ZengElsevierKidney International Reports2468-02492024-10-019103016302610.1016/j.ekir.2024.07.031Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA NephropathyJingyi Li0Jicheng Lv1Muh Goet Wong2Sufang Shi3Jincan Zan4Helen Monaghan5Vlado Perkovic6Hong Zhang7Hong ZhangVlado PerkovicRajiv AgarwalSean BarbourDaniel CattranAlan CassTak Mao ChanJohn FeehallyRichard GlassockMichelle A. HladunewichLai Seong HooiMeg J. JardineVivekanand JhaDavid W. JohnsonAdeera LevinZhi-Hong LiuJicheng LvHelen MonaghanHeather ReichGiuseppe RemuzziDavid C. WheelerMuh Geot WongMark WoodwardYangfeng WuMinghui ZhaoRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China; Correspondence: Jicheng Lv, Renal Division, Department of Medicine, Peking University First Hospital, Xishiku Street No. 8, Xicheng District, Beijing 100034, China.The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, AustraliaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaThe George Institute for Global Health, University of New South Wales, Sydney, New South Wales, AustraliaThe George Institute for Global Health, University of New South Wales, Sydney, New South Wales, AustraliaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaIntroduction: 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.http://www.sciencedirect.com/science/article/pii/S2468024924018618crescentic lesionsIgA nephropathytreatmentu-sCD163
spellingShingle Jingyi Li
Jicheng Lv
Muh Goet Wong
Sufang Shi
Jincan Zan
Helen Monaghan
Vlado Perkovic
Hong Zhang
Hong Zhang
Vlado Perkovic
Rajiv Agarwal
Sean Barbour
Daniel Cattran
Alan Cass
Tak Mao Chan
John Feehally
Richard Glassock
Michelle A. Hladunewich
Lai Seong Hooi
Meg J. Jardine
Vivekanand Jha
David W. Johnson
Adeera Levin
Zhi-Hong Liu
Jicheng Lv
Helen Monaghan
Heather Reich
Giuseppe Remuzzi
David C. Wheeler
Muh Geot Wong
Mark Woodward
Yangfeng Wu
Minghui Zhao
Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
Kidney International Reports
crescentic lesions
IgA nephropathy
treatment
u-sCD163
title Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
title_full Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
title_fullStr Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
title_full_unstemmed Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
title_short Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy
title_sort correlation of urinary soluble cd163 levels with disease activity and treatment response in iga nephropathy
topic crescentic lesions
IgA nephropathy
treatment
u-sCD163
url http://www.sciencedirect.com/science/article/pii/S2468024924018618
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