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

Jingyi Li; Jicheng Lv; Muh Goet Wong; Sufang Shi; Jincan Zan; Helen Monaghan; Vlado Perkovic; Hong Zhang; TESTING Study Biomarker Group

doi:10.1016/j.ekir.2024.07.031

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

Kidney Int Rep. 2024 Aug 3;9(10):3016-3026. doi: 10.1016/j.ekir.2024.07.031. eCollection 2024 Oct.

Authors

Jingyi Li^{1

2

3}, Jicheng Lv^{1

2

3}, Muh Goet Wong^{4

5

6}, Sufang Shi^{1

2

3}, Jincan Zan^{1

2

3}, Helen Monaghan⁴, Vlado Perkovic⁴, Hong Zhang^{1

2

3}; TESTING Study Biomarker Group

Collaborators

TESTING Study Biomarker Group:
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

Affiliations

¹ Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
² Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
³ Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, China.
⁴ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
⁶ Department of Renal Medicine, Concord Repatriation General Hospital, Concord, New South Wales, Australia.

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.

Keywords: IgA nephropathy; crescentic lesions; treatment; u-sCD163.