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. 2021 Dec 23:12:769802.
doi: 10.3389/fimmu.2021.769802. eCollection 2021.

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Shaomin Gong  1   2   3   4   5 , Shi Jin  1   2   3   4   5 , Yang Li  1   2   3   4   5 , Wuhua Jiang  1   2   3   4   5 , Zhen Zhang  1   2   3   4   5 , Ziyan Shen  1   2   3   4   5 , Jialin Wang  1   2   3   4   5 , Huili Zhou  1 , Xiao Liu  1 , Xialian Xu  1   2   3   4   5 , Xiaoqiang Ding  1   2   3   4   5 , Yiqin Shi  1   2   3   4   5 , Hong Liu  1   2   3   4   5
Affiliations

Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Shaomin Gong et al. Front Immunol. .

Abstract

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Keywords: IgA nephropathy; biomarker; macrophages; remission status; urinary soluble CD163.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of enrollment and exclusion.
Figure 2
Figure 2
Urinary sCD163 (u-sCD163) is associated with proteinuria and eGFR in IgAN patients. (A) Correlation between u-sCD163 levels and serum creatine. (B) Correlation between U-sCD163 levels and eGFR. (C) Correlation between U-sCD163 levels and 24-hour proteinuria; each dot represents a value from an individual patient. Coefficients of determination (r 2) and P-values are shown.
Figure 3
Figure 3
Urinary sCD163 levels are correlated with tubulointerstitial CD163+ macrophage infiltration. (A) CD163+ macrophages in IgAN classified according to Lee’s pathological grade. Bar: 50 µm. (B) Quantitative analysis of CD163+ cell counts in tubulointerstitial lesions from IgAN patients assigned different Lee’s pathological grades. **P<0.001. (C) Correlation between tubulointerstitial CD163+ cell count and u-sCD163 levels; each dot represents a value from an individual patient and the group mean is shown as a horizontal bar. Coefficients of determination (r 2) and P-values are shown.
Figure 4
Figure 4
Urinary sCD163 levels reflect patient histology. (A–E) Association between u-sCD163 levels in IgAN patients with Oxford Classification. **P<0.001. (F) Correlation between u-sCD163 levels and global glomerulosclerosis. (G) Correlation between u-sCD163 levels and segmental glomerulosclerosis. (H) Correlation between u-sCD163 levels and interstitial score. (I) Correlation between u-sCD163 levels and MEST-C score; each dot represents a value from an individual patient Coefficients of determination (r 2) and P-values are shown. (J) Quantitative analysis of u-sCD163 levels in IgAN patients with differing Lee’s pathological grades. **P<0.001.
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