Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis

Abstract

Background and objectives: ANCA-associated GN is a common cause of rapidly progressive GN, with high relapse rates. The early recognition of an ANCA-associated GN relapse is of importance to prevent loss of kidney function. Urinary soluble CD163 has been identified as a promising marker of active ANCA-associated GN. Previous studies, however, are limited by the lack of histologic data.

Design, setting, participants, & measurements: We analyzed urinary soluble CD163 in 95 patients with ANCA-associated vasculitis who underwent a kidney biopsy. In total, 125 kidney tissue sections (first kidney biopsy, n=67; repeated biopsy, n=58) with concurrent 24-hour urine samples were studied. Correlation analyses comparing urinary soluble CD163 levels and morphologic features of ANCA-associated GN were performed using Spearman rank correlation analysis. The diagnostic performance of biomarkers to detect relapsing ANCA-associated GN was evaluated using receiver operating characteristics curve analysis.

Results: High levels of urinary soluble CD163 were found in 96 (87%) of 110 biopsies with active ANCA-associated GN compared with one (7%) of 15 biopsies without active ANCA-associated GN and one (6%) of 17 healthy controls. Urinary soluble CD163 correlated with fibrinoid necrosis (Rho=0.48, P<0.001) and cellular crescents (Rho=0.70, P<0.001) on kidney biopsy. In repeated biopsies, urinary soluble CD163's sensitivity of 0.94 and specificity of 0.91 for the recognition of relapsing ANCA-associated GN appeared better than routine clinical measures. The presence of CD163⁺ cells in affected glomeruli confirmed urinary soluble CD163's origin.

Conclusions: Urinary soluble CD163 is associated with active ANCA-associated GN and correlates with histologic features as seen in ANCA-associated GN.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_17_CJN07210520_final.mp3.

Keywords: ANCA; Acute kidney injury; Biopsy; glomerulonephritis; kidney biopsy; kidney pathology; macrophages; vasculitis.