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.

Graphical abstract

Figure 1.

All biopsies are classified according to histologic classification of ANCA GN and presented with biopsy characteristics. Jones methenamine silver stain of representative sclerotic, normal, and crescentic glomeruli at ×630, ×400, and ×400 magnification, respectively. Data are presented as medians with interquartile ranges or numbers with percentages. ANCA GN, ANCA-associated GN; IFTA, interstitial fibrosis and/or tubular atrophy.

Figure 2.

Levels of urinary soluble CD163 (usCD163) corrected for urinary creatinine (uCreat) levels (nanograms per millimole) are increased in active ANCA-associated GN. (A) Patients with ANCA-associated GN (ANCA GN) active disease had higher usCD163 levels compared with patients without active ANCA GN (n=15) or healthy controls (HCs; n=17). (B) usCD163 levels divided according to the ANCA GN classification. Data are presented as medians with interquartile ranges (box).

Figure 3.

Urinary soluble CD163 (usCD163) correlated with histologic features of active ANCA-associated GN (ANCA GN). (A) Active ANCA GN lesions characterized by fibrinoid necrosis (arrows), capillary breaks (arrowheads), and cellular crescentic lesions (asterisk; Jones methenamine silver stain). Magnification, ×400. (B–D) Correlation between usCD163 and the percentage of glomeruli showing (B) capillary breaks, (C) fibrinoid necrosis, and (D) cellular crescents. (E) The percentage of normal glomeruli correlated inversely with usCD163 levels. Of note, three values of usCD163 (all >9000 ng/mmol) included in the correlation analysis are not included in (B–E) to improve visibility and decrease overlap of individual scatter points at lower usCD163 levels (i.e., <1000 ng/mmol). These values (i.e., >9000 ng/mmol) did not affect the significance of the findings. uCreat, urinary creatinine.

Figure 4.

Biopsies were stained for CD163⁺cells in active ANCA-associated GN (ANCA GN; n=40; i.e., focal [n=12], crescentic [n=8], mixed [n=13], and sclerotic [n=7] classes) and biopsies showing no activity (n=7). CD163⁺ cell staining in (A) glomeruli of active ANCA GN versus biopsies with no ANCA GN activity, (B) affected versus unaffected areas of glomeruli, (C) unaffected glomeruli in active ANCA GN versus biopsies with no ANCA GN activity, (D) periglomerular areas of unaffected versus active versus sclerosed glomeruli, and (E) tubulointerstitial areas of active ANCA GN versus biopsies with no ANCA GN activity. Each point represents the mean score of CD163⁺ cell staining per biopsy. Data are presented as medians with interquartile ranges.