The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis.

Abstract

BACKGROUND:

Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed.

METHODS:

We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls.

RESULTS:

We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis.

CONCLUSIONS:

usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

• Authors: Sarah M Moran, Jennifer Scott, Michael R Clarkson, Niall Conlon, Jean Dunne, Matthew D Griffin, Tomas P Griffin, Elizabeth Groarke, John Holian, Conor Judge, Jason Wyse, Kirsty McLoughlin, Paul V O'Hara, Matthias Kretzler, Mark A Little, Nephrotic Syndrome Study Network (NEPTUNE)
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 32 Issue 11 Pg. 2920-2932 (11 2021) ISSN: 1533-3450 [Electronic] United States
• PMID: 34518279 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 by the American Society of Nephrology.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Biomarkers
• CD163 antigen
• Receptors, Cell Surface

Topics

• Aged
• Aged, 80 and over
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (diagnosis, urine)
• Antigens, CD (urine)
• Antigens, Differentiation, Myelomonocytic (urine)
• Biomarkers
• Diagnosis, Differential
• Disease Progression
• Early Diagnosis
• False Positive Reactions
• Female
• Humans
• Male
• Middle Aged
• Nephrotic Syndrome (urine)
• Prospective Studies
• Proteinuria (urine)
• Receptors, Cell Surface
• Reference Values
• Single-Blind Method