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

Document Type

Article

Publication Date

11-1-2021

Publication Title

Journal of the American Society of Nephrology : JASN

Keywords

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

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 (

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.

Clinical Institute

Kidney & Diabetes

Department

Endocrinology

Department

Nephrology

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