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

Autor: Moran SM; Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland.; Department of Medicine, Queen's University, Kingston, Ontario, Canada., Scott J; Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland., Clarkson MR; Cork University Hospital, Ireland, University College Cork, Cork, Ireland., Conlon N; St James's Hospital, Dublin, Ireland., Dunne J; St James's Hospital, Dublin, Ireland., Griffin MD; REMEDI at CÚRAM SFI Centre for Research in Medical Devices, School of Medicine, National University of Ireland, Galway, Ireland.; Department of Nephrology, Saolta University Health Care Group, Galway University Hospitals, Galway, Ireland., Griffin TP; REMEDI at CÚRAM SFI Centre for Research in Medical Devices, School of Medicine, National University of Ireland, Galway, Ireland.; Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group, Galway University Hospitals, Galway, Ireland., Groarke E; St James's Hospital, Dublin, Ireland., Holian J; St Vincent's University Hospital, Dublin, Ireland., Judge C; Department of Nephrology, Saolta University Health Care Group, Galway University Hospitals, Galway, Ireland.; Centre for Endocrinology, Diabetes and Metabolism, Saolta University Health Care Group, Galway University Hospitals, Galway, Ireland., Wyse J; Discipline of Statistics and Information Systems, Trinity College Dublin, Dublin, Ireland., McLoughlin K; St James's Hospital, Dublin, Ireland., O'Hara PV; Beaumont Kidney Centre, Dublin, Ireland., Kretzler M; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan., Little MA; Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland.; Beaumont Kidney Centre, Dublin, Ireland.; Tallaght University Hospital, Dublin, Ireland.
Jazyk: angličtina
Zdroj: Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2021 Nov; Vol. 32 (11), pp. 2920-2932. Date of Electronic Publication: 2021 Sep 13.
DOI: 10.1681/ASN.2021030382
Abstrakt: 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.
(Copyright © 2021 by the American Society of Nephrology.)
Databáze: MEDLINE