Urinary Soluble CD163 in Active Renal Vasculitis

Abstract

A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.

Monocytes Promote Crescent Formation in Anti-Myeloperoxidase Antibody–Induced Glomerulonephritis

“…CD163 is expressed on monocytes and macrophages, and a soluble form (sCD163) was recently implicated as a clinical urinary biomarker in patients with active renal ANCA-associated vasculitis. 28 We studied sCD163 in our disease model and observed a strong increase in serum, but not in urine, with anti-MPO IgG treatment ( Figure 4C). Monocyte depletion significantly abolished serum sCD163.…”

Animal Models of ANCA Associated Vasculitis

“…They generate macrophage extracellular traps (METs) and ∼25% of CD68+ macrophages are positive for MPO protein by immunostaining (55). Furthermore elevated urinary soluble CD163, shed by monocytes and macrophages, is strongly associated with active renal vasculitis and has potential as a biomarker to detect renal relapses of AAV (66).…”

“…Activated by ANCA (10) Presence of monocytes and macrophages in renal biopsies Soluble CD163 in urine, which is shed by monocytes, is strongly associated with active renal vasculitis (66) Monocyte depletion reduces glomerular necrosis and crescent formation after passive transfer (9) Pre-clinical evaluation of monocyte-related biomarkers and therapies AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibodies; G-CSF, granulocyte colony stimulating factor; GN, glomerulonephritis; HLA, human leukocyte antigen; LAMP-2, lysosome-associated membrane protein-2; LPS, lipopolysaccharide; MPO, myeloperoxidase; NCGN, necrotizing crescentic glomerulonephritis; NETs, neutrophil extracellular traps; PR3, proteinase 3; TLR4, toll-like receptor 4; TNF, tumor necrosis factor. the disease is heterogeneous, with significant variability in genetic predisposition, environmental risk factors, severity, organ involvement, and risk of relapse.…”

Glomerular Diseases: Registries and Clinical Trials

“…The inflammatory glomerulonephritides have a relatively longstanding history of defined biomarkers associated with disease diagnosis and activity-anti-double stranded DNA, anti-C1q, and complement levels in lupus nephritis, and ANCAs for pauci-immune/ANCA-associated vasculitis-which has contributed to strong trial design. More recently, serum thiols and anti-C3b IgG have been proposed for lupus nephritis (11,12), and urinary soluble CD163 has been proposed for ANCA-associated vasculitis (13).…”