Utility of Measurements of Urinary Soluble CD163 & MCP-1 in the Identification of Subtle Renal Flares in ANCA-Associated Vasculitis

Sarah M Moran¹, Michelle Ryan¹, Paul A. Monach², David Cuthbertson³, Simon Carette⁴, Jean Dunne⁵, Gary S. Hoffman⁶, Nader A. Khalidi⁷, Curry L. Koening⁸, Carol A. Langford⁹, Carol A. McAlear¹⁰, Larry W. Moreland¹¹, Christian Pagnoux⁴, Philip Seo¹², Ulrich Specks¹³, Antoine G. Sreih¹⁴, Steven R. Ytterberg¹⁵, Lina Zgaga¹⁶, Peter A. Merkel¹⁷, Mark A. Little¹⁸ and the Vasculitis Clinical Research Consortium, ¹Clinical Medicine, Trinity Health Kidney Centre, Dublin, Ireland, ²Rheumatology, Boston University School of Medicine, Boston, MA, ³Biostatistics and Informatics, Department of Pediatrics, University of South Florida, Tampa, FL, ⁴Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ⁵Immunology Department, St James's Hospital, Dublin, Ireland, ⁶Rheumatology, Cleveland Clinic, Cleveland, OH, ⁷McMaster University, St Joseph's Healthcare Hamilton, Hamilton, ON, Canada, ⁸Rheumatology, University of Utah, Salt Lake City, UT, ⁹Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, ¹⁰University of Pennsylvania, Philadelphia, PA, ¹¹Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, ¹²Medicine, Johns Hopkins University, Baltimore, MD, ¹³Mayo Clinic, Rochester, MN, ¹⁴Rheumatology, The University of Pennsylvania, Philadelphia, PA, ¹⁵Rheumatology, Mayo Clinic, Rochester, MN, ¹⁶Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland, ¹⁷Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, ¹⁸Clinical Medicine, Trinity College Dublin, Dublin, Ireland

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ANCA, Biomarkers, renal disease and vasculitis, Urinary Biomarkers

Session Information

Date: Wednesday, November 16, 2016

Title: Vasculitis IV: Diagnosis and Assessment of Disease Activity

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose: Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples from patients with new diagnoses of ANCA-associated vasculitis (AAV) and highly active renal disease. This study focused on use of usCD163 in detection of the more clinically relevant state of mild renal flare, and to compare the performance of usCD163 directly to another proposed biomarker, urinary monocyte chemoattractant protein 1 (uMCP-1).

Methods: Patients with samples obtained during active AAV (n=88) with evidence of active renal involvement (n=34) or without current renal involvement (n=54) were identified within a serially-sampled longitudinal multi-center cohort. In addition, paired remission samples and samples from those with remission AAV were also identified. Creatinine-normalized usCD163 and uMCP-1 levels were measured simultaneously by ELISA. usCD163 and uMCP-1 levels during a flare of active renal vasculitis were compared to levels during remission or during active non-renal AAV.

Results: Samples were available from 320 study visits including times of active renal vasculitis (n=34), remission (n=278), and active extra-renal vasculitis (n=54). Mean creatinine levels in remission and during renal flare were 1.01 mg/dl (SD 0.47) and 1.43 mg/dl (SD 0.61), respectively. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extra-renal vasculitis, with median values of 5.2 pg/mmol (interquartile range (IQR) 1.5-19.4pg/mmol), 0.8pg/mmol (0.1-2.5pg/mmol) and 0.6pg/mmol (0.1-1.6 pg/mmol), respectively (p<0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extra-renal vasculitis, with median values of 12.6pg/mmol (IQR 5.1-25.1), 2.4pg/mmol (4.1-8.5) and 3.1pg/mmol (1.2-5.5), respectively (p<0.001, Figure 1). The optimal diagnostic cut-offs for usCD163 and uMCP-1 were 1.2pg/mmol and 10.0pg/mmol, respectively. Using these cut-offs, the specificities of usCD163 and uMCP-1 in identifying renal vasculitis flare were 91% and 80%, respectively. Specificities were the same whether comparison was made to remission or to active non-renal AAV. The corresponding sensitivities with these cut-offs were 68% and 64%. The addition of uMCP-1 to usCD163 did not further increase the specificity. usCD163 and uMCP-1 levels were moderately correlated (r² =0.36, p<0.001), suggesting that additional information may be obtained from sequential modelling that incorporates traditional biomarkers.

Conclusion: In the context of subtle renal vasculitis flare, both usCD163 and uMCP1 levels are tightly associated with active renal disease in AAV. Figure 1. Urinary sCD163 and MCP-1 levels in ANCA-associated vasculitis, stratified by disease activity

Disclosure: S. M. Moran, None; M. Ryan, None; P. A. Monach, Genentech and Biogen IDEC Inc., 2,Bristol-Myers Squibb, 2,MedScape, 5,GlaxoSmithKline, 2,Vasculitis Foundation Board of Directors, 6,Editorial Board of Arthritis and Rheumatology, 6; D. Cuthbertson, None; S. Carette, Genentech and Biogen IDEC Inc., 2,GlaxoSmithKline, 2; J. Dunne, None; G. S. Hoffman, None; N. A. Khalidi, Roche Pharmaceuticals, 2,Bristol-Myers Squibb, 2; C. L. Koening, None; C. A. Langford, Genentech and Biogen IDEC Inc., 2,GlaxoSmithKline, 2,Bristol-Myers Squibb, 2; C. A. McAlear, None; L. W. Moreland, None; C. Pagnoux, None; P. Seo, None; U. Specks, Genentech, 5; A. G. Sreih, Alexion Pharmaceuticals, Inc., 1,Bristol-Myers Squibb, 2,Celgene, 2,Chemocentryx, 2,Roche Pharmaceuticals, 2,GlaxoSmithKline, 2,Kropp and Partners, 5; S. R. Ytterberg, Sanofi-Aventis Pharmaceutical, 5; L. Zgaga, None; P. A. Merkel, Bristol Myers Squibb, 2,CaridianBCT, 2,Celgene, 2,Chemocentryx, 2,Genentech/Roche, 2,GlaxoSmithKline, 2,Kypha, 2,Bristol-Myers Squibb, 5,Chemocentryx, 5,Genentech/Roche, 5,GlaxoSmithKline, 5,PrinicipioBio, 5,Auven, 5,Proteon Therapeutics, 5; M. A. Little, None.

To cite this abstract in AMA style:

Moran SM, Ryan M, Monach PA, Cuthbertson D, Carette S, Dunne J, Hoffman GS, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Zgaga L, Merkel PA, Little MA. Utility of Measurements of Urinary Soluble CD163 & MCP-1 in the Identification of Subtle Renal Flares in ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utility-of-measurements-of-urinary-soluble-cd163-mcp-1-in-the-identification-of-subtle-renal-flares-in-anca-associated-vasculitis/. Accessed .

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