BACKGROUND: Macrophage infiltration and cytokine production are important in the pathogenesis of crescentic glomerulonephritis in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. The aim of this study was to investigate whether urinary levels of chemokines, monocyte chemoattractant protein-1 (MCP-1) and fractalkine, were useful tools for non-invasive assessment of renal vasculitis. METHODS: In a prospective study, concentrations of chemokines were measured in urine and serum samples using specific enzyme-linked immunosorbent assays, and related to the patients' clinical status. Renal expression of MCP-1 was studied by immunohistochemical staining of renal biopsies. RESULTS: Urinary levels of MCP-1 were significantly higher in patients with active (P<0.01) or persistent (P<0.05) renal vasculitis, in comparison with healthy volunteers, control patients, patients with inactive vasculitis and patients with extra-renal disease only. There were no differences in serum concentrations of MCP-1 between these groups. Reduction in urinary MCP-1 levels following treatment preceded the improvement of renal function by a median of 2 weeks. In one patient, rising urinary levels of MCP-1, despite immunosuppressive therapy, was associated with progression to severe renal failure. There were no differences in urinary fractalkine levels between the different groups of patients and controls. Immunohistology of renal biopsies from patients with crescentic glomerulonephritis showed increased staining for MCP-1 in glomerular and interstitial cells. Urinary MCP-1 levels correlated with glomerular, but not tubulointerstitial, macrophage infiltration (P<0.05). CONCLUSIONS: This study shows that measurement of urinary MCP-1, but not fractalkine, is a useful non-invasive technique for the assessment of renal involvement and monitoring the response to therapy in ANCA-associated vasculitis.
BACKGROUND: Macrophage infiltration and cytokine production are important in the pathogenesis of crescentic glomerulonephritis in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. The aim of this study was to investigate whether urinary levels of chemokines, monocyte chemoattractant protein-1 (MCP-1) and fractalkine, were useful tools for non-invasive assessment of renal vasculitis. METHODS: In a prospective study, concentrations of chemokines were measured in urine and serum samples using specific enzyme-linked immunosorbent assays, and related to the patients' clinical status. Renal expression of MCP-1 was studied by immunohistochemical staining of renal biopsies. RESULTS: Urinary levels of MCP-1 were significantly higher in patients with active (P<0.01) or persistent (P<0.05) renal vasculitis, in comparison with healthy volunteers, control patients, patients with inactive vasculitis and patients with extra-renal disease only. There were no differences in serum concentrations of MCP-1 between these groups. Reduction in urinary MCP-1 levels following treatment preceded the improvement of renal function by a median of 2 weeks. In one patient, rising urinary levels of MCP-1, despite immunosuppressive therapy, was associated with progression to severe renal failure. There were no differences in urinary fractalkine levels between the different groups of patients and controls. Immunohistology of renal biopsies from patients with crescentic glomerulonephritis showed increased staining for MCP-1 in glomerular and interstitial cells. Urinary MCP-1 levels correlated with glomerular, but not tubulointerstitial, macrophage infiltration (P<0.05). CONCLUSIONS: This study shows that measurement of urinary MCP-1, but not fractalkine, is a useful non-invasive technique for the assessment of renal involvement and monitoring the response to therapy in ANCA-associated vasculitis.
Authors: David R W Jayne; Annette N Bruchfeld; Lorraine Harper; Matthias Schaier; Michael C Venning; Patrick Hamilton; Volker Burst; Franziska Grundmann; Michel Jadoul; István Szombati; Vladimír Tesař; Mårten Segelmark; Antonia Potarca; Thomas J Schall; Pirow Bekker Journal: J Am Soc Nephrol Date: 2017-04-11 Impact factor: 10.121
Authors: Gunnar Tomasson; Michael Lavalley; Kahraman Tanriverdi; Javier D Finkielman; John C Davis; Gary S Hoffman; W Joseph McCune; E William St Clair; Ulrich Specks; Robert Spiera; John H Stone; Jane E Freedman; Peter A Merkel Journal: J Rheumatol Date: 2011-03-16 Impact factor: 4.666
Authors: Jason G Lieberthal; David Cuthbertson; Simon Carette; Gary S Hoffman; Nader A Khalidi; Curry L Koening; Carol A Langford; Kathleen Maksimowicz-McKinnon; Philip Seo; Ulrich Specks; Steven R Ytterberg; Peter A Merkel; Paul A Monach Journal: J Rheumatol Date: 2013-04-01 Impact factor: 4.666
Authors: A W S de Souza; W H Abdulahad; P Sosicka; J Bijzet; P C Limburg; C A Stegeman; M Bijl; J Westra; C G M Kallenberg Journal: Clin Exp Immunol Date: 2014-11 Impact factor: 4.330