Gremlin, A Potential Urinary Biomarker of Anca-Associated Crescentic Glomerulonephritis

Autor: María E. Burgos, Graciela Valderrama, Jesús Egido, Sergio Mezzano, Constanza Saka, Daniel Carpio, Marta Ruiz-Ortega, Alejandra Droguett
Přispěvatelé: UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Kidney Glomerulus
lcsh:Medicine
Diabetic nephropathy
urologic and male genital diseases
Gastroenterology
chemistry.chemical_compound
Glomerulonephritis
0302 clinical medicine
Chronic allograft nephropathy
Medicine
Urinary
lcsh:Science
Aged
80 and over
Kidney diseases
Multidisciplinary
medicine.diagnostic_test
Middle Aged
Nephrology
Intercellular Signaling Peptides and Proteins
Female
Renal biopsy
Gremlin (protein)
Adult
medicine.medical_specialty
Medicina
Urinary system
Article
Antibodies
Antineutrophil Cytoplasmic
03 medical and health sciences
Gremlin renal
Internal medicine
Humans
Renal functional
Aged
Creatinine
business.industry
lcsh:R
CCL18
medicine.disease
030104 developmental biology
chemistry
Case-Control Studies
lcsh:Q
business
CD163
Biomarkers
030217 neurology & neurosurgery
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
Scientific Reports
Biblos-e Archivo. Repositorio Institucional de la UAM
instname
ISSN: 2045-2322
DOI: 10.1038/s41598-019-43358-5
Popis: Gremlin renal overexpression has been reported in diabetic nephropathy, pauci-immune crescentic glomerulonephritis and chronic allograft nephropathy and has been implicated in the pathophysiology of the progression of renal damage. However, it is unknown whether urinary Gremlin can be associated with renal functional status, renal biopsy findings and outcome. To examine these associations we studied 20 patients with ANCA+ renal vasculitis and very high urinary Gremlin (354 ± 76 ug/gCr), 86 patients with other glomerular diseases and moderately elevated urinary Gremlin (83 ± 14 ug/gCr) and 11 healthy controls (urinary Gremlin 11.3 ± 2.4 ug/gCr). Urinary Gremlin was significantly correlated with renal expression of Gremlin (r = 0.64, p = 0.013) observed in cellular glomerular crescents, tubular epithelial cells and interstitial inflammatory cells. Moreover, urinary Gremlin levels were correlated with the number of glomerular crescents (r = 0.53; p < 0.001), renal CD68 positive cells (r = 0.71; p < 0.005), tubulointerstitial fibrosis (r = 0.50; p < 0.05), and serum creatinine levels (r = 0.60; p < 0.001). Interestingly, Gremlin expression was colocalized with CD68, CD163 (monocyte/macrophage markers) and CCL18 positive cells. ROC curve analysis showed that the cutoff value of urinary Gremlin in glomerular diseases as 43 ug/gCr with 72% of sensitivity and 100% of specificity [AUC: 0.96 (CI 95% 0.92–0.99] (p < 0.001). For ANCA+ renal vasculitis the value of urinary Gremlin of 241 ug/gCr had 55% of sensitivity and 100% of specificity [AUC: 0.81 (CI 95% 0.68–0.94) (p < 0.001]. Based on these results we propose that urinary Gremlin represents a non-invasive biomarker in ANCA+ renal vasculitis, and suggest a role of Gremlin in the formation of crescents.
This work was supported by the Fondecyt 1160465 (Chile) Proyecto PAI 82140017, Fondecyt de Iniciación 111-40242, and Division of Nephrology, Universidad Austral Valdivia, Chile; Instituto de Salud Carlos III and Fondos FEDER European Union (PI014/0041, PI14/00386, PI17/01495, PI17/00119), Red de Investigación Renal (REDinREN; RD16/009), Comunidad de Madrid (NOVELRENCM (B2017/BMD3751)
Databáze: OpenAIRE
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