Urinary CXCL10 Chemokine Is Associated With Alloimmune and Virus Compartment-Specific Renal Allograft Inflammation

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dc.contributor.authorHo, Julie
dc.contributor.authorSchaub, Stefan
dc.contributor.authorWiebe, Chris
dc.contributor.authorGao, Ang
dc.contributor.authorWehmeier, Caroline
dc.contributor.authorKoller, Michael
dc.contributor.authorHirsch, Hans
dc.contributor.authorHopfer, Helmut
dc.contributor.authorNickerson, Peter
dc.contributor.authorHirt-Minkowski, Patricia
dc.date.accessioned2020-09-11T21:45:43Z
dc.date.available2020-09-11T21:45:43Z
dc.date.issued2018-03
dc.date.submitted2020-09-11T19:02:08Zen_US
dc.description.abstractBackground: Urinary CXCL10 is a promising biomarker for subclinical tubulointerstitial inflammation, but limited data exists regarding its correlation with (micro)vascular inflammation. Furthermore, no study has evaluated whether concomitant serum CXCL10 improves the discrimination for (micro)vascular inflammation. Methods: We investigated whether serum/urinary CXCL10 reflect subclinical inflammation within different renal compartments. Patients (n=107) with 107 surveillance biopsies were classified as: normal histology (n=47), normal histology with BKV or CMV viremia (n=17), moderate-severe tubulointerstitial inflammation (tubulitis ≥2, n=18), pure microvascular inflammation (n=15), and isolated v-lesions (n=10). Serum and urinary CXCL10 ELISA was performed. An independent validation set was evaluated for urine CXCL10: normal histology (n=14), normal histology with BKV or CMV viremia (n=19), tubulitis ≥2 (n=15), pure microvascular inflammation (n=41), and isolated v-lesions (n=14). Results: Elevated urinary CXCL10 reflected inflammation within the tubulointerstitial (urinary CXCL10/creatinine 1.23ng/mmol vs. 0.46ng/mmol, p=0.02; AUC 0.69, p=0.001) and microvascular compartments (urinary CXCL10/creatinine 1.72ng/mmol vs. 0.46ng/mmol, p=0.03; AUC 0.69, p=0.02) compared to normal histology. Intriguingly, urinary CXCL10 was predominantly elevated with peritubular capillaritis, but not glomerulitis (p=0.04). Furthermore, urinary CXCL10 corresponded with BKV, but not CMV viremia (p=0.02). These urine CXCL10 findings were confirmed in the independent validation set. Finally, serum CXCL10 was elevated with BKV and CMV viremia but was not associated with microvascular or vascular inflammation (p≥0.19). Conclusions: Urinary CXCL10 reflects subclinical inflammation within the tubulointerstitial and peritubular capillary spaces, but not the vascular/systemic compartments; this was consistent with BKV (tubulointerstitial) and CMV viremia (systemic). Serum CXCL10 was not a useful marker for (micro)vascular inflammation.en_US
dc.description.sponsorshipElse Kröner-Fresenius-Stiftung (grant 2012_A255). Astellas foundation for biomedical research (grant CH-02-RG-248). Canadian Institutes of Health Research (grant 287559). CIHR New Investigator Salary Award. Flynn Family Chair in Renal Transplantation.en_US
dc.identifier.citationTransplantation 102(3): 521-529, 2018en_US
dc.identifier.doi10.1097/TP.0000000000001931
dc.identifier.issn0041-1337/18/10203-0521
dc.identifier.urihttp://hdl.handle.net/1993/35050
dc.language.isoengen_US
dc.publisherWolters Kluwer Health Incen_US
dc.rightsopen accessen_US
dc.subjectbiomarkeren_US
dc.subjectrejectionen_US
dc.subjectCXCL10en_US
dc.titleUrinary CXCL10 Chemokine Is Associated With Alloimmune and Virus Compartment-Specific Renal Allograft Inflammationen_US
dc.typeresearch articleen_US
local.author.affiliationRady Faculty of Health Sciencesen_US
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