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

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Ho, Julie
Schaub, Stefan
Wiebe, Chris
Gao, Ang
Wehmeier, Caroline
Koller, Michael
Hirsch, Hans
Hopfer, Helmut
Nickerson, Peter
Hirt-Minkowski, Patricia
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Wolters Kluwer Health Inc
Background: 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.
biomarker, rejection, CXCL10
Transplantation 102(3): 521-529, 2018