Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody-Mediated Kidney Allograft Rejection
Marion Rabant, Lucile Amrouche, Xavier Lebreton, Florence Aulagnon, Aurélien Benon, Virginia Sauvaget, Raja Bonifay, Lise Morin, Anne Scemla, Marianne Delville, Frank Martinez, Marc Olivier Timsit, Jean-Paul Duong Van Huyen, Christophe Legendre, Fabiola Terzi, Dany Anglicheau, Marion Rabant, Lucile Amrouche, Xavier Lebreton, Florence Aulagnon, Aurélien Benon, Virginia Sauvaget, Raja Bonifay, Lise Morin, Anne Scemla, Marianne Delville, Frank Martinez, Marc Olivier Timsit, Jean-Paul Duong Van Huyen, Christophe Legendre, Fabiola Terzi, Dany Anglicheau
Abstract
Urinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cell-mediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor-specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.
Keywords: antibody-mediated rejection; biomarker; kidney transplantation; noninvasive diagnosis.
Copyright © 2015 by the American Society of Nephrology.
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Source: PubMed