The urinary levels of CXCL9 and CXCL10 can noninvasively diagnose T cell-mediated rejection (TCMR) of renal allografts. Their performance as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown.

We investigated urinary CXCL9 and CXCL10 levels in 244 renal allograft recipients with 281 indication biopsies. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosticating ABMR.

Urinary CXCL9 and CXCL10 levels, normalized (CXCL9: Cr and CXCL10: Cr ratios) or not to urine creatinine levels, correlated well with the extent of tubulointerstitial (i+t score, all P<0.0001) and microvascular (g+ptc score, all P<0.0001) inflammation. In addition to be diagnostic of TCMR ([area under the curve {AUC}]=0.80; 95% confidence interval [CI]: 0.68-0.92; P=7.1E-04), CXCL10: Cr also noninvasively diagnosed ABMR with high accuracy (AUC=0.76; 95% CI: 0.69-0.82; P=1.5E-10) even in the total absence of associated tubulointerstitial inflammation (AUC=0.70; 95% CI: 0.61-0.79; P=4.8E-5). Although the mean fluorescence intensity of the immunodominant donor-specific antibody (iDSA) noninvasively diagnosed ABMR (AUC=0.75; 95% CI: 0.68-0.82; P=5.6E-12), combining the urinary CXCL10: Cr ratio with iDSA levels significantly improved the noninvasive diagnosis of ABMR (AUC=0.83; P=2.5E-15).

At time of ABMR, urinary CXCL10: Cr ratio was independently associated with an increased risk of graft loss.

Urinary CXCL10: Cr ratio is not only associated with tubulointerstitial but also with microvascular inflammation of the renal allograft. Compared with conventional assessments, the addition of the urinary CXCL10: Cr ratio in the evaluation of kidney transplant recipients with ABMR improves noninvasive diagnosis and stratification of patients at high risk for graft loss.

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