Introduction

The value of urinary biomarkers has already been demonstrated in diagnosing acute rejection of the renal allograft, but confounding factors, which may interfere with their interpretation, have been poorly evaluated. Our goal was to evaluate the respective impact of urinary tract infection, reactivation of BK virus (BKV) and acute rejection on these biomarkers in order to optimize a noninvasive strategy of acute rejection assessment.

Methods

A total of 391 urine samples collected in 330 patients at time of graft biopsy and BKV blood nucleic acid testing were included. Urinary concentrations of the CXCL9 and CXCL10 proteins and of CD3ε, CXCL9, CXCL10, granzyme B and perforin mRNAs were quantified. Serum DSA status at the time of biopsy was also determined by luminex® single antigen.

Results

Our results confirmed the impact of urinary tract infection on the urinary chemokine protein levels (1,6±2,1 vs 0,7±1,8; p<0.005 for CXCL9 and 2,1±1,7 vs 0,8±2,0; p<0,001 for CXCL10). During reactivation of BKV, while viruria had minimal impact, concentrations of urinary RNA (mainly CXCL9, CXCL10 and granzyme B) and protein biomarkers were significantly increased and remained similar in viremic patients and patients with proven BKV nephritis. After elimination of these confounding factors and multivariate analysis, a 3-parameter diagnostic model (urinary CXCL9 and CXCL10 proteins and serum DSA status) best diagnosed acute rejection with an area under the curve of 0.81 (P=9.93E-13). Restricted to unstable patients at time of indication biopsy (n=168), the rejection prediction was even more robust with an AUC of 0.85 (P = 5.09E-12).

Conclusion

After exclusion of confounding factors such as urinary tract infection and BK virus viremia, a model associating CXCL9 and CXCL10 protein levels and DSA status can predict acute rejection with a high accuracy, especially in unstable patients. Moreover, BKV viremia and BKV nephritis have similar urinary inflammatory signature.

CITATION INFORMATION: Vermorel A., Devresse A., Tinel C., Sauvaget V., Morin L., Amrouche L., Rabant M., Anglicheau D. Diagnostic Value and Confounding Factors of Urinary Biomarkers in the Non-Invasive Screening of Renal Allograft Inflammation Am J Transplant. 2017;17 (suppl 3).

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