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Urine Cell-Free Supernatant Metabolites Diagnostic of Antibody Mediated Rejection in Kidney Allografts.

M. Alkadi,1 J. Lee,1 D. Dadhania,1 T. Muthukumar,1 C. Snopkowski,1 C. Li,1 S. Salvatore,1 S. Seshan,1 K. Suhre,2 M. Suthanthiran.1

1Weill Cornell Medicine, NY
2Weill Cornell Medical College-Qatar, Doha, Qatar.

Meeting: 2016 American Transplant Congress

Abstract number: 124

Keywords: Antibodies, Kidney transplantation, Rejection

Session Information

Date: Sunday, June 12, 2016

Session Name: Concurrent Session: Kidney AMR: Making the Diagnosis

Session Time: 4:30pm-6:00pm

 Presentation Time: 5:42pm-5:54pm

Location: Veterans Auditorium

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Introduction:

Urine cell-free supernatant metabolite profiles provide a unique opportunity to interrogate intra-graft processes and have distinguished acute cellular rejection from no rejection in the Clinical Trials in Organ Transplantation-04 study. Antibody mediated rejection (AMR) has emerged as a major cause of kidney allograft failure; however, the critical issue of urine metabolite profiles as diagnostic of AMR in kidney transplantation has not been investigated.

Methods:

We performed untargeted metabolite profiling of 141 urine cell-free supernatants matched to biopsy-proven AMR (N=20 specimens from 20 patients), acute tubular injury (ATI) (N=61 specimens from 56 patients), or normal biopsy result (NORMAL) (N=60 specimens from 29 patients). We evaluated whether the previously discovered diagnostic biomarkers of ACR (3-sialyllactose [3SL], xanthosine [X], quinolinate [QUIN], and X-16397, 3SL/X, and QUIN/X16397) distinguish: (i) patients with AMR biopsies from the patients with ATI biopsies and (ii) patient with AMR biopsies from patients with normal biopsies.

Results:

Osmolarity-corrected 3SL, QUIN, and X-16397 were significantly higher in the AMR Group than in the NORMAL Group (see Table 1; P values: 0.02, <0.0001, and 0.05, respectively). Osmolarity-corrected QUIN was also significantly higher in the AMR Group than in the ATI Group (P value 0.02). The ratio of QUIN/X-16397 distinguished the AMR group from the Normal Group (median 2.31 vs. 1.54, P value 0.006) and AMR group from the ATI Group (median 2.31 vs. 1.39, P value 0.003) (Table 1).

Conclusion:

With the use of a comprehensive combination of nontargeted LC-MS/MS and GC-MS based metabolomics platforms, we demonstrate that the relative abundance of quinolinate and the ratio of quinolinate to X-16397 distinguish patients with AMR biopsies from patients with Normal biopsies and patients with AMR from patients with ATI biopsies. Quinolinate, a product of tryphtophan metabolism, by serving as a precursor for the biogenesis of NAD+, may help meet the metabolic demands of immune cells involved in allograft rejection.

CITATION INFORMATION: Alkadi M, Lee J, Dadhania D, Muthukumar T, Snopkowski C, Li C, Salvatore S, Seshan S, Suhre K, Suthanthiran M. Urine Cell-Free Supernatant Metabolites Diagnostic of Antibody Mediated Rejection in Kidney Allografts. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Alkadi M, Lee J, Dadhania D, Muthukumar T, Snopkowski C, Li C, Salvatore S, Seshan S, Suhre K, Suthanthiran M. Urine Cell-Free Supernatant Metabolites Diagnostic of Antibody Mediated Rejection in Kidney Allografts. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/urine-cell-free-supernatant-metabolites-diagnostic-of-antibody-mediated-rejection-in-kidney-allografts/. Accessed March 9, 2021.

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