Abstract: TH-PO918

A Multi-Platform Approach for the Noninvasive Differential Diagnosis of Acute Dysfunction of the Kidney Allograft

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medical College, New York, New York, United States
  • Li, Carol Y., Weill Cornell Medical College, New York, New York, United States
  • Snopkowski, Catherine, Weill Medical College of Cornell University, New York, New York, United States
  • Yang, Hua, Weill-Cornell , New York, New York, United States
  • Perry, Liana S., Weill Cornell Medicine, New York, New York, United States
  • Salvatore, Steven, Weill Cornell Medical College, New York, New York, United States
  • Lee, John Richard, Weill Cornell Medicine-, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medical Center, New York, New York, United States
  • Dadhania, Darshana, Weill Cornell Medical College, New York, New York, United States
Background

We tested a multi-platform approach for the noninvasive differential diagnosis of acute dysfunction of the kidney allograft.

Methods

We studied 118 kidney transplant recipients with acute kidney allograft dysfunction. All had kidney allograft biopsy done that were studied by light, immuno and electron microscopy and were stained for C4d and SV40 large T antigen. Serum samples were obtained at the time of biopsy for detecting donor-specific anti-HLA antibodies by Luminex single antigen bead assay (DSA). Urine specimen was obtained at the time of biopsy for urinary cell mRNA profiling. Using preamplification enhanced real-time quantitative PCR assays, we quantified CXCL10 mRNA, and CD3e mRNA levels as well as 18S rRNA levels and expressed their abundance as copies/υg total RNA. Using these three transcript levels, we derived our 3-gene molecular signature (Suthanthiran et al. N Engl J Med 2013). We also quantified BK virus VP1 mRNA levels (Ding et al. Transplantation 2002) in the biopsy matched urinary cells.

Results

Among the 118 kidney transplant recipients, biopsy revealed acute cell-mediated rejection (ACR) in 22 biopsies, acute antibody-mediated rejection (AMR) in 10 biopsies, acute tubular injury (ATI) in 49 biopsies, or polyomavirus nephropathy (PVAN) in 37 biopsies. All biopsies classified as ACR, AMR and ATI were negative for SV40.

The first step in the differential diagnosis was the identification of the patients based on DSA. This identified the 10 patients with AMR. The next step in the differential diagnosis was the measurement of urinary cell VP1 mRNA. Based on our previously published cutoff value of 6.5 x 108 BKV VP1 mRNA copy number, 77 of the 81 patients who did not have PVAN were identified and excluded, with a negative predictive value (NPV) of 95%. In the final step, ACR and ATI were distinguished based on our previously published cutoff value of -1.213 of the 3-gene signature. Based on this cutoff value, the NPV was 83%.

Conclusion

A multi-platform approach, which involves testing DSA in the serum, BK virus VP1mRNA in urinary cells and the 3-gene signature in the urinary cells, offers a noninvasive method for the differential diagnosis of acute dysfunction of the kidney allograft with a high degree of accuracy.

Funding

  • Other NIH Support