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Kidney Week

Abstract: FR-PO1012

Urinary mRNA Signature of Graft vs. Kidney Disease in Hematopoietic Stem Cell Transplant Recipients Mirror Acute Rejection of Kidney Allograft

Session Information

  • Onco-Nephrology: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Lubetzky, Michelle L., Weill Medical College of Cornell University, New York, New York, United States
  • Cassidy, Michael F., Weill Medical College of Cornell University, New York, New York, United States
  • Snopkowski, Catherine, Weill Medical College of Cornell University, New York, New York, United States
  • Van besien, Koen, Weill Medical College of Cornell University, New York, New York, United States
  • Muthukumar, Thangamani, Weill Medical College of Cornell University, New York, New York, United States
Background

Acute kidney injury (AKI) is a complication of hematopoietic stem cell transplants (HSCT). GVKD can resemble acute rejection (AR) of kidney allograft, with inflammation in the intersititium and tubules. In GVKD, the graft inflammatory cells attack the host kidney (compared to host versus graft disease in AR). HSCT recipients have multiple comorbid conditions and performing kidney biopsies in patients with AKI can be challenging. Development of urinary mRNA profiles as noninvasive biomarkers has been validated as a robust tool for the noninvasive assessment of kidney allograft status. We hypothesized that urinary mRNA cells in patients with GVKD would mirror AR in kidney allograft and could serve as a tool for the noninvasive diagnosis of AKI.

Methods

We obtained urine specimens from 9 HSCT recipients; 3 with AKI and biopsy diagnosis of GVKD; 2 with AKI that resolved spontaneously; and 4 with normal kidney function. We isolated RNA from urinary cells and quantified the CTOT-04 three-gene molecular signature for AR (urinary cell mRNA levels of 18S, CD3e and IP10, Suthanthiran et al, N Engl J Med 2013) by RT-qPCR assay.

Results

Of the 3 patients with AKI who received kidney biopsy, 2 had significant interstitial inflammation that stained positive for CD3 and/or Granzyme B in the interstitium and tubules. Figure 1 demonstrates the mRNA levels and 3 gene signature of the 3 patients with GVKD as compared to 2 HSCT patients with AKI that resolved and 4 HSCT patients with normal kidney function. The cell signature of GVKD most clearly resembles that found in AR.

Conclusion

Our results demonstrate an immune inflammatory signature in the urine of patients with HSCT who have GVKD. Our pilot study further advances urinary cell mRNA profiling as a noninvasive tool for the differential diagnosis of AKI in HSCT recipients.