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Abstract: SA-PO193

Urinary mRNA Profile in Recipients of Allogeneic Hematopoietic Cell Transplant with AKI

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Gutgarts, Victoria, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Jaffer Sathick, Insara, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
  • Nunez, Belen A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Jorgensen, Justine, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Abukoush Szczerba, Jessica M., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Mohan, Arianna, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Scordo, Michael, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background

Allogeneic hematopoietic cell transplantation (HCT) is curative for hematologic malignancies but carries risk of acute kidney injury (AKI) in up to 80% within the first 100 days. The etiology of AKI is multifactorial and includes non-immune (ischemic, drug toxicity) and immune-mediated mechanisms. Herein we investigated whether AKI in HCT recipients is associated with a urinary cell three-gene signature validated for kidney graft recipients to detect intragraft inflammation (Suthanthiran et al. NEJM 2013).

Methods

We prospectively collected urine specimens at baseline, weekly while inpatient, and monthly outpatient until day 100, from individuals who had their first allogeneic HCT at MSKCC. AKI was defined as > 7-day elevation of > 1.5x baseline serum creatinine. Urine samples closest to the time of AKI and time from transplant-matched samples from patients without AKI were analyzed. Using RT-qPCR assay, we measured the absolute quantity of panel of mRNAs (T cell marker CD3e, proinflammatory chemokine CXCL10/IP10, and cytokine TGFB1), and 18SrRNA in urinary cells and calculated the CTOT04 molecular signature.

Results

A total of 32 urine samples from 32 HCT recipients were analyzed; 16 with AKI and 16 without AKI. There was no statistically significant difference in the urinary cell molecular signature score between the group with AKI and without AKI (Table).

Conclusion

Our findings suggest that AKI in HCT recipients is not associated with increased trafficking of activated T cells through the kidney. Ongoing studies in our laboratory to profile the transcriptome of urinary cells in an unbiased way using RNA-sequencing would likely yield molecular clues to differentiate causes of AKI in this patient population that is difficult to biopsy.

Urinary Cell Levels of mRNAs in HCT Recipients With and Without AKI
Type of urinary cell transcriptAKI (N=16)
copies/μg total RNA
No AKI (N=16)
copies/μg total RNA
P value
18S rRNA1.55E+092.73E+090.82
TGFB1 mRNA1.25E+041.17E+040.60
CD3e mRNA3.53E+022.88E+020.80
CXCL10/IP10 mRNA3.94E+027.97E+020.52
CTOT04 Signature*-1.658-1.7930.82

*Validated molecular signature which correlates with kidney allograft-rejection (NEJM 2013 Jul 4;369(1):20-31).