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Abstract: FR-PO192

Pro-Inflammatory Urinary mRNA Profile in Allogeneic Stem Cell Transplant Patients With AKI

Session Information

Category: Onconephrology

  • 1600 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
  • Clurmaan, Annelie G., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Gerardine, Supriya, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Scordo, Michael, 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
  • 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 (allo-HCT) is an effective treatment for hematologic malignancies. However, allo-HCT has risk of acute kidney injury (AKI) in as many as 80% of patients within the first 100 days. The etiology of AKI is multifactorial but experimental studies suggest a role for immune mediated mechanisms which may have therapeutic implications. We hypothesized that the urinary cell mRNA expression of HCT recipients that develop AKI has higher levels of mRNA for genes associated with inflammation and tubular injury compared to those without AKI.

Methods

We prospectively studied a cohort of patients undergoing their first allo-HCT at MSKCC. Urine collections were performed at baseline, weekly while inpatient and every 3 weeks until day 100. AKI was defined as > 7-day elevation of > 1.5x baseline serum creatinine. Urine samples closest to time of AKI and matched samples from patients without AKI were analyzed. Absolute quantification of a panel of mRNAs (T cell marker CD3e, proinflammatory chemokine CXCL10/IP10, tubular markers NKCC2, E-cadherin, VIM, and TGFb1) and 18SrRNA were assessed in the urinary cells by RT-qPCR assay. We calculated the validated CTOT-04 (Suthanthiran et al, N Engl J Med 2013) urinary cell biomarker score.

Results

A total of 12 urine samples were analyzed, 6 patients with AKI and 6 patients without AKI. The table below shows the AKI group had a higher median absolute copy number per microgram of mRNA for all the genes tested.

Conclusion

Allo-HCT recipients who develop AKI have a urinary cell mRNA profile suggestive of pro-inflammatory mechanisms of injury based on higher level of expression of inflammatory and tubular genes. Ongoing analysis of additional prospectively collected samples will allow further characterization of this profile and may result in novel non-invasive tests for identification of patients at high risk for AKI and precision therapeutics.

Urinary Cell Levels of mRNAs in HCT Recipients With AKI Versus Time Matched Controls Without AKI
 18S rRNATGFB1CD3eIP10E-cadherinNKCC2VimentinCTOT-04 - Three Gene Signature Score
(Allograft Rejection Score: -1.213)
AKI Group



(copies/μg total RNA,
Median [IQR]; n=6)
3.32E+09

(1.41E+09 - 6.99E+09)
21100

(11618 – 35900)
1220

(383.5 - 4673)
1340

(668.8 - 8593)
6530

(656.0 - 16215)
1875

(786.5 - 5303)
331000

(52805 - 980500)
-0.9900

(-1.645 to -0.1125)
No AKI Group



(copies/μg total RNA,
Median [IQR]; n=6)
1.69E+09

(3.38E+08 - 3.40E+09)
3810

(1250 - 16475)
180.8

(12.5 - 16288)
721

(44.68 - 14280)
1580

(1031 - 3333)
1424

(209.5 - 4478)
29900

(15305 - 151500)
-2.416

(-3.819 to 0.07425)
Fold Change
AKI / No AKI
1.96E+005.546.751.864.131.3211.12.44