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Kidney Week

Abstract: PO0188

Urine Proteomics Among Children Developing AKI After Hematopoietic Stem Cell Transplant (HCT): A Pilot Study

Session Information

  • AKI Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Levy Erez, Daniella, Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Fazelinia, Hossein, Proteomics Core, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Ding, Hua, Proteomics Core, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Spruce, Lynn, Proteomics Core, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Laskin, Benjamin L., Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Sullivan, Kathleen E., Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
Background

AKI is common after HCT and contributes to high morbidity and mortality. Understanding the mechanisms of injury is essential to develop targeted therapies. Our objective was to examine urinary proteins among children after HCT to provide insights into the pathophysiology of AKI in a population whose immune system is newly developing.

Methods

Children (>2 years old) undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort had urine collected at baseline and monthly for the 4 months post HCT. Six patients were selected for pilot proteomic analysis (age 7-19 years, median 10 years, 66% male, 3 with AKI, 3 without AKI). Stored urine samples were tested pre-HCT and at 1 and 4 months post-HCT. Samples were tested with liquid chromatography/tandem mass spectrometry with data-independent acquisition. Proteins were assigned and intensities compared between AKI and controls using t-tests at p<0.05. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value compared to baseline.

Results

At 1 month post-HCT, 143 proteins were found distinct among the urine of children with AKI(n=3) compared to those without AKI (n=3). Pathway enrichment analysis linked these proteins to cell cycle and ubiquitous pathways. The 4 month time point resulted in identification of 67 proteins which were differentially expressed between AKI and control groups. These proteins were mostly involved in immune regulation. In both groups, unsupervised hierarchical clustering perfectly segregated the subjects based on AKI or control status (Figure).

Conclusion

The urinary proteomic fingerprint is distinct after AKI and are mostly cell cycle proteins in early AKI (first month) and immune mediated at 4 months, when most patients are fully engrafted. Additional studies are needed to define and understand the specific pathways.

Urine proteomics comparing AKI and controls at 1 and 4 months.

Funding

  • Private Foundation Support