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Abstract: SA-PO456

Evaluation of Urinary C5b-9 as a Biomarker of Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Benoit, Stefanie W., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Davies, Stella M., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Kathman, Thelma, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Patel, Jay, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Tepe, Melinda, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Lane, Adam, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Dixon, Bradley P., Children's Hospital of Colorado, Aurora, Colorado, United States
Background

Thrombotic microangiopathy (TMA) affects 39% of pediatric hematopoietic stem cell transplant (HSCT) patients. Renal involvement, characterized by hypertension, proteinuria, and kidney injury, may be confounded by the side effects of corticosteroids and calcineurin inhibitors, and highly sensitive and specific biomarkers for HSCT TMA are currently lacking. Urinary C5b-9 (uMAC) is associated with disease activity in other forms of TMA such as preeclampsia. However, complement activation has been demonstrated in vitro when plasma is acidified by mixing with urine. We hypothesized that uMAC would be associated with the diagnosis of HSCT TMA, but potentially confounded by BK cystitis.

Methods

uMAC was measured prospectively in 80 consecutive pediatric allogeneic HSCT patients weekly from Days 0 – 35, and Days 48, 60, and 100 using a commercial ELISA clinically validated for use with urine. Association of uMAC with patient, primary disease, and HSCT characteristics was assessed. We then analyzed the association between the clinical outcomes of measurable uMAC, hematuria, BK viremia, and BK cystitis with the diagnosis of TMA.

Results

48 patients had at least one uMAC >0ng/mL. There were no patient, primary disease, and HSCT characteristics associated with having measurable uMAC. In univariate analysis, TMA was associated with uMAC (p=0.04), hematuria (p<0.001), BK viremia (p<0.01), and BK cystitis (p<0.01). In multivariate analysis, uMAC was no longer associated with TMA (p=0.94), whereas BK viremia (p<0.01) and hematuria (p<0.05) maintained their association with TMA.

Conclusion

uMAC is not associated with HSCT TMA. uMAC is confounded by hematuria, which may have implications for its use and interpretation in other disease processes. Unexpectedly, hematuria demonstrated a strong association with TMA diagnosis in HSCT patients, perhaps suggesting its utility as an additional diagnostic criterion in establishing the diagnosis of TMA.