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Abstract: TH-PO081

Olfactomedin 4 as a Loop of Henle-Specific AKI Biomarker That Predicts Furosemide Response

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical‚ Outcomes‚ and Trials

Authors

  • Hasson, Denise Claire, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Krallman, Kelli A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Zhang, Bin, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Vandenheuvel, Katherine A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Menon, Shina, Seattle Children's Hospital, Seattle, Washington, United States
  • Kempton, Kristalynn May, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Devarajan, Prasad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Goldstein, Stuart, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Alder, Matthew N., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Acute kidney injury (AKI) is associated with bad outcomes. Olfactomedin 4 (OLFM4) is a glycoprotein expressed in neutrophils and stressed epithelial cells. In septic animals, OLFM4 expression localized to the loop of Henle (LOH). OLFM4 null septic murine pups had higher renal cell apoptosis and plasma creatinine. We hypothesized urine OLFM4 (uOLFM4) will increase in patients with AKI, and if localized to the LOH in humans, predict furosemide response.

Methods

A retrospective study used urine samples based on AKI and sepsis status from day 1 of intensive care unit (ICU) admission from a single center repository. A prospective validation study used convenience urine from ICU patients (pts). uOLFM4 was tested with a custom bead based Luminex immunoassay. Demographic, lab data (NGAL), were collected from the medical record. AKI was defined by KDIGO stage 2-3 (severe) creatinine criteria. Immunofluorescence on biopsies from pts with kidney injury was performed with antibodies for uromodulin, OLFM4. Furosemide response was >3 mL/kg/hr of urine made in 4 hrs after 1mL/kg IV furosemide given for clinical need. Mann Whitney U, Kruskal Wallis tests were performed, and linear mixed modeling accounted for lack of independence.

Results

Pts with severe AKI had higher uOLFM4 (retrospective, n=36, p=0.04; prospective, n=178, p=0.007). Although uOLFM4 and urine NGAL correlated (r 0.40, p=<0.0001), some pts had high uOLFM4 and low NGAL and vice-versa. On biopsy, OLFM4 signal colocalized with uromodulin, suggesting OLFM4 localizes to human LOH. uOLFM4 was higher in pts who were unresponsive to furosemide (p=0.04), AUC 0.75 (95% CI, 0.60-0.90); NGAL was not.

Conclusion

Severe AKI is associated with increased uOLFM4. OLFM4 colocalized to human LOH; higher uOLFM4 associated with furosemide resistance. OLFM4 may be a novel LOH-specific AKI biomarker that warrants further testing to determine whether it may enhance identification of pts likely to benefit from early kidney replacement therapy.

Funding

  • Other NIH Support