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Acute kidney injury biomarker olfactomedin 4 predicts furosemide responsiveness

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Abstract

Background

Acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. Olfactomedin 4 (OLFM4), a secreted glycoprotein expressed in neutrophils and stressed epithelial cells, is upregulated in loop of Henle (LOH) cells following AKI. We hypothesized that urine OLFM4 (uOLFM4) will increase in patients with AKI and may predict furosemide responsiveness.

Methods

Urine from critically ill children was collected prospectively and tested for uOLFM4 concentrations with a Luminex immunoassay. Severe AKI was defined by KDIGO (stage 2/3) serum creatinine criteria. Furosemide responsiveness was defined as > 3 mL/kg/h of urine output in the 4 h after a 1 mg/kg IV furosemide dose administered as part of standard of care.

Results

Fifty-seven patients contributed 178 urine samples. Irrespective of sepsis status or AKI cause, uOLFM4 concentrations were higher in patients with AKI (221 ng/mL [IQR 93–425] vs. 36 ng/mL [IQR 15–115], p = 0.007). uOLFM4 concentrations were higher in patients unresponsive to furosemide (230 ng/mL [IQR 102–534] vs. 42 ng/mL [IQR 21–161], p = 0.04). Area under the receiver operating curve for association with furosemide responsiveness was 0.75 (95% CI, 0.60–0.90).

Conclusions

AKI is associated with increased uOLFM4. Higher uOLFM4 is associated with a lack of response to furosemide. Further testing is warranted to determine whether uOLFM4 could identify patients most likely to benefit from earlier escalation from diuretics to kidney replacement therapy to maintain fluid balance.

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Data availability

The data underlying this article cannot be shared publicly for the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author.

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Acknowledgements

We would like to acknowledge the mentorship of our late division director, physician scientist, and pediatric intensivist, Dr. Hector Wong.

Funding

This study was supported by the following grants: MN Alder: National Institutes of Health K08GM12498 and P Devarajan and S Goldstein: National Institutes of Health P50DK096418.

Author information

Authors and Affiliations

  1. Division of Pediatric Critical Care Medicine, NYU Langone Health, Hassenfeld Children’s Hospital, 430 East 34Th Street, New York, NY, 10016, USA

    Denise C. Hasson

  2. Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Denise C. Hasson, Kelli Krallman, James E. Rose, Prasad Devarajan & Stuart L. Goldstein

  3. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Bin Zhang

  4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Bin Zhang, Prasad Devarajan, Stuart L. Goldstein & Matthew N. Alder

  5. Division of Critical Care, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Kristalynn M. Kempton & Matthew N. Alder

  6. Division of Anatomic and Clinical Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Paul Steele

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  1. Denise C. Hasson
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Contributions

DCH and MNA performed the study conception, data analysis, and interpretation and drafted and revised the manuscript. BZ performed the statistical analysis. KMK provided the critical study design organization and oversight. JES, KMK, and PS were responsible for the laboratory analyses. PD and SLG provided the study conception consultation and aided in editing/revising. All authors approved of the final version to be published.

Corresponding author

Correspondence to Denise C. Hasson.

Ethics declarations

Ethics approval

Study protocols were approved by and in accordance with the ethical standard of the CCHMC Institutional Review Board and in accordance with the 1964 Declaration of Helsinki. Given that urine samples were collected from an indwelling bladder catheter and considered to be discarded samples, the CCHMC IRB approved the TAKING FOCUS 2 study with a waiver of the need for patient or caregiver consent (IRB Number 2018–0724, PI Goldstein).

Competing interests

Financial interests: Stuart L Goldstein reports receiving personal fees from Baxter Healthcare, BioPorto Inc., CHF Solutions, Fresenius, MediBeacon, and Medtronic. Prasad Devarajan is a co-inventor on submitted patents for the use of NGAL as a biomarker for kidney injury.

Non-financial interests: MNA, DCH, SLG, and PD have patents for the use of OLFM4 as a renal injury biomarker.

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Hasson, D.C., Zhang, B., Krallman, K. et al. Acute kidney injury biomarker olfactomedin 4 predicts furosemide responsiveness. Pediatr Nephrol 38, 3153–3161 (2023). https://doi.org/10.1007/s00467-023-05920-2

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  • DOI: https://doi.org/10.1007/s00467-023-05920-2

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