Urinary Trace Elements Are Biomarkers for Early Detection of Acute Kidney Injury

David S Gardner; Jennifer C Allen; Deborah Goodson; Daniel Harvey; Andrew Sharman; Henry Skinner; Adam Szafranek; John S Young; Elizabeth H Bailey; Mark A J Devonald

doi:10.1016/j.ekir.2022.04.085

Urinary Trace Elements Are Biomarkers for Early Detection of Acute Kidney Injury

Kidney Int Rep. 2022 Apr 29;7(7):1524-1538. doi: 10.1016/j.ekir.2022.04.085. eCollection 2022 Jul.

Authors

David S Gardner¹, Jennifer C Allen^{1

2}, Deborah Goodson², Daniel Harvey³, Andrew Sharman³, Henry Skinner⁴, Adam Szafranek⁴, John S Young⁵, Elizabeth H Bailey⁶, Mark A J Devonald^{7

8}

Affiliations

¹ Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.
² Renal and Transplant Unit, Nottingham University Hospitals NHS Trust, Nottingham, UK.
³ Critical Care Unit, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁴ Trent Cardiac Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
⁵ National Horizons Centre, Teesside University, Middlesbrough, UK.
⁶ School of Biosciences, University of Nottingham, Nottingham, UK.
⁷ Renal and Transplant Unit, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
⁸ Liverpool Centre for Cardiovascular Science, Liverpool, UK.

Abstract

Introduction: Acute kidney injury (AKI) is common in hospitalized patients and associated with poor outcomes. Current methods for identifying AKI (rise in serum creatinine [sCr] or fall in urine output [UO]) are inadequate and delay detection. Early detection of AKI with easily measurable biomarkers might improve outcomes by facilitating early implementation of AKI care pathways.

Methods: From a porcine model of AKI, we identified trace elements (TEs) in urine that were associated with subsequent development of AKI. We tested these putative biomarkers in 2 observational cohort studies of patients at high risk of AKI: 151 patients undergoing cardiac surgery and 150 patients admitted to a general adult intensive care unit (ICU).

Results: In adults admitted to the ICU, urinary cadmium (Cd) (adjusted for urinary creatinine) had area under the receiver operating characteristic curve (AUROC) 0.70 and negative predictive value (NPV) 89%; copper (Cu) had AUROC 0.76 and NPV 91%. In humans (but not pigs), urinary zinc (Zn) was also associated with AKI and, in the ICU study, had AUROC 0.67 and NPV 80%. In patients undergoing cardiac surgery, Zn had AUROC 0.77 and NPV 91%; urinary Cd and Cu had poor AUROC but NPV of 93% and 95%, respectively. In control studies, we found that the urinary biomarkers are stable at room temperature for at least 14 days and are not affected by other confounding factors, such as chronic kidney disease (CKD).

Conclusion: Urinary Cd, Cu, and Zn are novel biomarkers for early detection of AKI. Urinary trace metals have advantages over proteins as AKI biomarkers because they are stable at room temperature and have potential for cheap point-of-care testing using electrochemistry.

Keywords: acute kidney injury; biomarker; cadmium; copper; trace elements; zinc.