Metals in urine may serve as early biomarkers for AKI
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Urinary cadmium, copper and zinc may be biomarkers for early detection of AKI, according to data published in Kidney International Reports.
Further, researchers of the study found urinary trace metals are stable at room temperature and unaffected by comorbidity, proteinuria, sex or age.
“Various urine and blood biomarkers of early AKI have been described, but none has all characteristics of an ideal biomarker — rapid, easy and cheap testing; high sensitivity and specificity; and ability to risk stratify and predict clinical outcomes. There remains need for a cost-effective biomarker for early detection of AKI in at-risk patients,” David S. Gardner, BSc PhD, DSc, a professor of physiology at the University of Nottingham in the United Kingdom, and colleagues wrote. “We previously reported a porcine model of ischemia-reperfusion AKI which replicates many features of human AKI. Using this model, we identified urinary cadmium (Cd), copper (Cu) and iron (Fe) as early biomarkers of AKI.”
Following the porcine model, researchers moved forward to examine the biomarkers in two observational cohort studies of patients at high risk of AKI. A total of 151 patients were undergoing cardiac surgery and 150 patients were admitted to a general ICU.
Researchers took urine samples at baseline from the patients undergoing cardiac surgery, then measured samples (5 mL to 10 mL) after 1, 2, 3, 4, 8 and 24 hours after the operation. Additionally, researchers took daily blood samples after the operation to determine serum creatinine (sCr).
Researchers followed a similar method among patients in the ICU cohort but considered ICU admission baseline.
Among the ICU cohort, Cd had an area under the receiver operating characteristic curve (AUROC) of 0.70 and a negative predictive value (NPV) of 89%, whereas Cu had an AUROC of 0.76 and an NPV of 91%. Researchers noted that urinary zinc (Zn) correlated with AKI among the human ICU cohort, but not in the pig study.
Similarly, among the cardiac surgery cohort, Zn had an AUROC of 0.77 and an NPV of 91%. Urinary Cd and Cu had poor AUROC but an NPV of 93 % and 95%, respectively.
“We have revealed, for the first time, that the [trace elements] Cd, Cu and Zn are potentially useful clinical biomarkers for early detection of AKI. Their concentrations in the urine rise significantly within an hour of cardiac surgery and are significantly elevated on admission to the ICU in adults who subsequently develop AKI defined by [Kidney Disease: Improving Global Outcomes] KDIGO sCr criteria,” Gardner and colleagues wrote.
Analyses revealed that the urinary biomarkers could be placed in room temperature for at least 14 days and were not affected by other confounding factors, like chronic kidney disease.
“This study is the culmination of 10 years work at Nottingham and is an example of how collaboration between animal scientists, clinicians and local companies can each utilize their expertise to make new and unique discoveries. It is our hope that the research can now be developed further by industry to truly move these discoveries from lab bench to bedside,” Gardner said in a press release.
Reference:
Metals found in people’s urine could detect acute kidney injury in very early stages, says new study. https://www.eurekalert.org/news-releases/954343. Published May 30, 2022. Accessed June 15, 2022.
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