By Karen Blum
Originally published by our sister publication Pharmacy Practice News
Measuring the urinary biomarkers neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) may be useful predictive tools alone or in combination to detect acute kidney injury (AKI) in populations such as critically ill children receiving vancomycin, according to a study presented at the 2022 ACCP Global Conference on Clinical Pharmacy, in San Freancisco.
If assays for these biomarkers are eventually approved by the FDA, the tests may help clinicians detect and prevent further renal damage in these vulnerable AKI patients, the investigators noted.
In the single-center, prospective, clinical observational cohort study, Autumn Spyhalsky, a PharmD and MS candidate at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, and five pharmacist colleagues studied the ability of these biomarkers to predict AKI in 48 pediatric patients aged 0 to 18 years who were admitted to the pediatric ICU at John R. Oishei Children’s Hospital, in Buffalo, N.Y., and given vancomycin.
The researchers used enzyme-linked immunosorbent assays to measure the biomarkers in three urine specimens collected during the patients’ admissions: a baseline measure within six hours of the first vancomycin dose; a second specimen 18 to 24 hours after the baseline specimen was collected; and a third specimen 24 to 36 hours after the baseline collection. AKI was defined as a 50% or greater increase in serum creatinine from baseline within the first seven days of vancomycin initiation. Investigators also performed receiver operating characteristic curve (ROC) analyses to evaluate the predictive performance of the biomarkers in detecting AKI.
“We selected the critically ill [pediatric] population because we know that up to a quarter of those patients will go on to develop AKI,” Ms. Spyhalsky told Pharmacy Practice News. “Specifically, we chose to evaluate those being treated with vancomycin because it is a first-line agent for the treatment of MRSA [methicillin-resistant Staphylococcus aureus], and it is also commonly associated with AKI, as it is a nephrotoxic lipopeptide antibiotic.”
During the first 72 hours of vancomycin treatment, uNGAL and uKIM-1 increased more in children who developed AKI (n=8) than those who did not (n=40). Specifically, uKIM-1 measured at 6,060+11,165 pg/mL in patients with AKI versus 340+542 pg/mL in patients without AKI, and uNGAL measured at 713,196+1,216,474 pg/mL in patients with AKI versus 16,101+37,812 pg/mL in patients without AKI. These results were presented in a poster (Sat-20).
In addition, the area under the curve of the ROC analyses increased throughout the course of admission, “and so that really tells us that throughout the course of admission, these biomarkers are better able to predict the onset of AKI,” Ms. Spyhalsky said. “This is really important in the field, because we may be able to employ specific modalities to be able to prevent further renal damage, because we know that AKI is independently associated with worse outcomes.”
Assays for these biomarkers lack FDA approval for diagnostics in the United States, but other published preclinical and clinical studies have successfully advocated for these biomarkers to be able to detect AKI in an earlier manner (by up to 48 hours) than serum creatinine in urinary output, she said.
“The main takeaway message for pharmacists is to recognize the drawbacks of serum creatinine in urinary output because it has a delayed ability in being able to detect AKI,” Ms. Spyhalsky said. It is also important, she stressed, “to keep an open mind to biomarkers that are up and coming in the field and stay on top of the clinical literature that exists to be able to use those once they come to fruition.”
Ms. Spyhalsky reported no relevant financial disclosures.
