From predictive association to decision-grade deployment: Refining the clinical role of urinary neutrophil gelatinase-associated lipocalin in acute kidney injury

Sir, We found the prospective cohort study assessing urinary neutrophil gelatinase-associated lipocalin (uNGAL) to predict severe acute kidney injury (AKI), utilizing both in-hospital mortality and renal replacement therapy (RRT) as a composite endpoint, with a 90-day outcome determination, to be of considerable interest.[1] The results continue to support the rationale for injury-specific biomarkers in helping to identify at-risk patients for AKI within clinical practice.[2] Nonetheless, in order to identify uNGAL as a decision-support tool, there are multiple items that must be addressed before moving away from its use solely as an association. The first consideration is the need for caution in interpreting composite endpoints such as this. Mortality and the initiation of RRT are unique clinical variables that are impacted by the severity of illness, clinical judgment, and institutional practice patterns. Presenting predictive performance separately for mortality and initiation of RRT, in addition to a composite outcome, will give added assistance in determining how well uNGAL performs clinically and improves its external validity. Second, the timing of uNGAL and its rate at which it rises or falls will greatly influence interpretations of kidney function of the uNGAL. Although NGAL represents an early indicator of tubular injury, a single collection of uNGAL will not reflect changes in kidney function over time, making it difficult to predict the severity of AKI and post-AKI complications, such as need for RRT.[3,4] In order to enhance the ability to predict AKI and post-AKI complications, the sample collection times and dates associated with the collection should be clearly stated in reports, which will allow for the identification of AKI and its associated complications to be better correlated with the uNGAL data collected. Next, clinical use of the Urology Nephrology Association (U.N.A.) requires clinical testing and validation of the U.N.A. Test. The variability of results between assays, dilution factors in urine, and the presence of other conditions (e.g., systemic inflammatory states) all impact the levels of U.N.A. present in a patient’s urine. Thus, clinical research to help clinicians’ decisions regarding the use of a U.N.A. Clinical research guiding the use of the U.N.A. test should report calibration statistics, discrimination indices, and predefined cutoff levels with corresponding confidence intervals, and where feasible, include decision curve analyses across clinically relevant thresholds to establish net clinical benefit.[3,4] Finally, the use of biomarkers in patient care must consider both feasibility and equity for patients with limited resources. This includes time, cost, laboratory services, and infrastructure and how the biomarkers will fit into the normal practice of clinical professionals. If the above factors are not clearly defined, the disparities of care related to AKI may continue to grow.[2,5] We propose a concise implementation framework outlining minimal reporting elements required to move uNGAL from prognostic association to clinical decision support. In conclusion, the study provides valuable evidence for the prognostic role of uNGAL in AKI.[1] Future investigations should focus on component-specific outcomes, kinetic profiling, calibration, and contextual feasibility to enable safe, equitable, and scalable implementation.[2–5] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.