The role of biomarkers in early identification of acute kidney injury among non-critically ill patients

Abstract

Background

Prediction and/or early identification of acute kidney injury (AKI) and individuals at greater risk remains of great interest in clinical medicine. Acute kidney injury continues to be a common complication among hospitalized patients, with an incidence ranging from 6 to 58%, depending on the setting. Aim of this study was to determine the performance of Insulin-like growth factor binding protein-7 (IGFBP7), tissue metallopeptidase inhibitor 2 (TIMP2), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in early detection of AKI among non-critically ill patients.


Methods

In this prospective observational study at Mayo Clinic Hospitals in Rochester, Minnesota, USA, non-critically ill patients admitted from the emergency department between October 31st, 2016 and May 1st, 2018, who had an acute kidney injury (AKI) probability of 5% or higher were included. Biomarkers were measured in residual urine samples collected in the emergency department. The primary outcome was biomarker performance in predicting AKI development within the first 72 h.


Results

Among 368 included patients, the mean age was 79 ± 12 years, and 160 (43%) were male. Acute kidney injury occurred in 62 (17%) patients; 11.5% stage 1, 2.5% stage 2, and 3% stage 3. Twelve patients (3%) died during hospitalization and 102 (28%) within nine months after admission. The median uNGAL and IGFBP7-TIMP2 were 57 [20–236 ng/ml], and 0.3 [0.1–0.8], respectively. The C-statistic of uNGAL and IGFBP7-TIMP2 of > 0.3 and > 2.0 for AKI prediction were 0.56, 0.54, and 0.53, respectively. In a model where one point is assigned to each marker of AKI (elevated serum creatinine, IGFBP7-TIMP2 > 0.3, and uNGAL), a higher score correlated with higher nine-month mortality [OR of 1.32 per point (95% CI 1.02–1.71)].


Conclusion

Among non-critically ill hospitalized patients, the performance of uNGAL and IGFBP7-TIMP2 for AKI prediction within 72 h of admission was modest. This suggests a limited role for these biomarkers in AKI risk stratification among non-critically ill patients.

Key learning points
What was known
Acute kidney injury (AKI) is a common complication among hospitalized patients. It is associated with increased morbidity and mortality. Various clinical prediction models and biomarkers have been developed to identify patients in special populations (such as ICU and cardiac surgery) who are at risk of AKI and diagnose AKI early.
This study adds
The performance of the biomarkers uNGAL, TIMP-2, and IGFBP-7 in predicting AKI within 72 h of admission in non-critically ill patients was modest. However, these biomarkers were found to have a prognostic value for predicting 9-month mortality. One potential application of these biomarkers is identifying patients at higher AKI risk before exposing them to nephrotoxic agents.
Potential impact
This study provides evidence regarding the real-world performance of current FDA-approved biomarkers (uNGAL, TIMP-2, and IGFBP-7) for predicting acute kidney injury (AKI) within 72 h of hospital admission among noncritically ill patients. While the performance of these biomarkers for predicting short-term AKI was modest, they may have a prognostic value for predicting 9-month mortality.


Graphical abstract