Association between the levels of urinary cell cycle biomarkers and non-recovery of renal function among critically ill geriatric patients with acute kidney injury

Abstract

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2–3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p < 0.001), with the optimal threshold set at 0.81 (ng/mL)²/1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score.

Keywords:

• Acute kidney injury
• geriatrics
• IGFBP7
• intensive care unit mortality
• renal recovery
• TIMP-2

Acknowledgments

We thank Professor Li-Rong Liang at Beijing Lu-he Hospital for the statistical analysis. We also thank Medjaden Inc. for the scientific editing of this manuscript.

Authors’ contributions

LC contributed to urine collection, data interpretation, manuscript drafting, and critical revision. H-MJ, XZ, and Y-JJ contributed to urine collection and data interpretation and performed the statistical analysis. XX contributed to data collection and data interpretation. W-XL chaired the group, conceived and designed the study, performed statistical analysis, and contributed to data collection, interpretation, and critical manuscript revision. All authors reviewed the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The study was approved by the Human Ethics Committee of Beijing Chao-yang Hospital, Capital Medical University (Beijing, China) (No. 2018-117). Before participation, written informed consent was obtained from patients or their next of kin.

Data availability statement

All data generated and/or analyzed during this study are included in this published article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.