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Urinary cell cycle biomarkers for the prediction of renal non-recovery in patients with septic acute kidney injury: a prospective study

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Abstract

Background

Poor prognosis has been associated with the absence of renal recovery after acute kidney injury (AKI). This study aimed to investigate whether urinary biomarkers at 0 and 24 h could be used independently or in conjunction with a clinical model to predict renal non-recovery in septic AKI.

Methods

A prospective observational study was conducted to measure the urinary levels of insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) at the time of AKI diagnosis (0 h) and 24 h later. Renal non-recovery within 7 days was defined as the outcome. The predictive value of urinary biomarkers for renal non-recovery in septic AKI was assessed using the area under the curve (AUC).

Results

A total of 198 individuals with septic AKI were included in the final analysis. Among them, 38.9% (n = 77) did not experience renal recovery within 7 days. The combination of urinary IGFBP7 and TIMP-2 at the initial time point demonstrated prognostic value for non-recovery of renal function, with an AUC of 0.782. When [TIMP-2]*[IGFBP7] was measured at 0 h, the clinical prognostic model, incorporating AKI stage 2–3 and the non-renal sequential organ failure assessment score, showed an improved AUC of 0.822 (with a sensitivity of 88.3% and specificity of 59.5%).

Conclusions

The combination of urinary [TIMP-2]*[IGFBP7] at 0 h exhibited moderate predictive ability for renal non-recovery in cases of septic AKI. However, there is potential to enhance the prognostic capabilities of the [TIMP-2]*[IGFBP7]–clinical prediction model.

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Availability of data and materials

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

Abbreviations

AKI:

Acute kidney injury

TIMP-2:

Tissue inhibitor of metalloproteinase-2

IGFBP7:

Insulin-like growth factor-binding protein 7

AUC:

The area under the curve

SOFA:

Sequential organ failure assessment

CKD:

Chronic kidney disease

ICU:

Intensive Care Unit

UO:

Urine output

RRT:

Renal replacement therapy

KDIGO:

Kidney Disease: Improving Global Outcomes

SCr:

Serum creatinine

GFR:

Glomerular filtration rate

APACHE II:

Acute physiology and chronic health evaluation

SD:

Standard deviation

IQR:

Interquartile range

ROC:

Receiver operating characteristic

PPV:

Positive predictive value

NPV:

Negative predictive value

CI:

Confidence interval

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Acknowledgements

We thank Professor Li-Rong Liang from Beijing Chao-Yang Hospital for the statistical analysis and Medjaden Inc. for the scientific editing of this manuscript.

Funding

This study is supported by Beijing Municipal Science & Technology Commission (No. Z181100001718204; No. Z191100006619032).

Author information

Authors and Affiliations

  1. Department of Surgical Intensive Critical Unit, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, China

    Li Cheng, Hui-Miao Jia, Xi Zheng, Yi-Jia Jiang & Wen-Xiong Li

  2. Department of Emergent Intensive Critical Unit, Beijing Lu-He Hospital, Capital Medical University, Beijing, 101100, China

    Li Cheng

  3. Gettysburg, PA, 17325, USA

    Tian-En Zhang

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  1. Li Cheng
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Contributions

LC contributed to urine collection, data interpretation, manuscript drafting, and critical revision. H-M J, XZ, and Y-J J contributed to urine collection and data interpretation and performed statistical analysis. H-M J, XZ, Y-J J, and T-E Z contributed to data collection and interpretation. W-X L chaired the group, conceived and designed the study, performed statistical analysis and contributed to data collection, interpretation, and critical manuscript revision. All the authors reviewed the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Wen-Xiong Li.

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Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

This study was approved by the Human Ethics Committee of Beijing Chao-Yang Hospital, Capital Medical University (Beijing, China). All procedures performed in studies involving human participants were per the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 2018-117) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from all individual participants included in the study.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1—Figure S1.

The comparisons of urinary [TIMP-2]*[IGFBP7] levels of AKI stage 1 and stage 2–3 at 0 and 24 h. a: The comparison of urinary [TIMP-2]*[IGFBP7] levels of AKI stage 1 and stage 2–3 at 0 h. b: The comparison of urinary [TIMP-2]*[IGFBP7] levels of AKI stage 1 and stage 2–3 at 24 h. Abbreviations: AKI, acute kidney injury; TIMP-2, Tissue inhibitor of metalloproteinase-2; IGFBP7, Insulin-like growth factor-binding protein 7 (TIF 109 KB)

Supplementary file 2—Figure S2.

AUCs of [TIMP-2]*[IGFBP7] at AKI diagnosis (0 h) for RRT use, 30 day mortality. a: The AUC of [TIMP-2]*[IGFBP7] at AKI diagnosis (0 h) for RRT use. b: The AUC of [TIMP-2]*[IGFBP7] at AKI diagnosis (0 h) for 30 day mortality. Abbreviations: ROC, receiver operating characteristic; AUC, the area under the curve; TIMP-2, Tissue inhibitor of metalloproteinase-2; IGFBP7, Insulin-like growth factor-binding protein 7 (TIF 165 KB)

Supplementary file 3 (DOC 51 KB)

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Cheng, L., Jia, HM., Zheng, X. et al. Urinary cell cycle biomarkers for the prediction of renal non-recovery in patients with septic acute kidney injury: a prospective study. Clin Exp Nephrol 27, 1051–1059 (2023). https://doi.org/10.1007/s10157-023-02397-z

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  • DOI: https://doi.org/10.1007/s10157-023-02397-z

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