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. 2023 Aug 9;12(16):5193.
doi: 10.3390/jcm12165193.

Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin

Antonio Lacquaniti  1 , Fabrizio Ceresa  2 , Susanna Campo  1 , Giovanna Barbera  3 , Daniele Caruso  3 , Elenia Palazzo  3 , Francesco Patanè  2 , Paolo Monardo  1
Affiliations

Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin

Antonio Lacquaniti et al. J Clin Med. .

Abstract

Background: Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI.

Patients and methods: This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery.

Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7-36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/L (0.7-7.8 nmol/L), with the highest values observed in septic shock patients (5.6 nmol/L (3.2-18 nmol/L)) and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values > 5.1 nmol/L and urine TIMP2*IGBP7 levels > 2 mg/L showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days.

Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Keywords: TIMP2*IGBP7; acute kidney injury; mid-regional pro-adrenomedullin; sepsis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Receiver operating characteristic curves of tissue inhibitor metal proteinase-2 and insulin growth factor binding protein-7 (TIMP2*IGBP7) considering diagnosis of AKI as status variable.
Figure 2
Figure 2
Receiver operating characteristics curves of mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), and C-reactive protein (CRP) considering diagnosis of sepsis as status variable. MR-proADM area was significantly different from that of PCT (p < 0.0001) and CRP (p < 0.0001). On the contrary, the difference between PCT and CRP areas was not significant (p: 0.17).
Figure 3
Figure 3
Kaplan–Meier survival curves of endpoints in patients with mid-regional pro-adrenomedullin (MR-proADM) levels above and below the optimal receiver operating characteristic cut-off level of 5.1 nmol/L.
Figure 4
Figure 4
Kaplan–Meier survival curves of endpoint in patients with combined tissue inhibitor metal proteinase-2*insulin growth factor binding protein-7 (TIMP2*IGBP7) and mid-regional pro-adrenomedullin (MR-proADM) levels above and below the optimal receiver operating characteristic cut-off levels of 2 mg/L and 5.1 nmol/L.
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