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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.
See this image and copyright information in PMC

References

    1. Uchino S., Kellum J.A., Bellomo R., Doig G.S., Morimatsu H., Morgera S., Schetz M., Tan I., Bouman C., Macedo E., et al. Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA. 2005;294:813–818. - PubMed
    1. Lacquaniti A., Caccamo C., Salis P., Chirico V., Buemi A., Cernaro V., Noto A., Pettinato G., Santoro D., Bertani T., et al. Delayed graft function and chronic allograft nephropathy: Diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin. Biomarkers. 2016;21:371–378. - PubMed
    1. Bolignano D., Coppolino G., Romeo A., Lacquaniti A., Buemi M. Neutrophil gelatinase-associated lipocalin levels in chronic haemodialysis patients. Nephrology. 2010;15:23–26. doi: 10.1111/j.1440-1797.2009.01163.x. - DOI - PubMed
    1. Tao X., Chen C., Luo W., Zhou J., Tian J., Yang X., Hou F.F. Combining renal cell arrest and damage biomarkers to predict progressive AKI in patient with sepsis. BMC. 2021;22:415. doi: 10.1186/s12882-021-02611-8. - DOI - PMC - PubMed
    1. Murray P.T., Mehta R.L., Shaw A., Ronco C., Endre Z., Kellum J.A., Chawla L.S., Cruz D., Ince C., Okusa M.D. ADQI 10 workgroup Potential use of biomarkers in acute kidney injury: Report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2020;180:513–521. - PMC - PubMed