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Observational Study
. 2023 Aug 1;51(8):992-1000.
doi: 10.1097/CCM.0000000000005853. Epub 2023 Mar 28.

The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study

Raphael Weiss  1 , Thilo von Groote  1 , Marlies Ostermann  2 , Nuttha Lumlertgul  2   3   4 , Kittisak Weerapolchai  2   5 , Manuel Ignacio Monge Garcia  6 , Jose Maria Martin Cano  6 , Beatriz Diez Del Corral  6 , María Jesús Broch-Porcar  7 , Marcos Perez Carrasco  8   9 , Arsenio De la Vega Sanchez  8 , Eduardo Sousa  10 , Ana Catarino  10 , Antonio Jorge Betbesé Roig  11 , Jaume Baldira Martinez de Irujo  11 , Silvia de Rosa  12 , Manuel Garcia-Montesinos de la Peña  13 , Teresa Tomasa  14 , Matteo Brivio  15 , Francisco Javier Gonzalez De Molina  16 , Joachim Gerss  17 , John A Kellum  18 , Carola Wempe  1 , Anna Leidereiter  1 , Melanie Meersch  1 , Alexander Zarbock  1
Affiliations
Observational Study

The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study

Raphael Weiss et al. Crit Care Med. .

Abstract

Objectives: Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) have a high risk for developing acute kidney injury (AKI) which is associated with an increased risk of death and persistent renal failure. Early prediction of AKI is crucial in order to implement preventive strategies. The purpose of this study was to investigate the predictive performance of tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) in critically ill patients with COVID-19-associated ARDS.

Design: Multicenter, prospective, observational study.

Setting: Twelve centers across Europe and United Kingdom.

Patients: Patients with moderate or severe COVID-19-associated ARDS were included and serial measurements of (TIMP-2) × (IGFBP7) were performed.

Interventions: None.

Measurements and main results: The primary endpoint was the development of moderate or severe AKI according to the Kidney Disease: Improving Global Outcomes definition. Three hundred patients were available for the primary analysis, and 39 met the primary endpoint. At enrollment, urinary (TIMP-2) × (IGFBP7) had high predictive value for the primary endpoint with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.84-0.93). (TIMP-2) × (IGFBP7) was significantly higher in endpoint-positive patients at enrollment and at 12 hours.

Conclusions: Urinary (TIMP-2) × (IGFBP7) predicts the occurrence of AKI in critically ill patients with COVID-19-associated ARDS.

Trial registration: ClinicalTrials.gov NCT04406688.

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Conflict of interest statement

Dr. Ostermann received research funding from BioMérieux and Baxter. Dr. Garcia received funding from Edwards Lifesciences. Dr. Cano disclosed work for hire. Dr. Broch-Porcar disclosed that she participated in a lecture in Nephroweek with economical compensation from BioMereiux. Drs. de la Peña, Meersch, and Zarbock received funding from Baxter. Dr. Brivio received funding from Jafron and Bbraun. Dr. de Rosa received lectures fees from ESTOR SpA. Drs. Kellum’s and Zarbock’s institutions received funding from BioMereiux. Drs. Kellum, Meersch, and Zarbock received funding from BioMereiux. Dr. Meersch received funding from FMC and Baxter. Dr. Gerss received honoraria from TESARO, QUIRIS Healthcare, Ecker+Ecker, Dr August Wolff, Roche, University Clinics Schleswig-Holstein, and RWTH Aachen University. Dr. von Groote was supported by a rotational position of KFO 342, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–ZA428/18-1. Dr. Zarbock’s institution received funding from DFG, Baxter, and Fresenius; he received funding from AM Pharma, Novartis, Alexion, Bayer, Guard Therapeutics, Paion, and Fresenius as well as independent research grants from the German Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Participant flow. AKI = acute kidney injury, ARDS = acute respiratory distress syndrome, eGFR = estimated glomerular filtration rate.
Figure 2.
Figure 2.
Urinary tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) levels at different time points. The box represents the 25th/75th percentile. Whiskers are drawn from the ends of the box to the largest and smallest observed values within 1.5 times the interquartile range. Outliers beyond the whiskers are represented by circles. AKI = acute kidney injury.
Figure 3.
Figure 3.
Predictive performance of (tissue inhibitor of metalloproteinases 2 [TIMP-2]) × (insulin-like growth factor binding protein 7 [IGFBP7]) for kidney outcomes. Receiver operating characteristic curves of urinary TIMP-2 and IGFBP7 for prediction of moderate/severe acute kidney injury (AKI) (A), prediction of persistent AKI (B), and for prediction of renal replacement therapy (C) (green line: at inclusion, red line: 12 hr after inclusion, orange line: 24 hr after inclusion).
See this image and copyright information in PMC

References

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