The Role of Cell Cycle Arrest Biomarkers for Predicting Acute Kidney Injury in Critically Ill COVID-19 Patients: A Multicenter, Observational Study
Raphael Weiß, Thilo von Groote, Marlies Ostermann, Nuttha Lumlertgul, Kittisak Weerapolchai, Manuel Ignacio Monge García, Jose Maria Martin Cano, Beatriz Diez del Corral, María Jesús Broch-Porcar, Marcos Pérez-Carrasco, Arsenio De La Vega Sánchez, Eduardo Sousa, Ana Catarino, Antonio Jorge Betbesé Roig, J. Baldirà Martínez de Irujo, Silvia De Rosa, Manuel Garcia-Montesinos de la Peña, Teresa Tomasa, Matteo Brivio, Francisco Javier Gonzalez De Molina, Joachim Gerß, John A. Kellum, Carola Wempe, Anna Leidereiter, Melanie Meersch, Alexander Zarbock
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.