Kinetics of the Cell Cycle Arrest Biomarkers (TIMP2 and IGFBP7) for the Diagnosis of Acute Kidney Injury in Critically Ill COVID-19 Patients

Abstract

Background: Acute kidney injury (AKI) is highly prevalent in critical COVID-19 patients. The diagnosis and staging of AKI are based on serum creatinine (sCr) and urinary output criteria, with limitations in the functional markers. New cell-cycle arrest biomarkers [TIMP2]*[IGFBP7] have been proposed for early detection of AKI, but their role in critically ill COVID-19 patients is poorly understood. Methods: We conducted an observational study to assess the performance of [TIMP2]*[IGFBP7] for the detection of AKI in critical COVID-19 patients admitted to our intensive care unit (ICU). We sampled urinary [TIMP2]*[IGFBP7] levels at ICU admission, 12 h, 24 h, and 48 h, and compared the results to the development of AKI, as well as baseline and laboratory data. Results: Forty-one patients were enrolled. The median age was 66 years [57–72] and most were males (85%). Thirteen patients (31.7%) developed no/mild stage AKI, 19 patients (46.3%) moderate AKI, and nine patients (22.0%) severe AKI. The ICU mortality was 29.3%. sCr levels in the Emergency Department or at ICU admission were not significantly different according to AKI stage. [TIMP-2]*[IGFBP-7] urinary levels were elevated in severe AKI at 12 h after ICU admission, but not at ICU admission or 24 h or 48 h after ICU admission. Conclusion: Urinary biomarkers [TIMP-2]*[IGFBP-7] were generally increased in this population with a high prevalence of AKI, and were higher in patients with severe AKI measured at 12 h from ICU admission. Further studies are needed to evaluate the best timing of these biomarkers in this population.

Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) as a Prognostic Biomarker in Acute Kidney Injury: A Narrative Review

“…Adding [TIMP-2] × [IGFBP-7] to clinical models enhanced risk prediction for AKI, outperforming clinical factors alone [74]. When measuring urinary biomarkers at 12 h after ICU admission, patients with severe AKI had higher [TIMP-2] × [IGFBP-7] levels [63]. In critically ill patients with COVID-19, the combination of [TIMP-2] × [IGFBP-7] and clinical data proved helpful in identifying subclinical AKI [75].…”

Long COVID: A Molecular, Cellular and Histopathology Overview

“…At the molecular level, serum levels of several biochemical markers are able to predict kidney tissue inflammation, including markers of damage and alteration in function such as TIMP-2 and IGFBP7, damage to proximal and distal tubules such as KIM-1 and NGAL, respectively, and loss of renal function due to the C Cystatin [87] [88]. High levels of creatinine and uric acid, associated with the evaluation of the presence or absence of proteinuria, albumin, and alpha-1-microglobulin also indicate a worse prognosis of the disease, as well as a higher rate of mortality [89].…”