The role of kidney injury biomarkers in COVID-19

Su, L. Joseph; Zhang, Jiahao; Peng, Zhiyong

doi:10.1080/0886022x.2022.2107544

Cited by 8 publications

(8 citation statements)

References 94 publications

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“…Cystatin C (CST3) has been previously also shown to be a predictive biomarker for COVID-19 severity 47, 48 . IGFBP7, a glycoprotein expressed in ECs and renal epithelial cells, has been extensively shown as a prognostic biomarker for early AKI along with TIMP2 52, 53 . LGALS3BP, an ECM associated glycoprotein, was shown to be differentially regulated in COVID-19 samples 19, 54 .…”

Section: Resultsmentioning

confidence: 99%

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

Anandakrishnan,

Yi,

Sun

et al. 2024

Preprint

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COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

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Section: Resultsmentioning

confidence: 99%

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

Anandakrishnan,

Yi,

Sun

et al. 2024

Preprint

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“…Acute kidney injury induced by COVID-19 has been recognized as a prominent source of morbidity and mortality. COVID-19-associated AKI has been linked to negative outcomes such as the development or worsening of comorbid diseases, increased mortality, and increased use of health care resources, according to previous research [26].…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2023

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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.

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“…Second, our data were collected during the first wave of the pandemic; consequently, our results should not be generalized to patients infected with novel SARS-CoV-2 variants [ 2 ]. Finally, interesting factors such as biomarkers of tubular function, Cystatin C (CysC) [ 36 , 42 ], liver-type fatty acid-binding protein (L-FABP) and α1-Microglobulin (α1M) [ 43 ] were not included in our analyses. Similarly, the combination of biomarkers with quantification of lung damage on chest CT [ 10 ] or with Doppler measurement of the renal resistive index [ 44 , 45 ] are promising tools that were not investigated in our study.…”

Section: Discussionmentioning

confidence: 99%

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

Larcher,

Bargnoux,

Badiou

et al. 2023

Renal Failure

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Tubular injury is the main cause of acute kidney injury (AKI) in critically ill COVID-19 patients. Proximal tubular dysfunction (PTD) and changes in urinary biomarkers, such as NGAL, TIMP-2, and IGFBP7 product ([TIMP-2]•[IGFBP7]), could precede AKI. We conducted a prospective cohort study from 2020/03/09 to 2020/05/03, which consecutively included all COVID-19 patients who had at least one urinalysis, to assess the incidence of PTD and AKI, and the effectiveness of PTD, NGAL, and [TIMP-2]•[IGFBP7] in AKI and persistent AKI prediction using the area under the receiver operating characteristic curves (AUCs), Kaplan–Meier methodology (log-rank tests), and Cox models. Among the 60 patients admitted to the ICU with proven COVID-19 (median age: 63-year-old (interquartile range: IQR, 55–74), 45 males (75%), median simplified acute physiology score (SAPS) II: 34 (IQR, 22–47) and median BMI: 25.7 kg/m 2 (IQR, 23.3–30.8)) analyzed, PTD was diagnosed in 29 patients (48%), AKI in 33 (55%) and persistent AKI in 20 (33%). Urinary NGAL had the highest AUC for AKI prediction: 0.635 (95%CI: 0.491–0.779) and persistent AKI prediction: 0.681 (95%CI: 0.535–0.826), as compared to PTD and [TIMP-2]•[IGFBP7] (AUCs <0.6). AKI was independently associated with higher SAPSII (HR = 1.04, 95%CI: 1.01–1.06, p = 0.005) and BMI (HR = 1.07, 95%CI: 1.00–1.14, p = 0.04) and persistent AKI with higher SAPSII (HR = 1.03, 95%CI: 1.00–1.06, p = 0.048) and nephrotoxic drug use (HR = 3.88, 95%CI: 1.20–12.5, p = 0.02). In conclusion, in critically ill COVID-19 patients, the incidence of PTD and AKI was relatively high. NGAL was the best urinary biomarker for predicting AKI, but only clinical severity was independently associated with its occurrence.

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The role of kidney injury biomarkers in COVID-19

Cited by 8 publications

References 94 publications

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury

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

Acute kidney injury in critical COVID-19 patients: usefulness of urinary biomarkers and kidney proximal tubulopathy

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