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The reported prevalence of acute kidney injury (AKI) is around 40% in patients hospitalized for severe COVID-19. Several blood and urine biomarkers have been proposed as predictors of AKI such as Neutrophil Gelatinase Associated Lipocalin [NGAL], Chemokine (C-C moGf) ligand 14 [CCL14], Cystatin C and Leucine Amino-Peptidase [LAP], and of morbi-mortality such as Soluble urokinase Plasminogen Activator [suPAR], a circulating marker of chronic inflammation. The aim of the present study was to determine the possible diagnostic and predictive value of these biomarkers in a cohort of COVID-19 patients constituted between mid-January and early May 2021 and followed during the first two weeks of hospitalization.
From a total of 122 patients (diagnosis confirmed by PCR), 116 patients hospitalized in Intensive Care Unit (ICU) or COVID Units agreed to be included in this prospective observational study. The occurrence of AKI between Day 0 and Day 3 was established according to AKIN criteria. Clinical and biological data were collected on Days 0, 3, 5, 7, 14 and compared with plasma NGAL, suPAR and cystatin C assays, as well as urinary NGAL, CCL-14 and LAP assays. Descriptive statistics were presented as median (percentile 25, percentile 75) for continuous variables and as absolute number (percentage) for qualitative data. Comparisons between AKI and non-AKI groups were made using Fisher's test and Wilcoxon-Mann-Whitney test for categorical and continuous variables, respectively. The significance threshold was set at p < 0.05.
Forty-eight of the 116 patients in the cohort (41%) developed AKI between Day 0 and Day 3. Twenty-nine were taken care in ICU. The overall mortality rate was 18%. In AKI patients, a statistically significant increase in urinary LAP levels was observed compared to the non AKI group, suggesting a massive urinary release of the apical brush border of the proximal tubular epithelium. In AKI patients, NGAL and CCL-14 levels were non-significantly higher than in the non AKI group but a great variability in the measurements was observed. Of interest, significantly higher plasma suPAR and cystatin C levels detected upon admission and persisting until Day 7 were measured in patients with a worse prognosis (ICU stay or death, respectively), independently of the prior onset of AKI.
Elevated urinary LAP levels measured from Day 3 after admission in patients developing AKI demonstrated the value of this marker in reflecting acute tubular necrosis as a possible mechanism of COVID-19 associated renal injury. Sustained elevated plasma suPAR and Cystatin C levels during the first week of hospitalization were found predictive of a significant short-term morbidity and mortality, irrespective of the occurrence of AKI.