Prospective multicenter study on early proximal tubular injury in COVID-19-related Acute Respiratory Distress Syndrome

Introduction During COVID-19, renal impairment is the most frequent after lung impairment and is associated with poor prognosis particularly in intensive care unit (ICU). We aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Methods In this prospective multicenter study, patients aged over 18 years with invasive mechanical ventilation for ARDS were enrolled in 3 ICUs. Precise evaluation of renal dysfunction markers including urinary proteins electrophoresis (UPE) and quantification, was performed within 24 hours after mechanical ventilation onset. Results From March 2020 to December 2021, 135 patients were enrolled: 100 COVID-19 ARDS and 35 non-COVID-19 ARDS. UPE found more tubular dysfunction in COVID-19 patients (68% vs. 21.4%, p<0.0001) and more normal profiles in non-COVID-19 patients (65.0% vs. 11.2%, p=0.0003). COVID-19 patients significantly displayed early urinary leakage of tubular proteins like beta-2-microglobulin and free-light chains, tended to display more frequently acute kidney injury (AKI) (51.0% vs 34.3%, p=0.088), had longer mechanical ventilation (20 vs. 9 days, p<0.0001) and longer ICU stay (26 vs. 15 days, p<0.0001). In COVID-19 ARDS, leakage of free lambda light chain was associated with the onset of KDIGO ≥2 AKI (OR: 1.014, 95%CI [1.003-1.025], p=0.011). Conclusions Patients with COVID-19-related ARDS display a proximal tubular dysfunction, prior to the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable non-invasive tool to assess proximal tubular dysfunction in the ICU.