Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the
angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with
COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with
COVID-19, as attested by low-molecular-weight
proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of
uric acid (46%) or
phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular
proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with
COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular
necrosis, intraluminal debris, and a marked decrease in the expression of
megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of
respiratory failure requiring invasive
mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into
COVID-19 severity and outcome.