Kidney Outcomes and Trajectories of Tubular Injury and Function in Critically Ill Persons with and without Coronavirus-2019.

Background: Coronavirus disease-2019 (COVID-19) may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point. To better understand mechanisms of AKI in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.

Methods: The COVID-19 Host Response and Outcomes (CHROME) study prospectively enrolled patients admitted to intensive care units in Washington state with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival. We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.

Results: At ICU admission, mean age was 55±16 years; 45% required mechanical ventilation; and mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater incidence of MAKE (95% CI 1.05, 2.74) and a 741% greater incidence of KRT (95% CI 1.69, 32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and eGFR increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.

Conclusions: Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction.