Urinary Biomarkers Predict Acute Kidney Injury in Patients with COVID-19

Acute kidney injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days. AKI causes a build-up of waste products in the blood and makes it hard for the kidneys to keep the right balance of fluid in the body.

Biomarkers of kidney injury, inflammation, and repair may offer further insight beyond current standard methods of characterizing COVID-19-associated. Biomarkers can help to differentiate various types of kidney injury, and may be uniquely helpful in quantifying tubular injury in COVID-19.

Nephrologists at the Johns Hopkins University School of Medicine (Baltimore, MD, USA) and their colleagues collected urine samples after a patient’s admission with a confirmed COVID-19 test, with repeat urine sample collections attempted weekly thereafter for patients who remained hospitalized. The team analyzed data from 153 patients hospitalized with COVID-19 treated at two academic medical centers between April 2020 and June 2020.

The scientists selected nine candidate urinary biomarkers as primary exposure variables based on our prior work demonstrating associations of such biomarkers with adverse short and long-term kidney outcomes in other clinical settings. They additionally investigated the association of 10 inflammatory biomarkers with the primary outcome: urinary IL-1β, 2, 4, 6, 8, 10, 12, and 13; tumor necrosis factor alpha (TNF-α); and interferon-γ (IFN-γ).

Urine microscopy scoring was completed in a subset of 59 patients, using the IDEXX SediVue Dx platform (IDEXX Laboratories, Westbrook, ME, USA), with all 59 urine microscopy samples generating an automated report with 70 images each, which were reviewed manually. Urinary albumin and creatinine were measured using the Randox RX Daytona clinical chemistry analyzer (Randox, Crumlin, UK). All other biomarkers were measured using the Meso Scale Discovery (MSD, Rockville, MD, USA) platform.

The investigators reported a 2-fold higher levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and kidney injury molecule-1 (KIM-1) were associated with increased risk of severe acute kidney injury or death in patients hospitalized with COVID-19. They also noted that subclinical AKI, defined by elevations in urinary biomarkers, was present in 30% to 50% of patients who did not manifest clinical AKI.

The authors concluded that they had identified significant associations between urinary NGAL, KIM-1, MCP-1, and EGF [epidermal growth factor] and the primary outcome of stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. The discriminatory ability of the individual biomarkers EGF, NGAL, and MCP-1 alone was higher than that of urinary albumin alone and improved in pairwise combinations of these three biomarkers. Neither urine microscopy score nor the presence of viral RNA in the urine of patients with COVID-19 were associated with the primary outcome. The study was published on October 25, 2021 in the American Journal of Kidney Diseases.

Related Links:
Johns Hopkins University School of Medicine
IDEXX Laboratories
Randox
Meso Scale Discovery