COVID-19 and the Kidney: Recent Advances and Controversies

Abstract

Kidney involvement is common in coronavirus disease-2019 (COVID-19), and our understanding of the effects of COVID-19 on short- and long-term kidney outcomes has evolved over the course of the pandemic. Initial key questions centered on the spectrum and degree of acute kidney injury (AKI) in patients hospitalized with severe COVID-19. Investigators worldwide have explored the association between COVID-19-associated AKI and short-term outcomes, including inpatient mortality and disease severity. Even as treatments evolved, vaccinations were developed, and newer viral variants arose, subsets of patients were identified as at continued high risk for major adverse kidney outcomes. In this review, we explore key topics of continued relevance including the following: (1) a comparison of COVID-19-associated AKI with AKI developing in other clinical settings; (2) the ongoing controversy over kidney tropism in the setting of COVID-19 and the potential for competitive binding of the severe acute respiratory syndrome coronavirus 2 virus with angiotensin converting enzyme-2 to prevent viral cell entry; and (3) the identification of high-risk patients for adverse outcomes to inform long-term outpatient management. Patients at particularly high risk for adverse kidney outcomes include those with APOL1 high-risk genotype status. Biomarkers of injury, inflammation, tubular health, and repair measured in both the blood and urine may hold prognostic significance.

Keywords: APOL1; Acute kidney injury; COVID-19; chronic kidney disease.

Figure 1

Heat map showing the percentage of patients with AKI in the setting of COVID-19, after cardiac surgery (TRIBE-AKI cohort), after brain death (DDS cohort), and in the setting of exercise stress (marathon-associated AKI). For exercise stress–associated AKI, blood and urine biomarkers were measured from biosamples obtained within 30 minutes of completing a marathon. The colors denote the percentage of patients by AKI stage with biomarker levels higher than the 90th percentile of the reference value, based on cardiac surgery preoperative values. Among patients with COVID-19–associated AKI, 40%, 50%, and 60% of patients with stages 1, 2, and 3 AKI, respectively, had KIM-1 levels higher than the 90th percentile of reference. Similarly, among kidney donors after brain death, 70%, 80%, and 90% of patients with stages 1, 2, and 3 AKI, respectively, had MCP-1 levels higher than the 90th percentile of the reference value. Sample sizes are by AKI stage: COVID-19: stage 1 (n = 56), stage 2 (n = 31), stage 3 (n = 20); cardiac surgery: stage 1 (n = 456), stage 2 (n = 34), stage 3 (n = 31); brain death: stage 1 (n = 275), stage 2 (n = 93), stage 3 (n = 76); and exercise stress: stage 1 (n = 9), stage 2 (n = 2). Abbreviations: AKI, acute kidney injury; COVID-19, coronavirus disease 2019; DDS, Deceased Donor Study; EGF, epidermal growth factor; IL, interleukin; KIM-1, kidney injury molecule 1; MCP1, monocyte chemoattractant protein 1; NGAL, neutrophil gelatinase-associated lipocalin; TRIBE-AKI, Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury; UMOD, uromodulin; YKL-40, chitinase-3-like protein 1.

Figure 2

Risk of stage 3 AKI, new dialysis initiation, or death within 60 days of hospital admission by urinary biomarker level, indexed to urine creatinine and adjusted for the World Health Organization disease severity scale. Abbreviations: AKI, acute kidney injury; EGF, epidermal growth factor; IL, interleukin; KIM-1, kidney injury molecule 1; MCP-1, monocyte chemoattractant protein 1; NGAL, neutrophil gelatinase-associated lipocalin; OPN, osteopontin; UMOD, uromodulin; WHO, World Health Organization; YKL-40, chitinase-3-like protein 1