Pathophysiology of COVID-19-associated acute kidney injury

Abstract

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

Abstract

Acute kidney injury (AKI) is a common complication of COVID-19. This Review describes current understanding of the pathophysiology of COVID-19-associated AKI, examining potential mechanisms by which SARS-CoV-2 infection might induce direct and indirect effects on the kidney and non-specific factors, including haemodynamic changes and/or organ crosstalk, that may adversely influence kidney function.

Key points

• Over a quarter of patients hospitalized with coronavirus disease 2019 (COVID-19) have been reported to develop acute kidney injury (AKI).

• Low molecular weight proteinuria, Fanconi syndrome and histological findings point towards tubular injury.

• Analyses of kidney biopsy samples from patients with COVID-19 and AKI have inconsistently reported viral infection of kidney cells.

• Collapsing glomerulopathy has been identified in patients with high-risk APOL1 genotypes, mostly in those without severe respiratory symptoms.

• Regional inflammation, endothelial injury and renal microthrombi have been reported but their implication in the pathogenesis of COVID-associated AKI remains uncertain.

• Anti-inflammatory drugs (for example, steroids and IL-6 receptor blockers) seem to limit the development of severe AKI in patients with COVID-19.