Kidney Disease and Viral Infection in COVID-19: Why Are Kidney Organoid and Biopsy Studies Not in Agreement?

Abstract

Context: The clinical course of coronavirus disease-19 (COVID-19) can be complicated by acute kidney injury and proteinuria. Kidney cells express receptors for SARS-CoV-2, the virus responsible for COVID-19. Direct infection of the kidney parenchyma by SARS-CoV-2 has been proposed as the cause of renal dysfunction in COVID-19. Subject of Review: Kidney organoids derived from human embryonic stem cells or induced pluripotent cells can be reproducibly infected by SARS-CoV-2 in vitro and used to study therapeutics. However, kidney biopsy studies of COVID-19 patients with renal dysfunction have shown no evidence of viral infection. Second Opinion: Kidney organoids are susceptible to SARS-CoV-2 infection, which is probably facilitated by their limited architectural complexity and maturation compared to the intact organ and by the in vitro culture conditions. Conversely, kidneys in COVID-19 patients appear resistant to infection and may be injured through indirect mechanisms mediated by the host response to the respiratory viral infection, genetic susceptibility to the immune response, physiological disturbances, and therapies. More studies are needed to better understand why kidney organoids are more susceptible than mature kidneys to SARS-CoV-2 infection and further characterize the mechanisms of kidney injury in COVID-19.