Acute kidney injury (AKI) emerged early in the COVID-19 pandemic as one of the major serious complications of the disease, which is caused by a novel coronavirus called SARS-CoV-2. In less than a year, investigators published hundreds of studies characterizing the epidemiologic, pathologic, and clinical features of COVID-19-associated AKI and identifying risk factors for it. The intense research focus may have benefits that go beyond improving the management of this new form of AKI. It could steer investigators in new directions and boost fundamental understanding of how AKI and other kidney problems develop at the cellular and molecular level.
Just figuring out how SARS-CoV-2 causes AKI could be enlightening. “There is still an ongoing debate about how precisely SARS-CoV-2 infection causes kidney injury,” said nephrologist C. John Sperati, MD, MHS, associate professor of medicine and director of the nephrology fellowship program at Johns Hopkins University School of Medicine in Baltimore, Maryland. “It hasn’t been fully resolved yet the extent to which direct viral infection of the kidney might mediate injury, although we do see proteinuria and microscopic hematuria in COVID-19-associated AKI at rates seemingly higher than in patients with other sepsis-associated AKI. Understanding this biology is likely to reveal new insights into kidney physiology.”
Most COVID-19-related kidney injury described in biopsy and autopsy series is acute tubular injury, but primary glomerular diseases, such as collapsing focal segmental glomerulosclerosis (FSGS), have been seen on occasion as well, Dr Sperati noted. Collapsing FSGS is strongly associated with the presence
of high-risk variants in the APOL1 gene, and it is well established that these variants are risk factors for kidney disease caused by other viruses, such as HIV and parvovirus B19, Dr Sperati said, adding that these variants also increase the risk for end-stage kidney disease in patients with chronic kidney disease.
“COVID-19 infection is providing a new disease in which to study these pathways and hopefully better understand the mechanisms by which APOL1 variants increase the risk for kidney disease in general,” Dr Sperati said. “As high-risk APOL1 variants are more common in African-Americans, better understanding the biology can lead to better therapies for a population disproportionately affected by CKD, both with and without COVID-19 infection.”
Among the most noteworthy consequences of the pandemic has been the rapid formation of large-scale, multicenter collaborations such as STOPCOVID (Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19), Dr Sperati said. “Single-center reports can be valuable, but the generalizability and power that emerge from multicenter collaborations can really move the field,” he said. “COVID-19 has forced the almost overnight creation of large institutional registries, frameworks for data sharing,
and novel approaches to data analysis. This transformation can serve as a framework for future collaborations throughout kidney disease research.”
New insight into basic physiologic processes in the kidney could come from probing differences between COVID-19-associated AKI and AKI due to other causes. “To move the field [of kidney research] forward, we need to start to appreciate how different AKI can be from one patient to the next in terms of risk factors, proximate causes, and outcomes,” said F. Perry Wilson, MD, associate professor of medicine at Yale University School of Medicine in New Haven, Connecticut. In a report published recently in JAMA Network Open, he and his collaborators describe a study of hospitalized patients with AKI showing that, following hospital discharge, kidney function declined faster and recovered more slowly in patients with COVID-19-associated AKI compared with patients whose AKI was not caused by COVID-19. The findings underscore that AKI is a heterogeneous syndrome, yet is diagnosed using creatinine measurements (“a very blunt tool”), which cannot distinguish among different forms of AKI. Dr Wilson said he hopes that by elucidating mechanisms by which COVID-19 adversely affects the kidney, “we can discover more broadly how different insults lead to kidney dysfunction.”