Although widely thought of as a respiratory ailment, COVID-19 has demonstrated its ability to impact multiple organs. For those with existing kidney disease, the dangers of the SARS-CoV-2 coronavirus are especially stark. Researchers at New York City’s Montefiore Medical Center reported that recipients of kidney transplants who contract COVID-19 appear to be at exceptionally high risk of severe illness. Additionally, a study of electronic health record data by CarePort Health found that people with chronic kidney disease were 2.5 times more likely to die than other hospitalized COVID-19 patients. Even patients without prior kidney disease are proving susceptible to acute kidney injury (AKI) associated with the virus.

Exactly which mechanisms are producing AKI are not known, but the medical community has some theories. Studies show that the coronavirus attaches in the lungs via ACE2 receptors in human cells. These are also plentiful in the kidneys. Other possibilities include injury resulting from the body's inflammatory response to COVID-19 or prolonged  depletion of extracellular fluid, which could damage to the renal tubule. “It is critical that we understand these mechanisms better,” says Jeffrey Silberzweig, MD, chief medical officer at the Rogosin Institute and co-chair of the ASN COVID-19 Response Team.

To learn more about the causes of kidney injury in COVID-19 patients and develop strategies for delivering care, ASN is asking Congress to appropriate $100 million in emergency supplemental funding for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Despite the link between COVID-19 and AKI, NIDDK did not receive any emergency supplemental funding in the CARES Act, the third phase the Congressional COVID-19 relief package. The amount ASN is requesting is identical to what was provided in the CARES act to the National Heart Lung and Blood Institute to study questions of similar urgency.

NIDDK has identified five opportunities for research on the impact of COVID-19 on kidneys and on people with kidney diseases.

• Clinical studies to better understand COVID-19 related AKI and interventions to prevent or treat it.
• Studies to gather data on whether outcomes vary for patients with COVID-19 and NIDDK-related diseases based on underlying factors or therapies used.
• In vitro and in vivo studies to identify pathogenic pathways and potential translational targets related to kidney diseases associated with COVID-19 infection.
• Studies to identify risk factors that could lead to modifying therapy in high risk individuals being treated with immunomodulators or biologic pathway inhibitors.
• Collection of biosamples that could inform the pathogenesis of COVID-19 associated kidney diseases.
   

The institute is seeking proposals on these topics, which would be funded with fiscal year 2020 dollars, limiting funds appropriated for established research priorities.

Daniel Weiner, MD, MS, a nephrologist at Tufts Medical Center and an associate professor at Tufts University School of Medicine, sees value in exploring the opportunities identified by NIDDK, but he’d like to see additional focus on the care of patients with advanced chronic kidney disease. “550,000 people are treated with dialysis every year, 500,000 in facilities where they are at exceptionally high risk for infections,” Weiner says. In his view, COVID-19 has highlighted kidney patients’ dependence on in-center hemodialysis and the need to develop innovative strategies to support greater use of home dialysis and improve the clinical management of kidney disease. “We don’t even know how to optimally vaccinate these people,” he adds. “We need that basic knowledge regardless of COVID-19.”

Dr. Silberzweig shares this concern. “We know from other viral infections that antibody responses in patients with kidney disease differ from those in the general population,” he says. “Their antibody responses to some vaccinations are blunted and short-lived.” As a result, kidney patients, whether or not they receive in-center dialysis, could remain vulnerable to COVID-19 even after a vaccine becomes available.

In Silberzweig’s view, research is critical to creating a scientific basis for providing better clinical care and is urgently needed before the likely resurgence of COVID-19. Weiner agrees. “Clinical medicine and clinical research are exceptionally synergistic,” he says. “They are two sides of the same coin. When you’re doing clinical medicine, every time you see a patient, you have questions.” Without timely research, the answers could remain anyone’s guess.