A review article published in the journal Frontiers in Physiology by researchers who are affiliated with the Federal University of Sao Paulo (UNIFESP) in Brazil explores the mechanisms that cause SARS-CoV-2 can damage kidneys, potentially serving as an underlying basis for further research in the search of treatments to prevent severe renal issues and even chronic kidney disease in COVID-19 patients.
The study shows that interaction with angiotensin-converting enzyme 2 (ACE2) not only enables the virus to infect and replicate in human cells but can cause a significant imbalance in the renin-angiotensin system, which regulates arterial blood pressure, and the kallikrein-kinin system, which is involved in inflammation, control of blood pressure, and other processes.
An impairment of ACE2’s biology can result in a decrease in renal blood flow and diminished glomerular filter (GFR), which affects the kidneys’ capacity to remove toxic substances (metabolites). It can also increase vasoconstriction in the kidneys, which can cause deterioration in renal function.
Studies and systematic reviews have demonstrated that patients with COVID-19 are at risk of suffering from acute renal injury between 20% and 40 percent. The data that is now published indicates that recovery is slower in some instances, and complications that require dialysis occur in others.”
Nayara Azinheira Nbrega Cruz, who was the first author of this article.
The study was conducted at the medical school (EPM-UNIFESP) The study was part of Cruz’s PhD research and was funded by FAPESP via three projects (18/16653-7, 17/17027-0 and 18/23953-7).
Another portion of the study, analyzing information on the presence of SARS-CoV-2 in pregnant women, and the role of ACE2 in the placenta, was also published in Clinical Science. It showed that pregnant women infected by the virus run a greater risk of developing pre-eclampsia, a disorder characterized by persistent high blood pressure that can cause serious harm to mother and baby (more at: agencia.FAPESP.br/36662/).
The possibility of an increase in the number of kidney injury due to the COVID-19 pandemic is of grave concern, according to Professor Dulce Elena Casarini, co-principal researcher for the study with Jose Medina Pestana, who is EPM-UNIFESP’s Kidney Hospital (HRIM) and is part of the Sao Paulo State Government’s Coronavirus Contingency Center.
Casarini said that if dialysis demand is rising it is possible that we will witness an increase in the demand for kidney transplants in the near future.
The number of kidney transplants that were performed in Brazil averaged a little over 5,900 each year between 2017 and 2019 according to figures from the Ministry of Health, but the waiting list grew from 28,351 to 29,554 over the span of.
A group of international scientists published their findings in the Journal of American Society of Nephrology on September 1st 2021. They used data from the United States to determine that seven out of 10,000 mild or moderate COVID-19 sufferers required dialysis or a transplant during the timeframe of March 2020-2021. The risk of acute renal injury in the first six months after infection was 23% higher for non-hospitalized patients than it was for non-infected individuals.
Lilian Caroline Goncalves De Oliveira UNIFESP’s Kidney and Hormone Laboratory head and co-author of the article said that one of the points analyzed was ACE2’s role in the pathogenesis COVID-19. “The importance of the ACE2 receptor to cell invasion by SARS-CoV-2 is been known for some time. The interaction between the virus and the receptor stops ACE2 from performing its protective functions,” Oliveira said.
The study’s report mentions that the mechanism behind renal involvement in COVID-19 is unknown and may be multifactorial. It also notes that infection with the virus can indirectly cause kidney damage via systemic inflammation as well as hypoxemia (low blood oxygen) and hypotension, shock and renin-angiotensin system imbalance.
A number of reactions form part of the renin-angiotensin (renin-angiotensin) system that regulates blood pressure. For instance when blood pressure decreases and the kidneys release an enzyme called renin into bloodstream. This enzyme is transformed by ACE to angiotensin 1. Angiotensin 2 is an active hormone that causes vasoconstriction by the action of small muscles that line the walls of arteries. Under normal conditions, a harmonious balance between ACE and ACE2 maintains renin-angiotensin system homeostasis.
Additionally, the virus could cause kidney cell damage directly, which can compromise the intra-renal renin angiotensin system and contributing to chronic and long-term conditions. Cruz stated that the review can be used as a foundation for future research. It also emphasizes the importance of COVID-19’s effect on other organs, in addition to the respiratory system.