Scientists are studying how the SARS infection-

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image: Loss of ACE2 leads to an imbalance in the systems that regulate essential metabolic functions, impairing blood filtration and causing kidney damage that may become permanent
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Credit: Holly Fischer / Holly Fischer / Wikimedia Commons https://commons.wikimedia.org/wiki/File:Kidney_Cross_Section.png

A review article published in the review Frontiers in physiology by researchers affiliated with the Federal University of São Paulo (UNIFESP) in Brazil discusses the mechanisms by which SARS-CoV-2 damages the kidneys, potentially serving as the basis for new research into pursuing treatments to prevent kidney problems severe and even chronic kidney disease in COVID-19 patients.

The study shows that the interaction with the angiotensin converting enzyme 2 (ACE2) not only allows the virus to infect and replicate in human cells, but can also cause a significant imbalance in the renin system. -angiotensin, which regulates blood pressure, and the kallikrein-kinin system, which is involved in inflammation, blood pressure control, and other processes.

Impaired biological functions of ACE2 can lead to reduced renal blood flow and reduced glomerular filtration rate (GFR), impairing the kidneys’ ability to eliminate toxic substances (metabolites) in excess. It can also increase vasoconstriction in the kidneys, leading to deterioration of kidney function.

“Studies and systematic reviews have confirmed a 20-40% incidence of acute kidney injury in COVID-19 patients. Currently published data shows that recovery is slower in some cases and complications requiring dialysis occur in others, ”said Nayara Azinheira Nobrega Cruz, first author of the article.

Conducted at the university’s medical faculty (EPM-UNIFESP), the study was part of Cruz’s doctoral research and was supported by FAPESP through three projects (18 / 16653-7, 17 / 17027-0 and 18 / 23953-7).

Another part of the study, analyzing data on SARS-CoV-2 infection in pregnant women and the role of ACE2 in the placenta, was also recently published in Clinical Science. It has shown that pregnant women infected with the virus are at greater risk of developing preeclampsia, a disorder characterized by persistent high blood pressure that can seriously harm both mother and baby (More than: agency.fapesp.br/36662/).

The prospect of an increase in the number of cases of severe kidney damage due to the COVID-19 pandemic is a serious concern, according to the professor Dulce Elena Casarini, co-principal investigator of the study alongside José Medina Pestana, who heads the EPM-UNIFESP Kidney Hospital (HRIM) and is a member of the São Paulo State Government’s Coronavirus Emergency Center.

“If the demand for dialysis increases now, we may see an increase in the demand for kidney transplants soon,” Casarini said.

The number of kidney transplants performed in Brazil averaged just over 5,900 per year between 2017 and 2019, according to The data Ministry of Health, but the waiting list increased from 28,351 to 29,554 during the period.

Research by an international group of scientists published on September 1, 2021 in the Journal of the American Society of Nephrology, using data from the United States, showed that seven out of 10,000 patients with mild to moderate COVID-19 required dialysis or kidney transplant during the period March 2020 to March 2021. Among patients hospitalized, the risk of acute kidney injury within six months of infection was 23% higher than in uninfected subjects.

Multiple functions

According to Lilian Caroline Gonçalves de Oliveira, head of the Kidney and Hormone laboratory at UNIFESP and co-author of the article, one of the points analyzed was the role of ACE2 in the pathogenesis of COVID-19. “The importance of the ACE2 receptor in cellular invasion by SARS-CoV-2 has been known for some time. The interaction between the virus and the receptor prevents ACE2 from performing its protective functions, ”said Oliveira.

The study article notes that the mechanism of renal involvement in COVID-19 is unknown and may be multifactorial, adding that infection with the virus can indirectly injure the kidneys via systemic inflammation, hypoxemia (low grade oxygen in the blood), shock, hypotension and imbalance of the renin-angiotensin system.

The renin-angiotensin system involves a series of reactions that help regulate blood pressure. When blood pressure drops, for example, the kidneys release the enzyme renin into the bloodstream, where it produces angiotensin 1, which is converted by ACE to angiotensin 2, an active hormone that causes vasoconstriction while acting on the muscles of the wall of the small arteries. Under normal conditions, a harmonious balance between ACE and ACE2 maintains homeostasis of the renin-angiotensin system.

In addition, the virus can infect kidney cells, causing direct damage, compromising the intra-renal renin-angiotensin system and contributing to acute and long-term illnesses. “Our review is a compilation that can serve as a basis for future research and shows the importance of the impact of COVID-19 on other organs besides the respiratory system,” said Cruz.

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About the São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution whose mission is to support scientific research in all fields of knowledge by awarding scholarships, scholarships and grants to researchers linked to educational institutions. Higher and Research Institute of the State of São Paulo, Brazil. FAPESP is aware that the best research can only be done by working with the best researchers at the international level. Therefore, it has established partnerships with funding bodies, higher education institutions, private companies and research organizations from other countries known for the quality of their research and has encouraged scientists funded by its grants to further develop their international collaboration. You can find out more about FAPESP at http://www.fapesp.br/en and visit the FAPESP press agency at http://www.agencia.fapesp.br/fr to keep abreast of the latest scientific advances, FAPESP contributes to the realization of its numerous programs, prizes and research centers. You can also subscribe to the FAPESP press agency at http://agencia.fapesp.br/subscribe.


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