Abstract: Since the beginning of the new crown pandemic, there have been some research on the relationship between the new crown virus and renal failure. The "Expert Consensus on Diagnosis and Treatment of New Coronavirus Infection and Acute Renal Injury" mentioned that acute kidney injury is one of the important complications of the new coronavirus. However, it is still unclear how likely the new coronavirus is to cause acute kidney damage and how serious the new coronavirus causes to the kidneys. Below, we will talk about the new coronavirus and acute kidney injury based on existing research.
In "Diagnosis and Treatment of New Coronavirus Pneumonia: Acute Kidney Injury cannot be ignored", scholars pointed out that "in addition to the respiratory system of the virus, the kidneys are also one of the main involved organs in the virus. In addition, the new coronavirus and acute kidney injury are independent risk factors for patients with poor prognosis." In addition, the paper pointed out that the kidney damage caused by new coronavirus is mainly renal tubular damage, and abnormal urine tests are obvious, but glomerular filtration function is also impaired, showing that serum creatinine and increased urea nitrogen level [1]. Therefore, it is necessary to let more people understand how much harm the new coronavirus will bring to the kidneys.
The new coronavirus infects the human kidneys and causes kidney organoid fibrosis
Although there is still controversy about the direct infection of the kidneys of the new coronavirus, a study based on an autopsy on showed that the renal tubular interstitial fibrosis in patients with COVID-19 was increased and suggested that the direct kidney infection of . In addition, in human kidney organoids, the new coronavirus infection has upregulated several pro-fibrosis and pro-inflammatory pathways .
In COVID-19 patients, acute kidney injury (AKI) is related to poor survival, but the pathophysiology of AKI in these infected patients is complex and cannot fully understand the situation. In addition, there is controversy over whether the new coronavirus directly infects the kidneys. If there is a direct infection of the kidneys, whether it will lead to the development of AKI in the infected person has not yet been clarified. To study the direct effect of the virus on the kidneys, researchers used the novel coronavirus to infect human-induced pluripotent stem cell-derived renal organoids. The final research results of show that the new coronavirus can directly infect kidney cells and induce cell damage and subsequently fibrosis . The relevant research results are titled "SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids" and are published on Cell Stem Cell.
Figure 1 Research results (Photo source: [1])
To show the impact of the new coronavirus on the kidneys, researchers collected kidney tissues from 62 people infected with the new coronavirus. Lung tissue infected by the new coronavirus was used as positive control stained with nucleocapsid protein, and autopsy and nephrectomy tissues not infected with the new coronavirus were used as negative controls. It was found that the nucleocapsid protein of the new coronavirus was found in the epithelial cytoplasm of the proximal renal tubules of the human body. Proximal tubular injury is manifested as the expression of renal injury molecule 1 (KIM1) in the lotus cotyledon lectin-positive tubules in the biopsy specimens. In addition, the researchers also observed the expression of renal injury molecule 1 in some proximal tubules in the renal tissue of people infected with COVID-19. This shows that the new coronavirus directly infects human kidneys . The researchers found that compared with the control group, the kidney interstitial fibrosis in patients with new coronavirus infection increased. No matter the type of injury, the reaction of kidney damage will eventually lead to fibrosis of .
Figure 2 The new coronavirus exists in the kidney cells of the infected person and induces renal fibrosis (Photo source: [1])
Further research, researchers detected upregulation of the new coronavirus infection-related genes PLCG2 and AFDN in the kidney cells. At the same time, the activity of proinflammatory and profibrosis-driven pathways in kidneys increased. tumor necrosis factor , transformed growth factor, etc. were found in the proximal renal tubules, podocyte and fibroblast of new coronavirus infected with kidney cells and induce the profibrosis pathway in renal cells.
researchers examined the gene expression spectrum and signaling pathway in infected renal organoids to analyze the underlying pathological mechanisms of novel coronavirus induction.They found that enriched genes associated with antiapoptotic and proinflammatory responses in proximal tubular cells and podocytes that showed viral transcripts. Compared with the control group, the signaling of transforming growth factor β in the proximal renal tubules and mesenchymal clusters of new coronary infection was upregulated, and these are very important in the pathogenesis of renal fibrosis.
In short, studies have shown that COVID-19 infection can lead to cell damage, dedifferentiation and pro-fibrosis signaling in kidney organoids, which explains why COVID-19 causes an increased risk of acute kidney injury in infected people, and the occurrence of chronic kidney disease after the recovery of COVID-19 infections.
People who recover from COVID-19 infection have an increased risk of kidney disease
Infected with COVID-19 Even after recovery, patients still have acute sequelae involving the lungs and multiple extrapulmonary organ systems, but there is no specific study on the evaluation of kidney results in COVID-19 sequelae. In November 2021, the American Academy of Nephrology published a research paper titled "Kidney Outcomes in Long COVID". Studies have shown that people with COVID-19 infection show a higher risk of acute renal injury, which shows an increased risk of renal outcomes in the acute late stages of the disease, and the risk of renal outcomes increases according to the severity of the acute infection.
Figure 3 Research results (Photo source: [3])
In this study, researchers selected 1.72 million U.S. veterans from users of the Veterans Health Administration (VHA) health care system, including 89,216 new coronavirus infections and 1637,467 uninfected (control group). The median follow-up time for COVID-19 patients was 164 days, and the median follow-up time for the VHA user group was 172 days. The risks of acute renal injury (AKI), glomerular filtration rate (eGFR), end-stage renal disease (ESKD), and major renal adverse events (MAKE) were examined.
study found that in addition to acute diseases, hindrances of COVID-19 infection showed a higher risk of AKI compared with the control group, showing excessive eGFR declines, and the eGFR of patients in acute infection, hospitalized and intensive care patients decreased by 3.26, 5.2, and 7.69, respectively.
According to the severity of the disease in the acute phase of infection (non-hospital, hospitalized and intensive care), the researchers further examined the risk and burden of kidney disease in infected people. They found that compared with the control group, the risk and burden of kidney disease of infected people after the acute phase of the disease increased, and the more severe the infection, the higher the risk of acute renal outcome.
The above study analyzed the relationship between the new coronavirus infection and the patient's kidney outcome. Infection with the new coronavirus will have a negative impact on the human kidneys, but previous studies have also shown that in addition to the new coronavirus, there are also viruses such as influenza , which will also have certain effects on the human kidneys, and this impact is not irreversible. Therefore, don’t be too afraid of the topic that “the new crown will lead to the renal failure of the whole people in the future” that is widely circulated, but at the same time, for the sake of your own health, you must also take good prevention and control measures to reduce infection.
Written by | Muzijiu
Typesetting | Feng Lixiao
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Reference materials:
[1] Yang Xianghong, Sun Renhua, Chen Dechang. Diagnosis and treatment of novel coronavirus pneumonia: acute kidney injury cannot be ignored [J]. Chinese Journal of Medicine, 2020,100 (16): 1205-1208.DOI: 10.3760/cma.j.cn112137-20200229-00520.
[2] Hassler L, Batlle D. Potential SARS-CoV-2 kidney infection and paths to injury. Nat Rev Nephrol. 2022 May;18(5):275-276. doi: 10.1038/s41581-022-00551-6. PMID: 35190715; PMCID: PMC8860288.
[3]Bowe B, Xie Y, Xu E, et al. Kidney Outcomes in Long COVID. J Am Soc Nephrol. 2021 Nov;32(11):2851-2862. doi: 10.1681/ASN.2021060734. Epub 2021 Sep 1. PMID: 34470828; PMCID: PMC8806085.
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