Will the new crown lead to devastating universal kidney failure in the future? how is the truth

Abstract: From the beginning of the COVID-19 pandemic, there has been research on the relationship between COVID-19 and kidney failure. According to the “Expert Consensus on Diagnosis and Treatment of Novel Coronavirus Infection Complicated with Acute Kidney Injury”, acute kidney injury is one of the important complications of the new coronavirus. However, the possibility of the new coronavirus causing acute kidney injury and the severity of the new coronavirus on the kidney are still inconclusive. Below, we start from the existing research and talk about the new coronavirus and acute kidney injury.

In “Diagnosis and Treatment of Novel Coronavirus Pneumonia: Acute Kidney Injury Should Not Be Ignored”, scholars pointed out that “in addition to the respiratory system being the main target organ of the virus, the kidneys are also one of the main affected organs. One, and the new coronavirus combined with acute kidney injury is an independent risk factor for poor prognosis of patients.” In addition, the paper pointed out that the kidney damage caused by the new coronavirus is mainly renal tubular damage, with obvious abnormal urine test, but there are also renal small Impaired spherical filtration function, manifested as elevated serum creatinine and blood urea nitrogen levels[1]. Therefore, it is necessary for more people to understand how the new coronavirus will harm the kidneys.

COVID-19 infects human kidney and causes renal organoid fibrosis

Although there is still controversy about direct infection of the kidneys by SARS-CoV-2, a largely autopsy-based study showed increased tubulointerstitial fibrosis in people with Covid-19 and suggested direct renal Infection. Furthermore, COVID-19 infection upregulated several profibrotic and proinflammatory pathways in human kidney organoids.

Acute kidney injury (AKI) is associated with poorer survival in patients with COVID-19, but the pathophysiology of AKI in these infected patients is complex and not fully understood. In addition, there is controversy about whether the new crown directly infects the kidneys, and if there is a direct infection of the kidneys, whether it will lead to the development of AKI in infected people, these issues have not yet been elucidated. To study the direct effects of the virus on the kidneys, the researchers infected kidney organoids derived from human induced pluripotent stem cells with SARS-CoV-2. The final research results show that SARS-CoV-2 can directly infect kidney cells to induce cell damage and subsequent fibrosis. The related research results are titled “SARS-CoV-2 infects the human kidney and drives fibrosis in kidneyorganoids” , published in Cell Stem Cell.

Figure 1 Research results (Source: [1])

To show the effects of the new coronavirus on the kidneys, researchers collected kidney tissue from 62 people with COVID-19. The 2019-nCoV-infected lung tissue was used as a positive control for nucleocapsid protein staining, and non-2019-nCoV-infected autopsy and nephrectomy tissues were used as negative controls, and it was found that the 2019-nCoV nucleocapsid protein was present in the cytoplasm of proximal renal tubular epithelial cells in humans . Proximal tubular injury is manifested by the expression of kidney injury molecule 1 (KIM1) in lotus cotyledon lectin-positive tubules in biopsy specimens. In addition, the researchers also observed some proximal renal tubules in the kidney tissue of patients with new coronary infection. Kidney injury molecule 1 expression. This indicates that COVID-19 directly infects human kidneys. The researchers found that compared with the control group, patients with new coronary infection had increased renal interstitial fibrosis. Regardless of the type of injury, the kidney’s response to injury ultimately leads to fibrosis.

Figure 2 The new coronavirus exists in the kidney cells of infected people and induces renal fibrosis (Source: [1])

Further research, researchers detected the up-regulation of 2019-nCoV infection-related genes PLCG2 and AFDN in kidney cells. At the same time, the activity of pro-inflammatory and pro-fibrosis-driven pathways in the kidneys increased, and tumor necrosis factor, transforming growth factor, etc. were found in the proximal renal tubules, podocytes, and fibroblasts of patients with COVID-19, indicating that COVID-19 Virus infects renal cells and induces a profibrotic pathway in renal cells.

Researchers examined gene expression profiles and signaling pathways in infected kidney organoids to analyze potential pathological mechanisms induced by SARS-CoV-2. They found that genes associated with anti-apoptotic and pro-inflammatory responses were enriched in proximal tubular cells and podocytes that displayed viral transcripts. Compared with controls, transduction of transforming growth factor β and other signaling in proximal tubules and mesenchymal clusters of SARS-CoV-2 infection was up-regulated, which are important in the pathogenesis of renal fibrosis.

In conclusion, studies have shown that 2019-nCoV infection causes cell damage, dedifferentiation, and pro-fibrotic signaling in kidney organoids, which explains why 2019-nCoV can cause acute kidney disease in infected individuals Increased risk of injury and chronic kidney disease after recovery from COVID-19.

Recovered COVID-19 patients are at increased risk of developing kidney disease

Even after recovery from SARS-CoV-2 infection, there are still patients with acute sequelae involving the lungs and multiple extrapulmonary organ systems, but there is no specific assessment of renal outcomes in Covid-19 sequelae Research. In November 2021, a research paper titled “Kidney Outcomes in Long COVID” was published in the American Society of Nephrology. Study shows that COVID-19 infected individuals have a higher risk of acute kidney injury, an increased risk of renal outcomes in the acute later stages of the disease, and that the risk of renal outcomes increases according to the severity of acute infection .

Figure 3 Research results (Source: [3])

For the study, researchers selected 1.72 million U.S. veterans, including 89,216 COVID-19 patients and 1,637,467 veterans, from users of the Veterans Health Administration (VHA) health care system. uninfected subjects (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 kidney injury (AKI), glomerular filtration rate (eGFR), end-stage renal disease (ESKD), and major adverse renal events (MAKE) were examined.

Study found that, in addition to acute illness, COVID-19 survivors exhibited a higher risk of AKI compared to controls, exhibited excessive eGFR decline, acute infection, hospitalization and the eGFR of patients in intensive care decreased by 3.26, 5.2, and 7.69, respectively.

The researchers further examined the risk and burden of kidney disease in infected individuals based on disease severity during the acute phase of infection (ambulatory, hospitalized, and intensive care). They found that the risk and burden of kidney disease increased in those infected after the acute phase of the disease compared with controls, and that the more severe the infection, the higher the risk of acute kidney outcomes.

The above study analyzed the relationship between the new coronavirus infection and the renal outcomes of patients. Infection with the new crown will have a negative impact on the human kidneys. However, previous studies have shown that in addition to the new coronavirus, there are viruses such as influenza It will also have certain effects on the human kidneys, and this effect is not irreversible. Therefore, don’t be too fearful about the widely circulated topic that “the new crown will lead to renal failure in the future”, but at the same time, for your own health, you must also take preventive and control measures to reduce infection.

Writing | Mu Zijiu

Typesetting|Feng Lixiao


[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.

[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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