COVID-19 Is Closely Related To Kidney Disease. These 4 Studies Tell You Coping Strategies

The COVID-19 epidemic at the end of 2019 seems to have faded away, but there are many people with a history of COVID-19 infection in our country. So, are patients with a history of COVID-19 infection more likely to develop kidney disease than patients who have not been infected with COVID-19? Is the development pattern of kidney disease different from that of uninfected people? In addition, how to prevent and treat kidney damage caused by COVID-19?

From April 13 to 16, 2024, the 2024 World Congress on Nephrology (WCN) opened in Argentina, the country farthest from our country. At this conference, a total of more than 1,000 abstracts were exhibited. Among these abstracts, 4 abstracts revealed the relationship between COVID-19 and kidney disease.

Click to Cistanche for kidney disease

   Important information

① COVID-19 patients are at increased risk of developing renal insufficiency;

② Obese COVID-19 patients have more severe glomerular damage, which may be related to an increased risk of kidney disease;

③ COVID-19 may cause excessive activation of the complement system in patients with IgA nephropathy;

For hemodialysis patients, tixagevimab and cilgavima can prevent infection and reduce the risk of patients becoming severely ill after being infected with COVID-19.

1 COVID-19 and renal insufficiency 1

Research background: Previous studies have shown that during the period of COVID-19 infection, patients' risk of renal dysfunction increases sharply, including acute kidney injury (AKI), glomerular disease, and chronic kidney disease (CKD). However, the long-term outcomes of people who have recovered from COVID-19/who have long-term COVID-19 still need to be further explored. In order to evaluate the impact of COVID-19 on human kidneys, scholars from Brazil conducted this study.

Research design: From July 2021 to October 2022, 45 COVID-19 patients were referred for follow-up in the nephrology clinic. Patient baseline characteristics, admission data, and renal function outcomes were recorded.

Research results: 31 patients were hospitalized due to COVID-19 complications, and the remaining patients were transferred to the Department of Nephrology after COVID-19 outpatient treatment. The main reasons for referral include COVID-19-related AKI, renal insufficiency after COVID-19 infection, and/or urinary system abnormalities (hematuria and proteinuria). The median age of patients was 61 (IQR 23 ~ 86) years, and 53.5% were male. The most common comorbidities were hypertension (80%), obesity (55.6%), and diabetes (42.2%). Among the hospitalized patients, 17 (54.8%) developed severe AKI requiring dialysis, and their renal function recovered before discharge. The median hospital stay was 32 days (IQR: 16-55 days), and the serum creatinine level at discharge was 1.32 (IQR: 1.05-1.70 mg/dL). Among all patients, hematuria occurred in 26.2% and proteinuria (>0.5g/g creatinine) in 21.2%. One patient with nephrotic-range proteinuria (4.7 g/g creatinine) underwent renal biopsy for minimal change nephropathy. After an average follow-up of 164 days (IQR: 38 to 458 days), the median creatinine was 1.4 mg/dL (IQR 0.6 to 4.3), and the median estimated glomerular filtration rate was 49.7 mL/min/1.73㎡ (IQR: 12.2 ~ 118.5). 26 patients (57.8%) had eGFR < 60 mL/min/1.73㎡. Age > 65 years (RR=3.65; 95% CI, 1.21~10.46) and having more than 3 comorbidities (RR=2.93; 95% CI, 1.27~6.76) are associated with eGFR < 60mL/min/1.73㎡. One patient eventually required chronic peritoneal dialysis.

Research conclusion: Similar to some reports, a considerable number of patients will develop renal dysfunction after COVID-19 infection. This emphasizes the importance of renal monitoring in the management of COVID-19 infection. A multidisciplinary approach including early nephrology referral, regular renal function monitoring, and personalized treatment strategies may help mitigate renal sequelae and improve quality of life in this patient population. Further studies with larger cohorts and long-term follow-up are recommended to better elucidate the long-term effects of COVID-19 on the kidneys.

So, which COVID-19 patients are more likely to develop kidney damage? The next study will tell you

2. Obese COVID-19 patients and glomerular damage 2

Research background: Previous studies have confirmed that the prognosis of obese COVID-19 patients is worse than that of non-obese COVID-19 patients, and may be associated with more complications, such as renal dysfunction. Systemic inflammation, related comorbidities, renal hemodynamics, and infection with COVID-19 in obese patients may directly damage the patient's glomerulus. So is this really the case?

Research design: This study included 91 unvaccinated severe COVID-19 patients from 2020 to 2021, and collected the patients' clinical data, laboratory indicators, renal indicators (proteinuria, albuminuria, creatinine, and urea), as well as the need for dialysis and symptom outcomes including ventilator support and death. ELISA method was used to detect renal biomarkers (NGAL, KIM-1, MCP-1, and Nephrin) and endothelial biomarkers (VCAM-1, angiopoietin, syndecan-1).

Research results: Among 91 severe COVID-19 patients, 23 (25%) were obese. Obesity is associated with younger age, comorbidities, and the need for dialysis. No association with death was observed. Analysis of most laboratory data, including traditional renal biomarkers, hematology, liver, and coagulation parameters, found no statistically significant associations. On the other hand, urinary MCP-1 and VCAM-1 were significantly increased in association with the obese group. In multivariate analysis, age was an independent influencing factor for the need for dialysis, while urinary MCP-1 and age were independent influencing factors for death.

Research conclusion: Compared with patients without obesity, severe COVID-19 patients with obesity have elevated levels of glomerular damage biomarkers, indicating glomerular damage.

So, will COVID-19 infection affect the clinical or pathological manifestations of kidney disease? See the next study.

3. COVID-19 and IgA nephropathy 3

Research background: A new coronavirus infection can cause the rapid emergence of immune-mediated diseases, forming an immune storm, which has a major impact on the patient's body. Some cases suggest that COVID-19 infection seems to increase the risk of IgA nephropathy because IgA nephropathy is an autoimmune-mediated disease. So, is this true? Moreover, compared with patients who have not been infected with COVID-19, are there any significant differences in the pathological manifestations of IgA nephropathy patients who have been infected with COVID-19?

Research design: 33 patients diagnosed with IgAN by renal biopsy at Beijing Anzhen Hospital from December 2022 to April 2023 and with COVID-19 infection before renal biopsy were included (Group A). At the same time, 44 IgAN patients (group B) diagnosed from December 2018 to April 2019 (the same period in the previous year) were selected as controls. Enzyme-linked immunosorbent assay was used to detect plasma FHR-5, MBL, C5a, soluble C5b-9, and serum Gd-IgA1 and IgA immune complexes. The immunofluorescence method was used to detect the expression of glomerular FHR-5, C3c, MAC, and Gd-IgA1. Immunohistochemistry was used to detect SARS-COV-2 nucleocapsid and RNA in renal biopsy specimens.

This study mainly analyzed the clinicopathological and immunological characteristics of the two groups of patients.

Research results: The median time from the onset of COVID-19 symptoms to renal biopsy was 12 (6, 18) weeks, with a range of 1 to 26 weeks. 30 cases (90.9%) had been vaccinated before being infected with COVID-19. SARS-COV-2 nucleocapsid antigen expression was observed in renal tubular epithelial cells in 11 patients (33.3%). Compared with group B, group A had significantly lower eGFR levels (p=0.010). Histologically, compared with group B, patients with IgA nephropathy in group A had a higher proportion of segmental glomerulosclerosis/adhesions (p=0.003) and a lower proportion of mesangial cell hyperplasia (p=0.017). Plasma C5a (p<0.001), soluble C5b-9 (p=0.018), and FHR5 (p<0.001) levels in group A were significantly higher than those in group B. Even though plasma MBL levels did not differ between groups A and B (p=0.318), we found that more patients in group A presented high-level MBL expression (p=0.025). Compared with group B, patients with IgA nephropathy in group A had stronger MAC deposition intensity (p=0.246). There was no statistically significant difference in serum IgA (p=0.129), Gd-IgA1 (p=0.734), and IgA immune complex (p=0.524) levels between groups A and B, but the glomerular mesangium of patients with IgA nephropathy in group A The Gd-IgA1 deposition intensity in the area and capillary area was higher than that in group B (p=0.005).

Research conclusion: Enhanced activation of the complement system was found in patients diagnosed with IgA nephropathy after COVID-19 infection. In addition, compared with IgA nephropathy patients without COVID-19, the pathogenic deposition of Gd-IgA1 in the glomerular mesangial area of IgA nephropathy patients with COVID-19 was more obvious. Excessive activation of the complement system and deposition of pathogenic Gd-IgA1 may be one of the reasons for the progression of renal disease in patients with COVID-19 combined with IgA nephropathy.

Since COVID-19 is so harmful to patients' kidneys, how can doctors manage patients with kidney disease and reduce COVID-19-related hazards? See the next study.

4 Hemodialysis patients and two monoclonal antibodies 4

Research background: After hemodialysis patients are infected with COVID-19, they are prone to develop severe disease, and their long-term prognosis is worse than that of healthy people. Moreover, due to the low immunity of hemodialysis patients, some COVID-19 vaccines cannot fully immunize hemodialysis patients against COVID-19 infection. Moreover, even hemodialysis patients who have been infected with COVID-19 may still be infected again. So, can the monoclonal antibodies tixagevimab and cilgavimab against different SARS-Cov-2 strains effectively prevent hemodialysis patients from being infected with the new coronavirus or reduce the development of severe disease in infected patients?

Research design: This study is a prospective open study, including a total of 26 long-term hemodialysis patients, with an average age of (57.4±19.6) years, 10 women and 16 men. All patients had other risk factors for severe COVID-19 infection (16 cases of cardiovascular disease, 6 cases of diabetes, and 4 cases of obesity). All participants had received the GAMCOVID-Vac vaccine (Sputnik V) 1 year ± 4 months ago. 12 patients were infected with COVID-19 1 year ago. There were 144 long-term hemodialysis patients in the control group, with an average age of (56.2±18.3) years, including 68 women and 76 men. In this study, 300 mg each of tixagevimab and cilgavimab was injected intramuscularly after hemodialysis.

This study was conducted from February 2023 to August 2023. The total titer of RBD-specific IgG antibodies was estimated using the SARS-CoV-2-RBD-ELISA kit. SARS-CoV-2 virus-specific IgG-negative serum samples with dilutions of 1:50 to 1:1638400 were initially prepared as controls. Using a "constant virus dose-multiple serum dilution" design, virus-neutralizing antibodies (VNA) levels were determined through neutralization reactions. Prepare 2-fold dilutions of control serum and test serum in DMEM medium containing 2% inactivated fetal calf serum, mix with 100 TCID50 SARS-CoV-2 virus, incubate at 37°C for 1 hour, and then add Vero E6 cells. Cells were grown at 37°C in a carbon dioxide-rich environment. After 96 hours, the cytopathic effects of the virus on the cell cultures were assessed visually by assessing the disruption of the cell monolayer. The SPSS-20 program was used to calculate the non-parametric Wilcoxon criterion analysis results, and the reliability of the criterion was p<0.05 (95%).

Research results: The study found that the total amount of IgG in patients increased significantly after 90 days. The dynamic changes in virus-neutralizing activity titers on cell lines show that both tixagevimab and cilgavimab can significantly improve the body's response to different SARS-Cov-2 strains.

Research conclusion: Although tixagevimab and cilgavimab have no specific antiviral activity against the new coronavirus strain, especially the new strain, they can effectively prevent hemodialysis patients from progressing to severe disease.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.