Causal association between cardiovascular proteins and membranous nephropathy: a bidirectional Mendelian randomization.

PURPOSE: Multiple circulating proteins have been reported to participate in human diseases. However, the association between cardiovascular proteins and membranous nephropathy (MN) remained profoundly elusive. METHODS: A bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal correlation between ninety cardiovascular proteins and MN. Genome-wide association study (GWAS) data of cardiovascular proteins and MN were all from European research. Inverse variance weighted (IVW) was used as the main approach. Moreover, MR-Egger, weighted median, weighted mode, and simple mode were also performed. Cochrane's Q test, MR-Egger, and MR-PRESSO were conducted for sensitivity analysis. RESULTS: According to IVW method, fatty acid-binding protein and thrombomodulin (TM) were identified as risk factors for MN, while a protective role was detected in tissue-type plasminogen activator. Additionally, MN was associated with an elevated level of macrophage colony-stimulating factor 1, stem cell factor, TM, and tissue factor. Reversely, MN was also correlated with a downregulated level of beta-nerve growth factor, Cathepsin D, hepatocyte growth factor, interleukin-6 receptor subunit alpha, macrophage colony-stimulating factor 1, and myeloperoxidase. In the sensitivity analysis, no significant pleiotropy and heterogeneity was detected. CONCLUSION: This was the first study to reveal the causal association between cardiovascular proteins and MN. These specific cardiovascular proteins could be novel biomarkers for MN, and is helpful for timely identify the risk of other diseases that might result from MN. However, further clinical studies are needed to confirm our results.

The causal association of specific gut microbiota on the risk of membranous nephropathy: a Mendelian randomization study.

PURPOSE: Gut microbiota transplantation has been reported to improve the renal function of membranous nephropathy (MN). However, whether there is a causal effect of gut microbiota on MN remained unclear. METHODS: We performed two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used as the main approach to evaluate the causal relationship between gut microbiota and MN. Additional methods including MR-Egger regression, weighted median, and MR-weighted mode were also conducted. Cochrane's Q test, MR-Egger regression, and MR-PRESSO were employed to detect heterogeneity and pleiotropy, respectively. RESULTS: A total of 196 gut microbiota were examined. After IVW and sensitivity analysis, eight gut bacteria taxa were observed causal effects on the risk of MN. Specifically, Genus. Oscillibacter was a protective factor (OR: 0.57; 95% CI 0.328-0.979; P = 0.042), while Class. Melainabacteria (OR: 1.51; 95% CI 1.004-2.277; P = 0.048), Genus. Butyricicoccus (OR: 2.16; 95% CI 1.005-4.621; P = 0.048), Genus. Catenibacterium (OR: 1.49; 95% CI 1.043-2.134; P = 0.028), Genus.Ruminiclostridium5 (OR: 1.74; 95% CI 1.053-2.862; P = 0.030), Genus. Ruminococcaceae UCG-003 (OR: 1.73; 95% CI 1.110-2.692; P = 0.015), Order. Bacillales (OR: 1.52; 95% CI 1.135-2.025; P = 0.0048) and Order. Gastranaerophilales (OR: 1.45; 95% CI 1.010-2.085; P = 0.044) were risk factors. Heterogeneity was not significant for most single-nucleotide polymorphisms, and no statistical difference in pleiotropy. CONCLUSIONS: This study first indicated the causal association between specific gut microbiota and MN, which would be of great significance to guide clinical prevention and treatment in MN.

New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review.

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN.

Combination of rituximab and short-term glucocorticoids in the treatment of anti-phospholipase A2 receptor antibody positive idiopathic membranous nephropathy.

Rituximab (RTX) has been the first option in idiopathic membranous nephropathy (IMN). However, the clinical effect was not very satisfactory. This study aimed to explore the clinical efficacy and safety of the combination of RTX and glucocorticoids (GC) in anti-phospholipase A2 receptor (anti-PLA2R) antibody positive IMN. Sixty-six patients were randomly divided into RTX/GC group (RTX infusion plus short-term oral GC) and RTX group (RTX infusion alone) in this prospective cohort study. Complete remission (CR) and partial remission (PR) were the primary outcomes. Adverse events were the secondary outcomes. The laboratory index including serum albumin, 24 h urinary protein, serum creatinine, estimated glomerular filtration rate, and anti-PLA2R antibody titer were also monitored. All patients were followed for at least 12 months. During the 12-month follow-up, the composite remission rates in RTX/GC and RTX groups were 74.3% and 67.7%, and the CR rates were 34.3% and 19.4%, respectively. The median time of remission in RTX/GC group was shorter than the RTX group (P < 0.001). Compared with RTX monotherapy, the combination of RTX and GC significantly decreased the anti-PLA2R antibody titer (P = 0.028). No significant difference was observed in the incidence of adverse events. The results of the Kaplan-Meier survival analysis indicated that the cumulative CR rate and cumulative composite remission rate in RTX/GC group were all better than the RTX group (P = 0.043, P = 0.040, respectively). The combination of RTX and GC was better than RTX monotherapy without increasing the adverse events in the treatment of IMN.

The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis.

Although the "multiple hits" theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-ß (TGF-ß), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule.

New Insights into Kidney Disease after COVID-19 Infection and Vaccination: Histopathological and Clinical Findings.

In addition to its pulmonary effects, COVID-19 has also been found to cause acute kidney injury (AKI), which has been linked to high mortality rates. In this review, we collected data from 20 clinical studies on post-COVID-19-related AKI and 97 cases of AKI associated with COVID-19 vaccination. Acute tubular injury was by far the most common finding in the kidneys of patients with COVID-19-related AKI. Among patients hospitalized for COVID-19, 34.0% developed AKI, of which 59.0%, 19.1%, and 21.9% were stage 1, 2, and 3, respectively. Though kidney disease and other adverse effects after COVID-19 vaccination overall appear rare, case reports have accumulated suggesting that COVID-19 vaccination may be associated with a risk of subsequent kidney disease. Among the patients with post-vaccination AKI, the most common pathologic findings include crescentic glomerulonephritis (29.9%), acute tubular injury (23.7%), IgA nephropathy (18.6%), ANCA-associated vasculitis (17.5%), minimal change disease (17.5%), and thrombotic microangiopathy (10.3%). It is important to note that crescentic glomerulonephritis appears to be more prevalent in patients who have newly diagnosed renal involvement. The proportions of patients with AKI stages 1, 2, and 3 after COVID-19 vaccination in case reports were 30.9%, 22.7%, and 46.4%, respectively. In general, clinical cases of new-onset and recurrent nephropathy with AKI after COVID-19 vaccination have a positive prognosis. In this article, we also explore the underlying pathophysiological mechanisms of AKI associated with COVID-19 infection and its vaccination by describing key renal morphological and clinical features and prognostic findings.

New-onset and relapsed thrombotic microangiopathy post-COVID-19 vaccination.

Thrombotic microangiopathy (TMA) associated with coronavirus disease 2019 (COVID-19) vaccination has been reported, however, the clinical characteristics and pathogenesis remained mysterious. We reviewed 84 TMA cases post-COVID-19 vaccination, including 64 patients diagnosed with thrombotic thrombocytopenic purpura (TTP), 17 cases presented as atypical hemolytic uremic syndrome (aHUS), and three cases manifested as unclassified TMA. TMA episodes were mostly associated with messenger RNA vaccines. For TTP, 67.6% of females developed symptoms after the first dose of the vaccine, and 63.0% of males were secondary to the second dose (p = 0.015). Compared with TTP, aHUS generally appeared within 7 days (p = 0.002) and showed higher levels of serum creatinine (p < 0.001). 87.5% of TTP received plasma exchange (PEX)-based treatment, and 52.9% of aHUS adopted non-PEX-based therapies (p < 0.001). Mechanistically, complement dysfunction, neutrophil activation, and the generation of pathogenic autoantibodies resulting from molecular mimicry contribute to explaining the pathogenesis of TMA post-COVID-19 vaccination.

Inverse association between caffeine intake and albuminuria in US adults: an analysis of NHANES 2005-2016.

OBJECTIVES: Albuminuria is a significant biomarker of various kidney diseases and is associated with renal outcome. Recently, caffeine intake has shown potential renoprotective effects. However, the relationship between caffeine intake and albuminuria remains profoundly elusive. METHODS: We conducted a cross-sectional study aimed to explore the association between caffeine intake and albuminuria in the American adult population using the data acquired from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Caffeine intake was assessed by 24-h dietary recalls, and albuminuria was assessed by albumin-to-creatinine ratio. Multivariate logistic regression was performed to explore the independent association between caffeine intake and albuminuria. Subgroup analysis and interaction tests were also conducted. RESULTS: Among 23,060 participants, 11.8% of the individuals exhibited albuminuria, and the prevalence of albuminuria decreased with higher caffeine intake tertiles (Tertile 1: 13%; Tertile 2: 11.9%; Tertile 3: 10.5%; P < 0.001). After adjusted potential confounders, the results of logistic regression indicated that a higher caffeine intake was associated with a decreased risk of albuminuria (OR = 0.903; 95% CI: 0.84, 0.97; P = 0.007), especially in females and the participants aged <60 years and chronic kidney disease stage II. CONCLUSION: The present study first indicated an inverse correlation between caffeine intake and albuminuria, which further confirmed the potentially protective effects of caffeine on the kidney.

SARS-CoV-2 infection and COVID-19 vaccination in cancer patients undergoing immune checkpoint inhibitors.

Cancer patients are susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Different antitumor treatments have attracted wide attention in the context of coronavirus disease 2019 (COVID-19), especially immune checkpoint inhibitors (ICIs) that have revolutionized oncology changes. It may also have protective and therapeutic roles in viral infections. In this article, we collected 26 cases of SARS-CoV-2 infection during ICIs therapy and 13 related to COVID-19 vaccination from Pubmed, EMBASE, and Wed of Science. Of these 26 cases, 19 (73.1%) presented mild cases and 7 (26.9%) were severe cases. Melanoma (47.4%) was a common cancer type in mild cases and lung cancer (71.4%) in severe cases (P = 0.016). The results showed that their clinical outcomes varied widely. Although there are similarities between the immune checkpoint pathway and COVID-19 immunogenicity, ICIs therapy overactivated T cells, which often leads to immune-related adverse events. In fact, the COVID-19 vaccine has been shown to be safe and effective in patients treated with ICIs. In this review, we report the vital clinical observations of SARS-CoV-2 infection or vaccination in cancer patients treated with ICIs and explore the potential interaction between them.

Membranous nephropathy caused by dimercaptosuccinic acid in a patient with Wilson's disease: a case report and literature review.

BACKGROUND: Dimercaptosuccinic acid (DMSA) therapy is a kind of chelation therapy for patients with Wilson 's disease (WD). While there have been reports of side effects associated with DMSA, the development of membranous nephropathy as a result of this therapy is uncommon. CASE PRESENTATION: We present a case of a 19-year-old male patient with Wilson's disease who experienced proteinuria while receiving long-term DMSA treatment. Further evaluation revealed abnormally low levels of serum ceruloplasmin and serum albumin, as well as a 24-hour urinary protein excretion of 4599.98 mg/24 h. A renal biopsy confirmed the presence of membranous nephropathy. After ruling out other potential causes, we determined that the patient's membranous nephropathy was likely caused by DMSA. Following treatment with glucocorticoids, there was a significant reduction in proteinuria. CONCLUSION: This case highlights the possibility of DMSA-induced membranous nephropathy and the importance of considering this diagnosis in patients receiving DMSA treatment. Given the widespread use of DMSA in the treatment of Wilson's disease, further research is needed to fully understand the potential role of this drug in the development of membranous nephropathy.

New insights of antineutrophil cytoplasmic antibody-associated vasculitis from the perspective of COVID-19 vaccination.

The occurrence of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) has been reported since the coronavirus disease 2019 (COVID-19) vaccination, but whether there is a causal relationship or coincidence remains to be verified. We combined the term COVID-19 vaccination with each word of AAV to search for case reports and case series published in PubMed, EMBASE, and Web of Science databases before 13 March 2023. A total of 56 patients who developed AAV after COVID-19 vaccination were identified from 44 research centers. Of the 56 subjects, 43 (76.7%) were vaccinated with the mRNA vaccine, followed by the adenovirus vaccine (14.3%) and inactivated vaccine (9.0%) (P = 0.015). Compared with relapsed AAV, new-onset AAV patients had at least two other diseases previously (P < 0.001). Twenty-five (44.6%) patients presented symptoms after the first injection, and the medium onset time was 12 (1-77) days, while Twenty-eight (50.0%) patients developed symptoms after the second dose, and their medium period was 14 (1-60) days. Forty-four (78.5%) patients achieved remission after immunosuppressive agents, plasma exchange, and hemodialysis. One (1.8%) patient died from progressive respiratory failure and nine (16.1%) did not recover, leaving five patients permanently dependent on hemodialysis. Pathogenic ANCA may be activated by enhanced immune response and epitope spreading after COVID-19 vaccination and induced the occurrence of AAV, especially in genetically susceptible populations.

Update on the Application of Monoclonal Antibody Therapy in Primary Membranous Nephropathy.

When first introduced, rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, brought about an alternative therapeutic paradigm for primary membranous nephropathy (PMN). Rituximab was shown to be effective and safe in PMN patients with kidney dysfunction, with. patients receiving second-line rituximab therapy achieving remission as effectively as those patients who had not previously received immunotherapy. No safety issues were reported. The B cell-driven protocol seems to be as efficient as the 375 mg/m2 × 4 regimen or 1 g × 2 regimen in achieving B cell depletion and remission, but patients with high M-type phospholipase A2 receptor (PLA2R) antibody levels may benefit from a higher dose of rituximab. While rituximab added another therapeutic option to the treatment regimen, it does have limitations as 20 to 40% of patients do not respond. Not all patients respond to RTX therapy for lymphoproliferative disorders either, therefore further novel anti-CD20 monoclonal antibodies have been developed and these may provide alternative therapeutic options for PMN. Ofatumumab, a fully human monoclonal antibody, specifically recognizes an epitope encompassing both the small and large extracellular loops of the CD20 molecule, resulting in increased complement-dependent cytotoxic activity. Ocrelizumab binds an alternative but overlapping epitope region to rituximab and displays enhanced antibody-dependent cellular cytotoxic (ADCC) activities. Obinutuzumab is designed to have a modified elbow-hinge amino acid sequence, leading to increased direct cell death induction and ADCC activities. In PMN clinical studies, ocrelizumab and obinutuzumab showed promising results, while ofatumumab displayed mixed results. However, there is a lack of randomized controlled trials with large samples, especially direct head-to-head comparisons. Alternative molecular mechanisms have been suggested in this context to explore novel therapeutic strategies. B cell activator-targeted, plasma cell-targeted and complement-directed treatments may lead to novel therapy paradigms for PMN. Exploratory strategies for the use of drugs with different mechanisms, such as a combination of rituximab and cyclophosphamide and a steroid, a combination of rituximab and a calcineurin inhibitor, may provide more rapid and efficient remission, but the combination of standard immunosuppression with rituximab could increase infection risk.

Clinical manifestations of COVID-19 infection in dialysis patients and protective effect of COVID-19 vaccine.

BACKGROUND AND OBJECTIVE: COVID-19 infection poses a special challenge to patients with dialysis patients. The purpose of this study was to evaluate the clinical manifestations of dialysis patients with COVID-19 and the protective effect of the vaccine. METHODS: We included 41 studies based on big data, mainly analyzing the clinical symptoms of dialysis patients with COVID-19, the proportion of severe patients before and after vaccination, and the humoral reaction of vaccine in the body. RESULTS: 6.1% to 35.7% of dialysis patients with COVID-19 developed respiratory distress symptoms and needed to be admitted to an intensive care unit for mechanical ventilation. The incidence and mortality of COVID-19 in dialysis patients before vaccination were 5.5% and 1.1%, respectively, and decreased to 4.5% and 0.6% in breakthrough infected patients. There was no statistical difference in serum conversion rates between dialysis patients and healthy controls, but the neutralizing antibody titer in the control group was 1922 (IQR 533 to 3186) AU/mL, and the neutralizing antibody titer in dialysis patients significantly decreased to 367 (IQR 171 to 1650) AU/mL (P=0.046). CONCLUSIONS: Dialysis is associated with an increased risk of severe COVID-19, and generally has a poor seroconversion response to vaccines. It also confirms the protective effect of vaccines on high-risk populations such as dialysis.

New insights into the mucosal immune pathogenesis of IgA nephropathy from the perspective of COVID-19 vaccination.

Large-scale SARS-CoV-2 vaccination is one of the key strategies to curb the COVID-19 pandemic; however, there are increasing reports of IgA nephropathy following COVID-19 vaccination. The clinical manifestation, treatment and prognostic effects are different in IgAN patients who have had an onset after the first and second dose of vaccination, as well as new and recurrent IgAN patients. These conditions bring about a relatively important window for understanding the pathogenesis of IgAN. Gd-IgA1 is the core of the pathogenesis of IgAN. Most IgA is produced at mucosal sites; however, antigen-activated Toll-like receptor activation pathways expressed by antigen-presenting cells and B-cell homing receptors are different in the intestinal and respiratory mucosa, and the link between respiratory and intestinal mucosa is not well understood in the pathogenesis of IgAN. Budesonide treatment of IgAN is thought to inhibit the intestinal immune response by binding to glucocorticoid receptors in the intestinal mucosa or submucosa; however, it is unclear whether there is a therapeutic effect in respiratory mucosa-derived IgA nephropathy. The present review firstly described the relationship between the gut and respiratory mucosa, and the differences in antigen-presenting cell activation pathways and B-cell homing from the perspective of COVID-19 vaccines.

New-onset IgA nephropathy following COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant economic and health damage worldwide. Rapid vaccination is one of the key strategies to curb severe illness and death due to SARS-CoV-2 infection. Hundreds of millions of people worldwide have received various COVID-19 vaccines, including mRNA vaccines, inactivated vaccines and adenovirus-vectored vaccines, but the side effects and efficacy of most vaccines have not been extensively studied. Recently, there have been increasing reports of immunoglobulin A nephropathy (IgAN) after COVID-19 vaccination, however, whether their relationship is causal or coincidental remains to be verified. Here, we summarize the latest clinical evidence of IgAN diagnosed by renal biopsy associated with the COVID-19 vaccine published by 10 July 2022 with the largest sample size, and propose a hypothesis for the pathogenesis between them. At the same time, the new opportunity presented by COVID-19 vaccine allows us to explore the mechanism of IgAN recurrence for the first time. Indeed, we recognize that large-scale COVID-19 vaccination has enormous benefits in preventing COVID-19 morbidity and mortality. The purpose of this review is to help guide the clinical assessment and management of IgA nephropathy post-COVID-19 vaccination and to enrich the 'multi-hit' theory of IgA nephropathy.

Efficacy of low or heavy rituximab­based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.

OBJECTIVE: Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment. METHODS: Randomized controlled trials (RCTs) and observational studies analyzing nine therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. RESULTS: Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6 months (92%) and 12 months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6 months (78.8% and 65.4%, separately) and decreased at 12 months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12 months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose). CONCLUSIONS: For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12 months was higher than that at 6 months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).

Comprehensive analyses of the microRNA-messenger RNA-transcription factor regulatory network in mouse and human renal fibrosis.

Objective: The aim of this study was to construct a microRNA (miRNA)-messenger RNA (mRNA)-transcription factor (TF) regulatory network and explore underlying molecular mechanisms, effective biomarkers, and drugs in renal fibrosis (RF). Methods: A total of six datasets were downloaded from Gene Expression Omnibus. "Limma" and "DESeq2" packages in R software and GEO2R were applied to identify the differentially expressed miRNAs and mRNAs (DEmiRNAs and DEmRNAs, respectively). The determination and verification of DEmiRNAs and DEmRNAs were performed through the integrated analysis of datasets from five mouse 7 days of unilateral ureteral obstruction datasets and one human chronic kidney disease dataset and the Human Protein Atlas (http://www.proteinatlas.org). Target mRNAs of DEmiRNAs and TFs were predicted by prediction databases and the iRegulon plugin in Cytoscape, respectively. A protein-protein interaction network was constructed using STRING, Cytoscape v3.9.1, and CytoNCA. Functional enrichment analysis was performed by DIANA-miRPath v3.0 and R package "clusterProfiler." A miRNA-mRNA-TF network was established using Cytoscape. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic value of the key hub genes. Finally, the Comparative Toxicogenomics Database and Drug-Gene Interaction database were applied to identify potential drugs. Results: Here, 4 DEmiRNAs and 11 hub genes were determined and confirmed in five mouse datasets, of which Bckdha and Vegfa were further verified in one human dataset and HPA, respectively. Moreover, Bckdha and Vegfa were also predicted by miR-125a-3p and miR-199a-5p, respectively, in humans as in mice. The sequences of miR-125a-3p and miR-199a-5p in mice were identical to those in humans. A total of 6 TFs were predicted to regulate Bckdha and Vegfa across mice and humans; then, a miRNA-mRNA-TF regulatory network was built. Subsequently, ROC curve analysis showed that the area under the curve value of Vegfa was 0.825 (p = 0.002). Finally, enalapril was identified to target Vegfa for RF therapy. Conclusion: Pax2, Pax5, Sp1, Sp2, Sp3, and Sp4 together with Bckdha-dependent miR-125a-3p/Vegfa-dependent miR-199a-5p formed a co-regulatory network enabling Bckdha/Vegfa to be tightly controlled in the underlying pathogenesis of RF across mice and humans. Vegfa could act as a potential novel diagnostic marker and might be targeted by enalapril for RF therapy.

ANCA-associated vasculitis following the CoronaVac vaccination.

With the coronavirus disease 2019 (COVID-19) pandemic, vaccination has become one of the cornerstones to contain the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large clinical trials have shown high efficacy and safety of SARS-CoV-2 vaccination against COVID-19. However, with the widespread use of SARS-CoV-2 vaccines worldwide, an increasing number of reports describe the onset of glomerular disease. Here, we report a case of a 70-year-old Chinese woman who developed new antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis within 4 h post the first dose of CoronaVac. CoronaVac is an inactivated SARS-CoV-2 vaccine developed by Sinovac Life Sciences (Beijing, China). Her clinical symptoms were nausea, fatigue, acute kidney injury, and proteinuria. Laboratory tests showed markedly elevated serum myeloperoxidase titers, and the renal biopsy showed microcellular fibrous crescent formation. Renal function of the patient responded favorably after treatment with steroids and cyclophosphamide. Although there is no direct evidence of a link between vasculitis and vaccination, similar complications should be monitored as potential adverse events with widespread vaccination globally.

The optimal interval before receiving SARS-COV-2 vaccination for patients who have received Anti-CD 20 monoclonal antibodies.

The optimal interval before receiving SARS-COV-2 vaccination for patients who have received anti-CD 20 monoclonal antibodies remains unclear. We considered original studies up to 29 October 2022 and conducted searches in Embase,Medrxiv, PubMed, and SSRN. We excluded search results that did not match our research question's subject. Human immune response outcomes were analysed inpatients who had previously received anti-CD20 antibody therapy. We analyzed the collected results using sensitivity curves and forest plots. Twenty-eight studies with a total of 1455 subjects receiving anti-CD20 monoclonal antibodies were included in the present analysis. The humoral immune response rates to the time between the last anti-CD20 treatment and vaccination for 3-6 months, 6 months,6-9 months, and 9-12 months were 0.23 (95% CI 0.14 to 0.36), 0.36 (95% CI 0.19 to 0.58), 0.49 (95% CI 0.35 to 0.64) and 0.64 (95% CI 0.48 to 0.77),respectively. The humoral immune response rates were.16 (95% CI 0.03 to 0.57) when B cell was 0/ul, and 0.49 (95% CI 0.38 to 0.61)when B cells were more than 5/ul. The humoral immune response rate for multiple sclerosis was 0.39 (95% CI 0.22 to 0.60) and 0.48 (95% CI 0.29 to 0.68) for B-cell non-Hodgkin lymphoma. The area underneath the curve(AUC) was 0.69 with a cut-off value of 5.5 months. The present results suggested that the optimal interval for SARS-COV-2 vaccination after the final dose of anti-CD20 monoclonal antibody was 5.5 months.

An update on the interaction between COVID-19, vaccines, and diabetic kidney disease.

Up to now, coronavirus disease 2019 (COVID-19) is still affecting worldwide due to its highly infectious nature anrapid spread. Diabetic kidney disease (DKD) is an independent risk factor for severe COVID-19 outcomes, and they have a certain correlation in some aspects. Particularly, the activated renin-angiotensin-aldosterone system, chronic inflammation, endothelial dysfunction, and hypercoagulation state play an important role in the underlying mechanism linking COVID-19 to DKD. The dipeptidyl peptidase-4 inhibitor is considered a potential therapy for COVID-19 and has similarly shown organ protection in DKD. In addition, neuropilin-1 as an alternative pathway for angiotensin-converting enzyme 2 also contributes to severe acute respiratory syndrome coronavirus 2 entering the host cells, and its decreased expression can affect podocyte migration and adhesion. Here, we review the pathogenesis and current evidence of the interaction of DKD and COVID-19, as well as focus on elevated blood glucose following vaccination and its possible mechanism. Grasping the pathophysiology of DKD patients with COVID-19 is of great clinical significance for the formulation of therapeutic strategies.