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.

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.

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.

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.

Sodium glucose cotransporter 1 (SGLT1) inhibitors in cardiovascular protection: Mechanism progresses and challenges.

In recent years, multiple clinical trials have shown that sodium glucose cotransporter 1 (SGLT1) inhibitors have significant beneficial cardiovascular effects. This includes reducing the incidence of cardiovascular deaths and heart failure hospitalizations in people with and without diabetes, as well as those with and without generalized heart failure. The exact mechanism responsible for these beneficial effects is not completely understood. To explain the cardiovascular protective effects of SGLT1 inhibitors, several potential arguments have been proposed, including decreasing oxidative stress, regulating cardiac glucose uptake, preventing ischemia/reperfusion injury, alleviating the activation of cardiac fibroblasts, attenuating apoptosis, reducing intermittent high glucose-induced pyroptosis, ameliorating cardiac hypertrophy, attenuating arrhythmic vulnerabilities, and improving left ventricular systolic disorder. This article reviews the advantages and disadvantages of these mechanisms, and attempts to synthesize and prioritize mechanisms related to the reduction of clinical events.

Treatment of Idiopathic Membranous Nephropathy for Moderate or Severe Proteinuria: A Systematic Review and Network Meta-Analysis.

Objective: Numerous studies have demonstrated that the efficacy of drugs differs in idiopathic membranous nephropathy (IMN) patients with moderate or high proteinuria. However, there is no systematic comparison confirming it. This network meta-analysis (NMA) was performed to respectively compare the efficacy of ten IMN treatments in patients with moderate and high proteinuria and compare the risk of adverse events with 10 IMN regimens. Methods: Randomized controlled trials (RCTs) and observational studies analyzing the main therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR), bone marrow suppression, and gastrointestinal symptoms. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions. Results: Seventeen RCTs and eight observational studies involving 1778 patients were pooled for comparison of ten interventions. Steroid + tacrolimus (TAC) showed the highest probabilities of TR whether patients had severe proteinuria or not (SUCRA 89.5% and 88.9%, separately). Rituximab (RTX) was more beneficial for TR on patients with proteinuria <8 g/d (SUCRA 66.0%) and was associated with a lower risk of bone marrow suppression and gastrointestinal symptoms (SUCRA 21.7% and 21.4%, separately). TAC + RTX and steroids + cyclophosphamide induced the highest rates of bone marrow suppression (SUCRA 90.6% and 88.3%, separately) and gastrointestinal symptoms (SUCRA 86.0% and 72.1%, separately). Conclusions: Steroids + TAC showed significant efficacy in patients with all degrees of proteinuria, while RTX was more effective in patients with moderate proteinuria and was safer in bone marrow suppression and gastrointestinal symptoms.

METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho.

BACKGROUND: N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. However, its functions in diabetic nephropathy (DN) have not been determined. Here, we investigated the role of METTL14, a key component of the m6A methyltransferase complex, in DN. METHODS: The expression of METTL14 was detected in DN patients and human renal glomerular endothelial cells (HRGECs). In vitro and in vivo experiments were performed to explore the functions of METTL14 on high glocse-induced HRGECs and renal injury of DN mice. We also investigated whether METTL14 works by regulating α-klotho expression through m6A modification. RESULTS: METTL14 were highly expressed in kidneys of DN patients and high glocse-induced HRGECs both at the mRNA and protein level. Overexpression of METTL14 increased ROS, TNF-α and IL-6 levels and apoptosis in HRGECs. Conversely, METTL14 silence decreased the levels of ROS, TNF-α and IL-6 and cell apoptosis. We confirmed that METTL14 down-regulated α-klotho expression in an m6A-dependent manner. In addition, we also found that METTL14 aggravated renal injury and inflammation of db/db mice, which could partially rescued by α-klotho. CONCLUSION: Our data revealed that METTL14 plays a vital role in high glucose-induced glomerular endothelial cells and diabetic nephropathy through m6A modification of α-klotho.

High-sensitive cardiac troponin for the diagnosis of acute myocardial infarction in different chronic kidney disease stages.

BACKGROUND: Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI. METHODS: In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min-1 (1.73 m2)-1. Hs-cTnI values were measured at presentation. RESULTS: AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL-1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001). CONCLUSIONS: Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.

Clinical efficacy and safety of full-dose versus half-dose corticosteroids plus leflunomide for IgA nephropathy.

BACKGROUND: The results of leflunomide (LEF) in patients with IgA nephropathy (IgAN) were inconsistent. METHODS: A total of 149 kidney biopsy-confirmed IgAN patients with an estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73 m2 and protein excretion levels ≥0.75 g/d were enrolled, with 65 subjects receiving half-dose CS plus LEF (LEF group), and the 84 counterpart patients accepting full-dose corticosteroid (Full CS group). The primary outcomes included the complete remission (CR) rates and incidence of adverse events (AEs). The secondary outcomes were the overall remission (OR) rates and a combined event (eGFR reduced ≥30%, end-stage renal disease [ESRD], hemodialysis, peritoneal dialysis or kidney transplantation). RESULTS: During the 18 months of follow-up, the CR rates were 72 and 64% in the LEF and Full CS groups (P = 0.299), respectively. The proportion of patients with OR rates in the LEF group and Full CS group was 89% versus 75%, respectively (P = 0.027). Serious AEs were observed only in the Full CS group (P = 0.017). The incidences of total AEs (P = 0.036) and infections (P = 0.024) were lower in the LEF group than in the Full CS group. CONCLUSIONS: LEF combined with half-dose CS is superior to full-dose CS in the treatment of IgAN.

Efficacy and safety of oral anticoagulants in atrial fibrillation patients with cancer-a network meta-analysis.

There are no guideline recommendations for the use of anticoagulant therapy in atrial fibrillation (AF) patients with cancer, which creates uncertainty about the optimal antithrombotic treatment in these patients. We conducted a network meta-analysis for the first time to assess the efficacy and safety of anticoagulant drugs in patients with AF and concurrent cancer. The PubMed, EMBASE, and Cochrane databases were searched up to March 2019. A search was made for the main anticoagulant drugs (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). Outputs were presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. We identified 414 relevant studies and included 5 trials involving 31,660 participants. In reducing the risk of stroke or systemic embolism, rivaroxaban and apixaban ranked the best and second best (SUCRA, 25.2% and 29.3%, respectively), followed by dabigatran, edoxaban, and warfarin. Apixaban and dabigatran were associated with lower probability of achieving at venous thromboembolism (VTE) (OR 0.12, 95% CI 0.05-0.52, SUCRA, 0.1%; and OR 0.24, 95% CI 0.07-1.00, SUCRA, 33.3%, respectively) than warfarin (SUCRA, 100.0%). For the prevention of all-cause death, apixaban was nonsignificantly less likely than warfarin. In addition, there were nonsignificant differences among all interventions in major bleeding, with the exception of apixaban vs. warfarin (OR 0.39, 95% CI 0.18-0.79; SUCRA 4.9%). In AF patients with cancer, nonvitamin K antagonist oral anticoagulants showed a lower incidence of stroke/systemic embolism, VTE, all-cause death, and major bleeding than warfarin, with apixaban being the best of those studied.

An update to the pathogenesis for monoclonal gammopathy of renal significance.

Monoclonal gammopathy of renal significance (MGRS) is characterized by the nephrotoxic monoclonal immunoglobulin secreted by an otherwise asymptomatic or indolent B cell or plasma cell clone, without hematologic criteria for treatment. These MGRS-associated diseases can involve one or more renal compartments, including glomeruli, tubules, and vessels. Hydrophobic residue replacement, N-glycosylated, increase in isoelectric point in monoclonal immunoglobulin (MIg) causes it to transform from soluble form to tissue deposition, and consequently resulting in glomerular damage. In addition to MIg deposition, complement deposition is also found in C3 glomerulopathy with monoclonal glomerulopathy, which is caused by an abnormality of the alternative pathway and may involve multiple factors including complement component 3 nephritic factor, anti-complement factor auto-antibodies, or MIg which directly cleaves C3. Furthermore, inflammatory factors, growth factors, and virus infection may also participate in the development of the diseases. In this review, for the first time, we discussed current highlights in the mechanism of MGRS-related lesions.

Interrupted or Uninterrupted Oral Anticoagulants in Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND AND PURPOSE: The safety and efficacy of uninterrupted, minimally interrupted (one dose skipped) or completely interrupted (24 h skipped) oral anticoagulant therapy in patients with atrial fibrillation (AF) ablation are poorly defined. We conducted a network meta-analysis to explore the effect of interrupted or uninterrupted oral anticoagulants in patients with AF undergoing ablation. METHODS: The Cochrane Library, PubMed and Embase databases were systematically searched for studies comparing uninterrupted, minimally interrupted or completely interrupted non-vitamin K antagonist oral anticoagulants (NOACs) with continuous or interrupted warfarin in patients undergoing AF ablation. RESULTS: Twelve randomized clinical trials (RCTs) with a total of 5597 patients with AF undergoing catheter ablation were included. For thromboembolism, minimally interrupted NOACs (OR 0.03, 95% CI 0.01-0.35), uninterrupted NOACs (OR 0.04, 95% CI 0.01-0.23) and continuous VKAs (OR 0.05, 95% CI 0.01-0.21) were better than interrupted warfarin. The risk of total bleeding appeared higher in the completely interrupted NOAC group compared with the minimally interrupted NOACs (OR 2.74, 95% CI 1.18-6.37), uninterrupted NOACs (OR 2.15, 95% CI 1.05-4.38) and uninterrupted warfarin (OR 2.04, 95% CI 1.02-4.08). To reduce the risk of total bleeding, minimally interrupted NOACs (OR 0.15, 95% CI 0.08-0.27), uninterrupted NOACs (OR 0.19, 95% CI 0.14-0.42) and uninterrupted warfarin (OR 0.24, 95% CI 0.15-0.39) were better than interrupted warfarin. In the event of major bleeding, there was no significant difference in the interrupted NOAC, uninterrupted NOAC, interrupted VKA and uninterrupted VKA groups. CONCLUSIONS: These three NOAC strategies may have similar safety and efficacy in terms of thromboembolism and major bleeding complications. The total bleeding risk of completely interrupted oral anticoagulants is higher than that of uninterrupted and minimally interrupted NOACs. For thromboembolism, minimally interrupted NOACs, uninterrupted NOACs and continuous VKAs were better than interrupted warfarin.

Effectiveness and safety of cyclophosphamide or tacrolimus therapy for idiopathic membranous nephropathy.

BACKGROUND: Guidelines recommend classical combined therapy of steroid and cyclophosphamide (CYC) for patients with idiopathic membranous nephropathy (IMN), while it is associated with severe adverse effects. AIMS: We conducted an observational and retrospective study to evaluate the effectiveness and safety of steroids plus tacrolimus (TAC) versus steroids plus CYC for IMN. METHODS: A total of 203 kidney-biopsy-proven IMN patients was enrolled in this study. One group (n = 142) received steroid combined with intravenous CYC (750 mg/m2 body surface) and the other group (n = 61) received steroid combined with oral TAC (target blood concentration of 4-8 ng/mL). The primary outcomes were achievement of remission. The secondary end-points included incidence of adverse events, relapse rates, 24 h urinary protein (UP), serum albumin, serum creatinine and estimated glomerular filtration rate. RESULTS: Over the 18-month observation period, the study suggested that the remission rates at the first 3 months were significantly higher in TAC group than in CYC group (72.1% vs 54.9%, P < 0.05). Although the cumulative incidence of serious and non-serious adverse events was not different significantly between the two groups, the incidence after first 3 months was lower in TAC group. Levels of 24-h UP and serum albumin improved in the TAC group more than in the CYC group (P < 0.05) over the observed period. CONCLUSIONS: Because of its short-term effectiveness and long-term safety profile, steroid plus TAC might be a better option for IMN.

The risk of bleeding for antiplatelet agents in Haemodialysis patients: a Meta-analysis.

BACKGROUND: The safety of antiplatelet therapy in haemodialysis (HD) patients remains controversial. we conducted the first meta-analysis to evaluate the bleeding risk with antiplatelet agents in these populations. METHODS: The relevant literature was searched using the following electronic databases without any language restrictions: the Cochrane Library, EMBASE, Global Health, MEDLINE, PubMed, and the Chinese Biomedical Database. RESULTS: Seven randomized controlled trials (RCTs) and 2 prospective cohort studies, consisting of 1131 patients, were identified for detailed evaluation. The meta-analysis suggested that the use of double antiplatelet agents increased the risk of bleeding in HD patients [odds ratio (OR) = 2.78; 95% confidence interval (CI) 1.63 to 4.76; I2 = 0], and antiplatelet agents increased the risk of bleeding in 7 RCTs [odds ratio (RR) = 1.40, 95% CI 1.08 to 1.79; I2 = 23%,]; however, the use of a single antiplatelet agent was not found to significantly increase the risk of bleeding (RR = 0.88; 95% CI 0.51 to 1.50; I2 = 0). CONCLUSION: The results suggested that the use of double antiplatelet agents increased the risk of bleeding in HD patients.

Clinical Efficacy and Safety of Jinshuibao Combined With ACEI/ARB in the Treatment of Diabetic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The present study aims to compare the relative efficacy and safety of jinshuibao (JSB) combined with angiotensinconverting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) in the treatment of diabetic kidney disease. METHODS: We searched EMBASE, MEDLINE, PubMed, China National Knowledge Internet, the Chinese Biomedical Database, and Wanfang database for articles from the building of the database to September 2018. RESULTS: Fifty-one randomized controlled trials with 3,955 participants were included. The meta-analysis indicated that compared with the controls, JSB combined with ACEI/ARB group could remarkably improve the overall response rate (odds ratio 4.91; 95% confidence interval [CI] 3.32-7.25) and reduce 24 h proteinuria (mean difference [MD] -0.16; 95% CI -0.19 to -0.13), urine albumin excretion ratio (MD -28.20; 95% CI -36.30 to -20.11), serum creatinine (MD -13.84; 95% CI -18.01 to -9.68), blood urea nitrogen (MD -1.00; 95% CI -1.36 to -0.63), systolic blood pressure (MD -4.57; 95% CI -6.78 to -2.37), diastolic blood pressure (MD -3.96; 95% CI -5.73 to -2.19), fasting blood glucose (MD -0.85; 95% CI -1.45 to -0.24), hemoglobin A1c (MD -0.52; 95% CI -0.83 to -0.21), serum total cholesterol (MD -0.53; 95% CI -0.86 to -0.20), and triglyceride (MD -0.53; 95% CI -0.55 to -0.51). CONCLUSIONS: JSB combined with ACEI/ARB in the treatment of diabetic kidney disease is superior to the single application of ACEI/ARB.

Factors Associated with a Large Decline in Renal Function or Progression to Renal Insufficiency in Hospitalized Atrial Fibrillation Patients with Early-Stage CKD.

Clinicians must consider renal function when administering anticoagulants for atrial fibrillation (AF). Determination of risk factors for renal function decline may enable identification of patients who require closer monitoring. We investigated the characteristics associated with renal function decline in patients with AF. The study cohort consisted of 631 AF patients who had at least one readmission during the follow-up period and stages 1-3 chronic kidney disease (CKD). The primary outcome measure was large renal function decline (≥30% decrease from baseline estimated glomerular filtration rate [eGFR]). The secondary outcome measure was a final eGFR < 60 mL/minute/1.73 m2 for those with a baseline eGFR above this level. The mean eGFR was 74.4 ± 18.5 mL/minute/1.73 m2, and the mean follow-up time was 30.2 ± 13.2 months. The primary outcome occurred in 155 patients (24.6%) and was associated with congestive heart failure (CHF), proteinuria, type of AF, and left atrial diameter (LAD) ≥ 45 mm. Among 478 patients with a baseline eGFR ≥ 60 mL/minute/1.73 m2, 137 (28.7%) progressed to renal failure (eGFR < 60 mL/minute/1.73 m2). A decreasing eGFR was associated with age ≥ 75 years, CHF, lower baseline eGFR, and LAD ≥ 45 mm. CHF, proteinuria, type of AF, and LAD ≥ 45 mm were associated with eGFR decline ≥ 30% in AF patients with CKD stages 1-3. Advanced age, CHF, lower baseline eGFR, and LAD ≥ 45 mm were associated with progression to renal insufficiency. These results should be considered when identifying patients who require more frequent monitoring of eGFR.

The pathogenesis of renal injury and treatment in light chain deposition disease.

Light chain deposition disease (LCDD) is a rare clinical disorder. The deposition of light chain immunoglobulins mainly affects the kidneys, which have different characteristics than other tissues. To date, the therapeutic approach for the treatment of LCDD has no evidence-based consensus, and clinical experience of reported cases guides current disease management strategies. The present systematic review investigates and summarizes the pathological mechanisms of renal injury and the subsequent treatments for LCDD.

Long noncoding RNA MALAT1 mediates high glucose-induced glomerular endothelial cell injury by epigenetically inhibiting klotho via methyltransferase G9a.

Several recent reporters have indicated the potential role of long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in diabetic nephropathy (DN). However, these studies mainly focus on renal tubular epithelial cells HK-2, the role of MALAT1 in human renal glomerular endothelial cells (HRGECs) remains unclear. Hence, this study aimed to explore the role of MALAT1 in high glucose (HG)-induced HRGECs injury and the underlying epigenetic mechanism. Increased MALAT1 and decreased klotho expression were observed in both renal tissues from DN patients and HG-exposed HRGECs. Furthermore, MALAT1 expression was negatively correlated with klotho expression. Moreover, both MALAT1 knockdown and klotho overexpression significantly abolished the HG-induced HRGECs injury. Importantly, klotho overexpression reversed the MALAT1 overexpression-mediated enhancement of the HG-induced HRGECs injury. In addition, MALAT1 recruited G9a to elevate H3K9me1, which can bind to the klotho promoter and thus inhibited klotho transcription. In conclusion, MALAT recruits methyltransferase G9a to elevate H3K9me1 and epigenetically inhibits klotho expression, and thus mediates HG-induced glomerular endothelial cell injury. © 2019 IUBMB Life, 1-9, 2019.

Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials.

The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5-10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Correction to: Early versus late initiation of renal replacement therapy impacts mortality in patients with acute kidney injury post cardiac surgery: a meta-analysis.

After publication of this article [1], it was noticed that the affiliations of Honghong Zhou were incorrect. The sole affiliation should be, "Department of Nephrology, the Second Affiliated Hospital of Nanchang University, China" and can be seen in the author details of this correction.