Effect of High-Dose Statin Pretreatment for Myocardial Perfusion in Patients Receiving Percutaneous Coronary Intervention (PCI): A Meta-Analysis of 15 Randomized Studies.

BACKGROUND For coronary artery disease, percutaneous coronary intervention (PCI) is the preferred treatment. Reperfusion injury is a common and serious complication of PCI. Studies showed that early statin therapy has a favorable prognostic impact for patients undergoing PCI. However, the effects of statins on improving post-PCI myocardial perfusion are still unclear. In this study we evaluated the potential effect of high-dose statin pretreatment on postprocedure myocardial perfusion and MACE rate in patients receiving PCI. MATERIAL AND METHODS We searched randomized controlled trials that evaluated the effect of high-dose statin pretreatment on post-PCI TIMI flow grade and MACE in patients undergoing PCI from the databases of PubMed, Embase, and Cochrane Library. All data were pooled for analysis and were stratified by type of statin, clinical presentation, and current statin therapy status in subgroup. RESULTS Fifteen RCTs with 4240 individuals were selected. The pooled analysis showed that high-dose statin pretreatment before PCI significantly improved the final TIMI flow grade compared with the control group (OR=0.61, 95% CI: 0.46 to 0.80, p=0.0005), and showed reduced incidence of MACE (OR=0.53, 95%CI: 0.39 to 0.71, p<0.0001). In subgroup analysis, the beneficial effect of high-dose statin was significant in statin-naive treatment patients, ACS patients, and patients on atorvastatin therapy, but no difference occurred in rosuvastatin, previous statin therapy, and stable angina patients. CONCLUSIONS High-dose statin pretreatment has an important effect on postprocedure myocardial perfusion by improving the TIMI flow in patients undergoing PCI, and high-dose statin preloading also reduces the incidence of MACE.

Bioinformatics analysis reveals CCR7 as a potential biomarker for predicting CKD progression.

Chronic kidney disease (CKD) inevitably progresses to end-stage renal disease if intervention does not occur timely. However, there are limitations in predicting the progression of CKD by solely relying on changes in renal function. A biomarker with high sensitivity and specificity that can predict CKD progression early is required. We used the online Gene Expression Omnibus microarray dataset GSE45980 to identify differentially expressed genes (DEGs) in patients with progressive and stable CKD. We then performed functional enrichment and protein-protein interaction network analysis on DEGs and identified key genes. Finally, the expression patterns of key genes were verified using the GSE60860 dataset, and the receiver operating characteristic curve analysis was performed to clarify their predictive ability of progressive CKD. Ultimately, we verified the expression profiles of these hub genes in an in vitro renal interstitial fibrosis model by real-time PCR and western blot analysis. Differential expression analysis identified 50 upregulated genes and 47 downregulated genes. The results of the functional enrichment analysis revealed that upregulated DEGs were mainly enriched in immune response, inflammatory response, and NF-κB signaling pathways, whereas downregulated DEGs were mainly related to angiogenesis and the extracellular environment. Protein-protein interaction network and key gene analysis identified CCR7 as the most important gene. CCR7 mainly plays a role in immune response, and its only receptors, CCL19 and CCL21, have also been identified as DEGs. The receiver operating characteristic curve analysis of CCR7, CCL19, and CCL21 found that CCR7 and CCL19 present good disease prediction ability. CCR7 may be a stable biomarker for predicting CKD progression, and the CCR7-CCL19/CCL21 axis may be a therapeutic target for end-stage renal disease. However, further experiments are needed to explore the relationship between these genes and CKD.

Association of uric acid with the decline in estimated glomerular filtration rate in middle-aged and elderly populations: evidence based on the China Health and Retirement Longitudinal Study.

OBJECTIVE: Whether uric acid (UA) has an effect on renal function remains controversial. We aimed to investigate the association between serum UA with the decline in estimated glomerular filtration rate (eGFR) in middle-aged and elderly populations in the China Health and Retirement Longitudinal Study (CHARLS). DESIGN: Longitudinal cohort study. SETTING: This was a second analysis of a public dataset (CHARLS). PARTICIPANTS: In this study, 4538 middle-aged and elderly individuals were screened after removing individuals younger than 45 years old, with kidney disease, malignant tumour and missing values. OUTCOME MEASURES: Blood tests were performed both in 2011 and 2015. Decline in eGFR was defined as an eGFR decrease of more than 25% or deterioration of the eGFR stage during the 4-year follow-up period. Logistic models corrected for multiple covariables were used to analyse the association of UA with the decline in eGFR. RESULTS: The median (IQR) concentrations of serum UA grouped by quartiles were 3.1 (0.6), 3.9 (0.3), 4.6 (0.4) and 5.7 (1.0) mg/dL, respectively. After multivariable adjustment, the OR of the decline in eGFR was higher for quartile 2 (3.5-<4.2 mg/dL: OR 1.44; 95% CI 1.07 to 1.64; p<0.01), quartile 3 (4.2-<5.0 mg/dL: OR 1.72; 95% CI 1.36 to 2.18; p<0.001) and quartile 4 (≥5.0 mg/dL: OR 2.04; 95% CI 1.58 to 2.63; p<0.001) when compared with quartile 1 (<3.5 mg/dL), and the p value for the trend was <0.001. CONCLUSIONS: Over a 4-year follow-up period, we found that elevated UA was associated with a decline in eGFR in the middle-aged and elderly individuals with normal renal function.

Evaluation of efficacy of rituximab for membranous nephropathy: A systematic review and meta-analysis of 11 studies.

INTRODUCTION: The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability. Research on M-type phospholipase A2 receptor antibodies has provided a new way for evaluating the efficiency and prognosis of treatment of membranous nephropathy. However, the relationship between rituximab, a monoclonal antibody against CD20, and antiphospholipase A2 receptor antibodies and the drug regimen of rituximab for membranous nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of rituximab treatments in membranous nephropathy and compared the clinical effects of first-line and second-line rituximab therapies. METHODS: PubMed, Embase, Web of Science, Scopus, the Cochrane Central Register ofControlled Trials, and ClinicalTrials.gov were searched to find articles about rituximab treatment of patients with membranous nephropathy between January 2000 and August 2020. The outcomes included remission, antiphospholipase A2 receptor antibodies, relapse, and adverse events. The Grading of Recommendations Assessment Development and Evaluation criteria were used to evaluate the strength of evidence. RESULTS: A total of 723 participants from 11 trials were included in this meta-analysis. The other treatments included cyclosporine, cyclophosphamide, steroids, and non-immunosuppressive antiproteinuric treatment. Rituximab significantly improved cumulative remission (P=0.007; Odds Ratio [OR]=3.06; 95% confidence interval [CI]=1.35-6.94) compared with other treatments. It significantly reduced relapse (P<0.00001; OR=0.06; 95% CI=0.02-0.19), antiphospholipase A2 receptor antibody levels (P=0.0009; SMD=-0.52; 95% CI=-0.83 to -0.21), and the proportion of patients positive for anti-PLA2R antibodies (P=0.003; OR=6.11; 95% CI=1.85-20.24) compared with other treatments. Compared with the second-line, first-line rituximab therapy achieved a higher rate of cumulative remission (P=0.03; OR=0.32, 95% CI=0.11-0.91). CONCLUSIONS: Rituximab can improve the rate of clinical remission in patients with membranous nephropathy. Rituximab was more effective than other treatments in reducing relapse, antiphospholipase A2 receptor antibody levels, and the proportion of patients positive for antiphospholipase A2 receptor antibodies. The clinical remission rate following first-line rituximab therapy was better than that of second-line rituximab therapy for membranous nephropathy.