Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics, or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to 22 July, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: −1.64 mg/L; 95% CI: −3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: −2.42 mg/L; 95% CI: −3.81, −1.04 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 6) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, whereas probiotic (n = 3) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed RCTs with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in the long term. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42021269146.

Background:The association between isolated diastolic hypertension (IDH) and cardiovascular events has been inconsistently reported. This meta-analysis of cohort studies was designed to investigate the effect of the 2018 European Society of Cardiology (ESC) definition of IDH on the risk of composite cardiovascular events, cardiovascular mortality, all-cause mortality, and all strokes including ischemic stroke (IS) and hemorrhagic stroke (HS).Methods:PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 6, 2021. Cohort studies that investigated the association between IDH and cardiovascular events risk, compared to normotension, were included. Pooled hazard ratios (HRs) and 95% CIs were calculated using a random-effects models and heterogeneity was evaluated usingQ-test andI²statistic. The robustness of the associations was identified using sensitivity analysis. The methodological quality of the studies was assessed using the Newcastle–Ottawa scale. Publication bias was assessed using funnel plot, trim-and-fill method, Begg's test, and Egger's test.Results:A total of 15 cohort studies (13 articles) including 489,814 participants were included in this meta-analysis. The follow-up period ranged from 4.3 to 29 years. IDH was significantly associated with an increased risk of composite cardiovascular events (HR 1.28, 95% CI: 1.07–1.52,p= 0.006), cardiovascular mortality (HR 1.45, 95% CI: 1.07–1.95,p= 0.015), all strokes (HR 1.44, 95% CI: 1.04–2.01,p= 0.03), and HS (HR 1.64, 95% CI: 1.18–2.29,p= 0.164), but not associated with all-cause mortality (HR 1.20, 95% CI: 0.97–1.47,p= 0.087) and IS (HR 1.56, 95% CI: 0.87–2.81,p= 0.137). Subgroup analysis further indicated that IDH in the younger patients (mean age ≤ 55 years) and from Asia were significantly associated with an increased risk of composite cardiovascular events, while the elderly patients (mean age ≥ 55 years), Americans, and Europeans were not significantly associated with an increased risk of composite cardiovascular events.Conclusion:This meta-analysis provides evidence that IDH defined using the 2018 ESC criterion is significantly associated with an increased risk of composite cardiovascular events, cardiovascular mortality, all strokes and HS, but not significantly associated with all-cause death and IS. These findings also emphasize the importance for patients with IDH to have their blood pressure within normal, especially in the young adults and Asians.Trial Registration:PROSPERO, Identifier: CRD42021254108.

As the current treatment of chronic kidney disease (CKD) is limited, it is necessary to seek more effective and safer treatment methods, such as Chinese herbal medicines (CHMs). In order to clarify the modern theoretical basis and molecular mechanisms of CHMs, we reviewed the knowledge based on publications in peer-reviewed English-language journals, focusing on the anti-inflammatory, antioxidative, anti-apoptotic, autophagy-mediated and antifibrotic effects of CHMs commonly used in kidney disease. We also discussed recently published clinical trials and meta-analyses in this field. Based on recent studies regarding the mechanisms of kidney disease in vivo and in vitro, CHMs have anti-inflammatory, antioxidative, anti-apoptotic, autophagy-mediated, and antifibrotic effects. Several well-designed randomized controlled trials (RCTs) and meta-analyses demonstrated that the use of CHMs as an adjuvant to conventional medicines may benefit patients with CKD. Unknown active ingredients, low quality and small sample sizes of some clinical trials, and the safety of CHMs have restricted the development of CHMs. CHMs is a potential method in the treatment of CKD. Further study on the mechanism and well-conducted RCTs are urgently needed to evaluate the efficacy and safety of CHMs.

Pyroptosis is a special way of programmed cell death which is dependent on the activation of cysteinyl aspartate specific proteinase 1 (Caspase-1) and Caspase-4/5/11. Ferroptosis is an iron-dependent cell death that characterized by the intra-cellular lipid peroxidation-mediated membrane damage. Pyroptosis or ferroptosis in macrophages, smooth muscle cells, and vascular endothelial cells are believed to be closely related to the progression of atherosclerotic plaques. Therefore, we discuss the role of pyroptosis and ferroptosis in the development of atherosclerotic plaques and may provide new strategies for the treatment of atherosclerosis.