Effect of Ascorbic Acid on Mineral and Bone Disorders in Hemodialysis Patients: a Systematic Review and Meta-Analysis

Background/Aims: Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%– 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis. Methods: A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted. Results: In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed. Conclusion: Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn’t influence the serum P or PTH levels but did raise serum Ca levels in the short-term

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

AbstractAim Renal tubular epithelial cell (RTEC) apoptosis is important in acute kidney injury (AKI). Calcium/calmodulin-dependent protein kinase II (CaMKII) plays an important role in cell apoptosis, but its potential role in AKI remains unknown.Methods Using co-immunoprecipitation, immunofluorescence, immunohistochemistry, western blotting, flow cytometry, and cell transfection, this study aimed to verify whether CaMKII is involved in RTEC apoptosis and to explore the underlying mechanism.Results We found that CaMKII was involved in RTEC apoptosis. In adriamycin-induced AKI mice, serum creatinine levels, cell apoptosis, CaMKII activity, and nuclear factor of activated T cells 2 (NFAT2) levels increased, whereas nuclear Yes-associated protein (YAP) expression decreased; inhibition of CaMKII activity reversed these changes. Phosphorylated CaMKII could bind to phosphorylated YAP in the cytoplasm and block it from entering the nucleus, thereby failing to inhibit NFAT2-mediated cell apoptosis. Sequestrated phosphorylated YAP in the RTEC cytoplasm was finally degraded by ubiquitination.Conclusion CaMKII may regulate RTEC apoptosis through YAP/NFAT2 in AKI mice. CaMKII may be a potent molecular target for AKI treatment

Cardio-selective versus non-selective β-blockers for cardiovascular events and mortality in long-term dialysis patients: A systematic review and meta-analysis.

BackgroundTrials in patients receiving dialysis have demonstrated that β-blockers reduce all-cause mortality and cardiovascular events. However, differences still exist within-class comparative effectiveness studies of the therapeutic benefits of β-blockers in dialysis patients.ObjectiveThe purpose of this systematic review is to examine whether cardiovascular events and all-cause mortality differed between dialysis patients receiving cardio-selective and non-selective agents.MethodsA comprehensive search of relevant articles from the PubMed, EMBASE, Cochrane Central Register and ClinicalTrials.gov was performed up to September 4, 2022, we included adults receiving β-blockers to evaluate the effects of cardio-selective versus non-selective agents on mortality and cardiovascular events in the dialysis population. Hazard ratios (HRs) and 95% confidence intervals (CIs) were examined for the negative outcomes of cardiovascular events and death for any reason. The risk of bias in randomized controlled trials (RCTs) was assessed using Cochrane's risk of bias tool and the risk of bias in observational studies was assessed using a table designed according to the ROBINS-I tool, the evidence grade was assessed using the GRADE guideline. For all-cause mortality and cardiovascular events, the RevMan software (version 5.3) was used to calculate pooled HRs with 95% CI. The heterogeneity (I2) in statistics was used to examine the degree of heterogeneity among studies.ResultsFour observational studies, including 58, 652 long-term dialysis patients, were included in the meta-analysis. Compared to dialysis patients who took non-selective β-blockers, who took cardio-selective β-blockers was probably associated with fewer cardiovascular events (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.81, 0.89, heterogeneity [I2] = 0%, three trials, 52,077 participants, moderate-quality evidence) and may have lower all-cause mortality (HR = 0.83, 95% CI = 0.69, 0.99, I2 = 91%, four trials, 54,115 participants, low-quality evidence).ConclusionsThis systematic review showed that cardio-selective β-blockers are probably associated with fewer cardiovascular events and may have lower all-cause mortality in long-term dialysis patients than non-selective β-blockers. The present study results need to be replicated using randomized controlled trials with longer observation durations

Soluble Urokinase Plasminogen Activator Receptor is Associated with Coronary Artery Calcification and Cardiovascular Disease in Patients Undergoing Hemodialysis

Background/Aims: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in hemodialysis patients. Vascular calcification is thought to play an important role in causing CVD. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker strongly predictive of cardiovascular outcomes in the pathogenesis of diabetic patients with renal disease treated with hemodialysis. We investigated the relationship between suPAR and coronary artery calcification (CAC) in patients undergoing maintenance hemodialysis. Methods: A total of 99 adult hemodialysis patients were enrolled in this study. Plasma samples were analyzed for suPAR with an enzyme-linked immunosorbent assay and the CAC score was determined with multidetector computed tomography. The occurrence of cardiovascular events and all-cause mortality during follow-up were recorded from January 1, 2010 to June 1, 2016. Results: In 99 patients treated with maintenance hemodialysis, 91 (91.9%) had varying degrees of CAC, and suPAR correlated positively with the CAC score in a Spearman analysis. In a mean follow-up period of 33 months, 36 patients (36.4%) experienced at least one cardiovascular event. When the quartiles of suPAR concentrations were used as the cutoff points for a subgroup analysis, the incidence of CVD and all-cause mortality was much higher in the higher quartiles of suPAR. In a univariate Cox regression analysis, high suPAR was a risk factor for CVD and all-cause mortality. Conclusion: suPAR is associated with the CAC score and is a risk factor for new-onset CVD in patients undergoing hemodialysis