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Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification. Keywords Endothelial microparticles • Vascular calcification • Astrocyte elevate gene-1 • Hyperphosphatemia Abbreviations CKD Chronic kidney disease VSMCs Vascular smooth muscle cells Pi Inorganic phosphate HP High inorganic phosphate HP-EMPs HP-induced-EMPs EMPs Endothelial microparticles ECs Endothelial cell HUVECs Human umbilical vein ECs AEG-1 Astrocyte-elevated gene-1 BMP-2 Bone morphogenetic protein-2 STAT3 Signal transducers and activators of transcription 3 ALP Alkaline phosphatase Yazhou Xiang, Yingjie Duan and Zhong Peng have contributed equally.

BackgroundHigh-protein (HP) diets have been recommended for weight loss including obese persons. However, the potential effects of HP regimens on kidney health for persons without chronic kidney disease (CKD) are still controversial. MethodsTo investigate the effects of HP diets versus standard protein/low protein (SP/LP) ones on renal function in individuals without CKD, we conducted this meta-analysis. ResultsThirty-nine RCTs including 3400 participants were considered in this meta-analysis. HP diets resulted in an increased GFR (standardized mean difference [SMD] = 0.64, 95% confidence interval [CI]: 0.03, 1.26) and concentrations of serum urea (MD = 1.05, 95% CI: 0.66, 1.44), creatinine (MD = 2.94, 95% CI: 1.30, 4.58), and uric acid (MD = 19.89, 95% CI: 12.35, 27.43) in obese subjects when compared with SP/LP diets. The results in T2D and health participants did not show a notable detrimental effect on renal outcomes. Subgroup analysis showed that an increase in GFR was presented in obese subjects following an intervention shorter than 6 months. No significant differences were found in the urinary albumin excretion between the HP and SP/LP diets in obese and T2D populations, except for the healthy participants which was reported by only one study.ConclusionsThis meta-analysis showed that HP diets were associated with increased GFR, serum urea, creatinine, and uric acid in obese adults. Future studies are warranted to examine whether resulted glomerular hyperfiltration from HP diet can cause kidney damage in obese individuals.

Background Hyperphosphatemia and anemia, which are common complications of chronic kidney disease (CKD), can independently contribute to cardiovascular events. Several previous studies have found that the iron-based phosphate binder, ferric citrate (FC), could be beneficial to both hyperphosphatemia and anemia. Methods Relevant literature from PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CCRCT) and MEDLINE databases were searched up to 21 February 2022, in order to conduct a meta-analysis to investigate the efficacy, safety and economic benefits of ferric citrate treatment in CKD patients with hyperphosphatemia and anemia. The meta-analysis was conducted independently by two reviewers using the RevMan software (version 5.3). Results In total, this study included 16 randomized clinical trials (RCT) involving 1754 participants. The meta-analysis showed that ferric citrate could significantly reduce the serum phosphorus in CKD patients compared to the placebo control groups (MD −1.76 mg/dL, 95% CI (−2.78, −0.75); p = 0.0007). In contrast, the difference between ferric citrate treatment and active controls, such as non-iron-based phosphate binders, sevelamer, calcium carbonate, lanthanum carbonate and sodium ferrous citrate, was not statistically significant (MD − 0.09 mg/dL, 95% CI (−0.35, 0.17); p = 0.51). However, ferric citrate could effectively improve hemoglobin levels when compared to the active drug (MD 0.43 g/dL, 95% CI (0.04, 0.82); p = 0.03) and placebo groups (MD 0.39 g/dL, 95% CI (0.04, 0.73); p = 0.03). According to eight studies, ferric citrate was found to be cost-effective treatment in comparison to control drugs. Most of the adverse events (AE) following ferric citrate treatment were mild at most. Conclusion Collectively, our review suggests that iron-based phosphate binder, ferric citrate is an effective and safe treatment option for CKD patients with hyperphosphatemia and anemia. More importantly, this alternative treatment may also less expensive. Nevertheless, more scientific studies are warranted to validate our findings.