<b><i>Introduction:</i></b> Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient’s quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. <b><i>Methods:</i></b> 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3–6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score. <b><i>Results:</i></b> In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. <b><i>Conclusion:</i></b> The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Abstract Background: Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the reports on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients were limited. Methods: Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints. Results: After screening, 271 patients were included in our present study. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. The in-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9%, 33.9%, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age (P < 0.033), AKI stage 3 (P < 0.001), the amount of blood transfusion after surgery (P = 0.019), mean arterial pressure (MAP) in the first postoperative day (P = 0.012), the use of extracorporeal membrane oxygenation (ECMO) (P = 0.02), and the peak total bilirubin (TB) concentration (P = 0.023) were independent risk factors of in-hospital mortality. The optimal cut-off value of peak TB on predicting in-hospital mortality was 121.2 μmol/L. Patients with post-operation TB ≥ 121 μmol/L was associated with worse long-term survival as well. Conclusions: Severe post-operation hyperbilirubinemia is a common clinical situation in patients had AAD repair. In AAD patients with severe post-operation hyperbilirubinemia, older age, lower MAP, increased blood transfusion, stage 3 AKI, the use of ECMO, and the increased peak TB lead to increase in-hospital mortality.

Background: China has the largest absolute burden of hypertension (HTN) in the world. Gut dysbiosis may be a potentially modifiable risk factor for HTN. However, the characteristics of gut microbiota in Chinese populations with HTN remain to be determined. Methods: We systematically searched for studies comparing the gut microbial in HTN with healthy controls in databases. The cut-off date was December 30, 2021. Semiquantitative analysis and meta-analysis with standardized mean differences of the alteration in gut microbiota were carried out. Results: A total of 16 studies involving 2372 patients with HTN and 849 controls were included, covering 16 Chinese provinces or regions. The present study supports that compared to healthy population, the diversity of patients with HTN is significantly compromised, while richness is overall preserved. To be specific, a significant increase of the Firmicutes(F)/Bacteroidetes(B) ratio is considered as a special parameter of gut microbiota in HTN patients. The increased abundance of phylum Firmicutes, genus Megasphaera, Escherichia_Shigella, and Klebsiella, while the lower abundance of phylum Bacteroidetes, genus Bifidobacterium, Faecalibacterium, Roseburia, and Ruminococcus may be associated with HTN. The gut microbial metabolism in HTN was more abundant in LPS biosynthesis, membrane transport, and steroid degradation. Conclusions: Variation in gut microbial parameters is likely associated with Chinese patients with HTN. Further investigations should distinguish geographical and ethnic characteristics to develop in-depth knowledge of the underlying mechanisms by which gut dysbiosis contributes to HTN.

Objective Hyperbilirubinemia is one of the common complications after cardiac surgery and is associated with increased mortality. However, to the best of our knowledge, the report on clinical significance of postoperative severe hyperbilirubinemia in Stanford type A aortic dissection (AAD) patients is limited. Therefore, the purpose of our present study is to assess the characteristics and outcomes of AAD patients with post-operation severe hyperbilirubinemia.Methods Patients who underwent surgical treatment for AAD in our center between January 2015 and December 2018 were retrospectively screened. In-hospital mortality, long-term mortality, acute kidney injury (AKI), and the requirement of continuous renal replacement therapy (CRRT) were assessed as endpoints. Univariate and multivariate regression models were employed to identify the risk factors of these endpoints.Results Of the 2210 screened patients, 271 (12.3%) were included. Of the included patients, 222 (81.9%) experienced postoperative AKI, and 50 (18.5%) received CRRT. In-hospital mortality was 30.3%. The 1-year, 2-year, and 3-year cumulative mortality were 32.9%, 33.9%, and 35.3%, respectively. Multivariate Logistic regression analysis indicated that age ( P < 0.033), AKI stage 3 ( P < 0.001), the total amount of blood transfusion after surgery ( P = 0.019), mean arterial pressure (MAP) in the first postoperative day ( P = 0.012), the use of extracorporeal membrane oxygenation (ECMO) after surgery ( P = 0.02), and the peak total bilirubin (TB) concentration ( P = 0.023) were independent risk factors of in-hospital mortality. The optimal cut-off value of peak TB on predicting in-hospital mortality was 121.2 μmol/l. Older age, high preoperative serum creatinine (SCr) concentration, and prolonged cardiopulmonary bypass (CPB) time were identified as the independent risk factors of AKI. High preoperative SCr concentration was identified as the only independent risk factor of the requirement of CRRT.Conclusions Post-operation severe hyperbilirubinemia is a common clinical presentation in AAD surgery patients. Post-operation severe hyperbilirubinemia AAD patients with older age, lower MAP, increased blood transfusion, stage 3 AKI, the use of ECMO, and the increased peak TB had higher risk of in-hospital mortality.

The Smad anchor for receptor activation (SARA) protein is a binding partner for Smad2/3 that plays an important role in the fibrotic promoting signaling pathway initiated by transforming growth factor-b1 (TGF-b1). The C-terminal 665-750 aa of SARA comprises the Smad-binding domain (SBD). By direct interaction through the SBD, SARA inhibits Smad2/3 phosphorylation and blocks the interaction between Smad2/3 and Smad4, thereby restrains the process of fibrosis. In this study, we constructed a SARA peptide aptamer based on the SBD sequence. The recombinant SARA aptamer, fused with a protein transduction domain (PTD-SARA), was cloned, purified from E. coli, and characterized for the first time. The full-length PTD-SARA coding sequence, created with E. coli favored codons, was cloned into a pQE-30 vector, and the recombinant plasmid was transformed into an M15 strain. After Isopropyl b-D-1-Thiogalactopyranoside (IPTG) induction and Ni 21 affinity purification, recombinant PTD-SARA was further identified by immunoblotting and protein N-terminal sequencing. Epifluorescence microscopy revealed that the recombinant PTD-SARA was transferred into the cytoplasm and nucleus more efficiently than SARA. Moreover, the recombinant PTD-SARA was found to up-regulate the level of E-cadherin and down-regulate the levels of a-SMA and phospho-Smad3 more efficiently than SARA (P < 0.05). Our work explored a method to obtain recombinant PTD-SARA protein. The recombinant PTD-SARA fusion protein could enter HK2 cells (an immortalized proximal tubule epithelial cell line) more efficiently than the SARA protein and reverse the renal epithelial-to-mesenchymal transdifferentiation process that was induced by TGF-b1 more effectively than the SARA protein. Recombinant PDT-SARA is likely to be a potential candidate for clinical prevention and treatment of renal fibrosis.

Background End-stage renal disease patients with maintenance hemodialysis have high-mortality risk. The association of different age of hemodialysis patients with mortality remains uncertain in China. This study aimed to assess the survival outcomes and risk factors affecting mortality between young and elderly patients with maintenance hemodialysis.Methods The multicenter retrospective cohort study enrolled adult patients undergoing maintenance hemodialysis from 24 hemodialysis centers in China between January 1, 2008, and September 30, 2015. The patients were assigned to young and elderly group according to age on the initiation of the hemodialysis. The primary outcome was all-cause mortality of patients. Survival outcomes of patients was performed using a Kaplan-Meier survival analysis. Multivariate cox proportional hazards regression models were implemented to identify risk factors affecting all-cause mortality of patients with maintenance hemodialysis.Results A total of enrolled 1601 patients undergoing maintenance hemodialysis, including 642 young patients and 959 elderly patients. The mean follow-up duration was 48.17 ± 25.59 months, the all-cause mortality was 64 (9.97%) in young group and 255 (26.59%) in elderly group, the hazard ratio [HR] of elderly patients relative to young patients, 1.699 (95% confidence interval [95% CI], 1.482 to 1.949, P＜0.001). The Kaplan-Meier survival curve showed that overall cumulative survival was lower in elderly group than young group (Log Rank tests = 63.31, P＜ 0.001). Multivariate cox regression analysis revealed that the cardiovascular disease (HR, 1.544; 95% CI, 1.103 to 2.161; P = 0.011), cerebrovascular disease (HR, 2.158; 95% CI, 1.309 to 3.557; P = 0.003), lower serum albumin (HR, 1.404; 95% CI, 1.001 to 1.968; P = 0.049), Charlson comorbidity index (CCI) scores with 4-5 (HR, 4.910; 95% CI, 2.327 to 10.357; P＜ 0.001), CCI scores with ≥6 (HR, 9.596; 95% CI, 4.807 to 19.158; P＜ 0.001) were the risk factors associated all-cause mortality of patients.Conclusions The elderly patients undergoing maintenance hemodialysis showed lower survival and higher mortality than young patients in China. Cardiovascular disease, cerebrovascular disease, serum albumin, CCI scores were the risk factors for all-cause mortality of young and elderly patients with maintenance hemodialysis.

Background The pathogenesis of immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) is characterized by immune dysregulation, which is related to gut dysbiosis. The aim of the study was to compare the gut microbiota of patients with IgAN and MN versus healthy controls. We used 16S rDNA amplicon sequencing to investigate the bacterial communities of 44 patients with kidney biopsy-proven IgAN, 40 patients with kidney biopsy-proven MN, and 30 matched healthy controls (HC). Results The abundance of Escherichia-Shigella and Defluviitaleaceae_incertae_sedis were significantly higher in IgAN than in HC, whereas lower abundances were observed for Roseburia, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Fusobacterium . Furthermore, the abundance of Escherichia-Shigella, Peptostreptococcaceae_incertae_sedis , Streptococcus, and Enterobacteriaceae_ unclassified increased, while that of Lachnospira, Lachnospiraceae_ unclassified, Clostridium_sensu_stricto_1, and Veillonella decreased in MN. The abundance of Megasphaera and Bilophila was higher, whereas that of Megamonas, Veillonella, Klebsiella, and Streptococcus was lower in patients with IgAN than in those with MN. Analysis of the correlations showed that in the IgAN group, Prevotella was positively correlated, while Klebsiella , Citrobacter, and Fusobacterium were negatively correlated with the level of serum albumin. Positive correlation also existed between Bilophila and Crescents in the Oxford classification of IgAN. In the MN group, negative correlation was observed between Escherichia-Shigella and proteinuria, Bacteroides and Klebsiella showed positive correlation with the MN stage. Conclusions Patients with IgAN and MN exhibited gut microbial signatures distinct from healthy controls. Our study suggests the potential of gut microbiota as specific biomarker and contributor in the pathogenesis of IgAN and MN.

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