Non-nitrogen-containing bisphosphonates and nitrogen-containing bisphosphonates for the treatment of atherosclerosis and vascular calcification: A meta-analysis.

BACKGROUND: The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from their inception to July 5th, 2023. Eligible studies comparing bisphosphonates (BPs) versus no BPs in the treatment of AS and VC were included. The data were analyzed using Review Manager Version 5.3. RESULTS: Seventeen studies were included in this meta-analysis. Twelve were randomized control trials (RCTs), and 5 were nonrandomized studies. Overall, 813 patients were included in the BPs group, and 821 patients were included in the no BPs group. Compared with no BP treatment, non-N-BP or N-BP treatment did not affect serum calcium (P > .05), phosphorus (P > .05) or parathyroid hormone (PTH) levels (P > .05). Regarding the effect on serum lipids, non-N-BPs decreased the serum total cholesterol (TC) level (P < .05) and increased the serum triglyceride (TG) level (P < .01) but did not affect the serum low-density lipoprotein cholesterol (LDL-C) level (P > .05). N-BPs did not affect serum TC (P > .05), TG (P > .05) or LDL-C levels (P > .05). Regarding the effect on AS, non-N-BPs did not have a beneficial effect (P > .05). N-BPs had a beneficial effect on AS, including reducing the intima-media thickness (IMT) (P < .05) and plaque area (P < .01). For the effect on VC, non-N-BPs had a beneficial effect (P < .01), but N-BPs did not have a beneficial effect (P > .05). CONCLUSION: Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.

Association of daytime napping with incidence of chronic kidney disease and end-stage kidney disease: A prospective observational study.

BACKGROUND AND AIMS: Few studies have examined the relationship between daytime napping and risk of kidney diseases. We aimed to investigate the association of daytime napping with the incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We also examined whether sleep duration modified the association of nap with CKD or ESKD. METHODS: We recruited 460,571 European middle- to older-aged adults without prior CKD or ESKD between March 13, 2006, and October 1, 2010, in the UK Biobank. Sleep behavior data were obtained through questionnaires administered during recruitment. The analysis of the relationship between napping and the occurrence of CKD and ESKD utilized Cox proportional hazards regression models. The modification role of sleep duration on the effect of nap on CKD and ESKD was also examined. RESULTS: After a mean follow-up of 11.1 (standard deviation 2.2) years, we observed 28,330 incident CKD cases and 927 ESKD cases. The daytime napping was associated with incident CKD (P for trend = .004). After fully adjusted, when compared with participants who did not take nap, those in sometimes and usually nap groups had higher risk of CKD. Nevertheless, the available evidence did not support a link between daytime napping and ESKD (P for trend = .06). Simultaneously, there was insufficient evidence suggesting that sleeping duration modified the association of daytime napping with incident CKD or ESKD. CONCLUSION: Daytime napping was associated with an increased risk of CKD. However, the absence of conclusive evidence did not indicate a connection between daytime napping and ESKD.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Effects of dexmedetomidine administration on outcomes in critically ill patients with acute kidney injury: A propensity score-matching analysis.

PURPOSE: To evaluate the effects of dexmedetomidine (DEX) on outcomes of critically ill patients with acute kidney injury (AKI). MATERIALS AND METHODS: Data were extracted from the Medical Information Mart for Intensive Care III database (MIMIC III). Propensity score matching (PSM) analysis (1 : 3), Cox proportional hazards model, linear regression and logistic regression model were used to assess the effect of DEX on clinical outcomes. RESULTS: After PSM, 324 pairs of patients were matched between the patients with DEX administration and those without. DEX administration was associated with decreased in-hospital mortality (hazard ratio (HR) 0.287; 95% CI 0.151 - 0.542; p < 0.001) and 90-day mortality (HR 0.344; 95% CI 0.221 - 0.534; p < 0.001), and it was also associated with reduced length of stay (LOS) in ICU (4.54 (3.13,7.72) vs. 5.24 (3.15,10.91), p < 0.001) and LOS in hospital (11.63 (8.02,16.79) vs 12.09 (7.83,20.44), p = 0.002). Subgroup analysis showed that the above associations existed only in the mild and moderate AKI subgroups, but not in the severe AKI subgroup. Nevertheless, DEX administration was not associated with recovery of renal function (HR 1.199; 95% CI 0.851 - 1.688; p = 0.300). CONCLUSION: DEX administration improved outcomes in critically ill patients with mild and moderate AKI and could be a good choice of sedation.

Comparison of different anastomosis angles in radiocephalic fistula with modified functional end-to-side anastomosis.

OBJECTIVE: Functional vein end to arterial side (ETS) anastomosis uses vein side to arterial side anastomosis with distal vein ligation, which is different from traditional ETS anastomosis. To date, there are no studies concerning different anastomotic angles of fistula with functional ETS anastomosis. The purpose of the study was to analyze the clinical outcomes concerning different anastomotic angles of functional ETS anastomosis in radiocephalic fistula. METHODS: Between January 2018 and December 2020, we performed a prospective cohort study concerning functional ETS anastomosis in radiocephalic fistula. According to vascular anatomy of patients, the anastomosis angles of fistula were designed at 30 ≤ angle ≤ 50°, 50 < angle ≤ 70°, and 135° smooth obtuse angle. The end points were the primary patency rate (PPR), the secondary patency rate (SPR) and the cumulative rate of reintervention (CRR) near anastomotic venous segment. RESULTS: 124 patients with functional ETS anastomosiss were enrolled in this study. Pearson χ2 test showed that the group of 135°anastomosis angle had the maximum distance between arteries and veins, and the group of 30-50°anastomosis angle had the minimum distance between arteries and veins (P < 0.01). 30-50°anastomosis angle had the highest PPR at 12 months (P = 0.03) and the lowest CRR near anastomotic venous segment at 3 months (P = 0.04) and 12 months (P = 0.01). There were no significant differences among different anastomosis angles concerning the SPR within 12 months (P > 0.05). Kaplan-Meier and log-rank analysis showed that 30-50°anastomosis had the highest PPR (P = 0.03) and the lowest CRR near anastomotic venous segment (P = 0.01). A multivariable Cox model showed anastomotic angle was an independent factor predictive of the PPR (P = 0.04) and the CRR near anastomotic venous segment (P = 0.03). 50-70°anastomosis angle was a risk factor of decreasing PPR (P = 0.03). 50-70° (P = 0.01) and 135° (P = 0.03) anastomosis angle were both obvious risk factors of increasing CRR near anastomotic venous segment. CONCLUSION: 30-50°were the best anastomotic angles for functional ETS anastomosis, which had the highest PPR and lowest CRR near anastomotic venous segment.

Endoscopic parathyroidectomy versus open parathyroidectomy for patients with refractory secondary hyperparathyroidism: a meta-analysis.

Introduction: Endoscopic parathyroidectomy(EPTX) has been gradually introduced as a minimally invasive treatment for refractory secondary hyperparathyroidism (SHPT). However, it is uncertain about the efficacy and safety compared between EPTX and open parathyroidectomy (OPTX) for refractory SHPT. Aim: This meta-analysis was conducted to evaluate the efficacy and safety of EPTX and OPTX for secondary hyperp arathyroidism (SHPT). Material and methods: Databases including PubMed, EMbase, Cochrane Library, CNKI, and Wanfang were searched. Eligible studies comparing EPTX and OPTX for refractory SHPT were included. Results: Compared with OPTX, EPTX has the shorter hospital stay (p < 0.01) and lower incidences of hoarseness or recurrent laryngeal nerve injury (p = 0.04). There was no significant difference between EPTX and OPTX concerning operation time (p = 0.49), intraoperative blood loss (p = 0.24), postoperative parathyroid hormone levels (p = 0.22), postoperative calcium levels (p = 0.93), postoperative phosphorus levels (p = 0.37), and complications including neck ecchymosis (p = 0.87), subcutaneous haematoma (p = 0.18), and wound infection (p = 0.11). Conclusions: EPTX and OPTX are both effective methods for refractory SHPT. EPTX had the shorter hospital stay and lower incidences of hoarseness or recurrent laryngeal nerve injury.

Macrophage­derived exosomal miRNA­155 promotes tubular injury in ischemia­induced acute kidney injury.

Tubule injury is a characteristic pathological feature of acute kidney injury (AKI) and determines the prognosis of kidney disease. However, the exact mechanism of tubule injury remains largely unclear. In the present study, the exact mechanism of tubule injury was investigated. Bilateral renal ischemia/reperfusion (I/R) injury (I/RI) was induced in mice and exosome secretion inhibitor GW4869 and miRNA­155 inhibitor were used. In addition, the exosomal microRNA (miR)­155­mediated cross­talk between macrophage and tubular cells was also investigated. It was determined that tubular injury was observed in an I/R­induced AKI model, which was closely associated with macrophage infiltration. Interestingly, blocking exosome production using GW4869 ameliorated tubular injury in I/R­induced AKI. Mechanistically, once released, activated macrophage­derived exosomal miR­155 was internalized by tubular cells, resulting in increased tubule injury through targeting of suppressor of cytokine signaling­1 (SOCS­1), a negative regulator of NF­κB signaling. In addition, a dual­luciferase reporter assay confirmed that SOCS­1 was the direct target of miR­155 in tubular cells. Notably, injection of these miR­155­enriched exosomes into renal parenchyma resulted in increased tubule injury in vivo. Thus, the present study demonstrated that exosomal miR­155 mediated the communication between activated macrophages and injured tubules, leading to progression of AKI, which not only provide novel insights into the pathophysiology of AKI but also offer a new therapeutic strategy for kidney diseases.

Procyanidin B2 suppresses hyperglycemia-induced renal mesangial cell dysfunction by modulating CAV-1-dependent signaling.

The dysfunction of renal mesangial cells (MCs) is a hallmark of diabetic kidney disease (DKD), which triggers glomerulosclerosis leading to end-stage renal disease. Procyanidin B2 (PB2), the main component of proanthocyanidin, is well known for its antioxidant and anti-inflammatory effects; however, it remains unclear as to whether it has protective effects on DKD. The present study investigated the protective effect of PB2 against hyperglycemia-induced renal MC dysfunction in mouse SV40-Mes13 (Mes13) cells. The Mes13 cells were treated with or without PB2 under HG conditions. Cell proliferation was assessed using an MTT assay and oxidative stress was assessed by examining intracellular ROS generation and H2O2 production. The changes in extracellular matrix accumulation- and cellular inflammation-related proteins were measured by western blot analysis, ELISA and immunofluorescence analysis. The results showed that PB2 treatment markedly attenuated hyperglycemia-induced cell proliferation, oxidative stress, extracellular matrix accumulation and cellular inflammation in Mes13 cells, which was accompanied by an inactivation of redoxosomes, TGF-ß1/SMAD and IL-1ß/TNF-α/NF-κB signaling pathways. The present study also demonstrated that hyperglycemia upregulated and activated caveolin-1 (CAV-1), whereas PB2 treatment potently reversed this effect. In accordance, CAV-1 overexpression abolished the protective effects of PB2 against hyperglycemia in Mes13 cells, indicating that the cytoprotective effect of PB2 was CAV-1-dependent. These findings form the basis of the potential clinical applications of PB2 in the treatment of DKD.

Impact of klotho on the expression of SRGAP2a in podocytes in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the major cause of kidney failure, and glomerular podocytes play critical roles in the pathogenesis of DN by maintaining the glomerular structure and filtration barrier. Klotho and Slit-Robo GTP activating protein 2a (SRGAP2a) have been indicated to play protective roles in reducing kidney injury, but whether there is an internal relationship between these two factors is unclear. METHODS: In this study, we cultured differentiated rat podocytes in vitro and measured the SRGAP2a expressions by immunofluorescence staining, quantitative real-time PCR (qRT-PCR) and western blotting, after siRNA-mediated transforming growth factor ß1 (TGF-ß1) silencing, TGF-ß1 overexpression and in the presence of a reactive oxygen species (ROS) inhibitor. And we detected the expressions of SRGAP2a, small mother against decapentaplegic (Smad)2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, and NAD(P)H oxidase 4 (NOX4), ROS levels and podocyte cytoskeletal remodelling under high glucose (HG) and exogenous klotho conditions. In addition, we performed haematoxylin-eosin (HE) staining and immunohistochemistry with diabetic rat models to confirm the in vitro results. RESULTS: The results indicated that SRGAP2a expression was significantly upregulated under siRNA-mediated TGF-ß1 silencing conditions or after adding a ROS inhibitor, but significantly downregulated with TGF-ß1 overexpression, in the presence of HG. The supplementation of exogenous klotho under HG conditions significantly increased the SRGAP2a expression, remodelled the actin cytoskeleton and altered the expressions of Smad2/3, p-Smad2/3, Smad7 and NOX4 and reduced the ROS generation in podocytes. Moreover, klotho administration protected kidney injury in DN rats. CONCLUSIONS: This study indicated that klotho may modulate the expression of SRGAP2a by regulating the ROS and TGF-ß1 signalling pathways and provided theoretical support for klotho protein as a novel therapeutic strategy for treating DN patients.

CCL5 Suppresses Klotho Expression via p-STAT3/DNA Methyltransferase1-Mediated Promoter Hypermethylation.

Background: Enhanced inflammation and reduced Klotho are common features in chronic kidney disease (CKD). Inflammation induces DNA hypermethylation. This study assessed the performance of inflammatory marker C-C motif chemokine 5 (CCL5) in epigenetic regulation of Klotho expression. Methods: Fifty CKD patients and 25 matched controls were enrolled, and serum CCL5 level, sKlotho level, and DNA methylation were evaluated in these subjects. A renal interstitial fibrosis (RIF) model with CKD was induced in mice via unilateral ureteral obstruction (UUO) in vivo and human proximal tubular epithelial (HK-2) cells treated with CCL5 in vitro. 5-aza-2'-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor was given to UUO mice. Hematoxylin and eosin (HE) and Masson trichrome staining were adopted to evaluate renal pathological changes. Methylation-specific PCR was performed to assess DNA methylation of Klotho promoter in the peripheral blood leucocytes (PBLs) from CKD patients and obstructive kidney from UUO mice. CCL5, Klotho, and DNA methyltransferases (DNMTs) were determined by ELISAs, immunofluorescence, or western blotting. HK-2 cells were exposed to CCL5 with or without 5-Aza and stattic, a p-signal transducer and activator of transcription 3 (STAT3) inhibitor, and expressions of p-STAT3, DNMT1, and Klotho were determined by western blotting. Results: CCL5 upregulation concomitant with Klotho downregulation in serum and global DNA methylation in PBLs were observed in CKD samples. UUO contributed to severe renal interstitial fibrosis and enhanced expressions of fibrotic markers. Moreover, UUO increased the CCL5 level, induced Klotho promoter methylation, suppressed Klotho level, activated p-STAT3 signaling, and upregulated DNMT1 level. A similar observation was made in HK-2 cells treated with CCL5. More importantly, 5-Aza inhibited UUO-induced Klotho hypermethylation, reversed Klotho, downregulated p-STAT3 expressions, and ameliorated RIF in vivo. The consistent findings in vitro were also obtained in HK-2 cells exposed to 5-Aza and stattic. Conclusion: The CCL5/p-STAT3/DNMT1 axis is implicated in epigenetic regulation of Klotho expression in CKD. This study provides novel therapeutic possibilities for reversal of Klotho suppression by CKD.

STAT6 contributes to renal fibrosis by modulating PPARα-mediated tubular fatty acid oxidation.

Lipid metabolism, especially fatty acid oxidation (FAO) dysfunction, is a major driver of renal fibrosis; however, the detailed regulatory mechanisms involved remain unclear. In this study, we showed that there existed an association between the signal transducer and activator of transcription 6 (STAT6) and tubular lipid metabolism in fibrotic kidneys. Specifically, STAT6 was activated along with the accumulation of lipids via the downregulation of FAO-related genes when mice were subjected to unilateral ureteral obstruction (UUO) or high-fat diet challenge. Tubular-specific depletion, or pharmacologic inhibitor of Stat6 in mice, and Stat6 knockdown in cultured tubular cells attenuated lipid accumulation and renal fibrosis by enhancing FAO. Mechanistically, STAT6 transcriptionally inhibited the expression of PPARα and its FAO-related target genes through a sis-inducible element located in the promoter region of the protein. In conclusion, our study demonstrates the mechanistic details of STAT6-mediated FAO dysregulation in the progression of renal fibrosis and provides a preclinical rationale for efforts to improve the management of renal fibrosis brought about by FAO dysregulation.

Relationship of complement activation pathway to clinical and pathological characteristics and renal outcome in patients with lupus nephritis.

BACKGROUND: Involvement of the complement system in the pathogenesis of lupus nephritis (LN) is well accepted, but its exact role remains unclear. The aim of this study was to investigate the relationship of complement activation pathway to clinical and pathological characteristics and renal outcome in patients with LN. MATERIAL AND METHODS: Patients with LN were divided into two groups: those in whom the complement system was mainly activated through the classical pathway (low serum C3 and C4 levels; CP group); and those in whom the complement system was solely activated through the alternative pathway (low serum C3 with normal C4 levels; AP group). Clinical and pathological data and renal outcomes were compared between the two groups. RESULTS: A total of 102 LN patients were enrolled in this study, 63 patients (61.8%) in the CP group and 39 patients (38.2%) in the AP group. LN patients in the CP group had significantly higher SLEDAI (p < 0.001), more anti-dsDNA (p = 0.001), higher renal activity index (p < 0.001), and more class IV LN (p = 0.008) than LN patients in the AP group. Mean length of follow-up was 50.6 ± 26.4 months. Renal outcome in the form of progression of kidney disease was significantly poorer in the CP group in the AP group (p = 0.037). CONCLUSION: Our findings suggest that evaluation of the complement activation pattern may be useful for evaluating disease activity and predicting the prognosis of LN.

m6A eraser FTO modulates autophagy by targeting SQSTM1/P62 in the prevention of canagliflozin against renal fibrosis.

The dysregulation of autophagy contributes to renal fibrosis. N6-Methyladenosine (m6A) RNA modification is a critical mediator of autophagy. Our previous studies have reported that the disorder of the PPARα/fatty acid oxidation (FAO) axis in renal tubular cells is suppressed by STAT6, which is involved in the regulation of renal fibrotic processes. Here, we found that canagliflozin significantly upregulates SQSTM1/P62, promoting PPARα-mediated FAO by inducing autophagy-dependent STAT6 degradation both in TGF-ß1-treated HK2 cells and in unilateral ureteral occlusion (UUO) and ischemia-reperfusion (I/R) renal fibrosis mouse models. Knockdown of P62/SQSTM1 led to the impairment autophagic flux and the dysregulation of the STAT6/PPARα axis, which was confirmed by SQSTM1/P62cKO mice with UUO treatment along with bioinformatics analysis. Furthermore, SQSTM1/P62 deficiency in renal tubular cells inhibited canagliflozin's effects that prevent FAO disorder in renal tubular cells and renal fibrosis. Mechanistically, the level of m6A eraser FTO, which interacted with SQSTM1 mRNA, decreased in the renal tubular cells both in vitro and in vivo after canagliflozin administration. Decrease in FTO stabilized SQSTM1 mRNA, which induced autophagosome formation. Collectively, this study uncovered a previously unrecognized function of canagliflozin in FTO in the autophagy modulation through the regulation of SQSTM1 mRNA stability in the renal tubular STAT6/PPARα/FAO axis and renal fibrosis.

A PLA2R-IgG4 Antibody-Based Predictive Model for Assessing Risk Stratification of Idiopathic Membranous Nephropathy.

Background: Known as an autoimmune glomerular disease, idiopathic membranous nephropathy (IMN) is considered to be associated with phospholipase A2 receptor (PLA2R) in terms of the main pathogenesis. The quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies by time-resolved fluoroimmunoassay (TRFIA) was determined, and the value of them, both in the clinical prediction of risk stratification in IMN, was observed in this study. Methods: 95 patients with IMN proved by renal biopsy were enrolled, who had tested positive for serum PLA2R antibodies by ELISA, and the quantitative detection of serum PLA2R-IgG and PLA2R-IgG4 antibodies was achieved by TRFIA. All the patients were divided into low-, medium-, and high-risk groups, respectively, which were set as dependent variables, according to proteinuria and renal function. Random forest (RF) was used to estimate the value of serum PLA2R-IgG and PLA2R-IgG4 in predicting the risk stratification of progression in IMN. Results: Out-of-bag estimates of variable importance in RF were employed to evaluate the impact of each input variable on the final classification accuracy. The variable of albumin, PLA2R-IgG, and PLA2R-IgG4 had high values (>0.3) of 0.3156, 0.3981, and 0.7682, respectively, which meant that these three were more important for the risk stratification of progression in IMN. In order to further assess the contribution of PLA2R-IgG and PLA2R-IgG4 to the model, we built four different models and found that PLA2R-IgG4 played an important role in improving the predictive ability of the model. Conclusions: In this study, we established a random forest model to evaluate the value of serum PLA2R-IgG4 antibodies in predicting risk stratification of IMN. Compared with PLA2R-IgG, PLA2R-IgG4 is a more efficient biomarker in predicting the risk of progression in IMN.

Associations of serum soluble klotho and fibroblast growth factor 23 with carotid artery calcification in patients undergoing continuous ambulatory peritoneal dialysis: A retrospective study.

ABSTRACT: This study aimed to assess the associations of serum soluble klotho and fibroblast growth factor 23 (FGF-23) with the occurrence of carotid artery calcification. Peritoneal dialysis patients treated from June 2018 to June 2019 were retrospectively analyzed. They were divided into the carotid artery calcification and non-carotid artery calcification groups according to color Doppler ultrasound findings. Basic indicators in both groups were compared, and the influencing factors of carotid artery calcification were analyzed by logistic regression. Among the 73 continuous ambulatory peritoneal dialysis (CAPD) patients enrolled, 40 (54.8%) had carotid artery calcification. Significant differences were found in age (68.85 ±â€Š7.45 vs 46.62 ±â€Š5.51 years), dialysis time (8.15 ±â€Š1.42 vs 6.02 ±â€Š1.14 months), klotho amounts (325.56 ±â€Š41.15 vs 436.65 ±â€Š45.58 pg/mL) and FGF-23 levels (114.45 ±â€Š15.56 vs 70.15 ±â€Š12.23 pg/mL) between the carotid artery calcification and non-carotid artery calcification groups (all P < .001). The above factors were associated with carotid artery calcification occurrence in univariate analysis. Multivariate analysis showed that elevated age (odds ratio [OR] = 1.55, 95% confidence interval [CI] 1.13-1.74; P = .025) and FGF-23 (OR = 2.16, 95% CI 2.01-2.44; P = .042), and lower klotho (OR = 0.66, 95% CI 0.47-0.85; P = .036) were independent risk factors for carotid artery calcification in CAPD. Serum FGF-23 and age are risk factors for carotid artery calcification in patients with CAPD, whereas klotho is a protective factor.

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease.

BACKGROUND: A novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data. METHODS: Candidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment. RESULTS: Fifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls. CONCLUSIONS: Our results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

Effluent Osteopontin levels reflect the peritoneal solute transport rate.

Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation and may eventually lead to peritoneal membrane injury with a high solute transport rate and ultrafiltration failure. Osteopontin (OPN) is highly expressed through the stimulation of pro-inflammatory cytokines in many cell types. This study aimed to investigate the potential of OPN as a new indicator of peritoneal deterioration. One hundred nine continuous ambulatory PD patients were analyzed. The levels of OPN and IL-6 in peritoneal effluents or serum were analyzed by ELISA kits. The mean effluent OPN concentration was 2.39 ± 1.87 ng/mL. The OPN levels in drained dialysate were correlated with D/P Cr (p < 0.0001, R = 0.54) and D/D0 glucose (p < 0.0001, R = 0.39). Logistic regression analysis showed that the OPN levels in peritoneal effluents were an independent predictive factor for the increased peritoneal solute transport rate (PSTR) obtained by the peritoneal equilibration test (p < 0.001). The area under the receiver operating characteristic curve of OPN was 0.84 (95% CI: 0.75-0.92) in predicting the increased PSTR with a sensitivity of 86% and a specificity of 67%. The joint utilization of effluent OPN with age, effluent IL-6, and serum albumin further increased the specificity (81%). Thus, OPN may be a useful indicator of peritoneal deterioration in patients with PD.

Thioredoxin relieves lipopolysaccharide-induced acute kidney injury in mice by reducing inflammation, oxidative stress and apoptosis.

Acute kidney injury (AKI) is a serious disease with rapid onset and a high mortality rate. It is therefore particularly important to identify a suitable method for treating AKI. Thioredoxin (Trx) is a potent anti-inflammatory and anti-oxidant protein that is prevalent in living organisms. The aim of the present study was to facilitate the clinical treatment of AKI via the study of Trx. Lipopolysaccharide (LPS) was used to construct an AKI model in mice and the mice were pre-treated with Trx to examine its effect on AKI. In addition, human renal tubular epithelial HK-2 cells were cultured and stimulated with Trx to examine its effect on inflammation, levels of oxidative stress and apoptosis in the HK-2 cells. The NF-κB signaling pathway is a classical inflammation-related pathway and the mechanism of Trx was investigated by evaluating the association between Trx and the NF-κB signaling pathway. Trx treatment reduced LPS-induced levels of inflammation, oxidative stress and apoptosis in the HK-2 cells. The activity of NF-κB signaling pathway was increased in LPS-induced HK-2 cells, while Trx treatment effectively reduced NF-κB signaling pathway activity. In addition, Trx treatment significantly reduced LPS-induced mouse AKI in vivo, which was characterized by a decrease in inflammatory factors in mouse serum, a decrease in AKI-associated molecules in mouse urine and a decrease in oxidative stress levels in mouse kidney tissue samples. Trx treatment reduced inflammation, levels of oxidative stress and apoptosis in HK-2 cells by inhibiting the NF-κB signaling pathway, thereby alleviating LPS-induced mouse AKI.

Association between serum elastin-derived peptides and abdominal aortic calcification in peritoneal dialysis patients: a cross-sectional study.

BACKGROUND: Peritoneal dialysis (PD) patients experience accelerated arterial aging, which is characterized by elastin degradation. Elastin-derived peptides (EDPs) are direct products of elastin fragmentation. This study tried to explore the association between serum EDPs and abdominal aortic calcification (AAC) in PD patients. METHODS: Serum levels of EDPs were analyzed in 126 eligible PD patients and 30 controls. PD patients were grouped according to the annularity of AAC evaluated by an abdominal computed tomography (CT) scan. Serum EDPs were analyzed in relation to the presence of AAC or severe AAC in PD patients by logistic regression analysis. RESULTS: Serum EDPs in PD patients were significantly higher than age-matched controls. In 126 PD patients, higher EDPs was associated with greater risk of present AAC (OR = 1.056, 95%CI 1.010-1.103) and severe AAC (OR = 1.062, 95%CI 1.004-1.123). A combination of EDPs substantially improved the accuracy of diagnostic performance for AAC and severe AAC. CONCLUSIONS: EDPs can predict the presence and extent of AAC in PD patients, indicating its possible role to recognize PD patients at risk for AAC and severe AAC.