The RADAR technique in reconstruction of failed autologous arteriovenous fistulas due to juxta-anastomotic stenosis is equivalent to that with traditional surgery in maintenance hemodialysis patients.

OBJECTIVE: Autologous arteriovenous fistula (AVF) is recommended as superior vascular access for hemodialysis but has a high rate of failure, and juxta-anastomotic stenosis (JAS) is one of the predominant causes of fistula failure. The aim of this study was to compare the primary patency in reconstruction of failed AVFs due to JAS between the radial artery deviation and reimplantation (RADAR) technique and traditional surgery (end-vein to side-artery neo-anastomosis) in maintenance hemodialysis (MHD) patients. METHODS: A total of 1215 MHD patients with failed AVF were enrolled in this retrospective cohort study, and 614 patients with failed AVF received surgical intervention. Among these surgical interventions, 417 patients experienced AVF failure due to JAS. Finally, 25 patients who received the RADAR technique were enrolled. Controls of 50 patients received traditional surgery were randomly selected matched by age and sex. Clinical data such as age, sex, comorbidities, and blood biochemical indices were collected. Kaplan-Meier survival curves and Cox proportional hazards analyses were used to explore the difference between the RADAR group and the traditional group in reconstruction of failed AVFs. RESULTS: The RADAR group and the traditional group shared common baseline characteristics. The primary patencies of the reconstructed AVFs were 88.8%, 79.0%, 72.2%, 57.4%, and 38.3% at 12, 24, 36, 48, and 60 months among the 75 patients, respectively. Kaplan-Meier survival curve analysis demonstrated similar primary patencies in the two groups (log-rank test, p = 0.73). Compared with the traditional group, the RADAR group had no difference in predicting AVF failure after adjusting for potential confounders, with an HR of 0.92 (95% CI, 0.18-4.63). CONCLUSIONS: The primary patency of the RADAR technique and the traditional surgery in the reconstruction of failed AVFs due to JAS is almost equal in 5 years.

Containing anti-PLA2R IgG antibody induces podocyte injury in idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear.Method: A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed.Results: Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008).Conclusion: The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy.

Construction of artificial intelligence non-invasive diagnosis model for common glomerular diseases based on hyperspectral and urine analysis.

OBJECTIVE: To develop a non-invasive fluid biopsy assisted diagnosis model for glomerular diseases based on hyperspectral, so as to solve the problem of poor compliance of patients with invasive examination and improve the early diagnosis rate of glomerular diseases. METHODS: A total of 65 urine samples from patients who underwent renal biopsy from November 2020 to January 2022 in Qianfoshan Hospital of Shandong Province were collected.By simultaneously capturing spectral information of the above urine samples in the 400-1000 nm range, more obvious differences were found in the spectra of urine from patients with glomerular diseases between 650 nm and 680 nm. We obtained the original hyperspectral images in this wavelength range through digital scanning, and sampled pixel points at intervals on the original images. The two-dimensional digital image generated from each pixel point served as a member of the subsequent training and test sets. . After manually labeling the images according to different biopsy pathological types, they were randomly divided into training set (n = 58,800) and test set (n = 25,200). The training set was used for training learning and parameter iteration of artificial intelligence non-invasive liquid diagnosis model, and the test set for model recognition and interpretation. The evaluation indexes such as accuracy, sensitivity and specificity were calculated to evaluate the performance of the diagnosis model. RESULTS: The model has an accuracy rate of 96% for early diagnosis of four glomerular diseases. CONCLUSION: The auxiliary diagnosis model system has high accuracy. It is expected to be used as a non-invasive diagnostic method for glomerular diseases in clinic.

Hyperspectral imaging to predict the effect of cyclophosphamide in primary membranous nephropathy.

BACKGROUND: Presently, there is a lack of accurate predictors of the efficacy of primary membranous nephropathy. The aim of this study is to explore the application value of hyperspectral imaging in predicting the efficacy of cyclophosphamide treatment in primary membranous nephropathy. METHOD: A total of 30 patients with primary membranous nephropathy who were treated with glucocorticoid combined with cyclophosphamide were collected. Hematoxylin-eosin stained renal pathological images were acquired by hyperspectral imaging system at the spectral range of 400-1000 nm. The remission group data set contained 23 samples, while the non-remission group data set contained 28 samples. A one-dimensional convolutional neural network model was established to train and test the hyperspectral data, and the performance of the model was evaluated. RESULT: From the spectral curve, the spectral difference between the remission group and the non-remission group was obvious between 525 and 700 nm. The spectral data in this band were analyzed by one-dimensional convolutional neural network, and the confusion matrix showed that the remission group and the non-remission group were successfully classified. The precision and recall were 0.89 and 0.81 for the non-response group and 0.83 and 0.90 for the response group, respectively, with an F1 score of 0.85 in both groups. The area under the AUC curve of the classification model reached 0.857. CONCLUSION: In this study, a one-dimensional convolutional neural network model was used to analyze the hyperspectral images of renal pathology of PMN patients, and the patients in remission group and non-remission group were successfully classified after glucocorticoid combined with cyclophosphamide treatment.

Research progress on exosomes in podocyte injury associated with diabetic kidney disease.

Diabetic kidney disease (DKD), a common cause of end-stage renal disease, is a serious complication that develops with the progression of chronic diabetes. Its main clinical manifestations are persistent proteinuria and/or a progressive decline in the estimated glomerular filtration rate. Podocytes, terminally differentiated glomerular visceral epithelial cells, constitute the glomerular filtration barrier together with the basement membrane and endothelial cells, and the structural and functional barrier integrity is closely related to proteinuria. In recent years, an increasing number of studies have confirmed that podocyte injury is the central target of the occurrence and development of DKD, and research on exosomes in podocyte injury associated with DKD has also made great progress. The aim of this review is to comprehensively describe the potential diagnostic value of exosomes in podocyte injury associated with DKD, analyze the mechanism by which exosomes realize the communication between podocytes and other types of cells and discuss the possibility of exosomes as targeted therapy drug carriers to provide new targets for and insights into delaying the progression of and treating DKD.

Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods: In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 µg, 2.5 µg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results: A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 µg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 µg and placebo group was 8.81 mm, but not statistically significantly different. Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5µg, 38.6% in 2.5 µg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions: Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

MRI Assessment of Renal Lipid Deposition and Abnormal Oxygen Metabolism of Type 2 diabetes Mellitus Based on mDixon-Quant.

BACKGROUND: Diabetic nephropathy (DN) is the main cause of end-stage renal failure. Multiecho Dixon-based imaging utilizes chemical shift for water-fat separation that may be valuable in detecting changes both fat and oxygen content of the kidney from a single dataset. PURPOSE: To investigate whether multiecho Dixon-based imaging can assess fat and oxygen metabolism of the kidney in a single breath-hold acquisition for patients with type 2 diabetes mellitus (DM). STUDY TYPE: Prospective. SUBJECTS: A total of 40 DM patients with laboratory examination of biochemical parameters and 20 age- and body mass index (BMI)-matched healthy volunteers (controls). FIELD STRENGTH/SEQUENCE: 3D multiecho Dixon gradient-echo sequence at 3.0 T. ASSESSMENT: The DM patients were divided into two groups based on urine albumin-to-creatinine ratio (ACR): type 2 diabetes mellitus (DM, 20 patients, ACR < 30 mg/g) and diabetic nephropathy (DN, 20 patients, ACR ≥ 30 mg/g). In all subjects, fat fraction (FF) and relaxation rate (R2*) maps were derived from the Dixon-based imaging dataset, and mean values in manually drawn regions of interest in the cortex and medulla compared among groups. Associations between MRI and biochemical parameters, including ß2-microglobulin, were investigated. STATISTICAL TESTS: Kruskal-Wallis tests, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: FF and R2* values of the renal cortex and medulla were significantly different among the three groups with control group < DM < DN (FF: control, 1.11± 0.30, 1.10 ± 0.39; DM, 1.52 ± 0.32, 1.57 ± 0.35; DN, 1.99 ± 0.66, 2.21 ± 0.59. R2*: Control, 16.88 ± 0.77, 20.70 ± 0.86; DM, 17.94 ± 0.75, 22.10 ± 1.12; DN, 19.20 ± 1.24, 23.63 ± 1.33). The highest correlation between MRI and biochemical parameters was that between cortex R2* and ß2-microglobulin (r = 0.674). A medulla R2* cutoff of 21.41 seconds-1 resulted in a sensitivity of 80%, a specificity of 85% and achieved the largest area under the ROC curve (AUC) of 0.83 for discriminating DM from the controls. A cortex FF of 1.81% resulted in a sensitivity of 80%, a specificity of 100% and achieved the largest AUC of 0.83 for discriminating DM from DN. DATA CONCLUSION: Multiecho Dixon-based imaging is feasible for noninvasively distinguishing DN, DM and healthy controls by measuring FF and R2* values. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

The prebiotic effects of soluble dietary fiber mixture on renal anemia and the gut microbiota in end-stage renal disease patients on maintenance hemodialysis: a prospective, randomized, placebo-controlled study.

BACKGROUND: Renal anemia is caused by end-stage renal disease (ESRD) but has a complex etiology. The application of dietary fiber (DF) to regulate the gut microbiota has shown effective therapeutic effects in some diseases, but its role in renal anemia is not clear. The aim of this study was to explore the effect of DF on renal anemia by regulating the gut microbiota and its metabolite, short-chain fatty acids (SCFAs). METHODS: A total of 162 ESRD patients were enrolled and randomly distributed into a DF or a control group (received oral DF or potato starch, 10 g/day for 8 weeks). Hemoglobin (Hb), serum iron (Fe2+), serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin and the dosage of recombinant human erythropoietin (rhEPO) before and after intervention in patients were analyzed. The gut microbiota and SCFAs in both groups were analyzed by 16S rDNA sequencing and gas chromatography-mass spectrometry, respectively. Spearman's correlation test was used to analyze the correlation between the gut microbiota, SCFAs and the hematological indicators. RESULTS: Compared with the control group, (1) the patients in the DF group had higher Hb [117.0 (12.5) g/L vs. 94.0 (14.5) g/L, p < 0.001], Fe2+ [13.23 (4.83) µmol/L vs. 10.26 (5.55) µmol/L, p < 0.001], and SF levels [54.15 (86.66) ng/ml vs. 41.48 (36.60) ng/ml, p = 0.003]. (2) The rhEPO dosage in the DF group was not significantly decreased (p = 0.12). (3) Bifidobacterium adolescentis, Lactobacillus and Lactobacillaceae were increased in the DF group, and Lactobacillus and Lactobacillaceae were positively correlated with Hb (r = 0.44, p < 0.001; r = 0.44, p < 0.001) and Fe2+ levels (r = 0.26, p = 0.016; r = 0.26, p = 0.016) and negatively correlated with rhEPO dosage (r = - 0.45, p < 0.001; r = - 0.45, p < 0.001). (4) Patients in the DF group had elevated serum butyric acid (BA) levels [0.80 (1.65) vs. 0.05 (0.04), p < 0.001] and BA levels were positively correlated with Hb (r = 0.26, p = 0.019) and Fe2+ (r = 0.31, p = 0.005) and negatively correlated with rhEPO dosage (r = - 0.36, p = 0.001). Lactobacillus and Lactobacillaceae were positively correlated with BA levels (r = 0.78, p < 0.001; r = 0.78, p < 0.001). CONCLUSION: DF may improve renal anemia in ESRD patients by regulating the gut microbiota and SCFAs. Trial registration This study was registered in the China Clinical Trial Registry ( www.chictr.org.cn ) on December 20, 2018 ( ChiCTR1800020232 ).

Association of plasma neutrophil gelatinase-associated lipocalin with parameters of CKD-MBD in maintenance hemodialysis patients.

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients. MATERIALS AND METHODS: First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD-MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT). RESULTS: According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P < 0.001) and intact parathyroid hormone (iPTH) (r = 0.256, P = 0.008); while inversely correlated with albumin(Alb) (r = - 0.201, P = 0.039). After adjusting for age, sex, vintage, Alb and all parameters of CKD-MBD(Ca, P, lg(ALP), lg(iPTH), Klotho and fibroblast growth factor 23(FGF23)), lg(NGAL) were positively correlated with Ca (r = 0.481, P < 0.001), P (r = 0.336, P = 0.037), lg(ALP) (r = 0.646, P < 0.001) in Partial correlation analysis; further multiple linear regression analysis showed same positive associations between lg(NGAL) and Ca (ß = 0.330, P = 0.002), P (ß = 0.218, P = 0.037), lg(ALP) (ß = 0.671, P < 0.001). During the 4-7 days after PTX + AT, plasma NGAL decreased from 715.84 (578.73, 988.14) to 688.42 (660.00, 760.26) ng/mL (P = 0.071), Klotho increased from 496.45 (341.73, 848.30) to 1138.25 (593.87, 2009.27) pg/mL (P = 0.099). CONCLUSION: Plasma NGAL levels were positively associated with ALP in MHD patients; and downtrends were shown after PTX + AT in patients with severe SHPT. These findings suggest that NGAL is a participant in CKD-MBD under MHD condition.

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy.

OBJECTIVE: Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear. METHODS: Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9-25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition. RESULTS: In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1-36.1; p = 0.039). CONCLUSIONS: The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.

The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment.

Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.

Serum levels of the endothelial glycocalyx constituents and the early failure of forearm autologous arteriovenous fistulas in end-stage renal disease patients: a prospective cohort study.

BACKGROUND: The relationship between the endothelial glycocalyx constituents and the early failure of autologous arteriovenous fistulas (AVFs) in ESRD patients is still unknown. METHODS: In this prospective cohort study, 181 ESRD patients (the mean age was 53.3 ± 11.8 years, 66.3% of them were males) received forearm AVFs surgery were consecutively enrolled with a median follow-up time of 10 months. The early AVF failure was defined as a fistula that never developed adequately for dialysis use or that failed within the first 3 months of use. The serum levels of glycocalyx constituents including glypicans-1 (GPC-1), syndecans-1 (SDC-1), and hyaluronan (HA), and the indicator of endothelial activation reflected by E-selectin (ES) were determined by ELISAs. RESULTS: The primary patencies of AVFs were 98.3%, 96.7%, 91.7%, and 89.5% at 3, 6, 12, and 18 months, respectively. The ROC curve was plotted and demonstrated that HA, not GPC-1, SDC-1 or ES, can diagnose the AVF failure, with the cut-off value of 6.37 ng/ml, the sensitivity of 87.5%, the specificity of 46.9%, and the Youden index of 0.34, respectively. The Kaplan-Meier survival analysis demonstrated that patients with HA < 6.37 ng/mL had better patency of AVFs than patients with HA ≥ 6.37 ng/mL (log-rank test, p = 0.008). In the Cox proportional hazards analysis, after adjusting for confounders, HA (≥ 6.37 ng/mL vs. < 6.37 ng/mL) was associated with the early AVFs failure, with the OR of 5.88 (1.21-28.60). CONCLUSIONS: This study demonstrated that HA can predict the early failure of forearm AVFs, when its serum level is more than 6.37 ng/mL.

Association Between Body Composition and Glomerular Hyperfiltration Among Chinese Adults.

High body mass index (BMI) is the most common parameter to assess excess adiposity, and has been linked to glomerular hyperfiltration (GH). However, BMI may be misleading in the estimation of body fat content due to its inability to discriminate between body fat and lean mass. In recent years, the convenient biological impedance analysis has made prediction of certain diseases somewhat feasible and accessible using body composition (BC). Accordingly, we conducted a cross-sectional study to explore the association between BC and GH among Chinese adult population. A total of 6902 adults (aged 38.6 ± 8.3 years, 70.1% males) who consecutively visited the Health Checkup Clinic were enrolled. BC including fat mass and lean body mass (LBM) was evaluated by biological impedance analysis. The upper quartile of eGFR which exceeded 117.3 mL/min/1.73 m2 was defined as GH, in comparison with the lower three quartiles (control group). As a categorical outcome, GH subjects had higher fat/LBM than the control group, which was 34.7 ± 10.9 (%) vs. 34.0 ± 10.5 (%), P = 0.01; however, the BMI in GH group was lower than in the control group, which was 24.5 ± 3.7 (%) vs. 24.9 ± 3.6 (%), P < 0.001. Fat/height and Fat/BSA were not significantly different between the two groups. Moreover, after adjusting for potential confounders, fat/LBM significantly correlated with GH (OR = 2.09, 95% CI, 1.11 to 3.93). The study revealed that fat/LBM significantly correlated with GH among Chinese adult population, which highlights that adiposity might be an important and potentially modifiable determinant of GH.

Clinical outcomes following the surgery of new autologous arteriovenous fistulas proximal to the failed ones in end-stage renal disease patients: a retrospective cohort study.

Background: Most prior studies have explored surgery for the treatment of failed autologous arteriovenous fistulas (AVFs) with limited follow-up times and a lack of end point mortality. Accordingly, we conducted a retrospective cohort study to evaluate the clinical outcomes of the surgery of new AVF proximal to the failed forearm AVF.Methods: In this study, 538 end-stage renal disease patients (group A, 418 with primary AVF; and group B, 120 with failed AVF) were consecutively enrolled between January 2013 and June 2016, with a median follow-up time of 41 months. Primary and secondary patency, all-cause mortality, and risk factors associated with AVF failure were explored by the Kaplan-Meier method or Cox proportional hazards model.Results: In group A (n = 418), the primary and secondary patencies of AVF were 85.6% vs. 96.8%, 79.7% vs. 95.0%, 75.1% vs.93.9%, 73.2% vs. 93.6% and 73.2% vs. 93.6% at 12, 24, 36, 48 and 60 months, respectively. The primary patencies of AVF in group B were 95.0%, 91.7%, 89.2%, 88.3% and 88.3% at 12, 24, 36, 48 and 60 months, respectively. After adjusting for potential confounders, age, angiotensin-converting inhibitors or angiotensin-receptor blockers (anti-RAAS) drugs and D-dimer were independent predictors of AVF failure. However, there were no differences between functional and failed AVF regarding all-cause mortality.Conclusions: The study revealed that the primary and secondary patiencies of the surgery of new AVF proximal to the failed ones were ideal operations to restore failed forearm AVF.

Dysbiosis of the gut microbiome is associated with CKD5 and correlated with clinical indices of the disease: a case-controlled study.

BACKGROUND: Chronic kidney disease (CKD) is a universal chronic disease in China. The balance of the gut microbiome is highly crucial for a healthy human body, especially for the immune system. However, the relationship between the gut microbiome and CKD has not yet been clarified. METHODS: A total of 122 patients were recruited for this study. Among them, 24 patients were diagnosed with CKD5 but did not receive hemodialysis therapy, 29 patients were diagnosed with CKD5 and received hemodialysis therapy and 69 were matched healthy controls. The gut microbiome composition was analyzed by a 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) technology was used to evaluate the levels of microbiome-related protein-binding uremic toxins level, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), in the patients. RESULTS: We compared the gut microbiome results of 122 subjects and established a correlation between the gut microbiome and IS and PCS levels. The results indicated that alpha and beta diversity were different in patients with CKD5 than in the healthy controls (p < 0.01). In comparison to healthy controls, CKD5 patients exhibited a significantly higher relative abundance of Neisseria (p < 0.001), Lachnoclostridium (p < 0.001) and Bifidobacterium (p < 0.001). Faecalibacterium (p < 0.001) displayed a notably lower relative abundance for CKD5 patients both with and without hemodialysis than for controls. It was also found that the concentrations of IS and PCS were correlated with the gut microbiome. CONCLUSIONS: Our results indicate that CKD5 patients both with and without hemodialysis had dysbiosis of the gut microbiome and that this dysbiosis was associated with an accumulation of IS and PCS. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of CKD5.

IQGAP1 mediates podocyte injury in diabetic kidney disease by regulating nephrin endocytosis.

Diabetic kidney disease (DKD) is a complication associated with diabetes and is a major public health problem in modern society. Podocyte injury is the central target of the development of DKD, and the loss or dysregulation of nephrin, a key structural and signalling molecule located in the podocyte slit diaphragm (SD), initiates potentially catastrophic downstream events within podocytes. IQGAP1, a scaffold protein containing multiple protein-binding domains that regulates endocytosis, can interact with nephrin in podocytes. It is hypothesized that IQGAP1 contributes to nephrin endocytosis and may participate in the pathogenesis of DKD. The dramatically increased histo-nephrin granularity score in DKD glomeruli showed a significant positive correlation with increased IQGAP1-nephrin interaction without changes in the total protein content of nephrin and IQGAP1. In cultured human podocytes, hyperglycaemia induced the intracellular translocation of IQGAP1 from the cytosol to the vicinity of the cytomembrane, reinforced the IQGAP1-nephrin interaction, and augmented nephrin endocytosis. Moreover, impaired podocyte function, such as migration, extensibility and permeability, were further aggravated by wild-type IQGAP1 plasmid transfection, and these effects were partially restored by siRNA-mediated IQGAP1 downregulation. Collectively, these findings show that IQGAP1, an intracellular partner of nephrin, is involved in nephrin endocytosis and the functional regulation of podocytes in DKD.

Effects of oral activated charcoal on hyperphosphatemia and vascular calcification in Chinese patients with stage 3-4 chronic kidney disease.

BACKGROUND: The relationship between oral activated charcoal (OAC) and hyperphosphatemia and vascular calcification is not completely clear. We observed and recorded the effects of OAC on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD). METHODS: In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the OAC group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multidetector computed tomography (MDCT) and were randomly divided into three groups: the OAC group, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. RESULTS: The first and second phases of the experiment were followed for 12 months. In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X2 = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the OAC group, the CC group and the LC group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01). CONCLUSION: Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. OAC appears to delay the development of vascular calcifications in stage 3-4 CKD patients.

Evaluation and prognostic significance of manganese superoxide dismutase in clear cell renal cell carcinoma.

The antioxidant enzyme manganese superoxide dismutase (MnSOD) is up-regulated in renal cell carcinoma (RCC) and has been implicated in multiple stages of RCC tumorigenesis and progression. However, the prognostic significance of MnSOD in RCC has not been fully elucidated. This study aimed to investigate the expression profile of MnSOD in clear cell RCC (ccRCC) tissues and evaluate the clinical significance of this enzyme in ccRCC patients. MnSOD mRNA was assessed in 42 ccRCC and 33 normal kidney tissues using the Oncomine database, and its protein was detected in 145 ccRCCs and 3 normal tissues by immunohistochemistry staining. The Oncomine database confirmed higher MnSOD mRNA expression in ccRCC than in normal tissues, and immunohistochemistry analysis revealed that MnSOD protein expression was inversely associated with pathologic grade, clinical stage, tumor size, M status, and cancer-specific survival. In addition, univariate survival analysis demonstrated that high-grade, late-stage, large tumors, stage M1, and low MnSOD expression were associated with a poorer prognosis for cancer-specific survival, and further multivariate analysis revealed that tumor grade, stage, M1 stage, and MnSOD were identified as independent prognostic factors for cancer-specific survival in patients with ccRCC. Collectively, these findings imply that MnSOD is a promising prognostic marker in ccRCC and implies that oxidative stress might be involved in the tumorigenesis and progression of ccRCC.

Arsenic trioxide increases expression of secreted frizzled-related protein 1 gene and inhibits the WNT/ß-catenin signaling pathway in Jurkat cells.

The aim of the present study was to investigate the demethylation effect of arsenic trioxide (As2O3) on the secreted frizzled-related protein 1 (SFRP1) gene and its ability to inhibit the Wingless-type MMTV integration site family (WNT) pathway in Jurkat cells. Methylation-specific polymerase chain reaction was used to examine the CpG island methylation status of the SFRP1 gene in leukemia cell lines. In addition, the effects on Jurkat cells of treatment with different concentrations of As2O3 for 48 h were investigated. Reverse transcription-quantitative polymerase chain reaction was employed to measure the expression of mRNAs, while western blot analysis was used to examine protein expression in cells. The SFRP1 gene was methylated in Jurkat cells. However, both methylated and unmethylated SFRP1 genes were detected in HL60 and K562 cells. In normal bone marrow mononuclear cells, the SFRP1 gene was unmethylated. Following treatment with As2O3 for 48 h, the SFRP1 gene was demethylated, and the mRNA and protein expression levels of the SFRP1 gene were increased. By contrast, the mRNA and protein expression levels of ß-catenin and cyclin Dl were downregulated. The protein expression of c-myc was also downregulated, but As2O3 exhibited no significant effect on the mRNA expression of c-myc. Abnormal methylation of the SFRP1 gene was detected in Jurkat cells. These results suggest that As2O3 activates SFRP1 gene expression at the mRNA and protein levels in Jurkat cells by demethylation of the SFRP1 gene. Furthermore, they indicate that As2O3 regulates WNT target genes and controls the growth of Jurkat cells through the WNT/ß-catenin signaling pathway.

Association between metabolic syndrome and chronic kidney disease in a Chinese urban population.

BACKGROUND: Few studies have examined the relationships between the prevalence of chronic kidney disease (CKD) and the metabolic risk factors in a developing country such as China, where genetic and environmental backgrounds differ from those in Western countries. METHODS: The subjects of this cross-sectional study were the individuals from 18 to 92y. The metabolic syndrome (MetS) was defined based on the criteria of Adult Treatment Panel Third Report (ATP III), but using body mass index (BMI) instead of waist circumference. CKD was defined as decreased estimated glomerular filtration rate (eGFR<60mL/min/1.73m2) or presence of proteinuria (urine protein≥1+) assessed using dipstick method. RESULTS: A total of 26,601 subjects (average age of 48.7y) were analyzed. Among them, the prevalence of the MetS and CKD was 36.4% and 3.0%, respectively. After adjustment for age, gender, cigarette smoking and alcohol drinking, the prevalence of CKD was significantly greater in subjects with than without MetS (OR 1.99, 95% CI 1.57-2.53, p<0.001). Multivariate-adjusted odd ratios for CKD in subjects with 3, 4 or 5 MetS components were 1.82 (95% CI 1.31-2.52, p<0.001), 2.92 (95% CI 2.09-4.09, p<0.001), and 3.07 (95% CI 1.67-5.67, p<0.001), respectively. After further adjustments were made for the other components of MetS, only high fasting glucose (OR 1.52, 95% CI 1.12-2.05) were significant risk factors for reduced renal function(eGFR<60mL/min/1.73m2). High blood pressure (OR 1.81, 95% CI 1,42-2.29), high triglycerides (OR 1.34, 95% CI 1.11-1.67) and high fasting glucose (OR 2.07, 95% CI 1.62-2.66) were significant risk factors for proteinuria. CONCLUSIONS: MetS was highly prevalent in the middle-aged and elderly Chinese population in the city of Jinan. There was a graded relationship between the number of MetS components and risk of CKD. High fasting blood glucose levels were the main risk factor of reduced renal function. High blood pressure, high fasting blood glucose levels and high triglycerides were main risk factors for proteinuria.