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  • 2018 Volue 34 Issue 6      Published: 15 June 2018
      

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  • Abstract ( ) PDF ( ) Knowledge map Save
    Objective To explore the optimal levels of serum calcium, phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients. Methods This study is a single center, retrospective cohort study. The associations between serum calcium, phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed. All patients started PD between January 1, 2008 and April 30, 2016 were enrolled and followed up to December 31, 2016. At baseline and every 3 months, biochemical and therapeutic information was collected. Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism. Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis. The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium, 1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis. Moreover, cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values. Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40 mmol/L for serum calcium, 1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH. These ranges need further validation by large population studies to further conform.
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    Objective To analyze the mutations of causal genes in 5 children with primary distal renal tubular acidosis (dRTA), and explore their association of genotype and phenotype, so as to raise the awareness of the disease. Methods The whole exome sequencing was used to identify mutations in these 5 children from 5 families. Results A total of 4 different mutations of ATP6V0A4 gene were found in 2 dRTA children, including a novel heterozygous intron mutation (c.639+1G>A), a reported heterozygous nonsense variant (c.580C>T, p.Arg194*) and 2 novel heterozygous duplications (c.1504dupT, p.Tyr502Leufs*22; c.2351dupT, p.Phe785Ilefs*28). Two novel heterozygous missense mutations of ATP6V1B1 gene (c.409C>T, p.Pro137Ser; c.904C>T, p.Arg302Trp) were identified in the third child, and a heterozygous missense mutation of SLC4A1 gene (c.1765C>A, p.Arg589Ser) previously reported was found in the fourth child. No mutation of the dRTA-related causal genes was found in the fifth child. Furthermore, the mutations of causal genes in each of the first three children were compound heterozygous, which were consistent with the autosomal recessive inheritance pattern, and the variant from the fourth child was de novo. Conclusions The present study has found 7 mutations, including 5 novel variants, which enriches the human gene mutation database (HGMD) and contributes to a better understanding of the disease mechanisms.
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    Objective To investigate the relationship between body composition and adequacy of dialysis, and analyze the related risk factors for inadequate delivery of hemodialysis. Methods In a prospective clinical trial, two different methods determining dialysis dose were simultaneously applied: Kt/Vdau (conventional method with Daugirdas' formula) and Kt/Vbcm [online clearance monitoring (OCM) measurement with V measured by body composition monitor (BCM)]. Using the value of 1.27 as the boundary, the patients were divided into two groups: Kt/Vbcm<1.27 group and Kt/Vbcm≥1.27 group. Clinical indices were compared between the two groups. Multiple linear regression was applied to analyze the potential impact factors of the difference between Kt/V values calculated by the two methods. Receiver operator characteristic (ROC) curve was applied to analyze meaningful factors. Results A total of 138 maintenance hemodialysis patients with age of (54.9±12.7) years old were enrolled, and 55.1% of them were males. There was no significant difference between Kt/Vdau and Kt/Vbcm [ 1.432(1.235, 1.718) vs 1.434 (1.244, 1.642), P=0.823]. Kt/Vdau was incidentally prone to falsely high values due to operative errors, whereas in these cases OCM-based measurement Kt/Vbcm delivered realistic values. An excellent correlation was observed between Kt/Vdau and Kt/Vbcm; the mean difference was 0.07, 95%CI (-0.66 - 0.79); the correlation coefficient was 0.842(0.821 - 0.862). The patients in Kt/Vbcm≥1.27 group had older age, lower body mass index (BMI), lower height and weight, lower total body water (TBW), lower extracellular water, lower intracellular water, and lower lean tissue index (LTI) compared to those in Kt/Vbcm<1.27 group. Excellent correlations were observed between Kt/Vbcm and TBW or LTI (r=-0.834, P<0.001; r=-0.721, P<0.001). ROC curve analysis showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 87.1% and 86.5%, with a threshold of 30 L for TBW. It also showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 60.4% and 94.6%, with a threshold of 11.05 kg/m2 for LTI. Conclusions BCM can give more accurate parameters of urea distribution volume, thus modifying the result of Kt/V. TBW and LTI are important risk influencing factors for inadequately dialysis, and special attention should be paid to patients with TBW>30 L or LTI>11.05 kg/m2.
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    Objective To assess the impact of physical training on physiological function of adult renal transplant recipients by meta-analysis and to provide theoretical guidance for clinical practice. Methods Randomized controlled trials of physical training for the treatment of renal transplant recipients until October 2017 were searched in the database of Cochrane library, PubMed, Embase, Web of Science, Wanfang Data and CNKI. Data extracted from the literatures were analyzed with RevMan software (version 5.3). Results A total of 10 studies in 10 manuscripts met the inclusion criteria, and 557 cases were included. Meta-analysis results were as follows. Compared with the control group (routine drug therapy), the level of peak exercise oxygen uptake (peak VO2) was significantly increased in physical training group (routine drug therapy and physical training) (MD=2.40, 95%CI 0.15-4.64, P=0.04). However, there was no statistically significant difference in the change of blood lipid, blood pressure, hemoglobin and serum creatinine between the two groups (all P>0.05). Conclusions Physical training can improve cardio respiratory fitness of renal transplant recipients in the early stage, but it has no obvious effect on blood pressure, blood lipid, hemoglobin and blood creatinine.
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    Objective To explore the potential mechanisms of low density lipoprotein receptor (LDLr) in high glucose peritoneal dialysis solution (PDS)-induced peritoneal fibrosis. Methods Human peritoneal mesothelial cells (PMCs) were applied. In pre-experiment, human PMCs were cultured with 1.5% PDS, 2.5% PDS and 4.25% PDS for 6 h, 12 h and 24 h. 4.25% mannitol was used as high osmotic pressure control. In formal experiment, PMCs were divided into the control group (treated with phosphate buffer saline) and the high glucose PDS group (treated with 4.25% PDS for 24 h). Morphological change of PMCs was observed by inverted microscope. The mRNA and protein expressions of extracellular matrix proteins such as α-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1) and collagenⅠ in PMCs were respectively measured by real-time PCR and Western blotting. The lipid accumulation was observed by oil red O staining and filipin staining, and the content of intracellular cholesterol ester was detected by high-performance liquid chromatography. The co-expression of the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) with golgin was observed with immunofluorescent staining. The mRNA and protein expressions of LDLr, SREBP-2 and SCAP were respectively detected by real-time PCR and Western blotting. The mRNA and protein expressions of mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E-binding protein 1 (4EBP1), and p70 S6 kinase (S6K1) were respectively detected by real-time PCR and Western blotting. Results (1) Compared with the 1.50% PDS stimulation, 4.25% PDS for 24 h intervention significantly increased the expression of LDLr in PMCs (P<0.05), and high osmotic pressure control at 6 h, 12 h and 24 h had no statistical difference (P>0.05). (2) Compared with those in the control group, in high glucose PDS group PMCs showed notable elongation consistent with the morphology of myofibroblasts, the expressions of α-SMA, FSP-1 and collagen Ⅰ were increased (all P<0.05), and the intracellular cholesterol were enhanced (P<0.05). Meanwhile, the co-expression of SCAP with golgin was enhanced, and the mRNA and protein expressions of LDLr, SREBP-2 and SCAP were up-regulated in high glucose PDS group (all P<0.05). Further, the mRNA and protein phosphorylation of mTOR, 4EBP1 and S6K1 were increased (all P<0.05). Conclusions The disruption of LDLr feedback regulation is involved in high glucose PDS-mediated cholesterol accumulation in PMCs by mammalian target of rapamycin complex 1 (mTORC1) pathway, which promotes the accumulation of extracellular matrix and peritoneal fibrosis.
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    Objective To investigate the protective effect of complement 5a receptor 1 (C5aR1) antagonist on ascending urinary tract infection in mice. Methods (1) Female C57BL/6 mice were randomly divided into experimental and control groups: 38 mice in each group, and inoculated with E. coli by urethral catheterization to set up the ascending urinary tract infection model. C5aR1 antagonist (W54011 or PMX53) and corresponding control (PBS or control peptide) were initially given either at 2 h before or 3 h after infection by intraperitoneal injection. Mice were sacrificed to assess the infection in bladder and kidney at 24 or 48 h after infection. The bacterial load of bladder and kidney tissue was measured by agar plate assay. The mRNA expression of renal inflammatory factors was detected by real-time RCR. The renal tissue injury and inflammatory cell infiltration were assessed by HE staining and pathological scores. (2) Primary cultured renal tubular epithelial cells were randomly divided into antagonist and control groups to detect and compare the bacterial adhesion to renal tubular epithelial cells in vitro. Results Compared with control groups, the initial delivery of C5aR1 antagonist (W54011 or PMX53) before E.coli inoculation reduced the bacterial load in bladder and kidney tissue 48 h after infection (all P<0.01). In experimental group given W54011 before infection, the renal pathological scores were reduced (both P<0.05), as well as renal inflammatory factor expressions: CXCL-1 mRNA, IL-6 mRNA and TNF-α mRNA (all P<0.05). Compared with corresponding control groups, the initial delivery of PMX53 after E. coli inoculation could also reduce the bacterial load in bladder and kidney tissue 48 h after infection (both P<0.01). Furthermore, C5aR1 antagonists W54011 and PMX53 could decrease bacteria adhesion to renal tubular epithelial cells in vitro, compared with control groups (both P<0.05). Conclusions C5aR1 antagonists can significantly attenuate renal tissue injury, ameliorate renal inflammation and the adhesion of bacteria to renal epithelial cells. C5aR1 may be an effective target for the prevention and treatment of urinary tract infection.
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    Objective To investigate the effect and potential mechanism of microRNA (miRNA)-377 on high glucose-induced proliferation and inflammation in human mesangial cells. Methods Cells were randomly divided into six groups: control group (5.5 mmol/L glucose), high glucose group (30.0 mmol/L glucose), negtive miRNA inhibitor transfection+high glucose group, negtive miRNA mimic transfection+high glucose group, miRNA-377 inhibitor transfection+high glucose group (miR-377i+high glucose group), miRNA-377 mimic transfection+high glucose group (miR-377m+high glucose group). miRNA-377 expression was detected by real-time PCR. Cell proliferation and cell cycle were detected by BrdU assay and flow cytometry, respectively. The release of tumor necrosis factor-α (TNF-α), interleukin (IL)-18, IL-6 and macrophages chemotaxis protein-1 (MCP-1) were evaluated by ELISA. The activations of NF-κB pathway, including the expressions of phosporylated (p)-IκBα, p-P65 and nuclear P65, were measured by Western blotting. Results Compared with those in control group, in high glucose group cell viability, miRNA-377 expression and cell proliferation rate increased (all P<0.05), proportions of S phase cell and G2/M phase cell in cell cycle increased (all P<0.05), the levels of TNF-α, IL-18, IL-6 and MCP-1 were higher (all P<0.05), as well as the expressions of p-IκBα/IκBα, p-P65/P65 and nuclear P65 were increased (all P<0.05). Compared with high glucose group, cell proliferation rate was restrained (P<0.05), proportions of S phase cell and G2/M phase cell in cell cycle was descreased (all P<0.05), the levels of TNF-α, IL-18, IL-6 and MCP-1 were lower (all P<0.05), as well as the expressions of p-IκBα/IκBα, p-P65/P65 and nuclear P65 were reduced (all P<0.05) in miR-377i+high glucose group. However, miR-377m+high glucose group presented opposite results (all P<0.05). Conclusions miRNA-377 knockdown can partially suppress high glucose-induced human mesangial cell proliferation and cell cycle transition, and restrain inflammatory molecules release. Its mechanism may be related to the inhibition of NF-κB pathway.