Objective To explore the association between serum FGF23 and Klotho protein, and bone mineral density in maintenance hemodialysis (MHD) patients. Methods A total of 125 MHD patients admitted in the Hospital between January 2015 and November 2015 was enrolled. Their bone mineral densities of femur neck and lumbar spine were studied by dual-energy X-ray absorptiometry. These patients were divided into three groups as normal, osteopenic and osteoporotic, according to World Health Organization criteria based on bone mineral density T scores. Levels of serum FGF23, Klotho protein and 1,25(OH)2VitD3 were measured by ELISA. The parameters including calcium, phosphorus, and parathyroid hormone were assessed. Results The incidences of osteopenia and osteoporosis at the femur neck and lumbar spine in MHD patients were 82.40% and 56.00% respectively. No significant difference was found in the levels of serum FGF23 among normal, osteopenic and osteoporotic groups on the basis of femur neck and lumbar spine bone mineral density (P﹥0.05). No correlation was found between FGF23 and bone mineral density. There however were significant differences in the levels of serum Klotho protein among three groups on the basis of femoral neck bone mineral density (P＜0.05). And the levels of Klotho protein in the osteoporotic group [(387.172±54.137) ng/L] were significantly decreased than those in normal group [(429.883±41.776) ng/L] and osteopenic group [(410.598±61.056) ng/L] (P＜0.05). There were also significant differences in the levels of serum Klotho protein among three groups in terms of lumbar spine bone mineral density (P＜0.05), while the levels of Klotho protein in the osteopenic group [(387.263±53.255) ng/L] were significantly decreased than those in normal group [(417.108±56.179) ng/L] (P＜0.05). A positive correlation was found between Klotho protein and bone mineral densities of femur neck and lumbar spine. Multiple linear regression analysis showed that one of the main factors influencing the degree of bone mineral density in MHD patients was Klotho protein. Conclusions CKD-MBD with low BMD is common and widespread in hemodialysis patients. FGF23 has no direct effect on bone mineral density in MHD patients; while Klotho protein is correlated with the severity of bone mineral density. High-level Klotho protein may reduce the severity of CKD-MBD with low BMD in MHD patients.

Objective To explore the effects of residual renal function (RRF) on quality of life (QOL) in patients with continuous ambulatory peritoneal dialysis (CAPD), and analyze the factors influencing QOL. Methods One hundred and eighteen patients treated with CAPD for at least 3 months in No.455 Hospital of People's Liberation Army were enrolled. All patients were divided into two groups according to residual glomerular filtration rate (rGFR): the group with RRF [rGFR≥1 ml?min-1?(1.73 m2)-1], and the group without RRF [rGFR＜1ml?min-1?(1.73 m2)-1]. The demographic characteristics, laboratory data, cardiothoracic ratio, dialysis adequacy parameters, rGFR, blood pressure, urine volume, ultrafiltration volume and dialysis prescription were investigated. Patient's QOL was evaluated by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Results There was no significant differences between the groups with and without RRF in the age, gender, causes of disease, complication, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), haemoglobin (Hb), cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, normalized protein catabolic rate (nPCR) and cardiothoracic ratio (all P＞0.05). Compared with the patients with RRF, PD duration, ultrafiltration volume, serum creatinine (Scr), calcium, phosphorus, C-reactive protein (CRP), parathyroid hormone (PTH) and peritoneal dialysis dose in the patients without RRF were significantly higher, and urine volume, serum albumin (Alb), potassium, and urea total Kt/V were significantly lower (all P＜0.05). The patients without RRF had a significantly lower score in physical function and physical component summary as compared to the patients with RRF (all P＜0.05). There was no significant differences in role physical, bodily pain, general health, vitality, social function, role emotional, mental health, mental component summary and SF-36 scores (all P＞0.05). Simple linear regression showed that there was no correlation between rGFR and SF-36 scores (β=1.330, P=0.070). Multiple linear regression revealed that SF-36 scores were correlated with CRP (β=-0.477, P＜0.001), Scr (β=0.020, P＜0.001), cardiothoracic ratio (β=-57.823, P=0.004), Alb (β=0.772, P=0.016) and ultrafiltration volume (β=-0.006, P=0.031), but not correlated with rGFR (β=0.099, P=0.302). Conclusions PD patients without and with RRF perceived different scores in physical health, but their scores were similar in mental health and QOL. RRF was no related to QOL in PD patients. Chronic inflammation, fluid overload and malnutrition were the main factors that affect QOL.

Objective To establish diagnosis model and explore related metabolic pathways by analyzing the serum metabolic profile of patients with primary nephrotic syndrome (PNS) through metabolomics. Methods Thirty PNS patients hospitalized in Huai'an First People's Hospital between December 2010 and April 2012 were enrolled. High performance liquid chromatography-mass spectrometry (LC-MS) was employed to detect metabolites in the serum of 30 PNS patients and 30 healthy controls. Metabolic fingerprint profiling and multivariate pattern recognition analysis were combined to establish disease-specific metabolic diagnosis model, and metabolic pathway analysis was performed. Results PNS group and control group could be well separated by principal component analysis (PCA) model as well as partial least-squares discriminant analysis (PLS-DA) model with Q2 of 0.300. There was well interpretation in PLA-DA model (R2X=0.581，R2Y=0.452). Compared with healthy controls，PNS patients had decreased cholestane 3, 7, 12, 15 alcohol, acyl glycerine, phytosphingosine and tryptophan, and increased sphingomyelin, arginine and glutamic acid (all VIP＞1, P＜0.05). The metabolic disorders pathways of PNS patients included sphingolipid metabolism, arginine and proline metabolism, linoleic acid metabolism and pyrimidine metabolism (all impact＞0.10 and P＜0.05). Conclusions Metabolomics combined with multivariate pattern recognition analysis may be a new tool for diagnosis and monitoring of PNS.

Objective To investigate the association of single nucleotide polymorphism (SNP) rs13333226 in uromodulin (UMOD) gene with diabetic kidney diseases (DKD) in Han population in Tianjin, China. Methods A total of 210 type 2 diabetes (T2DM), 90 normal controls (NC) and 280 DKD patients were recruited. According to the level of estimated glomerular filtration rate (eGFR), the DKD subjects were further subdivided into three groups: GFR≥90 ml/min group (n=105), 60 ml/mim≤GFR＜90 ml/min group (n=84) and GFR＜60 ml/min group (n=91). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for UMOD rs13333226C genotyping. Results The frequencies of AA, GA, GG genotype were 27.8%, 58.9%, 13.3% in NC group and 41.0%, 48.6%, 10.5% in T2DM group and 54.3%, 36.1%, 9.6% in DKD group．The frequency of G allele was 42.8% in NC group, 34.8% in T2DM group and 27.7% in DKD group. The genotype distribution of UMOD was statistically significant between NC group and DKD group, and between T2DM group and DKD group (P＜0.05). G allele of UMOD was an independent protective gene polymorphism of DKD in Logistic regression (B=-0.248, Wald=8.012, P=0.021, OR=0.780, 95%CI 0.612-0.968). Conclusion The G allele of UMOD gene may be an independent protective factor of DKD in Han population in Tianjin, China.

Objective To investigate the distribution of aldosterone synthase gene -344C/T polymorphism in patients with essential hypertension in Chinese Han population, and the association with hypertensive early renal damage. Methods Four hundred and eighteen essential hypertension cases in Shandong Provincial Qianfoshan Hospital from January 2012 to January 2015 were included in this study. According to urinary albumin/creatinine ratio, 182 cases were selected as hypertensive early renal damage group (RD group) and 236 essential hypertension without renal damage group (NRD group). Fast venous blood was collected to detect aldosterone synthase gene -344C/T polymorphism and blood lipids, blood glucose, aldosterone and other indicators. Results There were significant differences in genotype frequency and allele frequency distribution between RD group and NRD group (P＜0.05). The TT genotype and the T allele frequency in RD group were higher than those in NRD group (P＜0.05). The level of aldosterone in TT genotype was higher than that in CC and CT genotype (P＜0.05). The aldosterone synthase gene -344C/T polymorphism was not correlated with early renal damage in hypertension after correction of blood pressure (P＞0.05). Conclusions Aldosterone synthase gene -344C/T polymorphism is associated with hypertensive early renal damage. T allele is inclined to hypertensive early renal damage. Aldosterone synthase gene -344C/T polymorphism induces renal damage through elevated blood pressure.

Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography. Methods Pubmed, Embase, Cochrane library, Wanfang database and CNKI were searched. The literature limited range was from their start year to July 2015. Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed. Two investigators extracted data and performed quality analysis independently from all trials included. Rev man 5.3 software was used. Results 16 trials with a total of 15 897 patients were identified. There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group. The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35% vs 12.13%, P=0.04, OR=1.44, 95%CI 1.01-2.04). For patients with renal insufficiency, ACEI/ARB group had a higher CIN incidence than control group (12.23% vs 7.32%, P= 0.02, OR=1.80, 95%CI 1.10-2.94), and the serum creatinine changes in ACEI/ARB group were higher than those in control group. There was statistical difference in serum creatinine changes between groups (P=0.02, MD=0.08, 95%CI 0.02-0.15). Conclusions Renin-angiotensin system blockades can increase the incidence of CIN in patients undergoing angiography. Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency.

Objective To investigate the effect of 1,25(OH)2D3 on high glucose induced podocyte injury and its signal transduction mechanism. Methods Differentiated mouse podocytes were exposed to normal glucose, high glucose, and different concentrations of 1,25(OH)2D3 or LY294002 (a selective PI3K inhibitor) for 24 h. PCR and immunofluorescent staining were used to detect nephrin, podocin, and desmin. Western blotting was used to detect protein expression of nephrin, podocin, desmin, PI3K, Akt and p-Akt. Results Compared with high glucose group, 1,25(OH)2D3 (100 nmol/L and 1000 nmol/L) significantly up-regulated the expression of podocin and nephrin in podocytes induced by high glucose (P＜0.05). Meanwhile, 1,25(OH)2D3 (100 nmol/L) significantly reduced the expression of desmin (P＜0.05). PI3K and p-Akt were obviously reduced in high glucose group. In the presence of 1,25(OH)2D3, the trends were reversed. However the above effects of 1,25(OH)2D3 were abolished when p-Akt was blocked by the PI3K inhibitor LY294002. Conclusions 1,25 (OH)2D3 can inhibit high glucose-induced podocyte injury through PI3K/p-Akt signaling pathway.

Objective To observe the epithelial mesenchymal transition (EMT) of podocyte induced by high glucose, and to explore the potential protective mechanism of ursolic acid (UA). Methods The podocytes cultured in vitro were divided into four groups: normal group (glucose 5.5 mmol/L), mannitol group (glucose 5.5 mmol/L+mannitol 19.5 mmol/L), high glucose group (glucose 25 mmol/L) and UA group (glucose 25 mmol/L+UA 5 μmol/L). Podocyte morphology changes were observed by inverted phase contract microscope. The expression of zonula occludens-1 (ZO-1) and α-smooth muscle actin (α-SMA) were detected by immunofluorescence. The expressions of β-catenin and glycogen synthesis kinase-3β (GSK3β) were detected by Western blotting. The expressions of Wnt1, Wnt3a, Wnt5a, Wnt5b and GSK3β were detected by real-time PCR. Results Podocytes showed irregular arborization shape in normal glucose and transited to longer cobblestone-like shape as mesenchyme cell by high glucose culture. Compared with normal group, the expression of ZO-1 protein was down-regulated and the expression of α-SMA was up-regulated by high glucose culture (P＜0.05). The expression of Wnt5a mRNA was down-regulated; β-catenin mRNA and protein were up-regulated (P＜0.05); and GSK3β protein was down-regulated by high glucose culture (P＜0.05). Compared with high glucose group, ursolic acid inhibited podocyte EMT, up-regulated the expression of ZO-1 protein, Wnt5a mRNA, GSK3β (P＜0.05), and down-regulated the expressions of α-SMA protein, β-catenin mRNA and protein (P＜0.05). Conclusion Ursolic acid attenuates high glucose induced epithelial mesenchymal transition of podocyte by inhibiting Wnt/β-catenin signaling pathway.

Objective To investigate the expression of ErbB2 interacting protein (Erbin) in renal ischemia-reperfusion injury (IRI) in vivo and in vivo, and the effect of Erbin over-expression on IRI. Methods (1) In vivo, the model of renal IRI was constructed in mice, and set up sham group and reperfusion 3, 6, 12, 24 and 48 h IRI group. BUN and Scr were detected and PAS staining was used to observe the pathology change of renal tissues. Cell apoptosis was detected by TUNEL staining. Erbin and NF-κB expression in renal tissue was detected by Western blotting, and immunohistochemistry was used to detect the distribution of Erbin. (2) In vivo, IRI model in HK2 cells was constructed and cells were harvested after culturing in normal medium for 3, 6, 12 and 24 h. Erbin expression was detected by Western blotting. Flow cytometry and ELISA were used to evaluate the level of cell apoptosis and inflammatory cytokine secretion respectively. HK2 cells were transiently transfected with Prk5-myc-Erbin plasmid via lipofectamine 2000, and were divided into control group, IRI group, Erbin group and Erbin+IRI group. The protein expression of Erbin and NF-κB, cell apoptosis and inflammatory cytokine secretion was detected. Results (1) Compared with sham group, serum BUN and Scr were dramatically increased in IRI model, especially in 24 h after reperfusion (P＜0.05). Moreover, PAS staining showed that a lot of renal tubular epithelial cells were necrosis and fell off, and many protein cast were formed, renal injury score and apoptotic index were higher in 6 h, 12 h, 24 h, 48 h IRI model than those in sham group (all P＜0.05). The expression of Erbin, which was expressed in renal tubules, and nuclear NF-κB in 24 h IRI model were significantly increased, as compared with sham group (all P＜0.05). (2) Compared to those in control group, nuclear NF-κB expression, apoptosis and inflammatory cytokine secretion were significantly increased in IRI group. Meanwhile, Erbin expression was also induced and peaked at 24 h (P＜0.05). Compared to those in IRI group, cell apoptosis, the expression of nuclear NF-κB, inflammatory cytokine IL-6 and TNF-α were decreased in Erbin+IRI group (all P＜0.05). Conclusions Erbin expression is up-regulated in renal IRI, and over-expression of Erbin can partly inhibit NF-κB activation, cell apoptosis and inflammatory cytokine secretion in IRI group, which indicates Erbin may playing a protective role in renal IRI.