Calcium phosphate crystals promotes vascular calcification through BMP-2/Smad signaling / 中华肾脏病杂志

Objective To investigate the role of BMP-2/Smad signaling pathway in the osteogenic differentiation of human aortic smooth muscle cells (HASMCs) caused by hyperphosphatemia -induced calcium phosphate (CaP) crystals.Methods High-phosphate medium was incubated at 37℃ for 3 days.CaP crystals and supernatant were isolated by ultracentrifugation.Scanning electron microscope and energy dispersive X-ray spectroscopy were performed for analysis of physicochemical characteristics of CaP crystals.HASMCs were cultured in vitro,and divided into high-phosphate,control,crystals and supernatant groups.Calcification was visualized by Alizarin red staining.Calcium loads in cells were quantified by o-cresolphthalein complexone method.Protein expression of bone morphogenetic protein-2 (BMP-2),Runt-related transcription factor 2 (RUNX2),osteopontin (OPN),phospho-Smad1/5/9 (p-Smad1/5/9) were quantified by Western blotting.After knockdowns of BMP-2 and Smad1 with small hairpin RNA (shRNA) interfering respectively in HASMCs,protein expressions were measured by Western blotting.Results High-phosphate medium induced the formation of CaP crystals.Compared with the cells in control group,CaP crystals significantly induced HASMCs calcification,increased calcium loads and up-regulated the levels of BMP-2,RUNX2 and OPN proteins (all P ＜ 0.05).After the addition of CaP crystals into HASMCs,the level of p-Smad 1/5/9 protein peaked at 30 min (P ＜ 0.05).After BMP-2 was knocked down in HASMCs,the expression of p-Smad1 caused by CaP crystals was blocked completely,and the expressions of RUNX2 and OPN caused by CaP crystals were reduced significantly (all P ＜ 0.05).After Smad1 was knocked down in HASMCs,the expressions of RUNX2 and OPN caused by CaP crystals were decreased significantly (all P ＜ 0.05).Conclusions Hyperphosphatemia-induced CaP crystals promoted osteogenic differentiation of HASMCs through the BMP-2/Smad signaling pathway.

Predictors of response in patients with progressive IgA nephropathy treated with leflunomide and medium/low-dose corticosteroid / 中华肾脏病杂志

Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.

Association between serum soluble Klotho level and outcome in patients on maintenance hemodialysis / 中华肾脏病杂志

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.

Renji acute kidney injury score is a useful tool to predict acute kidney injury after cardiac surgery / 中华肾脏病杂志

Objective To validate the effect of Renji acute kidney injury score (RAKIS) on predicting patients with acute kidney injury (AKI) after cardiac surgeries,and make comparison with Cleveland score,simplified renal index (SRI) and acute kidney injury following cardiac surgery (AKICS).Methods Patients undergoing open heart surgery from 2008/01/01 to 2010/10/31 in Renji hospital were enrolled,and their scores of those four scoring models were calculated.AKI patients were diagnosed by KDIGO,and those scores of AKI patients and non-AKI patients were compared.Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to decide the predictive values of those models.Results A total of 1126 patients were chosen in this cohort,with the average age of (58.43±14.88) years (rang from 18 to 88).The male to female ratio was 1.47:1.And 355(31.5％) patients were developed AKI.AKI stage Ⅰ,Ⅱ and Ⅲ were 65.4％,23.7％ and 11.0％ respectively.RAKIS was significantly higher in AKI patients than in non-AKI patients (17.5 vs 9.0,P ＜ 0.001).The AUCs of RAKIS to predict AKI,AKI Ⅱ-Ⅲ stages,renal replacement therapy (RRT)and in-hospital death were 0.818,0.819,0.800 and 0.784 respectively.The AUCs of Cleveland score and SRI were 0.659 to 0.710,lower than those of RAKIS and AKICS.AKICS had lower value for predicting AKI and AKI Ⅱ-Ⅲ stages (AUC 0.766 and 0.793),but good value in predicting RRT and inhospital death after surgery (AUC 0.804 and 0.835) as compared with RAKIS.Conclusions RAKIS is valid and accurate in the discrimination of KDIGO defined AKI patients,while for predicting the composite end point,AKICS may be more useful.

Association of serum FGF23 with abdominal aortic calcification and outcomes in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Association of serum FGF23 with abdominal aortic calcification and outcomes in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Relationship between endothelial progenitor cells and cardiovascular diseases in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the relationship between the variation of endothelial progenitor cells (EPC) number and cardiovascular diseases (CVD) in maintenance hemodialysis (MHD) patients ,and discuss the function of EPC in the progression of CVD in MHD. Methods One hundred and fifteen MHD patients over 18 years whose dialysis vintage was over six months from Department of Nephrology, Renji Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. They were divided into CVD group and non ? CVD group by medical history, electrokardiographie (EKG), cardiac ultrasound, peripheral vascular imaging and cardiovascular imaging. Peripheral blood (5 ml) was collected for detecting EPC number by flow cytometry as CD34/CD133/vascular endothelial growth factor receptor 2 (VEGFR2) cells. The EPC number between CVD group and non?CVD group was compared. The relationship between the decrease of EPC number and CVD risks in MHD patients was analyzed by logistic regression analysis. In a three?year follow?up, the death and new CVD events of the two groups were compared in order to discuss the relationship between EPC number and adverse events. Results Among 115 MHD patients, the average age was 61.57 ± 12.76, male/female was 71/44, the average dialysis vintage was (86.24 ± 56.31) months, the average Kt/V was 1.69 ± 0.29 and average ultrafiltration volume was (2.48 ± 0.90) L. Forty?four patients in 115 (38.3%) were with concurrent CVD. The EPC number in CVD group was significantly lower than that in non CVD group (P=0.015). The CVD group had higher serum phosphate (P=0.013), higher glycosylated hemoglobin (P<0.001), but serum calcium, intact parathyroid hormone (iPTH) and other indicators had no significant difference between two groups. Multiple Logistic regression analysis showed that older age (OR=1.061), history of diabetes (OR=9.796), dialysis vintage (OR=1.015), serum phosphate (OR=3.766), decrease of EPC number (OR=0.909) were the independent impact factors of CVD events in MHD patients. There were 22 patients of the 115 MHD patients had encountered a new CVD event in a three?year follow?up between December 2012 and December 2015, 9 patients from the CVD group and 13 patients from the Non?CVD group, and there was no significant difference between two groups (P=0.776). Nine patients from the CVD group and 7 patients from the Non?CVD group died in the follow?up, and there was no significant difference (P=0.111). Seventy?one MHD patients from the non?CVD group were divided into two groups by the median of EPC number. There were 3 patients in the higher EPC number group encountered CVD events and 10 patients in the lower EPC number group encountered CVD events, which had significant difference (P=0.024). Conclusion The decrease of circulating EPC number may be related with CVD events in MHD patients. Even adjusted by age, sex, diabetes, dialysis vintage and serum phosphate, decreased EPC number is still the independent risk factor of CVD events in MHD patients. The decrease of EPC number in MHD patients may be used to predict the occurrence of cardiovascular events.

Leflunomide combined with medium/low dose corticosteroids vs full dose of corticosteroids in treatment of IgA nephropathy / 中华肾脏病杂志

Objective To compare the efficacy and safety of leflunomide (LEF) combined with medium/low dose corticosteroids and full dose of corticosteroids in the treatment of IgA nephropathy. Method Primary IgAN patients diagnosed by renal biopsy with 18?65 years old and eGFR≥30 ml·min?1·(1.73 m2)?1 and proteinuria>0.5 g/24 h were enrolled in a prospective controlled clinical study. They were randomly divided into leflunomide combined with medium/low dose corticosteroids (LEF group) and corticosteroids alone (steroid group). The primary outcomes were (1) end stage renal disease or dialysis (2) 50% increase in serum creatinine above the baseline. Secondary outcome was the remission of proteinuria. Results Ninety patients completed the follow?up. The 24?hour proteinuria at baseline were 2.00(1.10, 2.88) g and 1.87(1.13 ,3.08) g in LEF group and steroid group respectively. Compared with baseline, it was significantly decreased in both groups at 6 months [0.30(0.11, 0.93) g, 0.30(0.14, 1.33) g] and 12 months [0.30(0.09, 0.82) g, 0.32(0.14, 0.66) g], (P0.05]. At 6 and 12 months, there was no significant difference in terms of 24?hour proteinuria, serum creatinine and eGFR (CKD?EPI) between groups (P>0.05). There was no statistically significant difference in adverse events between groups during the treatment (9/40 cases in LEF group and 11/50 cases in steroid group, P>0.05). The average follow?up was 79 months, and there was no difference in the renal prognosis between the two groups. Multivariate Cox regression analysis revealed that serum creatinine at baseline and renal interstitial inflammatory cell infiltration predicted the risk of the progress of IgA nephropathy. Conclusion Leflunomide plus medium/low dose corticosteroids has a similar effect as full dose of corticosteroids in IgA nephropathy and does not increase the risk for adverse events during the treatment.

H2O2 decreases Klotho expression in mouse renal tubular epithelial cells / 中华肾脏病杂志

Objective To evaluate the effect of oxidative injury induced by peroxide oxidase on Klotho expression in mouse renal tubular epithelial cells (TCMK-1) and to explore the possible pathway.Methods TCMK-1 cells were exposed to H2O2 of different concentrations.Reactive oxygen species (ROS) was examined byflow cytometrry.Cell viability was assessed by CCK-8.Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining.The expression of Klotho,apoptosis-associated proteins and anti-oxidant enzymes were determined by Western blotting.Results Compared with control group,after H2O2 stimulating TCMK-1 cell,ROS was dramatically elevated (all P ＜ 0.05) and the expression of anti-oxidant enzymes,SOD2 and CAT went down (all P ＜ 0.05);the expression of Klotho was inhibited (all P ＜ 0.05);cell viability of TCMK-1 cells was decreased (all P ＜ 0.05) in a dose-dependent manner (0.3 to 0.9 mmol/L);cell apoptosis was significantly increased in TCMK-1 cells following the concentration of H2O2 (all P ＜ 0.05);Bax/Bcl-2 and the phosphororation of JNK and p38 were obviously elevated in TCMK-1 by H2O2 induction (all P ＜ 0.05).Conclusion Oxidative injuries induced by H2O2 significantly suppresses the expression of Klotho in TCMK-1 cells.And cell apoptosis was increased,p38 and JNK pathway was activated.

The level of the biomarkers at the time of nephrology consultation might predict the prognosis of acute kidney injury in hospitalized patients.

INTRODUCTION: The value of biomarkers at the time of nephrology consultation in predicting the prognosis of acute kidney injury (AKI) in hospitalized patients has not been well described. This study aimed to evaluate the possibility of biomarkers at the time of nephrology consultation in predicting the prognosis of AKI. METHODS: We prospectively enrolled 103 hospitalized patients who developed AKI. Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL), IL-6, IL-18, N-Acetyl-ß-D-Glucosaminidase (NAG), and serum Cystatin C (CysC) were measured at the time of nephrology consultation. Baseline values of serum creatinine (bScr), serum creatinine on consultation (cScr) and the peak level of serum creatinine (pScr) were recorded. All the patients were followed-up till 28 days since consultation. Serum and urinary levels of the biomarkers were compared according to the patient or kidney prognosis. Each marker was assessed for its predictive value using receiver operator characteristic (ROC) curves to predict AKI prognosis. RESULTS: Patients were aged 54.28 ± 19.05. Male patients constituted 65% of the study group and baseline Scr was 93.54 ± 35.98 µmol/l. The mortality rate of the patients was 25.2% and kidney loss rate was 18.8% at 28 days after consultation. The level of urinary NGAL was significantly higher in death patients than that in survival patients [147.00 (31.59, 221.87) µg/ml vs. 22.43 (6.48, 89.77) µg/ml, p = 0.001], while the level of bScr, cScr, pScr, urinary IL-6 and NAG were similar in both these groups. The AUC of urinary NGAL for predicting patients' death was 0.723 (p = 0.001). Serum CysC and urinary IL-18 concentration was higher in the death patients with a marginal p value (p = 0.065 and 0.059 respectively). All the urinary markers, including NAG, NGAL, IL-6 and IL-18 were significantly higher in patients with kidney loss than in those with kidney survival, while no difference was found in Scr and serum CysC levels. The AUCs of these urinary biomarkers for predicting kidney survival were 0.663, 0.655, 0.705 and 0.663 respectively (p < 0.05). The concentrations of cScr, pScr, serum CysC, urinary IL-6 and NGAL were significantly higher in RRT patients (p < 0.05). The AUCs for predicting RRT were 0.628, 0.781, 0.768, 0.672 and 0.775 respectively. CONCLUSIONS: The level of biomarkers at the time of nephrology consultation might predict the prognosis of AKI in hospitalized patients. Further studies should be done to understand the role of the serum and urinary markers in the prognosis of AKI.

Prognostic comparison of patients starting peritoneal dialysis within two weeks and more than two weeks after catheter implantation / 中华肾脏病杂志

Objective To compare the outcomes of patients starting peritoneal dialysis (PD)within two weeks and more than two weeks after catheter implantation.Methods All the patients undergoing Tenckhoff catheter implantation and initiating PD in Renji Hospital from January 2001 to December 2010 were enrolled in the study.Patients started PD within 2 weeks after catheter insertion were defined as urgent group,and those started PD 2 weeks later were defined as planned group.Kaplan-Meier curves and Log-rank tests were used to compare outcomes between two groups.Results Among 657 patients in this study,median break-in period was 6 days of 469 (71.4％)patients in urgent group and 26 days of 188 (28.6％) patients in planned group.Compared to planned group,patients of urgent group were younger [(52.6± 17.3) vs (56.1± 15.3) year,P =0.017],had less eGFR [(5.36±2.03) vs (6.50±2.50) ml· min-1 · (1.73 m2)-1,P ＜ 0.01],lower serum albumin [(34.0±5.7) vs (36.2±5.9) g/L,P ＜ 0.01] and hemoglobin [(76.9± 18.8) vs (80.8 ± 17.9) g/L,P =0.018],and higher phosphate [(2.19±0.67) vs (1.98±0.52) mmol/L,P＜ 0.01].Urgent group presented more catheter dysfunctions needed to transfer to hemodialysis (2.1％ vs 0％,P =0.044).The 1-,2-,3-and 5-year technique survival rates of urgent and planned group were 94％ vs 98％,92％ vs 94％,90％ vs 92％and 86％ vs 85％ respectively.There was no significant difference in technique survival (Log-rank =1.536,P =0.22) and peritonitis-free survival (Log-rank =0.035,P =0.85) between two groups.The 1-,2-,3-and 5-year patient survival rates of urgent and planned group were 90％ vs 95％,81％ vs 90％,74％ vs 79％ and 67％ vs 74％ respectively,and no significant difference was found (Log-rank =2.364,P =0.12).Conclusions Although patients needing urgent initial PD have poorer residual renal function and nutritional condition compared to those of planned initial PD,their outcomes are similar.Peritoneal dialysis may be a feasible and safe dialysis modality for patients who need urgent start.

Effect of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells / 中华肾脏病杂志

Objective To investigate the impact of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells (HASMCs).Methods Uremic serum was incubated at 37℃ for 3 days.Calcium phosphate crystals and uremic supernatant were isolated from uremic serum by uhracentrifugation.Scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX) were performed for analysis of morphological and chemical characteristics of the crystals.HASMCs were treated in vitro with control medium,uremic serummedium,calcium phosphate crystals-medium and uremic supernatant-medium.Calcification was visualizcd by Alizarin red staining.Calcium loads in cells were quantified by o-cresolphthalein complexone method.Gene expression of bone morphogenetic protein-2 (BMP-2),osteopontin (OPN) and core-binding factor α1 (Cbfα1),alkaline phosphate (ALP) and matrix gamma carboxyglutamic acid protein (MGP) were quantified by real-time PCR.Cbfα1,OPN and BMP-2 protein levels were determined by Western blotting or ELISA.Results Calcium phosphate crystals which induced by uremic serum displayed laminated shapes containing crystallized needle-like projections and ranged from 30-500 nm,with Ca/P ratios of 1.41 ±0.05.Compared with the cells in control group,uremic serum induced HASMCs calcification,increased calcium loads (P ＜ 0.05),up-regulated BMP-2,OPN,Cbfα1 mRNA and protein expression (all P＜ 0.01).Similar to uremic serum,calcium phosphate crystals also induced HASMCs calcification,increased calcium loads (P＜0.05),and up-regulated BMP-2,OPN,Cbfα1 mRNA and protein expression (all P ＜ 0.01).However,there was no significant difference between HASMCs growing in uremic supernatant and control medium in calcium loads or the expression levels of these osteogenic proteins (P ＞ 0.05).Conclusions Calcium phosphate crystals induced by uremic serum promote HASMCs calcification,which might be one of the mechanisms of uremic vascular calcification.

Application of objective score of nutrition on dialysis for evaluating nutritional status in maintenance hemodialysis patients for 75 cases / 中华临床营养杂志

Objective To evaluate the nutritional status in maintenance hemodialysis patients using objective score of nutrition on dialysis.Methods Patients on maintenance hemodialysis were randomly selected and divided into three groups based on objective score of nutrition on dialysis:normal nutritional status group,moderate nutritional status group,and low nutritional status group.Logistic regression analysis was performed to identify factors of malnutrition.Furthermore,the results were compared with those of subjective global assessment.Results Totally 75 patients(male:female =1.13∶1)with a mean age of(54.90 ± 12.10)years and a mean vintage of (85.37 ± 54.17)months were enrolled.As determined by objective score of nutrition on dialysis,15 patients (20％)were divided into normal nutritional status group,42(56％)into moderate nutritional status group,and 18(24％)into low nutritional status group.Compared with the normal nutritional status group,the low nutritional status group had significantly different body mass index[(19.81 ± 2.22)vs(23.90 ± 2.44)kg/m2,P =0.030]and dry weight[(50.85 ± 7.60)vs(59.94 ± 10.89)kg,P =0.020].In addition,compared with normal nutritional status group,the moderate nutritional status group and low nutritional status group had significantly different total cholesterol[(4.60 ± 0.84)and(3.73 ± 0.68)mmol/L vs(5.71 ± 1.64)mmol/L,P =0.011,P =0.000],normalized protein catabolic rate[1.17 and 1.15 g/(kg · d)vs 1.45 g/(kg · d),P =0.030,P =0.010],triceps skinfold thickness[(1.44±0.77)and(1.00±0.41)cmvs(1.80±0.63)cm,P=0.032,P=0.020],mid-ann circumference[(24.85±1.48)and(21.66±1.48)cmvs(24.99 ±2.30)cm,P=0.046,P =0.037].Logistic regression analysis indicated C-reactive protein(OR =12.482,95％ CI =0.190-130.928,P =0.035)and normalized protein catabolic rate(OR =0.128,95％ CI =0.022-0.736,P =0.021)were significantly correlated with malnutrition.Conclusion Malnutrition is common in hemodialysis patients,with inflammation and low protein intake being its independent factors.

Analysis of clinical characteristics of twice-weekly hemodialysis patients / 中华肾脏病杂志

Objective To investigate the clinical characteristics of twice-weekly hemodialysis patients.Methods Data were collected from Shanghai Renal Registry.A total of 1288 patients undergoing regular hemodialysis (HD) with dialysis adequacy index and other biochemical parameters in Shanghai in January 2007 were enrolled into the cohort study with 2 years follow-up.Clinical characteristics and outcome of twice-weekly HD patients were analyzed as compared with thrice-weekly HD patients.Results Compared with patients on thrice-weekly HD,the twice-weekly HD patients were significantly younger and had significantly shorter HD vintage,smaller body surface area,longer HD session time,higher single-pool Kt/V (spKt/V) and serum albumin but lower weekly Kt/V (P＜0.05).There was no statistical difference in ultrafiltration volume between two groups.Kaplan-Meier survival analysis indicated that both groups had similar two-year survival.Multivariate Cox regression analysis showed that age,body mass index,serum albumin and weekly Kt/V were predictors of patient mortality.Conclusion It is acceptable for some hemodialys patients with twice-weekly HD,and close monitor of dialysis adequacy and volume status is necessary for this therapy model.

Analysis of the incidence and risk factors of acute kidney injury in respiratory failure patients / 中华肾脏病杂志

Objective To determine the incidence and risk factors of acute kidney injury (AKI) in respiratory failure patients.Method Clinical data of 235 patients diagnosed as respiratory failure admitted in respiratory division and internal medicine intensive care unit in Renji Hospital from January 2006 to December 2008 were analyzed retrospectively.Patients'demographics,clinical data and laboratory examinations before and after respiratory failure were collected.The incidence,clinical risk factors and hospital mortality of AKI in the respiratory failure patients were analyzed.Multivariate Logistic regression analysis was used to investigate the independent risk factors of AKI in these patients.Results Of the total 235 patients,the average age was (70.05±12.85) years old,the ratio of male to female was 1.90:1.Seventy-seven patients developed AKI and the incidence was 32.8％.The incidence of AKI in those with hypertension (44.4％ vs 26.6％,P＜0.01) or chronic kidney disease(66.7％ vs 31.3％,P＜0.01) was significantly higher.The incidence of AKI in patients with mechanical ventilation was much higher than those without mechanical ventilation(44.8％ vs 13.3％,P＜0.01).The incidence of multi-organ system failure (33.8％ vs 5.7％,P＜0.01),the failure of weaning from mechanical ventilation(69.2％vs 32.5％,P＜0.01) and the mortality (51.9％ vs 13.3％,P＜0.01) in AK1 patients were higher than those without AKI.Multivariate Logistic regression analysis showed that age (OR=1.668),anemia (OR=0.980),baseline serum creatinine (OR=1.071) and mechanical ventilation (OR=3.222) were independent risk factors of AKI.Conclusions Incidence and mortality of AKI are quite high in respiratory failure patients.Age,baseline serum creatinine,anemia and mechanical ventilation are independent risk factors of AKI.

Association of fibroblast growth factor 23 with coronary artery calcification in patients with moderate and advanced stage chronic kidney diseases / 中华肾脏病杂志

Objective To elucidate the association of fibroblast growth factor 23 (FGF23)with coronary artery calcification in patients with moderate and advanced stage chronic kidney diseases (CKD). Methods Serum intact FGF23 levels in 150 patients with CKD stage 3 to 5 and 25 age- and sex-matched healthy controls were measured by ELISA.The association between FGF23 and coronary artery calcification was studied. Results Serum FGF23 levels in CKD patients were significantly higher than those in healthy controls [196.46 (83.09,355.02) ng/L vs 27.17 (21.63,51.20) ng/L,P＜0.01].The levels of FGF23 were significantly higher in dialyzed patients than those in non-dialyzed patients (P＜0.01),and hemodialysis patients had higher levels as compared to peritoneal dialysis ones [6048.29 (1129.08,34807.45) ng/L vs 1625.80 (602.83,7521.78) ng/L,P＜0.01].The incidence of coronary artery calcification was relatively high in patients with moderate and advanced stage CKD (74/130,56.9％ ).Serum FGF23 level was positively correlated with coronary artery calcification score (CaS) (r=0.177,P＜0.05).Logistic regression analysis showed that age (β=0.091,OR=1.095,P＜0.01),duration of dialysis (β=2.013,OR=7.483,P＜0.05) and FGF23 level (β=0.838,OR=2.311,P＜0.05) were independent risk factors for coronary artery calcification in patients with moderate and advanced stage CKD.ROC curve of coronary artery calcification revealed that area under curve (AUC) of FGF23 was 0.705 (P＜0.01).With the cut-off value of FGF23 as 786.73 ng/L,the diagnostic sensitivity and specificity in coronary artery calcification were 62.5％ and 75.9％.ROC curve of coronary artery calcification showed that AUC of alkaline phosphatase (AKP) was 0.626 (P=0.017).With the cutoff value of AKP as 79.75 U/L,the diagnostic sensitivity and specificity in coronary artery calcification were 84.5％ and 41.5％.There was no diagnostic value of serum phosphorus in coronary artery calcification. Conclusions Serum FGF23 level is correlated with coronary artery.calcification in patients with moderate and advanced stage CKD.The sensitivity of FGF23 is lower and the specificity is higher than those of AKP for the diagnosis of coronary artery calcification.

Value of urine L-FABP and its combination with urine NGAL in early diagnosis of acute kidney injury after cardiac surgery in adults / 中华肾脏病杂志

Objective To investigate the value of urinary liver-type fatty acid-binding protein (L-FABP),neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the development and the severity of acute kidney injury (AKI) following cardiac surgery in adults. Methods Scr,urinary L-FABP and NGAL corrected by urine creatinine at preoperation,0 h and 2 h postoperative time points were examined.The differences of above indexes between AKI and non-AKI groups were compared.Receiver operating characteristic (ROC)curves and area under curves (AUC) were used to evaluate the diagnostic value of urinary L-FABP,NGAL and their combination for AKI. Results The cohort consisted of 109 patients,26(23.9％) developed AKI,and AKIN stage Ⅰ, Ⅱ and Ⅲ was 46.2％,34.6％ and 19.2％ respectively.Levels of urinary L-FABP and NGAL were significantly higher in AKI patients at 0 h and 2 h postoperatively.AUC to predict AKI or AKI stage Ⅱ-Ⅲ was 0.81 to 0.87 using either of the biomarkers.The performance of combining two biomarkers was better with AUC of 0.911 to 0.927. Conclusions Urinary L-FABP and NGAL increase at the early stage after cardiac surgery.Combination of these two biomarkers enhances the accuracy of the early diagnosis of postoperative AKI after cardiac surgery before a rise of Scr.

The incidence and risk factors associated with prognosis of acute kidney injury in hospitalized patients / 中华肾脏病杂志

Objective To investigate the incidence and the prognosis of acute kidney injury (AKI) and to find out the risk factors associated with the outcome for better understanding and preventing AKI among inpatients. Methods All the hospitalized patients were screened by Lab Administration Network of Renji Hospital,Shanghai Jiaotong University School of Medicine from Jan.to Dec.2009.Study cohort was comprised of all the patients with AKI defined by Acute Kidney Injury Network (AKIN) and with complete clinical data recorded.The incidence,etiology and distribution characteristics, prognosis of AKI in hospitalized patients were retrospectively analyzed.Logistic regression analysis was used to investigate the risk factors of patients and renal outcome. Results A total of 934 patients with AKI were enrolled.The incidence of AKI in hospitalized patients was 2.41％ (934/38 734).The ratio of male to female was 1.88∶1.Age was (60.82±16.94) years old.Increasing incidence could be seen with age rising.There was 63.4％ AKI found in surgical department,35.4％ in internal medicine department and 1.2％ in obstetric and gynecologic department.Pre-AKI,acute tubular necrosis (ATN),acute glomerular and renal vascular injury (AGV),acute interstitial nephritis (AIN) and post-AKI were accounted for 51.7％,37.7％,3.8％,3.5％ and 3.3％ of the causes of AKI,respectively.On day 28,the survival rate was 71.8％,complete renal recovery rate was 65.7％,partial renal recovery rate was 16.9％ and renal loss rate was 17.4％ among all the patients with AKI.The mortality of AKI with stage Ⅰ,Ⅱ and Ⅲ among inpatients was 24.8％,31.2％ and 43.7％ respectively.Multivariate Logistic regression analysis showed that renal injury drugs [odds ratio (OR)=2.313],hypotension (OR=4.482),oliguria (OR =5.267),the number of failure organs except kidney (OR =1.376) and requiring renal replacement therapy (RRT)(OR=4.221) were independent risk factors for death among AKI patients.The number of failure organs except kidney (OR=1.529) and RRT (OR=2.117) were independent risk factors for kidney loss. Conclusions AKI is one of the most common complications in hospitalized patients.The mortality is high and renal outcome is poor after AKI.The prognosis is closely associated with the severity of AKI.Renal injury drugs,hypotension,oliguria,the number of failure organs except kidney and requiring RRT are independent risk factors for death among AKI patients,while the number of failure organs except kidney and requiring RRT are independent risk.factors for renal loss.

Short-term efficacy of sevelamer hydrochloride on hyperphosphatemia in patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective To evaluate the short-term efficacy and safety of sevelamer hydrochloride in treating maintenance hemodialysis (MHD) patients with hyperphosphemia.Methods A multicenter,open-labeled,self-control study was performed.Phosphate binders were discontinued during a two-week washout period.Patients with more than 1.78 mmol/L serum phosphorus after two-week washout period were eligible for the trial.The dose was adjusted every two weeks as necessary to achieve serum phosphorus control. Sevelamer hydrochloride was administered to 138 MHD patients for 10 weeks and a second two-week washout period followed.Results A total of 111 from 138 patients fulfilled the whole 14-week study. Mean serum phosphorus and calcium-phosphate products starte to decline after two-week sevelamer hydrochloride treatment. By the end of 10-week sevelamer hydrochloride treatment, mean serum level of phosphorus [(1.85±0.50) vs (2.57±0.54) mmol/L,P＜0.01],calcium-phosphate product [(4.16± 1.72) vs (5.79 ± 1.50) mmol2/L2,P＜0.01 ] and low density lipoprotein [(1.64±0.76) vs (2.31 ±0.87) mmol/L,P＜0.01] were significantly decreased,while the adjusted serum level of calcium and serum intact parathyroid hormone kept steady.Both serum phosphorus and calcium-phosphrus product increased after the second washout period, but the levels were still lower as compared to pre-treatment [(2.26±0.71) vs (2.57±0.54) mmol/L; (5.12±1.63) vs (5.79±1.50) mmol2/L2,P＜0.01].Of the 138 patients involved,214 episodes in 106 patients and 121 episodes in 89 patients were reported as adverse events and adverse drug reaction respectively. Gastrointestinal symptoms,of which most were mild or moderate,happened to 68.1％ (94/138) patients. Conclusions Sevelamer hydrochloride can control serum phosphorus and reduce the levels of calcium-phosphorus product and cholesterol.Slight gastrointestinal symptoms like constipation are common during the treatment.

The efficacy and safety of continuous erythropoietin receptor activator in dialytic patients with chronic renal anemia: an open, randomized, controlled, multi-center trial / 中华内科杂志

Objective To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb)maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO).Methods This was an open,randomized,controlled,multi-center trial.All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-β during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L.Eligible patients were randomized (2∶1 ) to accept either C.E.R.A.once every 4 weeks by subcutaneous administration ( C.E.R.A.group,n =187 ) or subcutaneous EPO-β 1-3 times weekly ( EPO group,n =94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period ). The starting dose of C.E.R.A.was converted according to the dose of EPO-β administered in the week preceding the first study drug administration.The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period.Results Totally 253 patients completed the whole 28-week treatment.The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A.group and + 1.23 g/L for EPO group,resulting in a treatment difference of 1.34 g/L (95％ CI - 1.11-3.78 g/L).Since the lower limit of 95％ CI was greater than the pre-defined non-inferiority margin -7.5 g/L( P ＜ 0.0001 ),C.E.R.A.once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level.The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups ( 69.0％ for C.E.R.A.group vs 68.9％ for EPO group,P ＞0.05 ).The overall incidence of adverse events was similar between the C.E.R.A.(41.7％)and EPO (46.2％ ) groups ( P ＞ 0.05 ).The safety findings were in accordance with the patients' primary diseases rather than the administration.Conclusions Conversion from EPO to C.E.R.A.once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia,and it was non-inferior to EPO.In general,subcutaneous administration of C.E.R.A.is well tolerated in dialytic patients with chronic renal anemia.