Objective     To compare the nephrotoxicity of the iso ? osmolar contrast media (iodixanol) to low?osmolar contrast media (LOCM) in intravenous contrast?enhanced CT.   Methods     Randomized controlled trials (RCTs) of iodixanol or low?osmolar contrast media in intravenous contrast?enhanced CT were searched in the database of VIP, CBM, CNKI, Wanfang, PubMed, EMBASE, Web of Science, Cochrane Library from their start year to July 2012. Screening and information extracted were did by two researchers independently. The quality of the included documents was evaluated by the criterion of Cochrane handbook. Revman software (version 5.0) of the Cochrane collaboration was used in data analysis.   Results     There was no significant difference in the incidence of contrast?induced nephropathy (CIN) among 6 trials recruited 907 patients between the iodixanol group and the LOCM group [RR=0.64, 95%CI (0.31 ? 1.32), P=0.22] by using serum creatinine increased by more than 44 μmol/L (0.5 mg/dl) as the diagnostic criteria. No considerable difference was existed by using serum creatinine increased by more than 25% as the diagnostic criteria between the two groups [RR=0.79, 95%CI (0.48?1.30), P=0.35]. Subgroup analysis showed there was no obvious difference [RR=0.57, 95%CI (0.30 ? 1.10), P=0.09] between the two groups in patients with increased baseline of serum creatinine. No obvious difference were gained in normal baseline group [RR=1.28, 95%CI (0.57?2.86), P=0.55] .   Conclusion     Compared with low?osmolar contrast media, iodixanol is not associated with less CIN in intravenous contrast?enhanced CT.

Objective     To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease（ESRD）.  Methods     Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials, EMBASE, CNKI, Wanfang database. Data extracted from the literatures were analyzed with the Cochrane Collaboration’s RevMan 5.1 software.  Results     Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR=1.00, 95％CI (0.92-1.09), P=0.97], and more effective than placebo [RR=4.69, 95％ CI (2.63 - 8.39), P＜0.01] (intervention dose≤1500 mg) and [RR=18.92, 95％ CI (7.42-48.22), P＜0.01] (intervention dose＞1500 mg). In comparison with calcium carbonate group, the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR=0.06, 95％CI (0.01-0.72), P=0.03],while the incidence of nausea [RR=1.80, 95％CI (0.70-4.64), P=0.22], vomiting [RR=3.94,95％ CI (0.45 - 34.38), P=0.22] and constipation [RR=0.82, 95％ CI (0.49 - 1.37), P=0.45] were similar. The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo, with lower incidence of constipation [RR=0.19, 95％ CI (0.06-0.59), P＜0.01].  Conclusions     The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate. The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate, and the incidence of gastrointestinal adverse effect such as nausea, vomiting and constipation are similar with calcium carbonate.

Objective  To assess the clinical usefulness and value of the 5 models for the prediction of acute kidney injury (AKI), severe AKI which renal replacement treatment was needed (RRT-AKI) and death after cardiac surgery procedures in Chinese patients.  Methods   One thousand and sixty - seven patients who underwent cardiac surgery procedures in the department of cardiac surgery in the Zhongshan Hospital, Fudan University between May 2010 and January 2011 were involved in this research. The predicting value for AKI (AKICS), RRT-AKI (Cleveland, SRI and Mehta score) and death (EURO score) after cardiac surgery procedures was evaluated by Hosmer-Lemeshow goodness-of-fit test for the calibration and area under receiver operation characteristic curve (AUROC) for the discrimination.  Results  The incidence of AKI was 20.34%(217/1067), and 63.13% of their renal function recovered completely. The incidence of RRT-AKI was 3.56%(38/1067) and the mortality of AKI and RRT - AKI was 9.68%(21/217) and 44.73%(17/38) respectively. The total mortality was 3.28%（35/1067）. The discrimination and calibration for the prediction of AKI of AKICS were low. For the prediction of RRT-AKI, the discrimination and calibration of Cleveland score were high enough, but the predicated value was lower than the real value (1.70% vs 3.86%). The discrimination of Mehta score and the calibration of SRI were low. The discrimination and calibration for the prediction of death of EURO score was low.  Conclusion  According to the 2012 KDIGO AKI definition, none of the 5 models above is good at predicting AKI after cardiac surgery procedures. Cleveland score has been validated to have a proper impact on predicting RRT-AKI after cardiac surgery procedures, but the predicting value is still in doubt. EURO score has been validated to have an inaccurate predicting value for death after cardiac surgery procedures.

Objective    To evaluate the efficacy and safety of calcium polystyrene sulfonate in treating hyperkalemia patients with chronic kidney disease.  Methods    A single-arm, open, multi- center, phase Ⅳ clinical trial was carried out. Ninety-eight patients were enrolled in 11 centers from September 5, 2011 to June 21, 2012. The patients took calcium polystyrene sulfonate 15 g/d for one week. Total 5 visits were on 0, 2, 4, 8 and 14 days respectively.  Results    One day after treatment, potassium levels decreased rapidly from (5.85±0.26) mmol/L to (5.16±0.51) mmol/L (P＜0.01) and average value dropped to normal range. Three days after treatment, serum potassium levels decreased to (4.88±0.58) mmol/L(P＜0.01). After one week of treatment, serum potassium levels decreased to (4.67±0.57) mmol/L (P＜0.01). A week after the withdrawal, potassium levels were (4.96±0.66) mmol/L (P＜0.01). Serum potassium levels in all visits during the treatment and after discontinuation of calcium polystyrene sulfonate were all significantly decreased comparing to the baseline level (all P＜0.01). At the same time, serum levels of sodium, phosphorus, calcium showed no significant changes during the treatment. Constipation (9.2% ) was the commonest side effect. There was no treatment-related serious adverse effect.  Conclusions    This single-arm, open, multi-center clinical study shows that calcium polystyrene sulfonate is effective and safe in treating hyperkalemia due to chronic kidney disease.

Objective    To determine whether triggering receptor expressed on myeloid cells-1 (sTREM - 1) and urinary neutrophil gelatinase - associated lipocalin (NGAL) were early biomarkers of acute kidney injury (AKI) secondary to sepsis.  Methods     A total of 141 eligible patients were enrolled in this prospective study. Blood and urine samples were collected at different time points as soon as sepsis was diagnosed. The concentrations of serum creatinine (Scr), urine sTREM-1 and NGAL were measured. According to AKI criteria, patients were divided into the AKI group and non - AKI group. Dynamic changes of levels of Scr, urine sTREM-1 and NGAL were observed in two groups. The receiver operating characteristic curves were used to evaluate the early diagnostic value of urine sTREM-1 and NGAL.  Results     Among 141 septic patients, 44 (31.2%) cases had concomitant AKI. Twenty four hours after sepsis diagnosed, the level of Scr rose to 1.91 times of the baseline [(140.5±13.6) vs (82.6±15.3) μmol/L, P＜0.05], which met the diagnostic criteria of AKI. In the AKI group, urinary concentrations of sTREM-1 and NGAL at 8 h after the diagnosis of sepsis began to rise significantly from baseline [(100.5±17.4) vs (38.9±14.7) ng/L; (144.6±51.9) vs (56.2±43.8) μg/L, both P＜0.05].And at the following time points, urinary concentrations of sTREM - 1 and NGAL were significantly higher than the baseline levels and that of the non-AKI group (all P＜0.05). At 8 h time point, the area under the curve of urine sTREM-1 was 0.877 (95%CI 0.756-0.914), the sensitivity was 89.1% and specificity was 82.0% with a cutoff value of 70 ng/L. At 8 h time point, the area under the curve of urine NGAL was 0.862 (95% CI 0.703-0.958)，the sensitivity was 87.4% and specificity was 85.5% with a cutoff value of 90 μg/L.  Conclusions     Urinary concentrations of sTREM-1 and NGAL at 8 h time point after the diagnosis of sepsis have predictive value for AKI and their diagnostic time is much earlier than that of Scr. Therefore, urinary sTREM-1 and NGAL can be used as early biomarkers of septic AKI.

Objective    To evaluate the efficacy and safety of calcium acetate in treating hemodialysis(HD) patients with hyperphosphatemia. Methods    A randomized, controlled multicenter study was performed. Phosphate binders were discontinued during a two-week washout period． A total of 171 hemodialysis patients from 10 sites with serum phosphorus during 1.94-2.75 mmol/L after two-week washout period were randomized to calcium acetate or calcium carbonate for 8 - week treatment period. Patients with serum phosphorus between 1.94-2.26 mmol/L were given elemental calcium 1000 mg/d and between 2.27- 2.75 mmol/L were given elemental calcium 1500 mg/d. The dose was constant during the 8 - week treatment period. Results     All of 171 patients entered the safety analysis set, including 123 cases who completed the study into effect analysis set. In terms of efficacy: compared with the baseline, serum phosphorus, calcium - phosphorus products, parathyroid hormone (iPTH) levels were significantly decreased (all P＜0.05) and serum calcium levels increased slightly in both groups; compared with the calcium carbonate group, calcium acetate group had a significant advantage in the change of serum phosphorus content [(1.73 ± 1.85) vs (0.99 ± 1.60) mmol/L, P＜0.05] and drug response ratio (compared with the baseline serum phosphorus level fell more than 25%) (51.6% vs 32.8%, P＜0.05). In safety aspects, calcium acetate group and the control group had no significant differences in the incidence of adverse events (19.8% vs 18.8%) and adverse reactions (8.1% vs 4.7%), all P＞0.05. The main adverse reactions of calcium acetate were mild to moderate gastrointestinal reactions, including nausea, vomiting. Conclusions     In hemodialysis patients with hyperphosphatemia, calcium acetate can decrease serum phosphorus and reduce the levels of calcium - phosphorus product and iPTH. In the phosphate binding capacity, calcium acetate is superior to calcium carbonate. Mild to moderate gastrointestinal reactions are most common after administration.

Objective     To investigate the impact of low calcium dialysate on survival in continuous ambulatory peritoneal dialysis（CAPD）patients.  Methods    CAPD patients at our PD center between January 1,2006 and December 31,2010 were retrospectively studied. The patients were divided into standard - calcium dialysate (SCD) group and low - calcium dialysate (LCD) group. Cox regression analysis was used to compare patient survival and determine the related risk factors  Results    A total of 982 eligible PD patients were included in this study, of whom 634 patients treated with standard-calcium dialysate, and 348 with low-calcium dialysate. During a median follow-up of 24.2 - month, 162(16.5% ) died, 71(43.8% ) of them due to cardiovascular and cerebrovascular diseases. The overall 1-, 3-, and 5-year patient survival rates were 90.9%, 74.2% and 58.9% in SCD group and 98.6%, 94.0% and 76.4% in LCD group. Cox regression analysis demonstrated that low calcium dialysate treatment reduced 59% risk of all-cause death, as compared with standard calcium dialysate exposure. Old age, diabetes status and lower hematoglobin were independent risk factors of all - cause death in CAPD patients.  Conclusion    The survival rate of CAPD patients using LCD is obviously higer than that using SCD. Old age, diabetes status and lower haematoglobin are independent risk factors of all-cause death in CAPD patients.

Objective    To investigate the role of surfactant protein (SP) - A and SP - D in urinary tract infection mouse model, and evaluate the effects of SP-A and SP-D absence on urinary tract infection.  Methods    SP-A and SP-D double knockout (SP-A/D KO) mice were made. SP-A/D KO and wild-type (WT) C57BL/6 female mice were used for this study. The expression of SP-A and SP-D in kidney was detected by immunohistochemistry (IHC). The levels of p - p38 and p38 protein in kidneys were measured by Western blotting. Uropathogenic Escherichia coli or buffer was delivered into the bladder of female mice. At 24 and 48 h after inoculation, CFU of Escherichia coli in the kidney and urine of the treated and control mice were measured. Histological, cellular and molecular analysis were performed by several methods of H/E staining, IHC and Western blotting. The effects of SP-A and SP-D on bacterial growth were studied in vitro.  Results     SP-A and SP-D in kidney were located in the proximal tubules and collecting tubules. Compared with WT mice, infected SP - A/D KO mice with UPEC had higher CFU in kidneys and urine at 24 h and 48 h, increased inflammatory cells infiltration in kidneys（P＜0.05）. Compared with WT mice, SP - A/D KO mice had higher p38 MAPK phosphorylation levels in kidneys（P＜0.05）. Growth of Escherichia coli was greatly inhibited by both SP-A and SP-D（P＜0.05）.  Conclusions     Both SP-A and SP-D are expressed in kidney. SP-A and SP-D can attenuate UTI induced by UPEC which may be through inhibiting bacterial growth and modulating renal inflammation.

Objective    To investigate the effects of continuous venovenous hemodiafiltration (CVVHDF) on plasma lipopolysaccharide (LPS), interleukin(IL) 1β, IL-4, high mobility group box 1 (HMGB-1) in multiple organ dysfunction syndrome (MODS ) dogs, to explore the therapeutic mechanism of CVVHDF.  Methods     Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model, then they were randomly divided into 2 groups: CVVHDF group (n=6) and MODS group (n=6). After endotoxin injection completed, the CVVHDF group received CVVHDF treatment for 24 h; MODS group did not receive CVVHDF treatment. The LPS, IL-1β, IL-4, HMGB-1 levels in plasma and ultrafiltrate were measured at different time points(before operation, before intravenous infusion of endotoxin, 0 h, 3 h, 6 h, 9 h, 12 h, 18 h, 24 h after intravenous infusion completion of endotoxin), then the sieving coefficient (SC) was calculated.  Results    Compared with MODS group, the LPS, IL-1β, IL-4, HMGB-1 levels in plasma were significantly decreased in the CVVHDF group at 9 h, 12 h, 18h,24h(P ＜0.05).SomeconcentrationofIL-1β,IL-4andHMGB-1wasdetectedintheultrafiltrate,the SC for IL-1β, IL-4 and HMGB-1 was 0.60±0.12, 0.83±0.11, 0.70±0.09 respectively, and LPS could not be detected in the ultrafiltrate, its SC was 0. After treatment, the damage level of lung and renal had been significantly reduced in CVVHDF group.  Conclusion     CVVHDF can effectively reduce the levels of pro-inflammatory mediator and anti-inflammatory cytokine related to MODS, cut off the vicious circle of cytokine network and reduce the damage level of organism in the treatment of MODS.

Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on angiogenesis and peritoneal function of uremic peritoneal dialysis rats. Methods Forty - eight male SD rats were selected, and they were randomly divided into five groups: normal control group(n=8), sham operation group(n=8), uremia group(5/6 nephrectomy, n=8), PD group [4.25% PD solution, 2 weeks PD model(n=8) and 4 weeks PD model(n=8)], PD + celecoxib intervention group[treated by celecoxib(20 mg/kg) via oral gavage, n=8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures, functions, peritoneal tissue capillary density (microvessel density, MVD) and COX-2, vascular endothelial growth factor (VEGF) expression level, and the impacts of celecoxib on uremic peritoneal dialysis rats peritoneal angiogenesis and peritoneal function were study. Results With the conduct of the peritoneal dialysis, peritoneal thickness increased, the inflammatory cells infiltrated, peritoneal equilibration test (PET) showed that ultrafiltration volume decreased significantly (P＜0.05), the amount of glucose transport rate rised significantly (P＜0.05), but the celecoxib could improve net ultrafiltration volume (P＜0.05), and reduce the glucose transport rate (P＜0.05). The peritoneal tissue MVD and COX - 2, VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group (all P＜0.05), were significantly lower in PD + Celecoxib intervention group than that in uremia group (P＜0.05). The correlation analysis showed that the level of COX-2 protein expression with MVD, VEGF protein expression was positively correlated (both P＜0.05), the level of VEGF protein expression and MVD was positively correlated (P＜0.05). Conclusions    In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised, and the capillaries production increased in peritoneal tissue. Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats. Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats, possibly through inhibition of COX-2 expression to reduce the production of VEGF.

Objectives    To investigate the role and mechanism of p38 mitogerra activated protein kinase (p38MAPK) in up - regulation of prostanoid 2 induced by uric acid in rat glomerular mesangial cells (GMCs). Methods    Rat glomerular mesangial cells were cultured in vitro, then stimulated with different concentrations of uric acid (50, 100, 300 μmol/L), or stimulated with different concentrations of uric acid (50, 100, 300 μmol/L) after pretreatment with p38MAPK specific inhibitor SC68376 (10 μmol/L) for 30 min. Activated p38MAPK was detected by Western blotting. The expression of prostanoid 2 was measured by ELISA. Cyclooxygenase - 2 mRNA expression was determined by RT-PCR. Results    Uric acid could activate p38MAPK and up-regulate the mRNA expressions of prostanoid 2 and cyclooxygenase - 2 in rat glomerular mesangial cells (all P＜0.05). SC68376 inhibited those effects of the above-described induced by uric acid. Conclusion    Uric acid can promote the expression of prostanoid 2 in rat glomerular mesangial cells, whose mechanism may be related to the activation of p38MAPK and the promotion of cyclooxygenase - 2 synthesis, and further up-regulation of prostanoid 2 expression.