Objective    To investigate the relationship between plasma activated protein C (APC) and the development of atherosclerosis (AS), and illustrate the mechanism of AS in type 2 diabetic nephropathy.    Methods    A total of 30 non-dialysis patients of type 2 diabetic nephrology and 26 control subjects were enrolled. APC, soluble vascular adhesion molecular-1 (sVCAM-1), soluble endothelial cell protein C receptor (sEPCR) and soluble thrombomodulin (sTM) were assayed by ELISA. Carotid intima-media thickness (IMT) was measured by ultrasonography.    Results    APC levels were significantly decreased in type 2 diabetic nephropathy compared with that in controls [(2 865.99±571.38) ng/L vs (3 227.70±300.44) ng/L, P＝0.005]. APC levels had negative correlation with IMT, 24 h albuminuria, sEPCR, sVCAM-1, sTM (r＝-0.720, -0.402, -0.477, -0.437, -0.505, all P＜0.05). Significant difference were observed in different proteinuria groups and IMT groups by ANOVA analysis(P＜0.05).    Conclusions    In type 2 diabetic nephropathy patients, plasma APC is negatively correlated with severity and IMT. Decreased plasma APC may lead to high levels of inflammatory mediators and endothelial cell injury, which may involved in the occurrence and development of atherosclerosis in diabetic nephropathy.  

Objective    To compare the efficacy of different antibiotics strategy, introperitoneal (IP) cefazolin plus third-generation cephalosporin versus IP Vancomycin plus third-generation cephalosporin on peritoneal dialysis (PD)-related peritonitis.    Methods    All episodes of PD-associated peritonitis happened in prevalent PD patients between January 2008 and December 2012 were recruited from the PD Center of Peking University First Hospital. According to their empiric antibiotics scheme, episodes were divided into group A (where IP cefazolin plus third-generation cephalosporins were administrated) and group B (where IP Vancomycin plus third-generation cephalosporins were administrated). Multivariable logistic regression model was used to explore the influence of different empiric antibiotics scheme on peritonitis outcome.    Results    Patients in Group B had significantly lower level of serum albumin (33.5±6.0 vs 35.3±5.2 g/L) and cholesterol (4.6±1.3 vs 4.9±1.1 mmol/L) than those in group A. In group A, the percentage of gram-positive bacteria was similar to group B (43.2% vs 43.3%, P＝0.96), but gram-negative bacteria was numerically lower (16.9% vs 24.7%, P＝0.08). Different empiric antibiotics strategy was not independent predictor of peritonitis outcome [OR＝1.07, 95%CI(0.45, 2.56), P＝0.87].    Conclusion    Both cefazolin and vancomycin can be selected as first-line empiric antibiotic covering gram-positive organisms in the treatment of PD related peritonitis.

Objective    To investigate the effects of high-flux hemodialysis (HFD) on fibroblast growth factor-23 (FGF-23) levels in maintenance hemodialysis (MHD) patients and its clinical significance.    Methods    Sixty uremia patients were divided into HFD group and hemodialysis (HD)group and observed for 12 months. Flow mediated dilation (FMD), cardiac ultrasonography, levels of FGF-23, serum phosphorus, serum calcium, 25-(OH)D3, parathyroid hormone (PTH), homocysteine(Hcy) and interleukin-6 (IL-6) were tested in all patients before and after treatment. The correlation of above indexes were analyzed.    Results    No statistical difference were found in primary disease, age and duration of dialysis in two groups. The levels of FGF-23 [(56.07±26.63) vs (85.53±40.54) ng/L, P＜0.01], IL-6 [(3.37±2.48) vs (5.59±2.53) ng/L, P＜0.05] and Hcy [(21.13±6.95) vs (29.40±11.66) μmol/L, P＜0.05] decreased and FMD, 25-(OH)D3 [(27.3±10.26) vs (23.15±10.73) μg/L, P＜0.05] increased significantly after the treatment of HFD. There were no significant changes in the HD group. The baseline FMD was negatively correlated with FGF-23 (r＝-0.413, P＜0.05) and Hcy (r＝-0.301, P＜0.05). The baseline LVMI was correlated with FGF-23 (r＝0.464 P＜0.05). After one year's trearmeat of HFD, the changes of FMD(△FMD) was negatively correlated with the changes of FGF-23 (△FGF-23)(r＝-0.347, P＜0.05).   Conclusions    HFD can improve FMD and decrease FGF-23 levels. The improvement of FMD may be related to the decreased level of FGF-23. The effect of FGF-23 on FMD should be independent of serum phosphate.

Objective    To access the early diagnosis value of kidney injury molecule-1 (KIM-1) in patients with acute kidney injury (AKI) by Meta-analysis.    Methods    Databases MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and WanFang Data were retrieved to collect the diagnostic tests on KIM-1 for AKI published before July 2013. The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria, the data were extracted, and the methodological quality was assessed. Statistic software Meta-Disc 1.4 and STATA 12.0 were used to conduct analyses.    Results    Eighteen articles were included in this study with a total of 3 427 patients. The summary for urinary KIM-1 in the diagnosis of AKI were sensitivity 0.67(95%CI: 0.63, 0.70), specificity 0.80 (95%CI: 0.78, 0.81), positive likelihood ratio 3.53(95%CI：2.73, 4.56), negative likelihood ratio 0.30 (95%CI: 0.21, 0.42), diagnostic odds ratio 15.13(95%CI: 8.40, 27.25), and the area under the curve (AUC) of summary receiver operating characteristic curves (SROC) was 0.865 2. Subgroup analysis revealed the sensitivity, specificity and diagnostic odds ratio of urinary KIM-1 measured after 2 to12 h post operation in diagnosis of AKI after cardiac surgery were 0.88(95%CI: 0.81, 0.93), 0.75(95%CI: 0.71, 0.79) and 30.22 (95%CI: 16.19, 56.42), respectively. The AUC of SROC was 0.923 7.    Conclusions    KIM-1 as a single indicator has moderate accuracy for early diagnosing AKI, especially with a high diagnostic accuracy in AKI after cardiac surgery. 

Objective    To investigate the diagnostic value of urine neutrophil gelatinase apolipoprotein (NGAL) and kidney injury molecule 1 (KIM-1) as markers of CIN, and the effectiveness of hydration therapy in the prevention of CIN.    Methods    One hundred and twenty patients were randomly divided into control group and treatment group. The patients of treatment group received hydration therapy through intravenous fluid infusion. Urine samples were taken for detecting the value of albumin (mAlb), NGAL, and KIM-1 before surgery (T0), after surgery 12 h (T1), 24 h (T2), 48 h (T3), 72 h (T4) by ELISA assay. The levels of urinary mAlb, Scr, BUN and cystatin C were detected at the same time.    Results    ⑴ The urine NGAL/Cr and KIM-1/Cr significantly increased and were more than twice the baseline value at the time of 12 h after PCI in 87 of 120 cases of the participants. There are eight cases occurred CIN (6.67%) and one case occurred in hydration treatment group (1.7%), seven cases were in control group (11.7%). The difference was statistically significant. ⑵ There were no significant difference in BUN, Scr, mAlb/Cr, Cys-C and GFR between two groups (P＞0.05). ⑶ NGAL/Cr, KIM-1/Cr were elevated at T1 in both groups (P＜0.01). In hydration treatment group, levels of NGAL/Cr and KIM-1/Cr decreased substantially to the level of T0 at T4(P＜0.01), while in the control group they didn't. ⑷ Area under the ROC curve (AUC) of NGAL/Cr and KIM-1/Cr 12 h after PCI were 0.931 [95% CI (0.889, 0.973)] and 0.811 [95% CI(0.736, 0.886)] respectively (all P＜0.05).    Conclusions    NGAL and KIM-1 are sensitive and specific indicators for predicting early renal injury induced by contrast medium and can be used for early diagnosis of CIN. Hydration therapy can prevent the contrast agent-induced renal damage.

Objective    To sort the clinical features associated with hyperphosphatemia in peritoneal dialysis (PD) patients.    Methods    The patients who had been on stable PD at least three months were eligible to enroll. All patients were instructed to record 3 days food diary in order to obtain the daily dietary phosphorus, protein and calorie intake. The peritoneal and renal clearance of phosphorus, residual renal function (RRF) and total creatinine clearance (Ccr) were calculated. Laboratory parameters, including serum albumin, phosphorus, calcium, intact parathyroid hormone (iPTH), high sensitivity C reactive protein (hs-CRP), potassium were measured. Prescription of oral phosphorus binders and active vitamin D were recorded.    Results    A total of 100 PD patients were enrolled and divided into two groups according to their serum phosphorus levels, including high serum phosphorus group (≥1.6 mmol/L, n＝50) and normal serum phosphorus group (＜1.6 mmol/L, n＝50). Compared to the patients with normal serum phosphorus, hyperphosphatemic PD patients had significantly higher dietary phosphorus [(13.03±3.39) vs (10.65± 3.04) mg·kg IBW-1·d-1] and protein intake [(0.96±0.30) vs (0.80±0.27) mg·kg IBW-1·d-1], while peritoneal phosphorus clearance [(21.8±9.90) vs (27.74±11.23) L·wk-1·(1.73 m2)-1], renal phosphorus clearance [1.38(0, 12.38) vs 10.30(0, 21.97) L·wk-1·(1.73 m2)-1] and total Ccr [(59.7±18.5) vs (68.3±23.1) L·wk-1·(1.73 m2)-1] were lower (all P＜0.05). Patients with hyperphosphatemia showed higher prevalence of anuria (46% vs 24%) and more frequent usage of dialysate with 1.25 mmol/L calcium (66% vs 40%) compared to their counterparts with normal serum phosphorus (all P＜0.05). In addition, serum potassium levels in patients with hyperphosphatemia were higher [(4.4±0.8) vs (3.9±0.6) mmol/L, P＜0.05]. Multiple stepwise regression analysis showed that dietary phosphorus intake (β＝0.043, P＜0.01), peritoneal phosphorus clearance (β＝-0.008, P＜0.05), RRF (β＝-0.07, P＜0.01) and log[iPTH] (β＝0.262, P＜0.01) were independently associated with serum phosphorus level in PD patients.    Conclusions    PD patients with hyperphosphatemia have higher dietary phosphorus intake, lower phosphorus clearance and are more tended to be anuric. Dietary phosphorus intake, peritoneal phosphorus clearance, residual renal function and serum iPTH are independent factors associated with serum phosphorus levels in PD patients.

Objective    To investigate association between serum uric acid (SUA), albuminuria and glomerular filtration rates (eGFR) in type 2 diabetic patients.    Methods    A total of 220 patients were enrolled in this cross-sectional study. According to urinary albumin excretion rates, patients were divided into 3 groups: normoalbuminuria (NAU) group, microalbuminuria (MAU) group, and macroalbumnuria group (MAAU). The first two groups were subdivided at SUA＞420 μmol/L (＞357 μmol/L, female) into normouricemia group and hyperuricemia group, at eGFR＞90 ml/min into high and low renal function groups. General information, blood biochemical results were collected to analyze the association between serum uric acid, eGFR, UAER and urine albumin quantification among different groups.    Results    The difference of SBP, duration of diabetes (DD), Scr, SUA and eGFR between every two groups were significant (P＜0.05). SBP, DD, Scr and SUA were highest in subjects with macroalbumnuria, second in microalbuminuria group, and lowest in normoalbuminuria group, while eGFR was lowest in macroalbumnuria group and highest in normoalbuminuria group. Prevalence of hyperuricemia in macroalbumnuria group (56.9%) and microalbuminuria group (51.2%) were also significantly higher than that in normoalbuminuria group (17.5%) (all P＜0.01). The difference of UAER in the subgroups of normouricemia and hyperuricemia was more significant in microalbuminuria   group than in normoalbuminuria group. eGFR was significantly lower in hyperuricemia subgroups (P＜0.01). Age and SUA were significantlg higher in subjects with low renal function compared with high eGFR (P＜0.05). Linear regression analysis indicated SUA was negatively correlated with eGFR after adjusted age, DD and UAER (β＝-0.430, P＜0.01). Binary logistic regression analysis found that increased age, DD and SUA were risk factors of microalbuminuria [β＝1.092, 95％CI(1.025, 1.163), P＜0.01; β＝1.005, 95%CI(1.001, 1.009), P＜0.05; β＝1.407, 95％CI(1.052, 1.881), P＜0.05)] and SUA, age were risk factors of early renal function decline [β＝1.015, 95％CI(1.00, 1.023), P＜0.01; β＝1.098, 95％CI(1.006, 1.199), P＜0.05].    Conclusion    SUA is independently associated with albumnuria and renal function decline in type 2 DM patients.

Objective    To investigate the role of autophagy in podocyte damage, and the intracellular mechanism of autophagy activation through passive Heymann nephritis (PHN) animal model.    Methods    Male Sprague-Dawley rats (n=40) were studied on day 0, 2, 4, 7, and 21 after induction of PHN by injection of anti-Fx1A. Podocyte morphology and autophagosomes were observed by transmission electron microscopy. Podocyte numerical density was estimated by Weibel-Gomez method. Cell apoptosis was detected by TUNEL assay and caspase-3 immunohistochemical staining. Expressions of autophagy markers and endoplasmic reticulum stress (ERS)-associated proteins were analyzed by Western blotting.    Results    (1) In PHN rats, immunohistochemical staining showed that C5b-9 deposited along glomerular basement membrane on day 4 to day 21. Small subepithelial electron-dense deposits and a part of foot process fusion were detected in the glomerulus of PHN rats on day 4 by transmission electron microscope, and podocyte damage was aggravated on day 21. Furthermore, compared with control, the urinary protein levels of PHN rats began to increase on day 3, and reached the top on day 21 [(50.6±6.0) mg/24 h]. (2) The number of podocytes significantly decreased in PHN rats compared with control group on day 21(P＜0.05). (3) In PHN rats, apoptotic podocytes were found by caspase-3 immunohistochemical staining and TUNEL assay on day 21. (4) The expression of autophagy marker LC3Ⅱwas markedly increased on day 7 and 21, but down-regulated on day 21 compared with day 7. Moreover, accumulated autophagosomes in podocytes were detected on day 7 and 21 by transmission electron microscope. (5) The level of GRP78 was significantly increased on day 2 and 7 but reduced to baseline on day 21. At the same time, the downstream pathways (ATF6α,              p-PERK and p-JNK) of unfolded protein response were also up-regulated in the early process of PHN and down-regulated later.   Conclusions    Autophagy is an important way to protect against immune-mediated podocyte injury in membranous nephropathy. Autophagy activation is mainly related to endoplasmic reticulum stress induced by complement attack. This provides an important basis for a thorough understanding of the role of autophagy in the process of podocyte damage and the pathogenesis of membranous nephropathy.

Objective    To evaluate the effects of KIM-1 on high glucose induced the expression of MCP-1 and FN in rat tubular epithelial cells and to explore the possible mechanisms of KIM-1 involved in renal interstitial fibrosis of DN.    Methods    The rat renal tubular epithelial cells (NRK52E) were cultured in vitro and divided into five groups: Normal control group (D-glucose 5.6 mmol/L), Hypertonic group (D-glucose 5.6 mmol/L＋D-mannitol 24.4 mmol/L), High glucose group (D-glucose 30 mmol/L), Control siRNA group，KIM-1 siRNA group. ELISA assay was used to assess the levels of MCP-1 and FN in the cells supernatant; Western blotting was used to detect the protein expression of KIM-1; RT-PCR was used to detect mRNA expression of KIM-1, MCP-1 and FN.    Results    Compared with the control group, the protein and mRNA expression of KIM-1 in the high glucose group were increased at 12 h (P＜0.05), and reached the peak at 48 h (P＜0.05); the protein and mRNA expression of MCP-1 and FN in high glucose group were increased at 24 h significantly (P＜0.05), and peaked at 48 h (P＜0.05). Compared with the high glucose group, the protein and mRNA expressions of MCP-1 and FN in KIM-1 siRNA group were decreased (P＜0.05).    Conclusions    Down-regulating the expression of KIM-1 can significantly inhibit the expression of MCP-1 and FN, which suggests that KIM-1 may be involved in renal interstitial fibrosis of DN by regulating expression of MCP-1 and FN.