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  • 2013 Volue 29 Issue 8      Published: 15 August 2013
      

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    Objective     To analyze the impact factors for early renal damage in type 2 diabetic patients by the classification tree model.   Methods     A total of 601 patients with type 2 diabetes were enrolled. According to glomerular filtration rates and urine albumin quantification, the patients were divided into type 2 diabetes group ( 418 cases ) and early diabetic renal damage group ( 183 cases ). The clinical data of the patients were recorded to analyze the main influential factors for the microalbuminuria of type 2 diabetic patients using the Exhaustive CHAID classification tree algorithm.   Results     Six important explanatory variables were screened out by the classification tree model from the 34 candidate variables related to early renal damage, including fibrinogen, history of hypertension, retinopathy, Cys C levels, SBP and peripheral neuropathy. Elevated fibrinogen was the main factor.   Conclusion     The classification tree model can analyze the major influential factors of early renal damage in type 2 diabetic patients effectively, and it can help develop the prevention and treatment methods.

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    Objective  To investigate the association of vascular calcification, fetuin A and C- reaction protein (CRP), and explore the influence on cardiovascular events.  Methods  Sixty peritoneal dialysis (PD) patients were enrolled in this study. Carotid intima-media thickness (cIMT), fetuin A and CRP, along with the other serum related parameters were detected to find out their influence on vascular calcification in PD patients. The relationship between cIMT, fetuin A, CPR and cardiovascular events was analyzed in PD patients with 18 months followed-up.  Results  Of the 60 PD patients, carotid intima-media thickness (cIMT) was increased in 38 patients(63.3%). Compared with the non-increased cIMT patients, serum fetuin A concentration was significantly decreased(P<0.05), CRP(P<0.01) and calcium × phosphate products(P<0.05) were significantly increased in the high - increased cIMT group. Compared with the low - increased cIMT patients, fetuin A concentration was obviously lower(P<0.05) and calcium×phosphate products were obviously higher(P<0.05) in the high- increased cIMT group. Linear regression analysis discovered an obvious negative correlation between CRP and fetuin A(R 2=0.629,F =47.522, P<0.01) , as well as fetuin A and calcium×phosphate products (R 2=0.299, F =11.948, P=0.002). Multiple regression analysis indicated that fetuin A was independently negatively correlated with cIMT(B =-0.019,t =-6.042, P<0.01). At 18 months, there were 36 newly - happened cardiovascular events and among which 6 cases died. Logistic regression analysis found that increased cIMT was risk factor to cardiovascular events in PD patients(OR =3.691, 95%CI 1.467-9.258,P=0.006).  Conclusion  Decreased fetuin A and increased calcium×phosphate products deteriorate carotid calcification in PD patients. Micro-inflammation of PD patients represented by high CRP levels may increase calcium×phosphate products by depressing the fetuin A level, and in the end will stimulate carotid calcification. Increased cIMT is a risk factor for cardiovascular events.

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    Objective  To study whether citrate lock is superior to heparin lock in the prevention of catheter related infections, bleeding complications and catheter malfunctions among hemodialysis patients with tunneled catheters.  Methods  By searching in Pubmed, the Cochrane Library, EMBASE, Ovid, WanFang, VIP, CNKI and CBM databases as well as related journals, qualified randomized controlled trials were included in a Meta - analysis using Revman 5.0 and STATA 10.0 software. The endpoints included catheter related infection, bleeding complication, thrombolytic treatment, catheter removal for malfunction, catheter thrombosis and all - cause death.  Results  Fifteen randomized controlled trials were included with 1621 patients involved. Eight studies compared citrate alone with heparin lock, while 7 trials focused on citrate in combination with other antimicrobials. Pooled analysis demonstrated that incidence of catheter related infections in patients receiving citrate lock decreased by 47% compared with those on heparin (RR=0.53, 95%CI 0.36-0.77, P<0.01). Subgroup analysis by types of citrate lock indicated that all combined lock solutions of citrate and other antimicrobials (citrate + gentamicin, citrate + taurolidine, citrate + methylene blue + methylparaben + propylparaben) were superior to heparin lock in preventing catheter-related infections (P=0.01, 0.04, 0.01, respectively); citrate alone seemed to reduce catheter-related infection risk (RR=0.68), but no statistically significant difference was observed (95%CI 0.38-1.21, P=0.19). There were fewer patients with bleeding complications in citrate group (RR=0.53, 95%CI 0.34-0.84, P<0.01), while citrate showed no advantage over heparin lock in terms of thrombolytic treatment (P=0.93), catheter removal for malfunction (P=0.35), catheter thrombosis (P=0.64) and all - cause death (P=0.35).  Conclusions  For hemodialysis patients with tunneled catheters, combined lock solutions of citrate and other antimicrobials, rather than citrate alone, are superior to heparin in preventing catheter related infections. Citrate locks are associated with less bleeding complications, and are comparable to heparin in the maintenance of catheter patency.

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    Objective     To analyze the islet α-cell function in type 2 diabetic patients with different levels of glomerular filtration rate(eGFR).   Methods     Three hundred and eighty-eight cases of type 2 diabetic patients were classified into four groups according to eGFR: glomerular hyperfiltration group, normal renal function group, mild renal dysfunction group and moderate-severe renal dysfunction group. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were conducted to compare the changes of glucagon(GLA), insulin/glucagon ratio(INS/GLA), glucose/glucagon ratio(GLU/GLA), the area under the curve of glucagon(AUCGLA) among the groups and correlation analysis were performed among glucagon and glomerular filtration rate and other indicators.   Results     With the decline of eGFR, the change curve of glucagon level was“J”shaped; the level of fasting glucagon in each group were(82.21±15.06)ng/L,(74.25±15.34)ng/L,(81.16±20.18)ng/L, (100.21 ± 24.73)ng/L, respectively. Compared with normal renal function group, GLA, AUCGLA in glomerular hyperfiltration group and renal dysfunction group increased significantly(P<0.05), GLU/GLA, INS/GLA decreased significantly. Pearson correlation coefficient analysis showed that fasting glucagon had a negative correlation with eGFR(r=-0.360,P<0.01), plasma albumin (ALB)(r= -0.170,P<0.01)and high - density lipoprotein cholesterol (HDL - C)(r=-0.128,P<0.05), had a positive correlation with fasting venous blood glucose (FPG)(r=0.339,P<0.01), postprandial 2 hours venous blood glucose(2hPG)(r=0.443,P<0.01), the area under the curve of blood glucose (AUCG)(r=0.475,P<0.01), duration(r=0.257,P<0.01)and glycosylated hemoglobin(HbA1c) (r=0.202,P<0.01). Multiple stepwise regression analysis showed that fasting glucagon was negatively correlated with eGFR(β =-0.290,t=-5.393,P<0.01) and HDL - C(β =-0.157,t= -3.026,P<0.01).   Conclusions     Glucagon level is influenced by eGFR in type 2 diabetic patients. Glucagon in patients with glomerular hyperfiltration or renal dysfunction is significantly higher than those with normal renal function. The inhibition effect of blood glucose and insulin to glucagon are both weakened.

     
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    Objective  To investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients.  Methods  A total of 371 MHD patients at Zhongshan Hospital, Fudan University between March 2009 and February, 2011 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. All patients were followed for one year to investigate the risks for CVD event and mortality. Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters. Difference in categorical factors between two groups were determined with Chi-square test, Difference in continuous values between two groups were assessed with t test. Kaplan - Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors.  Results  Patients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51, P<0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15, P<0.01) than those without CVD event. Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk, 95%CI: 0.136-0.719, P<0.01) and that an increased monocyte count was associated with increased mortality risk, 95% CI: 2.657 - 74.396, P<0.01) after adjustment for hsCRP.  Conclusion  Decreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one - year all - cause mortality risk in MHD patients.

     
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    Objective  To observe the level of serum hepcidin and the relationship of hepcidin with renal anemia and micro - inflammation state in peritoneal dialysis(PD) patients.  Methods    Serum hepcidin, interleukin-6(IL-6), soluble transferrin receptor (sTfR) and erythropoietin (EPO) were measured in 50 PD patients with anemia, 30 PD patients without anemia and 40 cases of normal control by ELISA. The indexes of blood routine examination, biochemistry and iron metabolism were also detected at the same time.  Results  The level of hepcidin in PD patients was significantly higher than that in normal control[(103.65±43.6) μg/L vs (56.39±35.7) μg/L,P<0.05]. Furthermore, the level of hepcidin in PD patients with anemia was higher than that in PD patients without anemia [(122.67±36.6) μg/L vs (83.65±26.4) μg/L,P<0.05]. The results of correlation analysis showed that serum IL-6, sTfR, EPO and ferritin were positively correlated with hepcidin(R =0.821, 0.742, 0.711, 0.531,all P<0.05 ), while creatinine clearance of residual kidney in 24 hours and hemoglobin were negatively correlated with hepcidin(R =-0.533, -0.685,all P<0.05 ).  Conclusions  The higher level of hepcidin in PD patients is related with the residual renal function and the micro-inflammatory state. The higher level of hepcidin may induce the iron metabolism imbalance, and then influence the state of renal anemia. The adjustment of hepcidin may provide clinical research value of improving renal anemia and micro-inflammatory state in PD patients.

     
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    Objective   To improve standards of diagnosis and therapy for acute focal bacterial nephritis by comparing the characters of acute focal bacterial nephritis and acute pylonephritis.  Methods  Thirty-five patients of upper urinary tract infection whoever accepted ultrasonographic and computed tomographic (CT) examinations in Beijing Hospital from January 2007 to January 2013 were studied retrospectively. Eighteen patients were diagnosed as acute focal bacterial nephritis (AFBN) according to CT imaging features, the other 17 patients were diagnosed as acute pyelonephritis (non-AFBN). The clinical feature, laboratory and imaging examination were compared between the two groups.  Results  Leukocyte count, percentage of neutrophil, fasting blood-glucose, ESR, NAG/Cre of urine, the combination of more than one kind of antibiotics and duration of antibiotic treatment were higher or much more in AFBN group patients than non AFBN patients, the differences between two groups were statistical significance(P<0.05). Urine microorganism culture was mainly Escherichia coli no matter in AFBN group or non-AFBN group, microorganism species of AFBN patients were more complex than non-AFBN patients. The most common contrast-enhanced CT feature of AFBN included local distribution of inflammatory area, wedge - shaped or unregular-shaped hypodense lesions on bilateral or single kidney, and mass-like hypodense lesions in more severe cases. NAG/CRE of urine was higher in AFBN group patients with bilateral kidney lesions than with single kidney lesions and non AFBN patients. The remission time of AFBN and non - AFBN was (3.4 ± 2.9) d, (3.0 ± 1.8)d respectively. The relapsing rate of AFBN and non - AFBN within half a year was 2/18, 2/17, respectively.  Conclusions  The symptoms of acute focal bacterial nephritis are not specific. Abdominal contrast-Enhanced CT, ESR, leukocyte count, urine NAG/CRE are probably a predictor of AFBN. Antibiotic treatment with appropriate usage and sufficient duration could bring satisfactory outcomes and prognosis in acute focal bacterial nephritis and pyelonephritis patients.

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    Objective  To observe the vascular lesions of renal small arteries and arterioles as well as clinco - pathological characteristics among patients with IgA nephropathy associated with malignant hypertension (IgAN-MHT). To explore the clinical significance of peritubular capillary (PTC) loss and renal tubulointerstitial macrophage infiltration in the same population.  Methods  Thirty - four (1.9%) IgAN-MHT patients were diagnosed among the 1765 cases of primary IgA nephropathy in Peking Union Medical College Hospital from January 2003 to March 2012. Their clinical records were reviewed and the lesions of glomeruli, tubules, interstitium and renal vessels were semi-quantitatively re-evaluated. PTC and renal tubulointerstitial macrophages were demonstrated by immunohistochemical staining.  Results  The IgAN-MHT patients were mainly young males with very high blood pressure. They had variant renal function impairment and urinary protein excretion. Acute and chronic vascular changes coexisted in the renal small arteries and arterioles, but all the vascular lesions failed to correlate with renal function. The renal tubulointerstitial macrophage infiltration was prominent and correlated well with renal function. PTC loss was also prominent and the PTC proportion was correlated with renal function.  Conclusions  In IgAN - MHT patients, the renal vascular changes do not correlate with renal function, but PTC loss and renal tubulointerstitial macrophage infiltration are both prominent and may reflect renal function impairment.

     
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    Objective  To investigate whether gut microbiome dysbiosis and translocation occurred in experimental uremia, and whether they consequently contribute to microinflammation. Methods  Health male SD rats were randomly divided into uremic group and sham group. Uremic group were operated for 5/6 nephrectomy to establish uremic models, while sham group were only operated for nephrocapsulotomy. Postoperative blood, livers, spleens, and mesenteric lymph nodes (MLNs) were subjected to bacterial 16S ribosomal DNA amplification to determine if bacteria were present. Bacterial genomic DNA samples from the MLNs and colon were amplified with specific primers designed by the 16SrRNA sequence of the species obtained from blood, livers and spleens. Pyrosequencing was used to analyze the ileum and colonic microbiome of each subject. Intestinal permeability to 99mTc-DTPA, plasma hs-CRP, and IL-6 were measured.  Results  Bacterial DNA in extraintestinal sites and altered colonic microbiomes at the phylum, family, and genus levels were detected in some rats in the uremic group. Bacterial genomic DNA in MLNs and colon were obtained by primers specific for bacterial species observed from blood, livers, and spleens of identical individuals. Intestinal permeability, plasma hs-CRP, and IL-6 levels were statistically higher in the uremic group compared with that in sham group(all P<0.05).  Conclusion  Gut microbiome dysbiosis occurs and presumably bacteria translocate to the systemic and lymph circulation, thereby contributing to microinflammation in experimental uremia.

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    Objective   To explore the role of 12 - lipoxygenase (12 - LO) in the pathogenesis of diabetic renal mesangial cells (MC) hypertrophy and its related mechanisms.   Methods  WT and 12-LO knockout mice were induced as type 1 diabetes to investigate the renal hypertrophy and expression of p21, p27 in glomeruli. The ratio of total protein to cell number was detected as cellular hypertrophy diagnosis to explore the role of 12-LO in hyperglycemia induced mesangial cellular hypertrophy. Real-time PCR and Western blotting were used to detect the changes of p21 as well as p27 induced by 12(S)-HETE which was 12 - LO metabolic product.   Results  12(S) - HETE promoted p21 gene expression (P<0.05), increased p21 and p27 protein levels in MC (all P<0.05), therefore induced cellular hypertrophy (P<0.05). MC from 12-LO knockout mouse showed less hypertrophy and decreased expression of p21 and p27 compared with WT MC under high glucose condition (all P<0.05). On the contrary, over - expression of 12 - LO significantly enhanced p21 and p27 protein expression in MC (P<0.01). Compared to WT mice, 12-LO knockout mice showed less renal hypertrophy and decreased expression of p21 and p27 in glomeruli induced by hyperglycemia (all P<0.05).   Conclusion  12-LO involves in the process of diabetic renal hypertrophy through regulating the expression of p21 and p27.