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    临床研究

  • MENG Li-qiang;WANG Yu;ZHANG Lu-xia;LV Ji-cheng;WANG Hai-yan.
    2011, 27(8): 555-560.
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    Objective To identify the risk factors for progression of advanced chronic kidney disease (CKD) patients who were cared by nephrologists in a specific CKD outpatient management clinic. Methods A prospective monocentric cohort study was performed. CKD patients of stage 3, 4 and 5 without renal replacement treatment were followed up regularly by nephrologists in this specific CKD management clinic. Patients with established atherosclerotic renal artery stenosis (ARAS) and chronic tubulointerstitial nephritis, and those who had not been followed-up for at least 12 months before Jun. 30, 2010 were excluded. Clinical and laboratory data including blood pressure (BP), proteinuria, hemoglobulin (Hb), calcium phosphate product (Ca×P) and serum creatinine were consecutively collected. The treatment regimen was also recorded. Estimated glomerular filtration rate (eGFR) was calculated with the formula modified for Chinese to evaluate the change of renal function. The progression of kidney disease was defined as initiation of renal replacement therapy, the annual decrease of eGFR>4 ml•min-1•(1.73 m2)-1, and/or death associated with renal disease. Results A total of 138 patients were enrolled in the final analysis with 84 patients of CKD stage 3, 36 of CKD stage 4 and 18 of CKD stage 5, respectively. At the time of enrollment, patients had an average age of (56.5±16.7) years old with an average eGFR of (32.3±13.4) ml•min-1•(1.73 m2)-1. During a mean follow-up interval of (27.1±12.1) months, the patients were well-controlled with an average blood pressure of (126.5±12.4)/(76.4±7.9) mm Hg in 50.7% (70/138), less than or equal to 130/80 mm Hg, an average Hb of (123.8±17.1) g/L in 73.9% (102/138), above or equal to 110 g/L and an average Ca×P of (45.2±7.7) mg2/dl2 in 89.1%(123/138), less than or equal to 55 mg2/dl2. Sixty-two patients (44.9%) had progression of kidney disease. On univariate analysis, factors predicting progression were low eGFR at referral, high systolic pressure, low Hb level, high Ca×P and proteinuria during follow-up, and renin-angiotensin system inhibitors treatment did not affect the progression. After the adjustment, multivariate analysis revealed proteinuria and low Hb level were independent factors for the progression of kidney disease. Conclusions The co-morbidities of advanced CKD patients can be managed efficiently in specific CKD outpatient management clinic. Control of proteinuria and correction of anemia may be beneficial to prevent the progression of advanced CKD.
  • XU Yan;ZOU Jian-zhou;TENG Jie;LIU Zhong-hua;SHEN Bo;XU Shao-wei;DING Xiao-qiang.
    2011, 27(8): 561-566.
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    Objective To investigate the correlation between plasma pentraxin 3 (PTX3) and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods Plasma was obtained from 98 MHD patients before and after a session of HD and 50 age-matched healthy subjects. Plasma PTX3 was measured by enzyme-linked immunosorbant assay (ELISA). Spearman correlation and linear regression were used to examine the correlation between plasma PTX3 level and other laboratory parameters. Binary Logistic regression was used to assess the correlation between plasma PTX3 level and CVD. Receiver operator characteristic (ROC) curve was used to analyze the correlation among PTX3, high sensitive C-reactive protein (hsCRP) and CVD. Results Plasma PTX3 level was significantly higher in MHD patients compared to healthy controls [1.87(1.34-2.50) μg/L vs 1.11 (0.86-1.51) μg/L, P<0.01], and increased after a single HD session [post-HD 2.18 (1.80-3.14) μg/L vs pre-HD 1.87 (1.34-2.50) μg/L, P<0.01]. Patients with CVD had higher concentrations of PTX3 than those without CVD [2.18(1.48-2.74) μg/L vs 1.76 (1.25-2.26) μg/L, P<0.05]. High plasma PTX3 (>1.87 μg/L) was positively and independently associated with CVD [OR=3.15, 95%CI (1.17-8.50), P<0.05]. ROC curve analysis showed the PTX3 was more closely correlated to CVD than hsCRP in MHD patients with hsCRP >3 mg/L, and the area under the curve of PTX3 and hsCRP was 0.655±0.083 (P<0.05) and 0.562±0.083 (P>0.05) respectively. Plasma PTX3 level was negatively correlated with body mass index(ρ=-0.248, P<0.05), pre-albumin (ρ=-0.218, P<0.05), total cholesterol (ρ=-0.265, P<0.01), triglyceride (ρ=-0.246, P<0.05), LDL-cholesterol(ρ=-0.254, P<0.05), hemoglobin(ρ=-0.212, P<0.05), and positively with erythropoietin dose per week (ρ=0.184, P<0.01), cardiac troponin T (ρ=0.287, P<0.01), carotid artery intima-media thickness (ρ=0.294, P<0.05). Conclusions PTX3 level is markedly elevated in HD patients. HD procedure induces PTX3 elevation. Plasma PTX3 could be a useful marker of CVD risk factors in MHD patients.
  • ZHOU Ying;GU Hui-fang;XIE Qiong-hong;XU Zhong-ye;MA Shuai;YOU Huai-zhou;KUANG Ding-wei;GU Yong;HAO Chuan-ming;LIN Shan-tan;DING Feng.
    2011, 27(8): 567-571.
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    Objective To elucidate the malnutrition in patients with hospital-acquired acute kidney injury (AKI), and to examine the association between subjective global assessment (SGA) and prognosis. Methods Adult patients with hospital-acquired AKI were prospectively enrolled in this cohort study. Nutritional evaluations, including SGA, anthropometric and serum nutritional markers were conducted at enrollment. Overall survival at 90 days among different SGA scores was analyzed using Kaplan-Meier methods, and differences were tested using the log-rank test. The Cox model was used to analyze the relationship between SGA scores and all-cause mortality after adjusting for confounders. Results A total of 170 patients were enrolled. The prevalence of moderate malnutrition (SGA B) and severe malnutrition (SGA C) was 51.8% and 22.9% respectively, while patients with normal nutrition (SGA A) accounted for 25.3%. After 90 days follow-up, all-cause mortality was 9.8% in SGA A group, 34.9% in SGA B group and 56.8% in SGA C group respectively. After adjusting for age, sex, dialysis, ventilation, hemoglobin, platelets and bilirubin,the hazard ratio (HR) of 90 days all-cause mortality was 4.0 (95% CI 1.42-11.22, P=0.008) in malnutrition group (SGA B group and SGA C group) compared with SGA A group. The Kaplan-Meier curve also revealed that the worse the SGA score was, the lower the cumulative survival became (P<0.01). Conclusion SGA score is an independent risk factor for all-cause mortality within 90 days in patients with hospital-acquired acute kidney injury.
  • LIU Wei-hua;ZHOU Qiao-ling;AO Xiang;PENG Wei-sheng;YANG Jing-hua;LI Xiao-zhao.
    2011, 27(8): 572-575.
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    Objective To explore the association between fibroblast growth factor 23 (FGF-23) and calcium (Ca)-phosphorus(P) metabolism and bone mineral density (BMD) in patients on peritoneal dialysis. Methods Fifty-nine patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were enrolled in this study. These patients were divided into three groups as normal, osteopenic and osteoporotic, according to World Health Organization criteria based on bone mineral density T scores. Another 30 healthy people were also enrolled as control group. Levels of serum FGF-23 and 1,25(OH)2VitD3 were measured by ELISA. Parathyroid horomone (PTH) was detected by immunoradiometric assay. Calcium and phosphorus were assessed with autobiochemistry machine. Bone density was studied by dual-energy X-ray absorptiometry (DEXA). Results The incidences of osteoporosis at the femur neck and lumbar spine in CAPD patients were 23.7% and 35.6%, respectively. Among three groups of CADP patients, no significant differences were found in the levels of serum FGF-23, while the level of serum FGF-23 in CAPD group was higher than that in control gronp (P<0.01). A positive correlation was found between log[FGF-23] and serum phosphorus (r=0.604, P<0.01). However, a negative correlation was found between log[FGF-23] and 1,25(OH)2VitD3 and GFR (r=-0.401, P<0.05; r=-0.651, P<0.01). There were no correlations of log[FGF-23] with PTH, Ca, T scores and the duration of dialysis. Conclusions In CAPD patients, serum FGF-23 increases significantly. Serum phosphorus, renal function and 1,25(OH)2VitD3 may play an important role in adjusting the level of serum FGF-23, while FGF-23 has no direct effect on bone mineralization in CAPD patients.
  • JIN Xiao-hong;WANG Ying;FAN Wei-feng;ZHANG Qi;LUO Li-hong;QIAN Ying-jun;LI Peng;ZHANG Li-hong;NIU Jian-ying;GU Yong.
    2011, 27(8): 576-580.
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    Objective To investigate the management and control of hypertension in patients with chronic kidney disease (CKD) and its associated factors. Methods Data of 726 in-patients with CKD and hypertension who hospitalized in our hospital from March 2009 to April 2010 were studied. Results 91.74% of patients was treated with antihypertensive medications, and 21.21%, 22.59%, 19.56%, 28.37% of patients received 1, 2, 3, ≥4 antihypertensive drugs, respectively. 42.4% of patients with CKD and hypertension could be controlled up to the standard,and the mean blood pressure was (137.86±20.75)/(76.30±11.35) mm Hg. There was significant difference among stage 1 plus 2, 3, 4 plus 5 (non-dialysis), 5 (dialysis) kidney diseases, with the hypertension control rate being 50.8%, 46.7%, 42.0%, 33.5%, respectively. The hypertension control rate of non-dialysis patients was significantly higher than that of dialysis (44.9% vs 33.5%, P<0.05). There was no significant difference between blood dialysis group and peritoneal dialysis group (32.3% vs 38.7%, P>0.05). Multivariate Logistic regression analysis showed that female (OR=1.787, 95%CI 1.045-3.056)and ACEI application(OR=4.378, 95%CI 1.830-10.472) were positively associated with hypertension control. Whereas, diabetes (OR=0.415, 95%CI 0.188-0.919) and pulse pressure (OR=0.847, 95%CI 0.811-0.885) were associated with inadequate blood pressure control. Conclusions Despite almost universal hypertension treatment is used in patients with CKD and high blood pressure, the hypertension control rate is still suboptimal. Female and ACEI are positively associated with adequate hypertension control, whereas diabetes and pulse pressure are negatively associated with the standard.
  • LI Zhong-xin;CHEN Xiang-dong;MENG Juan;ZHANG Xin;PENG Li-ren.
    2011, 27(8): 581-584.
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    Objective To determine the correlation between thrombomodulin and atherosclerosis in chronic kidney diseases (CKD) patients. Methods A total of 96 CKD patients in our hospital were enrolled in the study, including 32 maintenance hemodialysis (MHD) patients and 64 non-hemodialysis CKD patients with stage 2 to 5 (non-HD) and 30 age- and gender-matched healthy volunteers were used as control. Intima-media thickness (IMT) and atherosclerotic plaques of the extracranial common carotid artery were detected by high-resolution B-mode ultrasonography. Blood level of thrombomodulin was measured using ELISA, and creatinine, triglycerides, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol were measured routinely as well. Correlation analysis of thrombomodulin with other parameters was performed. Results The thrombomodulin level was significantly higher in CKD patients as compared to healthy controls [(12.15±3.04) mg/L vs (3.12±0.23) mg/L, P<0.05], and also significantly higher in MHD patients as compared to non-HD patients [(16.89±3.35) mg/L vs (9.78±2.49) mg/L, P<0.05]. The atherosclerotic plaques incidence and IMT value of carotid artery increased significantly in CKD patients compared with healthy volunteers. Thrombomodulin was positively correlated with IMT in CKD patients (r=0.335, P<0.01). Multiple stepwise regression analysis showed that thrombomodulin, Tm (OR=1.13, 95%CI 1.010-1.121), SBP (OR=1.09, 95%CI 1.009-1.114), CRP (OR=1.22, 95%CI 1.216-2.007), and Scr were independent risk factors of IMT. Conclusion Thrombomodulin is correlated with carotid atherosclerosis in CKD patients and may be used as a marker to evaluate the endothelial damage.
  • 基础研究

  • TANG Qi*;MEI Chang-lin;ZHANG Li-ming;LU Yi-zhou;WU Bi-bo;LIU Jian-guo;SU Ding-feng;HU Hui-min.
    2011, 27(8): 585-590.
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    Objective To determine the effects of trimetazidine (TMZ) on pathology and energy metabolism of myocardium in chronic renal failure (CRF) rats. Methods CRF models were built in Sprague-Dawley (SD) rats with 5/6 subtotal nephrectomy, and animals were randomyly divided into sham group, control group and three groups treated with different doses of TMZ (3 mg/kg, 6 mg/kg or 9 mg/kg). TMZ was intragastrically administrated to CRF rats for 17 weeks, while physiological saline was used as control. Transthoracic echocardiography was performed and myocardial morphosis was observed. Left ventricular weight/body weight (LVW/BW) and heart weight/body weight (HW/BW) were measured, and heart rate, and mean arterial pressure (MAP) were detected at the end of the study, while several parameters were detected, including urea nitrogen(BUN), creatinine (Scr), triphosaden (ATP), adenosine diphosphate (ADP), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Results (1)Left ventricle end-systolic dimensions, anterior wall end-diastolic and end-systolic thicknesses, and posterior wall end-diastolic thickness were significantly lower in rats treated with either medium dose or high dose of TMZ, as compared with control group (P<0.05). (2)LVW/BW and HW/BW in rats treated with either medium dose or high dose of TMZ were significantly lower than those in control group (P<0.05). (3)Various pathological changes were observed in control group, such as irregular arrangement and hypertrophy of the cardiomyocytes, myocardial fibrosis, mitochondrial swelling, focal muscle fiber dissolution, etc. However, all these pathological changes were apparently ameliorated in TMZ-treated groups, while the beneficial effects of TMZ therapy were dose-dependent. (4)No difference was observed in heart rate among all the groups. Although no difference existed in all the CRF rats, concerning on the systolic/diastolic blood pressure and mean arterial pressure(P>0.05), these parameters were elevated in CRF rats, as compared with sham-operated group (P<0.01). (5)ATP and ADP in TMZ-treated rats were significantly higher as compared with control (P<0.05), moreover, medium dose and high dose of TMZ were superior to low dose (P<0.05). (6)SOD was significantly increased in TMZ-treated rats (P<0.05), while IL-6, TNF-α and MDA were significantly decreased in medium dose and high dose of TMZ, as compared with control (P<0.05). Conclusion TMZ may prevent myocardial fibrosis and left ventricular hypertrophy in chronic renal failure via ameliorating myocardial energy metabolism and alleviating inflammatory reaction and oxidative stress.
  • TAN Min*;CHEN Yi-pu;TANG Gong-yao;RUI Hong-liang.
    2011, 27(8): 591-596.
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    Objective To investigate the effects of adiponectin on angiotensinⅡ-induced extracellular matrix production of mesangial cells (MCs) and its possible signaling pathway. Methods RT-PCR and indirect immunofluorescence examination were performed to detect the adiponectin receptors in MCs. Quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) were used to observe the effects of adiponectin on angiotensinⅡ-induced transforming growth factor β1 (TGF-β1) and fibronectin production of MCs. Western blotting was used to measure the ratio of p-AMPK to total AMPK. Results (1)Adiponectin receptors 1 and 2 were found in MCs. (2)The up-regulated mRNA and protein expression of TGF-?茁1 and fibronectin in MCs induced with 10-7 mol/L angiotensinⅡ (AngⅡ) was significantly inhibited by 10 mg/L adiponectin (P<0.05). (3)The p-AMPK/AMPK ratio was significantly increased after incubation with adiponectin for 15 min and 30 min (vs 0 min, P<0.05), which suggested that adiponectin could activate the AMPK signaling pathway in MCs. The activation of AMPK signaling pathway was blocked by 40 ?滋mol/L compound C, a specific inhibitor of AMPK. (4)The inhibitory effects of adiponectin on angiotensinⅡ-upregulated TGF-β1 and fibronectin expression in MCs were significantly relieved by 40 ?滋mol/L compound C (P<0.05). Conclusions There are adiponectin receptors 1 and 2 in MCs. Adiponectin has inhibitory effects on the angiotensinⅡ-upregulated TGF-β1 and fibronectin expression in MCs. AMPK signaling pathway may play an important role in the effects of adiponectin above-mentioned.
  • DANG Jian-zhong;JIA Ru-han;TU Ya-fang;XIAO Sheng-shun;DING Guo-hua.
    2011, 27(8): 597-601.
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    Objective To investigate the renoprotective effect of erythropoietin (EPO) in streptozotocin-induced diabetic rats and to explore the possible mechanism. Methods The SD rats were randomly divided into there groups: normal control rats, diabetic, diabetic treated with EPO(NC, DM, DE groups). The rats were sacrificed after 8 weeks treatment. Renal morphology was observed by light microscopy. The expression of erythropoietin receptor (EPOR) in kidney was detected by immunofluorescence and Western blotting. The expression of p47phox, transforming growth factor (TGF) β1 and fibronectin (FN) protein in kidney was detected by immunohistochemistry and Western blotting. The activity of antioxidants including total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in kidney were also measured. Results EPO treatment notably attenuated renal pathologic and functional changes. The expression of EPOR was found in kidney, but there was no difference among groups (P>0.05). Compared with normal rats, diabetic rats showed an elevated expression of p47phox, TGF-β1, FN proteins and MDA levels in kidney as well as reduced activities of SOD, GSH-Px and T-AOC (all P<0.01). Compared with diabetic rats, EPO could decrease the protein expression of p47phox,TGF-β1 and FN in kidney (all P<0.05). Meanwhile, elevated MDA level in the kidney was decreased as well as decreased SOD, GSH-Px, T-AOC activities were significantly remitted in DE group (all P<0.01). Conclusion EPO can ameliorate renal damage via the inhibition of oxidative stress and TGF-β1 and FN protein expression in streptozotocin-induced diabetic rats.
  • ZHANG Chun-yan*;YANG Ye;CHEN Yan;LI Hong;ZHAO Chun-ling.
    2011, 27(8): 602-605.
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    Objective To obtain two-dimensional gel electrophoresis maps of the renal tissue proteins of normal and chronic intermittent hypoxia (CIH) rats for identifying the diferentially expressed proteins in the CIH rats. Methods CIH rat models were established, and the proteins in the renal tissue underwent two-dimensiona1 gel electrophoresis with immobiline pH gradient isoeleclric focusing as the first dimension and vertica1 SDS-PAGE as the second dimension. Analysis of 2-DE maps was used to determine differential expression of proteins between the two groups by ImageMaster 2D Platinum 5.0, and four protein spots expressed differently were picked up for further identification by MALDI-TOF-MS. Results Matched and compared with those of control group, 112 protein spots were determined with differently expressive levels in CIH group. By MALDI-TOF-MS, three protein spots of them were identified as ATP synthase delta subunit of mitochondrial precursor, catechol O-methyltransferase, apurinic/apyrimidinic endonudease. Conclusions There is obvious difference in expressive proteomes in renal tissue between normal and chronic intermittent hypoxia rats. The functions of those identified proteins are involved in cellular energy metabolism, apoptosis, signal transduction, anti-cell injury and hormone metabolism, so that proteomics can serve as a new approach in the study of obstructive sleep apnea-hypopnea syndrome to discover new therapeutic targets.
  • 新技术与方法

  • YU Lei;ZHOU Xu-jie;LV Ji-cheng;DING Jia-xiang;ZHU Li;ZHANG Hong.
    2011, 27(8): 606-610.
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    Objective To establish heterologous expression system of Na+-glucose cotransporter 2 (SGLT2) gene. Methods Human SGLT2 cDNA from normal kidney, generated by RT-PCR, was subcloned into PEXL-GFP vector and transfected into HEK293 cells. After 24 hours of incubation, the expression of SGLT2-GFP fusion protein was detected by Western blotting and laser confocal microscopy. Transport activity of SGLT2-GFP fusion proteins in cultured human HEK293 cells was evaluated with the uptake test of glucose analogue. Results SGLT2-GFP fusion protein was expressed in cultured human HEK293 cells. Furthermore, confocal microscopy using green fluorescent protein (GFP) revealed a punctate membrane pattern of SGLT2. Glucose analogue uptake increased in HEK293 cells transfected with SGLT2-GFP at least by 3.5 folds compared with HEK293 cells transfected with GFP vector only (P<0.01). Conclusion Heterologous expression of SGLT2 gene in HEK293 cells is successfully established, which provides valuable approach for the functional and pathological study of SGLT2 gene.