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    临床研究

  • FAN Xiao-hong;CAI Jian-fang;GAO Bi-xia;MOU Li-jun;LI Jin-hong;LIU Xue-jiao;WU Jun-xue;MENG Qing-yan;WANG Hai-yun;LIU Li-li;LI Hang;LI Xue-mei;LI Xue-wang
    2010, 26(11): 807-811.
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    Objective To investigate the discriminator value of Han Chinese first morning urine albumin creatinine ratio (ACR) for determining the microalbuminuria. Methods A total of 1056 participants (494 males and 562 females) were selected from epidemiologic study of the metabolic syndrome and chronic kidney disease in Pinggu district, Beijing. Eight-hour overnight urinary albumin excretion (UAE) was regarded as the gold standard for defining the albuminuria, and the ROC curve analysis was used to determine the ACR discriminator value for microalbuminuria. Results (1)Microalbuminuria was found in 12.5% of participants, macroalbuminuria in 1.7%. (2)The ACR discriminator value for microalbuminuria by ROC curve analysis was 1.95 g/mol(sensitivity 97.6% and specitivity 88.6%) for men, 3.62 g/mol(sensitivity 83.8% and specitivity 89.1%) for women, 2.78 g/mol (sensitivity 88.7% and specitivity 85.9%) for overall. The upper boundary of microalbuminuria by ROC curve analysis was 22.59 g/mol (sensitivity 100.0% and specitivity 98.8%) . (3)The inter-rater agreement of the result in this study showed that sensitivity was 91.3% and specitivity was 88.2%, positive likelihood ratio was 7.56 and negative likelihood ratio was 0.10, positive predictive value was 56.9% and negative predictive value was 98.4%. Conclusions The ACR discriminator value for determining microalbuminuria is obviously higher in women than that in men, and is higher than recommendation of international guidelines. The result by ROC curve analysis has better sensitivity and specitivity.
  • SUN Yan-bei;LIU Hong;WU Ming;WANG Yan-li;WU Jing-zhi;SUN Wei-xin;YANG Jin-fang;LIU Bi-cheng
    2010, 26(11): 812-817.
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    Objective To survey the epidemiology of chronic kidney disease (CKD) among elderly people in two districts of Jiangsu province, China. Methods A total of 1404 residents aged 60 years or older in Huaian and Suzhou city in Jiangsu province were randomly recruited from the community population. All the people were screened for albuminuria (increased morning spot urine albumin-to-creatinine ratio, UACR) and reduced renal function (decreased eGFR by simplified MDRD equation). Urinary creatinine and albumin, serum creatinine, uric acid, cholesterol, triglyceride, low density lipoprotein-cholesterol, high-density lipoprotein cholesterol and fasting blood glucose (FBG) were investigated. CKD was defined as reduced renal function [eGFR<60 ml&#8226;min-1&#8226;(1.73 m2)-1] and/or albuminuria (UACR ≥30 mg/g). The associations between healthy characteristics and indicators of kidney damage were examined. Results A total of 1316 (93.7%) elderly people completed the study. The prevalence of CKD was 32.3% and the awareness rate was only 9.6%. Albuminuria and reduced renal function were found in 30.2% and 3.2% of subjects respectively. The Logistic regression model showed that age, gender, hypertension, hypercholesterinemia and hyperuricaemia were independently associated with CKD. Systolic blood pressure (SBP) of 140-159 mm Hg exhibited a lower adjusted OR value (0.675) for CKD, while SBP of 160-179 mm Hg and of at least 180 mm Hg exhibited higher adjusted OR values (1.330 and 1.146). Similarly, FBG of 5.6-6.9 mmol/L exhibited a lower adjusted OR value for CKD as compared to FBG of at least 7.0 mmol/L (0.628 vs 1.941). Conclusions The prevalence of CKD in elderly people of Jiangsu province is quite high. Age, gender, hypertension, hypercholesterinemia and hyperuricaemia are independent risk factors for the development of CKD.
  • LI Yi;ZHU Ming-li;QIAN Jia-qi;XIA Qiang;WANG Si-yue;LU Ren-hua;CHE Miao-lin;DAI Hui-li;WU Qing-wei;NI Zhao-hui;YAN Yu-cheng
    2010, 26(11): 818-823.
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    Objective To investigate the value of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding proteins (L-FABP) in early diagnosis of acute kidney injury (AKI) after liver transplantation. Methods During 2007-2008, 25 liver transplant recipients were recruited. Blood and urinary samples were collected before operation and at 2, 4, 6, 12, 24, 48, 72, 120 h after portal vein opening, and used to determine serum creatinine (Scr), as well as urinary NGAL and L-FABP, which were normalized to urinary creatinine. According to the Acute Kidney Injury Network(AKIN) criteria of AKI, all the patients were divided into AKI and non-AKI groups. Standard statistics were used along with ROC analysis to evaluate the diagnose value of selected markers. Results There were no significant differences in clinical parameters between non-AKI (n=14) and AKI (n=11) groups. Both groups had a transient rise in Scr 2-12 hours after surgery, but the rise lasted longer in AKI patients (2-24 hours). While urinary L-FABP rose transiently in both groups 2-120 hours following surgery, urinary NGAL was only slightly elevated at 2 h in the non-AKI group, but rose and stayed high from 2 to 6 h in the AKI group. ROC analysis revealed that NGAL (cut-off 43.02, 26.97 and 17.19 ng/mgCr, AUC 0.766, 0.773 and 0.773 at 2, 4 and 6 h, respectively) was better than L-FABP (cut-off 3451.75 ng/mgCr, AUC 0.760 at 4 h). Conclusion Urinary NGAL appears to be a sensitive and specific marker of AKI in liver transplant recipients, but these data need to be validated in larger prospective studies.
  • JI Jun;DING Xiao-qiang;FANG Yi;SHAN Yi-sheng;TENG Jie;FU Chen-sheng;YUAN Min;CHEN Li-ming
    2010, 26(11): 824-828.
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    Objective To study the efficacy of low-dose daytime ambulatory peritoneal dialysis (DAPD) and low-dose CAPD in diabetic end-stage renal disease (ESRD) patients with better residual renal function (RRF). Methods Forty stable diabetic ESRD patients with better RRF (rGFR≥5 ml/min and urine volume ≥750 ml/d) were enrolled. They were randomly divided into two groups: low-dose DAPD group (n=20) and low-dose CAPD group (n=20). DAPD group received three 1.5 L to 2 L daily exchanges with a nocturnal empty belly, dwelling for 3 to 4 hours. CAPD group received three 1.5 L to 2 L daily exchange or four 1.5 L daily exchange regimens and dwelled during the night. At the beginning of the study and 6 months later, total weekly Kt/V and Ccr (peritoneal+renal), rGFR were calculated. Meanwhile 24-hour urinary protein, serum albumin(Alb), hemoglobin(Hb), fasting plasma glucose, glycosylated hemoglobin and insulin dosage were measured. Nutritional status was assessed by SGA. Results Thirty-five patients fulfilled the study. There were no significant differences between two groups in age, gender, BMI, PD time, D/Pcr, etc. At the end of the 6th month, the insulin dose[(33.6±10.9) U/d] and 24-hour dialysate protein [(11.13±4.95) g] in CAPD group were significantly higher as compared to DAPD group[(20.6±6.2) U/d, P<0.05 and (5.66±2.88) g, P<0.01 respectively]. Alb in CAPD group [(29.7±4.2) g/L] was significantly lower than that in DAPD group [(36.5±3.9) g/L, P<0.05]. While the net ultrafiltration [(554±187) ml vs (309±177) ml], 24-hour urine volume [(1090±361) ml vs (750±258) ml] and rGFR [(8.21±2.40) ml/min vs (4.88±2.11) ml/min] in DAPD group were all significantly higher than those in CAPD group (all P<0.05). Conclusion For the diabetic ESRD patients with better RRF, the low-dose DAPD regimen is more effective to control plasma glucose, improve nutritional status and protect RRF than the low-dose CAPD.
  • GUO Bao-chun;JIANG Xin-yan;ZHANG Xin-zhou;HE Xiao-lei;WANG Xiang-yang;ZHENG Xue;LI Yong-quan;LI Xiong-gen
    2010, 26(11): 829-833.
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    Objective To study the relationship between cardiovascular diseases (CVD) and 24-h peritoneal protein losses(PPL) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods One hundred and seventy-eight CAPD patients in our department were enrolled in this study. Their 24-h PPL was measured and other clinical data were recorded at the beginning. Meanwhile, Doppler ultrasound examination was performed. They were then followed-up prospectively for the development of CVD. Results The average of 24-h PPL was (5.0±1.8) g. Patients with diabetic status or preexisting CVD or carotid arteries arteriosclerosis had higher 24-h PPL than those without (t=2.082, P=0.039; t=2.601, P=0.010; t=2.217, P=0.029). 24-h PPL was positively correlated with left ventricular end-diastolic diameter (LVDd), interventricular septal thickness (IVSTd), posterior wall diameter of left ventricle at end-diastolic (LVPWd) and left ventricular mass index(LVMI) (r=0.222, P=0.040; r=0.217, P=0.043; r=0.339, P=0.002; r=0.305, P=0.007). It was negatively correlated with ejection fraction of left ventricle (r=0.221, P=0.040). One hundred and fourteen CAPD patients were prospectively followed-up for at least twelve months. Patients developing CVD were 40.4% and 19.3% for high and low PPL groups respectively(χ2=6.035, P=0.014). In the multivariable logistic regression analysis, the 24-h PPL was one of the independent factors for developing CVD. Conclusions There is a significant and independent relationship between 24-h PPL and new cardiovascular events. 24-h PPL may be an important predictor of cardiovascular disease.
  • 基础研究

  • LIU Jiao;DING Guo-hua;HU Feng-qi;LIANG Wei
    2010, 26(11): 834-839.
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    Objective To determine the surfactant protein A (SP-A) subtype distribution and expression in human renal tissue and cultured human renal tubular epithelial cells(HK-2), and to explore the influence of Lipopolysaccharide (LPS) on the expression of SP-A subtypes mRNA and SP-A protein. Methods Immunohistochemical staining was performed using SP-A polyclonal antibodies. RT-PCR was performed with mRNA from HK-2 cells and normal human kidney. Restriction fragment length polymorphism(RFLP) and sequencing were used to evaluate the subtypes of SP-A. The relative content of SP-A mRNA in human kidney and human lung was compared by real-time PCR. Western blotting analysis for SP-A was performed on protein from renal tissue and cultured HK-2 cells. SP-A protein in human urine and culture supernatant of HK-2 cells was measured by enzyme-linked immunosorbent assay (ELISA) and Western blotting respectively. HK-2 cells were treated with LPS at various concentrations(0,0.1,1,2,5,10 mg/L) for 8 h and at 5 mg/L for various time points (0,2,4,8,16,24 h). Expression of SP-A mRNA and protein was analyzed by RT-PCR and Western blotting. Results SP-A was localized in renal tubular epithelial cells of both proximal and distal convoluted tubules. SP-A1, SP-A2 mRNA and protein could be detected in normal HK-2 cells and human kidney. The significant secretion of SP-A[urine: (106.614±72.772) nmol/L, n=30; culture supernatant: (85.533±58.622) nmol/L, n=10] was shown. The levels of SP-A1, SP-A2 mRNA and SP-A protein in HK-2 cells were significantly decreased after treatment with LPS. Conclusions Human renal tubular epithelial cells can express both SP-A1 and SP-A2 genes which may play an important role in inflammation modulation of kidney.
  • WAN Jian-xin;YANG Xia;CUI Jiong;ZOU Zhen-huan
    2010, 26(11): 840-844.
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    Objective To investigate the effects of erythropoietin (EPO) on the number and function of peripheral blood endothelial progenitor cells (EPCs) from rats with chronic renal failure (CRF). Methods The model of chronic renal failure was established by a two-stage 5/6 nephrectomy procedure in rats. Experimental rats were randomly divided into four groups(n=7, respectively): sham operation group, CRF group, CRF rats treated with 30 U/kg EPO (low-dosage group) and with 50 U/kg EPO (high-dosage group). CRF rats were given EPO by hypodermic injection for 6 weeks, then EPCs were isolated by density gradient centrifugation from peripheral blood mononuclear cells. The ability of cell proliferation, adhesion and vasculogenesis in vitro was further observed. Results Compared to sham operation group, the ability of cell proliferation, adhesion and vasculogenesis in vitro in CRF rats was remarkably decreased (P<0.05, respectively). Such ability was promoted significantly in dose-dependent manner by EPO treatment (P<0.05, respectively). Conclusion EPO can improve the number and ability of endothelial progenitor cells from rats with chronic renal failure.
  • CHEN Ying;ZHANG Ai-hua;HUANG Song-ming;PAN Xiao-qin;FEI Li;GUO Mei;CHEN Rong-hua
    2010, 26(11): 845-850.
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    Objective To detect the signaling pathways involved in aldosterone (ALDO)-induced mesangial cell (MC) proliferation. Methods The incorporation of 3H-thymidine (3H-TdR) and cell count were used as the measure of mesangial cell (MC) proliferation. Reactive oxygen species (ROS) production was determined by DCFDA fluorescence. Epidermal growth factor receptor (EGFR) activation was assayed by Western blotting. Results ALDO induced MC proliferation. When incubation with 100 nmol/L ALDO for 24 h, the 3H-TdR incorporation and cell number increased by 2.63- and 2.15-fold, respectively. Mineralocorticoid receptor (MR) antagonist EPLE almost completely blocked ALDO-induced MC proliferation (P<0.01), however, glucocorticoid receptor (GR) antagonist RU-486 had no effect on MC proliferation. ALDO increased intracellular ROS production in cultured human MCs. When incubation with ALDO (100 nmol/L) for 60 min, ROS production increased by 2.14-fold. ALDO-induced ROS generation was completely blocked by EPLE as well as mitochondrial complex I inhibitor rotenone (P<0.01), NADPH oxidase inhibitors diphenyleneiodonium sulfate (DPI) and apocynin inhibited ALDO-induced ROS production by 30% to 35% (P<0.05). In contrast, inhibitors of other oxidant-producing enzymes, including allopurinol, indomethacin, nordihydroguiaretic acid, ketoconazole and G-nitro-L-arginine methyl ester (L-NAME) had no effect on ALDO-induced ROS production. Antioxidant N-acetyl-L-cysteine (NAC) and ROT inhibited ALDO-induced MC proliferation by 75% to 80%, whereas the inhibition of NADPH oxidase inhibitor apocynin and DPI on ALDO-induced MC proliferation was 25% to 30%. ALDO induced EGFR transactivation. When incubation with 100 nmol/L ALDO for 60 min, EGFR phosphorylation was increased by 4.95-fold, which was completely inhibited by EPLE and antioxidant NAC (P<0.01). NAC and EGFR antagonist AG1478 significantly blocked ALDO-induced MC proliferation (P<0.01). Conclusions ALDO-induced MC proliferation is mediated by ROS-dependent EGFR transactivation. ALDO-stimulated ROS is mainly generated by mitochondria.
  • 新技术与方法

  • LIU Shao-jun*;LIU Ling;LI Ming-xin;WANG Yan;DING Gui-fu;XUE Jun;GU Yong;HAO Chuan-ming;LIN Shan-tan
    2010, 26(11): 851-856.
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    Objective To observe the growing shape and function of Madin-Darby canine kidney (MDCK) cells implanted on the polysilicon nanopore membrane by micro-electro-mechanical system (MEMS). Methods The polysilicon nanomembrane was made by silicon film processed via whirling photoresist, wet etching, electroplating and so on, and then it was coated by extracellular matrix and implanted with MDCK cells. The cell growth shape and function was observed or examined by scanning electron microscope or MTT test and Trypan Blue staining. Results The nanomembrane with regular slit pores was successfully fabricated. Extracellular matrix-coated nanomembrane, especially for collagen Ⅳ coating, was more suitable for MDCK cells to adhere and proliferate without membrane injury. The polysilicon nanomembrane coated with extracellular matrix did not induce the cell death and also not stimulate cells releasing the cytokines such as interleukin-1β(IL-1β) and tumor necrosis factor α(TNF-α). Under scanning electron microscope, MDCK cells formed a flat single-cell fusion with tight junction on the surface of polysilicon nanomembrane and there was a large number of microvillus on the top of cells. Conclusion The collagen-coated polysilicon nanomembrane made by MEMS techniques, with no cytotoxicity and good biocompatibility, is valuable to frame the artificial glomerular filtration membrane