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CCN family, a group of six extracellular matrix-associated proteins, plays an important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the development of human lung fibrosis. However, whether WISP3 involved in the activation and proliferation of renal fibroblast, and ultimately inhibited fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F cells induced by transforming growth (TGF-ß1), which was further confirmed in a rat renal fibrosis induced by unilateral ureteral obstruction (UUO). In the present study, we aimed to investigate the roles of WISP3 in NRK-49F fibroblast-myofibroblast transdifferentiation, and the underlying mechanism. Results showed that after TGF-ß1 treatment, significant increased cell proliferation, and up-regulated expressions of TGF-ß1, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), vimentin, as well as increased concentrations of collagen types I (COL I), collagen types III (COL III) and hydroxyproline in cell culture supernatant were observed, demonstrating a successful establishment of fibroblast-myofibroblast transdifferentiation of NRK-49F cells. Besides, siRNA-WISP3 remarkably promoted the fibrogenesis of NRK-49F cells with or without TGF-ß1 treatment, and increased mRNA levels of Axin, demonstrating that activating WNT signaling pathway was the underlying mechanism. However, lentivirus-mediated WISP3 overexpression exerted an opposite effect, protecting NRK-49F cells from transdifferentiation, and decreasing mRNA levels of Axin. In conclusion, the WISP3 played an anti-fibrotic role in NRK-49F cells, and WNT signaling pathway was the potential mechanism. WISP3 was an anti-fibrotic factor in fibroblast-myofibroblast transdifferentiation, and may be used as a possible target for prevention and treatment of human renal fibrosis.
Asunto(s)
Proteínas CCN de Señalización Intercelular/metabolismo , Transdiferenciación Celular , Riñón/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Transdiferenciación Celular/efectos de los fármacos , Fibrosis , Humanos , Riñón/patología , Miofibroblastos/efectos de los fármacos , Ratas , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología , Proteínas Wnt/metabolismoRESUMEN
Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3%) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2%and 47.5%, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2% to 73.6% (P<0.001), the target rate of Hb increased from 47.5% to 56.1% (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.
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The treatment of diabetic nephropathy (DN) currently extent to control the occurrence and development of it and delay renal failure on a certain stage.However,the effect is not satisfactory.Some traditional hypoglycemic,antihypertensive,lipid and anticoagulant drugs in DN patients with renal protective effect.And some have been in clinical use of drugs such as vitamin D,aldose reductase inhibitors,tripterygium wilfordii glycoside has proved to have the effect of the slow progress in DN,could be used more widely.For new drugs,such as renin inhibitors,phosphodiesterase inhibitors and methyl bartholomew sauron,while partialy was confirmed in a role in the treatment of DN,but before the clinical promotion,its effectiveness and safety still need further study to verify.
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Objective To study the effects of low calcium dialysate on bone mineral density (BMD) in old patients with low turnover renal osteodystrophy under maintenance hemodialysis.Methods Totally 72 elderly patients aged≥ 60 years under MHD for 6 months or more with parathyroid hormone(iPTH)<100 ng/L were selected and randomly divided into treatment group(n=36,calcium 1.25 mmol/L in dialysate)and a control group(n =36,calcium 1.5 mmol/L in dialysate),for 12 months of treatment.The changes of albumin-corrected calcium and phosphorus,calciumphosphorus product,iPTH level,bone mineral density,and other indicators as well as related adverse events were observed before and 12 months after the study.Results There was no statistically significant difference in general conditions and the correlated laboratory examinations between the two groups before and after treatment (P > 0.05).After dialytic treatments with dialysate containing calcium 1.25 mmol/L for 12 months,the therapy group versus pre-therapy and control group showed statistically significant decrease in parameters of mean arterial pressure(MAP) [(88.6 ± 9.2) vs.(92.6±10.4)and(93.7±8.8)mmHg],serum calcium[(2.4±0.1)vs.(2.6±0.3)and(2.6±0.2)mmol/L,t =5.061,5.074],phosphorus[(2.0±0.2)vs.(2.1 ±0.2)and(2.1±0.3)mmol/L,t=2.276,2.271],calcium-phosphorus product[(4.7 ± 0.5) vs.(5.3 ± 0.6) and (5.4 ± 0.7) mmol2 / L2,t =4.682,4.627](all P<0.05),and showed statistically significant increase in parameters of iPTH levels[(132.6 ±37.8) vs.(71.3 ± 11.48) and (69.7 ± 16.0) ng/L;t value 8.824 and 9.048,respectively],bone mineral density values(Lumbar:0.8±0.9 vs.-1.2±1.1 and-1.2±1.1;t value 2.170 and 2.170,respectivly.Femoral neck:-0.8± 1.0 vs.1.3±1.2 and-1.3±1.3;t value 2.258 and 2.243,respectively) (all P<0.05).In the control group after 12 months of treatment with calcium 1.5mmol/L dialysate,there was no significant difference in related parameters (P> 0.05).There was no significant difference in the adverse reactions between study and control groups (P > 0.05).Conclusions The low calcium dialysate(calcium 1.25 mmol/L)used in elderly patients with iPTH<100 ng/L under MHD can effectively improve the excessive depression of parathyroid function and the decreased BMD,and better control the albumin corrected calcium,phosphorus,calcium-phosphorus product level,and has a good security.
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Objective To study the short-term clinical efficacy and its possible mechanism of refractory hypertension(RH) treated by continuous veno-venous hemofiltration (CVVH) in maintenance hemodialysis (MHD) patients. Methods Thirty-four MHD patients with RH treated with CVVH enrolled in the treatment group,all these patients were treatment of 2 -3 times,each time 8 - 10 hours. Thirty MHD patients with wellcontroled blood pressure were recruited as control. Changes of blood pressure, dry weight, plasma levels of parathyroid hormone (PTH), renin ( RA), angiotensin Ⅰ , Ⅱ ( AT Ⅰ , AT Ⅱ ), aldosterone ( Ald ) were observed before and after hemodialysis. Results In the treatment group,compared with pre-treatment, the blood pressure decreased significantly with an effective rate of 64.7% and efficient rate of 100. 0%. Before treatment, plasma RA was ([1.10 ±0.25] μg/(L · h)and [0:78 ±0.26] μg/(L · h),AT Ⅰ was [0.89 ±0.21] μg/L and [ 0. 52 ± 0. 14 ] μg/L, AT Ⅱ was [ 177.68 ± 89.46 ] ng/L and [ 89. 25 ± 12. 84 ] ng/L, Ald was [72. 06 ± 11.47 ]ng/L and [ 48.92 ± 8. 65 ] ng/L, PTH was [ 306. 81 ± 69. 37 ] ng/L and [ 248.76 ± 134. 62 ] ng/L in the treatment and control group respectively. All the measurements in the treatment group were significantly higher than those in the control group (P < 0. 05 ). In the treatment group, compared to pre-treatment, plasma RA significantly decreased ( [ 1.10 ± 0. 25 ]μg/ ( L · h) vs [ 0. 76 ± 0. 17 ] μg/( L · h ), as well as AT Ⅰ ( [ 0. 89 ±0.21]μg/L vs [0.50 ±0.12] μg/L),ATⅡ([177.68±89.46]ng/L vs [ 87.13±14.22] ng/L),Ald ([72.06±11.47]ng/Lvs [ 46. 01± 9. 86 ] ng/L ) and PTH ( [ 306. 81 ±69.37]ng/L vs [ 186.53 ±32.93 ] ng/L) ( P < 0. 05 ). However, there was no significant changes in the above mentioned measurements between before and after hemodialysis in the control group (P > 0. 05). Conclusion CVVH may be an effective methods in the treatment of MHD patients with RH, and its antihypertensive mechanisms may be that CVVH can effectively remove the excess water in the body, and reduce plasma RA, AT Ⅰ , AT Ⅱ ,Ald and PTH levels.
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Objective To investigate disorders in calcium and phosphorus metabolism and abnormity in parathyroid function and their related factors in maintenance hemodialysis(MHD)patients.Methods We collected serum Hb,SCr,BUN,calcium,phosphorus,iPTH,high sensitivity C-reactive protein(hs-CRP),albumin and calculated albumin-corrected Ca and Kt/V from 198 patients with MHD in Jing'an District Central Hospital,Shanghai from Jan.2009 to Dec.2010.The calcium and phosphorus metabolism and parathyroid function were evaluated according to the guidelines of bone metabolism and controlling of bone disease in Kidney Disease Outcome Quality Initiative(KDOQI)recommended by National Kidney Foundation of the United States.198 patients were classified into the standard group(150-300 ng/L),lower than the standard group(<150 ng/L)and higher than the standard group(> 300 ng/L)according to serum iPTH levels.Results In the 198 cases,110 cases were normal in serum Ac-Ca(55.6%); 118 cases were normal in serum phosphorus (59.6%); 143 cases were normal in Ca × P(72.3%); 39 cases were normal in iPTH(19.7%).All four items up to the standard were 28 cases(14.1%)among 198 cases.However,132(66.7%)patients showed lower than 150 ng/L in serum iPTH.The average serum iPTH gradually decreased with age.The senior patients demonstrated the highest average serum Hs-CRP,the lowest average serum phosphorus and the lowest albumin.There were no statistical significance in sex,hemodialysis duration,diabetes,blood pressure,Hb,Bun,SCr,Ac-Ca and Kt/V among three groups.Conclusion The disorders in calcium and phosphorus metabolism and abnormity in parathyroid function is common in the MHD patients.We should pay attention to hypofunction of parathyroid gland in the patients with MHD,which may be related to aging,malnutrition and potential infection.These findings need further investigation.
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Objective To study the feature of bone metabolism in different phase of elder type 2 diabetic nephropathy (DN) patients.Methods One hundred and fifty elder type 2 DN patients (non-microalbuminuria group,microalbuminuria group,clinic proteinuria group,DN renal inadequacy group and DN uremia group,each group was 30 cases),60 elder non-DN patients in chronic renal failure (CRF) (non-DN renal inadequacy group and non-DN uremia group,each group was 30 cases) ,and 30 elder healthy people (control group) were selected to observe the changes of osteocalcin (OT),β -crosslaps,parathyroid hormone ( iPTH),alkaline phosphatase (AKP),serum calcium (Ca),serum phosphorus (P) and Ca × P.Results In non-microalbuminuria group,microalbuminuria group and clinic proteinuria group,OT and β -crosslaps levels were lower than those in control group,and the lowest in microalbuminunia group (P<0.01).In DN renal inadequacy group and DN uremia group,OT and β -crosslaps levels were higher than those in control group(P<0.01).In the phase of CRF,OT,β -crosslaps and iPTH had no statistic difference between DN patients and non-DN patients,but had linear correlation.Serum P level was higher in DN renal inadequacy group and DN uremia group than that in control group(P<0.01).Either DN or non-DN,serum P had more influence to Ca × P than serum Ca.Conclusions In the different phase of elder type 2 DNpatients,the effect of bone metabolism is different because of the different injury of renal function.Bone metabolism in the different phase has respective feature and mechanism,with low turnover in the first and high turnover in the end.
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Objective To investigate the efficiency and safety as well as the effect of chronic intravenous iron supplementation on the improvement of anemia in the patients with maintain hemodialysis (MHD). Methods Fifty-six patients with MHD were involved in the six-month, controlled trail and randomly divided into two groups: intravenous iron group (IV group) and oral iron group (oral group). The patients of IV group (n=28) were intravenously pumped 100 mg iron dextran during each hemodialysis session for the total amount of 1000 mg,after that,100 mg iron dextrin each two weeks. Patients in the oral group took 525 mg ferrous sulfate a day during the first three months and received iron dextran on the above methods under stopping oral iron supplement during the second three months. The efficacy was assessed by determining the change of hemoglobin (Hb), hematocrit (Hct), serum ferritin (SF) and transferring saturation (TSAT). Results The levels of Hb, Hct, SF, TSAT were increasing in the IV group after trail and there were evidently difference in those markers in the first three months, compared to the oral group, P