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Objective:To investigate the injury effect of hyperoxali acid on human arterial endothelial cells (HAECs) and its mechanism.Methods:HAECs were divided into intervention group and control group according to whether oxalic acid was used for intervention. The cells in the intervention group were stimulated with 30, 100, 200 and 300 μmol/L oxalic for different time. The effect of oxalic acid on the proliferation of HAECs was detected by MTT colorimetry. The change of cell cycle was analyzed by flow cytometry. The content of intracellular calcium was detected by fluorescence detection technology. The protein and mRNA expressions of cell cycle and anion transporter-related proteins were detected by Western blotting and fluorescence quantitative PCR. Besides, JAK2/STAT3 signaling pathway-related proteins were measured by Western blotting.Results:MTT colorimetry results showed that the intervention groups with high concentration of oxalic acid (100, 200, 300 μmol/L) could significantly inhibit the proliferation of HAECs, which was significantly different from the control group (all P<0.05). Fluorescence detection showed that the contents of intracellular calcium of HAECs in the intervention groups with high concentration of oxalic acid (100, 200, 300 μmol/L) were significantly higher than those in the control group after 48 hours ( P<0.05, P<0.001, P<0.001, respectively). Flow cytometry showed that the proportion of S phase of cells in the 200 μmol/L oxalic acid intervention group was significantly higher than that in the control group ( P<0.05). The results of Western blotting and PCR showed that the relative protein and mRNA expressions of anion transporter-related proteins slc26a1, slc26a5, slc26a11 in the intervention groups were higher than those in the control group (all P<0.05). Western blotting showed that the expression of p-JAK2 and p-STAT3 in the intervention groups after 24 hours were significantly higher than those in control group (all P<0.05). Conclusions:Hyperoxalic acid may enter HAECs through transporters slc26a1, slc26a5 and slc26a11 to inhibit cell proliferation and increase the intracellular calcium concentration. The mechanism may be through the activation of JAK2/STAT3 signaling pathway. Therefore, oxalic acid may be one of the uremic toxins leading to atherosclerosis.
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Objective:To explore the role and mechanism of C3a-C3a receptor (C3aR) in the progression of autosomal dominant polycystic kidney disease (ADPKD).Methods:Renal tissues of ADPKD patients and PKD1 knockout mice were collected. Then the expression of C3a-C3aR, Ki67 and F4/80 in renal tissues was observed. Macrophages were stimulated with lipopolysaccharide (LPS) and interleukin 4 respectively. The expression of C3aR, TNF-α, typing markers and related signal pathway proteins was detected in each group. PKD1 knockout mice were treated with C3aR inhibitor SB290157 (1 mg/kg). Renal pathology, cyst-related indicators and renal function were observed. Results:The expression of C3a and C3aR in ADPKD was up-regulated (both P<0.05); C3aR and F4/80 were co-located in the kidney of polycystic kidney disease (PKD) mice, indicating that C3aR was mainly expressed on membrane of macrophages. In vitro, the expression of C3aR was up-regulated in M1 macrophages ( P<0.05). After the stimulation of C3a, the expression of iNOS, TNF-α and IL-6 mRNA in M1 macrophages were up-regulated (all P<0.05), as well as the secretion of TNF-α, indicating that C3a not only affected the expression of inflammatory factors of M1 macrophages, but also affected the inflammatory microenvironment. In addition, C3a significantly activated Akt in M1 macrophages ( P<0.05). Compared with the control group, the treatment group showed a decrease in C3a-C3aR as well as serum BUN, Scr, cyst index, and two kidneys weight/body weight (2KW/BW) (all P<0.05), and ADPKD related pathway protein expression such as p-ERK and p-P65 was significantly down-regulated (all P<0.05). Conclusions:The increased C3a in polycystic kidney tissue causes infiltration and activation of macrophages through C3aR, and then promotes ADPKD progression. The mechanism may be mediated by Akt activation and increased TNF-α production. C3aR antagonist is a potential research direction in the treatment of ADPKD.
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Objective To screen the chronic kidney disease (CKD) patients among the high-risk groups in Jing'an district of Shanghai,and provide suggestions for the screening and analysis of CKD.Methods Retrospective analysis was used to analyze the disease status of high-risk groups of CKD who participated in community screening from July 2016 to November 2018.A total of 25 199 subjects underwent two laboratory examinations at intervals of more than 3 months.The CKD was diagnosed in high-risk groups according to the diagnostic criteria,and the patients with CKD were classified and stratified.The screening population was divided into groups according to gender,age and medical history to compare the difference in the detection rate of CKD.Results There were 788 CKD patients diagnosed previously in this screening population,and 3 713 CKD patients were confirmed by this district-level hospitals screening.Potential CKD patients were 4.71 times as many as previously known CKD patients.The CKD detection rate was 14.73％.The CKD detection rate of female high-risk group was higher than that of male (16.00％ vs 13.00％,x2=44.213,P ＜ 0.001).The CKD detection rate in the elderly group (≥65 years old) was higher than that in the non-elderly group (14.94％ vs 13.76％,x2=4.001,P=0.046).The CKD detection rate in high-risk group with hypertension,hyperuricemia and family history of chronic nephritis was significantly higher than those in the group without such diseases (all P ＜ 0.05).Conclusions The number of patients detected in high-risk groups of CKD is 4.71 times as much as previously known patients,indicating that it is very necessary to carry out CKD screening in community high-risk group.Women,elder,hypertension,hyperuricemia,and a family history of chronic nephritis are independent risk factors for patients at high risk of CKD.
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Objective@#To screen the chronic kidney disease (CKD) patients among the high-risk groups in Jing'an district of Shanghai, and provide suggestions for the screening and analysis of CKD.@*Methods@#Retrospective analysis was used to analyze the disease status of high-risk groups of CKD who participated in community screening from July 2016 to November 2018. A total of 25 199 subjects underwent two laboratory examinations at intervals of more than 3 months. The CKD was diagnosed in high-risk groups according to the diagnostic criteria, and the patients with CKD were classified and stratified. The screening population was divided into groups according to gender, age and medical history to compare the difference in the detection rate of CKD.@*Results@#There were 788 CKD patients diagnosed previously in this screening population, and 3 713 CKD patients were confirmed by this district-level hospitals screening. Potential CKD patients were 4.71 times as many as previously known CKD patients. The CKD detection rate was 14.73%. The CKD detection rate of female high-risk group was higher than that of male (16.00% vs 13.00%, χ2=44.213, P<0.001). The CKD detection rate in the elderly group (≥65 years old) was higher than that in the non-elderly group (14.94% vs 13.76%, χ2=4.001, P=0.046). The CKD detection rate in high-risk group with hypertension, hyperuricemia and family history of chronic nephritis was significantly higher than those in the group without such diseases (all P<0.05).@*Conclusions@#The number of patients detected in high-risk groups of CKD is 4.71 times as much as previously known patients, indicating that it is very necessary to carry out CKD screening in community high-risk group. Women, elder, hypertension, hyperuricemia, and a family history of chronic nephritis are independent risk factors for patients at high risk of CKD.
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Objective To screen Oxalobacter formigenes (OxF) from fresh feces of healthy adults,and study its effect on the the prevention of calcium oxalate kidney stones.Methods OxF was screened and cultured from fresh feces of healthy adults.The rat model of calcium oxalate stone was established by esophageal gavage of 0.8％ of ethylene glycol.Rats were divided into a control group and four groups of rats with ethylene glycol-induced calcium oxalate kidney stones according to random number table.Three groups were treated with 106 CFU,107 CFU,108 CFU viable OxF every day,respectively,for 4 weeks.The blood and 24-hour urine samples were collected to detect the serum creatinine,urea nitrogen,serum and urine calcium,phosphorus,magnesium and urine oxalate every week.At the end of the 4th week,the rats were sacrificed and the kidney tissues were stained with HE and Yasue.The deposition and content of calcium oxalate crystals were observed under a light microscope.Results The bacteria strain isolated from fresh feces of healthy adults was 100％ as same as the known ATCC35274 bacteria strain,which means the strain screened is OxF.Among the 5 groups,there were no significant differences in body weight,Scr,BUN,serum calcium,blood magnesium,blood phosphorus,urinary magnesium and urinary phosphorus.The 24-hour urinary calcium excretion in the model group was significantly lower than that of the control group (P ＜ 0.05).After intervention with OxF solution,the 24-hour urinary calcium excretion in the 108 CFU OxF group was significantly higher than that in the model group (P ＜ 0.05),while there was no significant difference between the other intervention groups and the model.The oxalic acid excretion of 106 CFU OxF group and 107 CFU OxF group was lower than that of the model,but the difference did not reach statistical significance (P＞ 0.05).The 24 h oxalic acid excretion in the 108 CFU OxF group was significantly lower than that of the model at the end of first week (P ＜ 0.05),and continued to decrease for the next 3 weeks.After 4 weeks of intervention,no crystal formation was observed in the control group under the deflection microscope,but a large amount of calcium oxalate crystals were formed in the renal cortex and renal medulla.The crystals were piled up and connected to each other.Yasue staining coincided with the calcium oxalate crystal in the same part of the kidneys.Compared with the model,there was no significant change in the score of calcium oxalate crystal in the kidneys of 106 CFU OxF group and 107 CFU OxF group,while the score of calcium oxalate crystal in the kidneys of 108 CFU OxF group was significantly lower (P ＜ 0.05).Conclusions OxF are successively screened from healthy adults.Daily administration of 108 CFU OxF can safely and effectively reduce the urinary oxalic acid excretion,prevent the formation of calcium oxalate crystals and inhibit the formation of stones in kidneys of rats.
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Objective To explore the causes of nocturnal hemodialysis (NHD) patient dropout and the risk factors for dropout.Methods We collected the clinical data of patients receiving NHD for more than 3 months,of whom 47 patients dropped out and 64 kept receiving NHD from Feb.2009 to Nov.2016 in Changzheng Hospital of Second Military Medical University.We investigated the general conditions;and we compared the differences of the blood parameters between the two groups when the patients received NHD for the first time and for the last time,including hemoglobin,platelet,albumin,ferritin,serum calcium,serum phosphorus and parathyroid hormone.We also analyzed the risk factors for NHD dropout or for death using Cox regression analysis model.Results Among 111 patients,47 patients had withdrawn from NHD,with their average time for NHD being (31.55±20.30) months,and the causes for dropout included death,transferring to other hospitals,turning to conventional hemodialysis (CHD),renal transplantation and others.Univariate Cox regression analysis showed that hypertensive nephropathy (P=0.007,HR=2.913,95％CI:1.348-6.293) and diabetic nephropathy (P=0.047,HR=2.401,95％CI:1.014-5.685) were risk factors for NHD patient dropout,while chronic nephritis syndrome (P＜0.001,HR=0.095,95％CI 0.046-0.195) was a protective factor;blood albumin (P=0.007,HR=0.904,95％CI:0.840-0.973) and age (P=0.027,HR=1.052,95％CI:1.006-1.101) were risk factors for NHD patient dropout.Multivariate Cox regression analysis showed that albumin level (P=0.007,HR=0.911,95％CI:0.848-0.991) was an independent risk factor for death in NHD patients.Conclusion Hypertensive nephropathy and diabetic nephropathy are the risk factors for NHD patients dropout,while chronic nephritis syndrome was a protective factor.Low serum albumin level is an independent risk faetor for death in NHD patients.
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Objective To compare the difference of mortality risk between patients undergoing nocturnal hemodialysis (NHD) and conventional hemodialysis (CHD) and to explore the related factors of mortality.Methods The study cohort comprised the maintenance hemodialysis patients receiving either NHD (n=111) or CHD (n=722) in Changzheng Hospital of Second Military Medical University from Feb.2009 to Feb.2017.The demographic information,clinical characteristics,survival status,causes of death and laboratory examination indexes were obtained from hemodialysis management system.The urea clearance index (Kt/V),hemoglobin,blood phosphorus concentration and mortality were compared between NHD and CHD patients.The multivariate-adjusted Cox model was used to analyze the mortality risk of all patients.Results Compared with the patients receiving CHD,the proportion of male was more in the NHD group,and the baseline age was younger (P＜0.01) and baseline dialysis vintage was longer (P＜0.01).There was no significant difference in incidences of primary disease and comorbidities,or laboratory examination results.Compared with the CHD group,the levels of Kt/V and hemoglobin in the NHD group were significantly higher (P＜0.01),and the blood phosphorus concentration was significantly lower (P＜0.05).Mortality in the NHD and CHD groups was 3.5 per 100 patients-years and 6.2 per 100 patients-years,respectively.After the adjustment by baseline age,dialysis vintage,gender,and comorbidities,Cox model analysis showed that the mortality risk in the NHD group was lower than in the CHD group (HR=0.67,95％CI:0.39-1.00,P=0.05).Subgroup analysis showed NHD was of more survival benefit for male (P＜0.05),non-diabetic patients (P =0.05) and patients with conventional dialysis vintage ＞3 years (P＜0.05).Conclusion NHD can effectively increase the solute clearance,improve anemia and calcium and phosphate metabolism,and thus reduce the mortality risk of maintenance hemodialysis patients.
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Objective To explore the role of Hippo pathway in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD),and find potential targets for drug therapy.Methods By means of immunofluorescence staining,Western blotting,Real-time PCR,the differences of sublocalization,expression and phosphorylation level about Hippo pathway molecules in Han:SPRD (cy/+) and ADPKD patients compared with the control were observed.Knockdown Yes kinaseassociated protein (YAP),transcriptional coactivator with PDZ binding motif (TAZ) and large tumor suppressor kinase1 (LATS1) in cystic lining epithelium cell line WT9-12 were took by siRNA interference,and then their effects on cell proliferation,apoptosis and cell cycle were assessed.Results In cystic lining epithelium of Han:SPRD(cy/+),decreased expression of LATS1 and increased expression of YAP were found compared with the control,and the immunofluorescence of YAP was distributed both in cytoplasm and nucleus,while distribution and expression level of TAZ were without significant variance.Abnormal mRNA expressions of Hippo pathway components in ADPKD patients were found (P ＜ 0.05).Down-regulation of LATS1 in WT9-12 cells could prohibit phosphorylation of YAP,and prompted proliferation and cell division.Knockdown YAP in WT9-12 cells could inhibited cell proliferation by arresting cell cycle in G0/G1 phase,but down-regulating TAZ showed no significant differences in proliferation and cell cycle.Conclusions Altered Hippo signaling exists in ADPKD,and YAP activation may be one leading cause of autosomal dominant polycystic kidney disease onset.In vitro,knockdown YAP in WT9-12 cells can inhibit cell proliferation by arresting cell cycle and depressing cell division,suggesting the expression level and activity of YAP are potential targets for ADPKD treatment.
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Objective To investigate the changes of thyroid function and carotid atherosclerosis in patients on maintenance hemodialysis (MHD).Methods A total of 110 stable MHD patients undergoing hemodialysis for at least three months were enrolled in the study.Serum free-T3 (FT3), free-T4 (FT4) and thyroid stimulating hormone (TSH) concentrations were measured by electrochemiluminescence.Plasma levels of homocysteine (Hcy) and C-reactive protein (CRP) were detected.Clinical data and biochemical indicators were collected.These patients were divided into thyroid dysfunction group and euthyroidism group.Prevalence of atherosclerosis was detected by carotid ultrasonography.The associations between the changes of thyroid function and carotid atherosclerosis were analyzed by Logistic regression model.Results Among these 110 patients, 42 (38.18％) patients had thyroid dysfunction.Hcy and CRP concentrations were significantly higher in thyroid dysfunction group than those in euthyroidism group (P ＜ 0.05).The intima-media thickness, number of plague and arteriostenosis of carotid were higher in thyroid dysfunction group than those in euthyroidism group (P ＜ 0.05).Multivariate logistic regression analysis showed that increased Hcy and CRP, decreased serum FT3 were independent risk factors for carotid atherosclerosis.Conclusions Thyroid dysfunction with low serum FT3 is frequently found in MHD patients.In MHD patients, FT3 is closely correlated to carotid atherosclerosis.
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Objective To observe the impact of heparanase on glomerular endothelium glycocalyx during sepsis and to investigate the prevention of glycocalyx injury.Methods C57/BL6 mice were injected with lipopolysaccharide (LPS) or tumor necrosis factor-α(TNF-o) and sacrificed one hour later.Glomerular endothelium glycocalyx traced with lanthanum was observed by transmission electron microscope(TEM).Western blotting was used to observe heparanse protein expression of renal cortex tissue.Human renal glomerular endothelial cells (HRGECs) were stimulated with TNF-α and active heparanase protien expression was detected by Western blotting.Mice were administrated with heparin sodium or heparinase Ⅲ and renal endothelium glycocalyx was observed by TEM.Urine during twenty-four hours was collected to measure urinary albumin and creatinine.The ratio of albumin to creatinine was calculated and compared among groups.Results The glomerular endothelium glycocalyx of LPS group and TNF-α group was degradated and the one of podocyte was integrated.Renal cortex tissue heparanase protein expression was significantly increased since one hour after LPS injection (P ＜ 0.01).The protein expression of activited heparanase of HRGECs which were stimulated with TNF-α was increased (P ＜ 0.05).Administration of heparin sodium which could inhibit the activity of heparanase could prevent the glycocalyx form degradation.The ratio of urine albumin to creatinine of heparin sodium group was decreased compared with LPS group (P ＜ 0.05) and the ratio of heparinase Ⅲ group was higher than control group(P ＜ 0.01) as a result of degradation of glomerular endothelium glycocalyx.Conclusions During the early stage of sepsis,TNF-α can induce glomerular endothelium heparanase to increase and active,and consequently the glycocalyx is degradated which leads to albuminuria.Inhibition of heparanase can protect glomerular endothelium glycocalyx and prevent albuminuria.
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Objective To investigate the migration of bone-marrow mesenchymal stem cells (BMSCs) under acute kidney injury (AKI) microenvironment in vitro and the effect of erythropoietin (EPO) intervention,and to explore its underlying mechanism.Methods Renal tubular epithelial cells (RTECs) were cultured in hypoxia/re-oxygenation (HR) condition for 12 h,respectively,in order to establish HR-RTEC.BMSCs and RTECs were co-cultured by Transwell system and were divided into 7 groups:control group (group①,only BMSC cultured),BMSC-RTEC co-culturing group (group ②),BMSC-HR-RTEC co-culturing + EPO intervention groups (group ③to group ⑦,EPO concentration:0,1,5,10,50 IU/ml).All the groups were cultured for 48 h and the number of migrating BMSCs was detected.Western blotting was applied for the detection of SDF-1 expression in RTECs and pMAPK and MAPK levels in BMSCs.SDF-1 concentration in the RTECs culture supernatant was tested by ELISA.Results The number of BMSCs migrating to the low chamber where HR-RTECs were cultured was increased,and EPO intervention further enhanced this migration which reached the peak at the concentration of 10 IU/ml [Compared with group③,(46.67±7.37) cells vs (19.00±2.37) cells,P ＜ 0.05].Intracellular expression level and the secreated level of SDF-1 in HR-RTECs in group③ were higher than those in RTECs of group② [0.37±0.01 vs 0.19±0.01,P ＜ 0.05; (61.64±4.88) μg/L vs (35.26±8.78) μg/L,P ＜ 0.05].EPO intervention increased above SDF-1 levels and reached the peak at the concentration of 10 IU/ml [group⑥ vs group③:(173.53± 14.66) μg/L vs (61.64±4.88) μg/L,P＜0.05],accompanied with enhanced phosphorylation of MAPK in BMSCs.Conclusions AKI microenvironment has obvious chemotaxis effect on BMSCs,and EPO intervention can strengthen this effect.The increased SDF-1 level and enhanced phosphorylation of MAPK,the downstream signal protein of SDF-1/CXCR4 axis,are the possible mechanism for EPO performance.
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Objective CXCR4-overexpressing bone marrow-derived mesenchymal stem cells (CXCR4-BMSC) were constructed and co-cultured with hypoxia/re-oxygenation pretreated renal tubular epithelial cells (HR-RTEC).Repair of HR-RTEC was detected and the possible mechanism was also discussed.Methods CXCR4-BMSC (CXCR4-BMSC/eGFP,eGFP as the tracer gene) and null-BMSC (BMSC/eGFP) were obtained by gene transfection technique,and the level of CXCR4 in the transfected cells was detected.RTEC was cultured under hypoxia/re-oxygenation condition for 12 h,respectively,to obtain HR-RTEC,which was used to simulate AKI in vitro.BMSC and HR-RTEC were co-cultured for 12 h,and the proportion of apoptotic cells among the HR-RTEC was assayed by immunofluorescence technique.Western blot was used to test the protein levels of cleaved Caspase-3 and Bcl-2.The number of migrating BMSC was also assayed.After culturing with the HR-RTEC culture supernatant,the expression of cytokeratin 18 (CK18) in BMSC was tested by immunofluorescence staining.Cytokines including bone morphogenetic protein-7 (BMP-7),hepatic growth factor (HGF) and interleukin-10 (IL-10) in the BMSC culture supernatant were detected by ELISA method.Results Expression of CXCR4 was enhanced in CXCR4-BMSC.Proportions of the apoptotic cells among HR-RTEC after being co-cultured with BMSC,CXCR4-BMSC and null-BMSC were all decreased,especially in the C/H group.The decreased cleaved Caspase-3 and enhanced Bcl-2 were also observed in HR-RTEC.The number of migrating CXCR4-BMSC was the highest.Proportions of CK18+ cells in BMSC,CXCR4-BMSC and null-BMSC were all low and showed no difference.However,CXCR4 overexpression in BMSC stimulated secretions of BMP-7,HGF and IL-10.Conclusions CXCR4-overexpressing BMSC has more repair effect on the co-cultured HR-RTEC,the enhanced migration ability and secretion ability of CXCR4-BMSC are the possible mechanisms.
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Objective To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb)maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO).Methods This was an open,randomized,controlled,multi-center trial.All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-β during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L.Eligible patients were randomized (2∶1 ) to accept either C.E.R.A.once every 4 weeks by subcutaneous administration ( C.E.R.A.group,n =187 ) or subcutaneous EPO-β 1-3 times weekly ( EPO group,n =94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period ). The starting dose of C.E.R.A.was converted according to the dose of EPO-β administered in the week preceding the first study drug administration.The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period.Results Totally 253 patients completed the whole 28-week treatment.The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A.group and + 1.23 g/L for EPO group,resulting in a treatment difference of 1.34 g/L (95％ CI - 1.11-3.78 g/L).Since the lower limit of 95％ CI was greater than the pre-defined non-inferiority margin -7.5 g/L( P ＜ 0.0001 ),C.E.R.A.once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level.The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups ( 69.0％ for C.E.R.A.group vs 68.9％ for EPO group,P ＞0.05 ).The overall incidence of adverse events was similar between the C.E.R.A.(41.7％)and EPO (46.2％ ) groups ( P ＞ 0.05 ).The safety findings were in accordance with the patients' primary diseases rather than the administration.Conclusions Conversion from EPO to C.E.R.A.once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia,and it was non-inferior to EPO.In general,subcutaneous administration of C.E.R.A.is well tolerated in dialytic patients with chronic renal anemia.
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Objective To analyze the causes of 652 hospitalizations in the patients with autosomal dominant polycystic kidney disease (ADPKD).Methods The medical records of all ADPKD inpatients in our hospital from January 1,1990 to December 31,2010 were collected.The differences of hospitalization causes in different age,gender and period were analyzed.Results (1)In 652 hospitalizations,the most common cause was lumbar pain (15.2％),followed by cystic bleeding (14.6％),aggravating renal failure (10.1％),dialysis-related problems (9.4％),renal transplant related issues (8.3％),renal replacement therapy for ESRD (8.0％),urinary tract infection (6.4％),end stage renal failure (5.8％),hypertension (4.1％),renal cyst volume enlargement (3.7％),finding polycystic kidney disease (2.1％),urinary lithiasis (1.8％) and others (10.4％).(2)Younger patients were admitted into hospital because of polycystic kidney bleeding and finding PKD.With the increase of patients age,hospitalization due to dialysis-related problems increased,while many middle-aged patients were hospitalized because of back pain.(3)Male patients were admitted into hospital for aggravating renal failure,ESRD,kidney transplantation-related problems and urinary lithiasis,while female patients mainly for lumbar pain,dialysis-related problems and urinary tract infection.(4)The proportion was significantly reduced with time of finding PKD,renal failure and polycystic kidney bleeding,the proportion of renal cysts increasing and aggravating renal failure increased,there was a significant increase in the proportion of patients with hypertension,while a significant decrease in the proportion of patients with uncontrolled hypertension,and the average SBP was also significantly reduced.Conclusions The highest rate of hospitalization of ADPKD patients is in 40 to 60 age group.Cause of admission varies with age and gender,and changes with the change of time.Over the past decade,the proportion of hospitalization due to renal cysts enlargement and renal failure aggravation increased significantly.The incidence of hypertension is higher than that in the first 10 years,but hypertension control rate increases compared with the previous.Prevention should focus on finding the suppression measures of renal cysts enlargement.
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Objective To seauch the ideal management for gross hematuria in autosomal dominant polycystic kidney disease (ADPKD).Methods ADPKD patients who were ever hospitalized and followed up in our department since 1993 were enrolled in the study.Demographic and clinical data were colloected,such as gender,age of gross hematuria,level of renal function,causative factors,management strategies,duration of gross hematuria,blood platelet count,activated partial thromboplastin time,prothrombin time,international normalized ratio,size of kidney cyst and so on.ADPKD patients were divided into different groups according to causative factors or management.The clinical data were compared among groups.Results A total of 905 ADPKD patients were screened,among whom 279 patients ever had gross hematuria (male/female:150/129),One hundred and forty-six patients had integrated therapeutic process records,while only 101patients could provide relevant laboratory examination results.In these 101 patients,gross hematuria was found in any stage of chronic kidney disease (CKD); the average eGFR was (56.4±44.1) mml·min-1 ·(1.73 m2)-1; the duration of gross hematuria was (8.8±8.0) d; no significant difference between male and female in duration of gross hematuria existed [(8.2±7.3) d vs (9.5±8.8) d,P=0.426]; coagulation parameters were all normal.The platelet count was also normal in 91 patients.Duration of gross hematuria among groups divided according to different causative factors was significantly different (P＜0.05).The patients in bed rest group had significantly shorter duration of gross hematuria compared with other groups (P＜0.05).The platelet count,prothromhin time and international normalized ratio were all at similar level in different groups.Conclusions The causative factors in ADPKD patients with gross hematuria should be confirmed as the first step of management strategies.Bed rest is the key point in management.Antifibrinolytic agent is a proper choice in the cases receiving bemostatic drugs.It is unnecessary to use antibiotic agent for prevention.
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Objective To investigate the effects of a novel PPARγ agonist DH9 on Wntβ-catenin pathway in human polycystic kidney cystic-lining epithelial cells (WT9-12).Methods WT9-12 cells were treated with different concentrations of DH9 for 72 hours and the proliferation was assessed by MTT.WT9-12 cells were pretreated with SB216763 or GW9662 for two hours and then treated with DH9 for 72 hours.Western blotting was applied to detect the protein expression of β-catenin,phospho-β-catenin,GSK3β,phospho-GSK3β.Results DH9 could effectively inhibit the proliferation of the cells.60 μmol/L DH9 could facilitate β-catenin down-regulation (P＜0.01) and phospho-β-catenin up-regulation (P＜0.01).Inhibition of GSK3β by SB216763 could protect WT9-12 cells against DH9-facilitated β-catenin repression in a dose-dependent manner despite phosphorylating deactivation,but PPARγ inhibitor GW9662 couldn't.Conclusions DH9can effectively block the proliferation of WT9-12 cells.The effect may be mediated by facilitating the down-regulation of β-catenin via GSK3β-dependent mechanism.
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Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats (CRF). Methods A total of 55 male SD rats were randomly divided into sham group (n=10),model group (n=15),low dose (300 mg/kg),medium dose (600 mg/kg) and high dose (900 mg/kg) L-carnitine group(n=10,each).5/6 subtotal nephrectomy was performed in these rats without sham group.One week after the operation,normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks.Transthoracic echocardiography,mean arterial pressure (MAP),heart rate (HR) and heart weight/body weight were assessed.Moreover,24h urine protein,renal function,SOD,MDA,IL-6,ATP,ADP were measured at the end of the study.Additionally,pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results (1) ATP (μmol/g·wt)in L-carnitine groups (2.35±0.24,3.59±0.28,3.78±0.25) was significantly higher than that in model group (1.61±0.12) (all P＜0.01).(2) Thickness of posterior wall of left ventricle (mm) in high dose L-carnitine group was thinner than that in model group (3.74±0.23 vs 4.18±0.48,P＜0.05). (3) The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups (3.92±0.27,3.65±0.2) were significantly lower compared to model group (3.99±0.27) (all P＜0.01). (4) Under light microscopy,disarrangement and hypertrophy of cardiac myocytes,increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-carnitine groups (7.14±1.07,6.13±0.99),as compared with model group (9.88±1.13) (all P＜0.01).Under electron microscopy,typical changes in cardiac hypertrophy were observed,including dissolution of myocardial fibers,increasing and swelling of mitochondria,membrane rupture as well as matrix increase in model group,while these changes were ameliorated by L-carnitine in a dose-dependent manner. (5) Seventeen weeks after the treatment,both IL-6 and MDA were decreased in all L-carnitine-treated groups than those in model group [IL-6 (ng/L):261.86±13.18,240.12±18.7,233.34±36.88 vs 596.64±81.41; MDA (nmol/L):15.23±2.01,12.41±0.6.10.97±1.9 vs 21.84±2.71).Whereas,SOD (U/ml) were increased in L-carnitine-treated groups (51.2±6.11,58.51±5.52,60.63±6.94) than that in model group(32.01 ±5.69 )(all P＜0.05).(6) No significant differences of systolic,diastolic blood pressure or MAP were found among groups. Conclusion L-carnitine can improve energy metabolism,micro-inflammation and oxidative stress in myocardium of CRF rats,which may be associated with the amelioration of cardiac hypertrophy and fibrosis.
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Objective To summarize the clinical characteristics and outcome of renal cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods Clinical data of 40 ADPKD patients with 43 episodes of renal cyst infection admitted in Shanghai Changzheng Hospital from 1st January 1991 to 31st December 2010 were retrospectively analyzed.Differences of microbiological data and treatments between 1st January 1991 to 31st December 2000 and 1st January 2001 to 31st December 2010 were compared. Results Among 473 identified patients with ADPKD and 662 episodes of hospitalization,40 patients had 43 episodes of renal cyst infection,including 8 definite and 35 likely cases.Microbiological documentation was available for 34 episodes (79.0％),Escherichia coli accounting for 82.4％ of all retrieved bacterial strains.Resistant Escherichia coli to quinolone and certain β-lactamine increased in recent decade.Clinical efficacy of initial antibiotic treatment was noted in 69.8％ of episodes. Antibiotic treatment modification was more frequently required for patients receiving initial monotherapy compared with those receiving combination therapy.In the first ten-year group,initial combination therapy and clinical efficacy were noted in 30.0％ and 60.0％ of episodes respectively,and hospital stay was (20.2±6.7) d.In the second ten-year group,initial combination therapy and clinical efficacy were noted in 61.9％ and 78.2％ of episodes respectively,and hospital stay was (16.3±3.2) d.Large infected cysts (diameter ＞5 cm) frequently required drainage. Conclusions In renal cyst infection,the source of the organisms is often a gram negative enteric organism.Empiric therapy is often initiated with two antibiotics.The drainage of large infected cysts remains the main treatment for cyst infection.
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Objective To evaluate the short-term efficacy and safety of sevelamer hydrochloride in treating maintenance hemodialysis (MHD) patients with hyperphosphemia.Methods A multicenter,open-labeled,self-control study was performed.Phosphate binders were discontinued during a two-week washout period.Patients with more than 1.78 mmol/L serum phosphorus after two-week washout period were eligible for the trial.The dose was adjusted every two weeks as necessary to achieve serum phosphorus control. Sevelamer hydrochloride was administered to 138 MHD patients for 10 weeks and a second two-week washout period followed.Results A total of 111 from 138 patients fulfilled the whole 14-week study. Mean serum phosphorus and calcium-phosphate products starte to decline after two-week sevelamer hydrochloride treatment. By the end of 10-week sevelamer hydrochloride treatment, mean serum level of phosphorus [(1.85±0.50) vs (2.57±0.54) mmol/L,P＜0.01],calcium-phosphate product [(4.16± 1.72) vs (5.79 ± 1.50) mmol2/L2,P＜0.01 ] and low density lipoprotein [(1.64±0.76) vs (2.31 ±0.87) mmol/L,P＜0.01] were significantly decreased,while the adjusted serum level of calcium and serum intact parathyroid hormone kept steady.Both serum phosphorus and calcium-phosphrus product increased after the second washout period, but the levels were still lower as compared to pre-treatment [(2.26±0.71) vs (2.57±0.54) mmol/L; (5.12±1.63) vs (5.79±1.50) mmol2/L2,P＜0.01].Of the 138 patients involved,214 episodes in 106 patients and 121 episodes in 89 patients were reported as adverse events and adverse drug reaction respectively. Gastrointestinal symptoms,of which most were mild or moderate,happened to 68.1％ (94/138) patients. Conclusions Sevelamer hydrochloride can control serum phosphorus and reduce the levels of calcium-phosphorus product and cholesterol.Slight gastrointestinal symptoms like constipation are common during the treatment.
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Objective To observe the influence of nocturnal prolonged hemodialysis (INHD) on patients＇ nutrition status. Methods Thirty-two maintenance hemodialysis patients received INHD (3 times per week and 7.5 hours each session) and thirty-five maintenance hemodialysis patients received conventional hemodialysis (3 times per week and 4 hours each session) as control were observed for 6 months.The nutrition status of these patients on various aspects which concluded physical measurements,laboratory tests,and dietary record at baseline(0month) and exit (6 months) were recorded. Results (1)There were no differences in age,sex,body weight,and primary diseases between two groups.(2)The body weight,triceps skinfold thickness (TSF),and hand grip strength increased at exit point,but no statistical difference compared with the control group.Mid-upper arm circumference (MAC) increased signicantly from (27.1±4.2) to (30.5±6.1) cm (P＜0.05).Compared with the control group (26.9±3.4) cm,there was a significant difference (P＜0.05).(3)Serum phosphate decreased significantly from (0.5±0.5) to (0.1±0.6) μ mol/L (P=0.001) in INHD group.(4)The nutrition status were improved in INHD group evaluated by subjective global assessment (SGA)(P=0.03).(5) Dietary intake was recorded by a 3-day food record.Dietary intake of energy,protein,lipid,calcium,potassium,and phosphate increased in INHD group.None of the differences achieved statistical significance between two groups. Conclusion As compared with conventional hemodialysis,INHD can increase the dietary intake,decrease serum phosphate level,and improve patients nutrition status.