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Objective To analyze the predictive value of apolipoprotein B (ApoB) in the risk of progression to renal replacement therapy (RRT) in diabetic kidney disease (DKD) patients with chronic kidney disease (CKD) stage 3-5. Methods The data of DKD patients with CKD stage 3-5 who were hospitalized and followed up with detailed clinical data from January 2011 to November 2014 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively collected. Estimated glomerular filtration rate (eGFR) was calculated according to the CKD-EPI formula. After 2 years of follow-up, the patients were divided into RRT group and non-RRT group according to whether they had entered renal replacement therapy. Cox regression analysis was used to analyze the influencing factors of DKD progression to RRT. The predicted value of ApoB in the risk of progression to renal replacement therapy (RRT) of DKD patients within 2 years of follow-up was analyzed by plotting the receiver operating characteristic curve (ROC). By establishing multiple Cox models, the effect of ApoB elevation on the progression of DKD patients to RRT was analyzed after adjusting for the influencing factors gradually. Results A total of 258 cases were included in this study, including 156 males and 102 females. They were (66.13±11.88) years old (27-91 years old). CKD 3-5 patients were 181 cases, 50 cases and 27 cases respectively. There were 165 cases in the non-RRT group and 93 cases in the RRT group. There were statistically significant difference in hemoglobin, hematocrit, blood phosphorus, ApoB, serum creatinine, urea nitrogen, serum cystatin C, eGFR and in the proportion of using angiotensin converting enzyme inhibitor, diuretic, β blockers between the two groups (all P＜0.05). Multivariate Cox regression analysis showed that ApoB was an independent predictor of progression to RRT in patients with DKD within 2 years (HR=2.203, 95% CI 1.352-3.589, P=0.002). The area under the ROC curve of ApoB for DKD progression to RRT within 2 years of follow-up was 0.641 (C-index=0.749, P＜0.01). After adjusting for confounding factors, Cox regression analysis showed that for every 1 mmol/L increase in ApoB, the risk of RRT increased by 1.038 times in DKD patients with CKD stage 3-5 (HR=2.038, 95% CI 1.312-3.168, P=0.002). Conclusions ApoB is an independent predictor of progression to RRT with CKD stage 3-5 diabetic kidney disease (DKD). For every 1 mmol/L increase in ApoB, the risk of progression to RRT in patients with CKD 3-5 DKD increases by 1.038 times.
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Objective To investigate the related factors and prognosis of pulmonary hypertension (PAH) in hemodialysis (HD) patients for early diagnosis and intervention of PAH.Methods A retrospective cohort study was conducted in 183 long-term hemodialysis patients with complete follow-up data from January 1,2010 to December 30,2015 from the blood purification center of the Third Affiliated Hospital of Sun Yat-sen University.The follow-up deadline was December 30,2017,and the endpoints were death and cardiovascular events.The clinical data,laboratory examinations,cardiac color Doppler ultrasound parameters and prognosis of patients with and without PAH were compared.Multivariate logistic regression was used to analyze the risk factors for PAH in HD patients.The survival rates were calculated by Kaplan-Meier method,and the survival curves were compared by Log-rank test between the two groups.A multivariate Cox proportional hazard regression model was used to examine the association between PAH and all-cause mortality in HD patients.Results Of the 183 hemodialysis patients,79(43.2％) were female,104(56.8％) were male,and the age was (56.1±16.9) years,of which 72(39.3％) were complicated with PAH.Compared with the non-PAH group,patients in the PAH group was older and had a longer duration of dialysis (both P ＜ 0.05).The left atrial diameter (P=0.002) and the proportion of valvular calcification (P=0.004) were significantly higher in the PAH group than that in the non-PAH group.Logistic regression analysis showed increased age (OR=1.027,95％ CI 1.001-1.053,P=0.041) and increased duration of dialysis (OR=1.129,95％ CI 1.004-1.269,P=0.042) were risk factors for PAH in HD patients.After a median follow-up of 27.8 months,Kaplan-Meier survival analysis showed that all-cause mortality was higher in the PAH group than that in the non-PAH group ~x2=5.636,P=0.018).The main cause of death in two groups was cardiovascular event.Afteradjusting for age,diabetes mellitus,duration of dialysis,valvular calcification,and hypertension,Cox regression showed that PAH increased the risk of all-cause mortality in HD patients (HR=1.894,95％ CI 1.083-3.313,P=0.025).Conclusions HD patients complicated with PAH are more common and the prognosis is poor.Increased age and increased duration of dialysis may be risk factors for PAH in HD patients.Regular color Doppler echocardiography is helpful for early detection and diagnosis of PAH.
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Objective@#To analyze the relationship between serum uric acid (SUA) level and clinical indicators in maintenance hemodialysis (MHD) patients, and explore its influence on all-cause mortality and cardiovascular mortality.@*Methods@#This study was a retrospective cohort study. Patients who received MHD from the blood purification center of the Third Affiliated Hospital of Sun Yat-sen University from January 1, 2011 to December 30, 2015 were enrolled in the queue. They were divided into 3 groups according to the first and third quantile of the SUA level quartiles, and the baseline data of clinical and laboratory examinations were compared. The correlation between SUA level and clinical indicators was analyzed by Pearson correlation coefficient. Kaplan-Meier method and Cox proportional hazard regression model were used to examine the association between SUA and all-cause mortality and cardiovascular mortality in MHD patients.@*Results@#A total of 201 patients were enrolled in the study. The age of the patients was (56.9±16.7) years and the baseline SUA level was (531.1±137.9) μmol/L. Patients were divided into 3 groups with the first quantile (442 μmol/L) and the third quantile (620 μmol/L) of the SUA quartiles as the boundary points: group 1 (SUA<442 μmol/L, n=52), group 2 (SUA 442-620 μmol/L, n=101) and group 3 (SUA>620 μmol/L, n=48). The results showed that the patients in group 1 were older and had more proportion of patients with diabetes mellitus and cardiovascular diseases than those in group 3 (all P<0.05). Compared to group 3, the serum albumin, serum phosphorus and serum creatinine were lower in group 1, while the hypersensitive C-reactive protein was higher (all P<0.05). Pearson correlation analysis showed that SUA level was positively correlated with albumin (r=0.135, P=0.047), blood phosphorus (r=0.269, P<0.001) and serum creatinine (r=0.333, P<0.001), and negatively correlated with hypersensitive C-reactive protein (r=-0.216, P=0.002). After a median follow-up of 49.8 months, 66(32.8%) all-cause deaths and 32(15.9%) cardiovascular deaths were recorded. Kaplan-Meier method showed that with the decrease of SUA, all-cause mortality (Log-rank χ2=18.27, P<0.001) and cardiovascular mortality (Log-rank χ2=15.04, P=0.001) increased. After adjusting for age, gender, comorbidity and other factors using the Cox proportional hazards model, the all-cause mortality and cardiovascular mortality decreased by 20.1% (HR=0.799, 95% CI 0.651-0.980, P=0.031) and 29.6% (HR=0.704, 95% CI 0.524-0.946, P=0.020) for each 100 μmol/L increase in baseline SUA. Compared to group 1, all-cause mortality (HR=0.332, 95%CI 0.142-0.774, P=0.011) and cardiovascular mortality (HR=0.140, 95%CI 0.030-0.657, P=0.013) were lower in the group 3.@*Conclusion@#Low SUA level increases the risk of all-cause mortality and cardiovascular mortality in MHD patients.
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Objective To analyze the relationship between serum uric acid (SUA) level and clinical indicators in maintenance hemodialysis (MHD) patients, and explore its influence on all-cause mortality and cardiovascular mortality. Methods This study was a retrospective cohort study. Patients who received MHD from the blood purification center of the Third Affiliated Hospital of SunYat-sen University from January 1, 2011 to December 30, 2015 were enrolled in the queue. They were divided into 3 groups according to the first and third quantile of the SUA level quartiles, and the baseline data of clinical and laboratory examinations were compared. The correlation between SUA level and clinical indicators was analyzed by Pearson correlation coefficient. Kaplan-Meier method and Cox proportional hazard regression model were used to examine the association between SUA and all-cause mortality and cardiovascular mortality in MHD patients. Results A total of 201 patients were enrolled in the study. The age of the patients was (56.9 ± 16.7) years and the baseline SUA level was (531.1±137.9)μmol/L. Patients were divided into 3 groups with the first quantile (442μmol/L) and the third quantile (620 μmol/L) of the SUA quartiles as the boundary points: group 1 (SUA<442 μmol/L, n=52), group 2 (SUA 442-620 μmol/L, n=101) and group 3 (SUA>620 μmol/L, n=48). The results showed that the patients in group 1 were older and had more proportion of patients with diabetes mellitus and cardiovascular diseases than those in group 3 (all P<0.05). Compared to group 3, the serum albumin, serum phosphorus and serum creatinine were lower in group 1, while the hypersensitive C-reactive protein was higher (all P<0.05). Pearson correlation analysis showed that SUA level was positively correlated with albumin (r=0.135, P=0.047), blood phosphorus (r=0.269, P<0.001) and serum creatinine (r=0.333, P<0.001), and negatively correlated with hypersensitive C-reactive protein (r=-0.216, P=0.002). After a median follow-up of 49.8 months, 66(32.8％) all-cause deaths and 32 (15.9％) cardiovascular deaths were recorded. Kaplan-Meier method showed that with the decrease of SUA, all-cause mortality (Log-rank χ2=18.27, P<0.001) and cardiovascular mortality (Log-rank χ2=15.04, P=0.001) increased. After adjusting for age, gender, comorbidity and other factors using the Cox proportional hazards model, the all-cause mortality and cardiovascular mortality decreased by 20.1％(HR=0.799, 95％CI 0.651-0.980, P=0.031) and 29.6％(HR=0.704, 95％CI 0.524-0.946, P=0.020) for each 100μmol/L increase in baseline SUA. Compared to group 1, all-cause mortality (HR=0.332, 95％CI 0.142-0.774, P=0.011) and cardiovascular mortality (HR=0.140, 95％CI 0.030-0.657, P=0.013) were lower in the group 3. Conclusion Low SUA level increases the risk of all-cause mortality and cardiovascular mortality in MHD patients.
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Objective To explore the relationship between clinical manifestations and pathological changes in diabetic nephropathy (DN) and to assess the predictive power of the pathologic classification for DN established by the Renal Pathology Society in 2010.Methods Patients with type 1 or type 2 diabetes and biopsy-proven DN in the Third Affiliated Hospital of Sun Yat-sen University between January 2004 to June 2014 were enrolled in the present study and were followed-up until 31 December 2014.The outcome was defined as renal end-points including renal replacement therapy and doubling of serum creatinine as well as all-cause mortality.The laboratory and histologic data were analyzed and outcomes were assessed using survival analysis.Results Fifty-seven people enrolled in this study were categorized into Class Ⅱa (n=9),Class Ⅱb (n=9),Class Ⅲ (n=25) and Class Ⅳ (n=14) while no participants belonged to Class Ⅰ.The changes of Class Ⅱa were slight and those of Class Ⅳ were severe both in the clinical data (diabetic duration,blood pressure,estimated glomerular filtration rate,urine protein excretion rate,albumin and hemoglobin) and the pathological data (percentage of global glomerulosclerosis,percentage and scoring of interstitial fibrosis and tubular atrophy,scoring of interstitial inflammation and incidence of large vessel lesions).There were no significant differences between Class Ⅱb and Ⅲ in the above variables except for the scoring of arteriosclerosis.The mean follow-up duration was 25.9 months.Twenty-five patients (43.9％) reached the renal outcomes and six people (10.5％) reached all-cause mortality.The survival analysis showed that there were significant differences among the renal survival curves of different glomerular classes and of different interstitial and vascular scorings,but not in the survival curves related to all-cause mortality.Conclusions The glomerular classes are not completely associated with renal prognosis.The clinical manifestations and renal outcomes are benign in Class Ⅱa,moderate but similar in Class Ⅱb and Ⅲ and severe in Class Ⅳ.The glomerular classification and interstitial and vascular scorings are associated to renal prognosis while their associations with mortality remain to be verified.
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Objective To cxplore the optimal levels of serum calcium,phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients.Methods This study is a single center,retrospective cohort study.The associations between serum calcium,phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed.All patients started PD between January 1,2008 and April 30,2016 were enrolled and followed up to December 31,2016.At baseline and every 3 months,biochemical and therapeutic information was collected.Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism.Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis.The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis.Moreover,cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values.Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH.These ranges need further validation by large population studies to further conform.
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Objective To analyze the related factors of micro-albuminuria and macroalbuminuria in type 1 diabetes mellitus (DM) in the classification tree model,and to screen the high risk population of diabetic kidney disease.Methods 394 patients with type 1 diabetes were enrolled in the hospital from 2008 to 2015.According to glomerular filtration rates and urine albumin quantification,the patients were divided into type 1 diabetes group (299 cases),micro-albuminuria group (73 cases) and macro-albuminuria group (22 cases).The classification tree model was utilized to analyze related factors of the different stages of proteinuria,and the high-risk population was screened by node gain analysis.Results Four important explanatory variables were screened out by the classification tree model from the 27 candidate variables related to primary renal damage,including retinopathy,fibrinogen,waist-hip ratio (WHR),red blood cell distribution width (RDW).Retinopathy was an major factor of DKD.The probability of macro-albuminuria in retinopathy and WHR ＞ 0.82 group was 43.8％,and if at the same time RDW ＞ 0.14,the probability of macro-albuminuria was 88.9％.Conclusions The classification tree model can analyze factors of the separate stages of proteinuria in type 1 diabetic patients effectively.Retinopathy is the major influential factors of type 1 diabetic patients with proteinuria.
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Objective To study the effcts of total parathyroidectomy with autotransplantation (tPTX+AT) on fibroblast growth factor-23 (FGF-23) in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SPTH). Methods Maintenance hemodialysis patients with severe SPTH treated in our hospital from 2014 to 2016 were enrolled and divided into two groups:tPTX+AT group and non-surgical group. Two groups' biochemical indexes and FGF-23 level before and after 6 months treatment were compared. Results A total of 48 patients were included in the study, including 22 in the tPTX+AT group and 26 in the non-surgical group. Age, duration of dialysis, primary disease, rate of hypertension, parathyroid hormone (iPTH), FGF - 23, cholesterol (TCH), triglyceride (TG), albumin (ALB), and hemoglobin (HGB) level showed no significant difference between the two groups (P>0.05); but serum calcium and alkaline phosphatase (ALP) of that tPTX+AT group were significantly higher than those of the non-surgical group (P<0.01). After 6 months the blood iPTH, calcium, phosphorus and the calcium-phosphorus product level of tPTX+AT group were significantly lower than those of non-surgical group (P<0.05). Blood lipids, propagated, HGB, and ALP level had no statistical differences in the two groups (P>0.05); serum FGF-23 progressive declined after 1 week, 1 month, 3 month and 6 month in tPTX+AT patients, and after 6 months, the level of FGF-23 was significantly lower than that of non-surgical patients[1462.9(903.7, 5826.9) ng/L vs 12627.9(5488.9, 16844.4) ng/L, P<0.01]. Conclusion tPTX+AT can significantly alleviate calcium and phosphorus metabolism disorders and in 6 months gradually reduce FGF-23 level in patients receiving MHD.
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Objective To analyze the related factors of micro-albuminuria and macroalbuminuria in type 1 diabetes mellitus (DM) in the classification tree model,and to screen the high risk population of diabetic kidney disease.Methods 394 patients with type 1 diabetes were enrolled in the hospital from 2008 to 2015.According to glomerular filtration rates and urine albumin quantification,the patients were divided into type 1 diabetes group (299 cases),micro-albuminuria group (73 cases) and macro-albuminuria group (22 cases).The classification tree model was utilized to analyze related factors of the different stages of proteinuria,and the high-risk population was screened by node gain analysis.Results Four important explanatory variables were screened out by the classification tree model from the 27 candidate variables related to primary renal damage,including retinopathy,fibrinogen,waist-hip ratio (WHR),red blood cell distribution width (RDW).Retinopathy was an major factor of DKD.The probability of macro-albuminuria in retinopathy and WHR ＞ 0.82 group was 43.8％,and if at the same time RDW ＞ 0.14,the probability of macro-albuminuria was 88.9％.Conclusions The classification tree model can analyze factors of the separate stages of proteinuria in type 1 diabetic patients effectively.Retinopathy is the major influential factors of type 1 diabetic patients with proteinuria.
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[Objective] To investigate the effects and mechanisms of Nrf2-ARE (nuclear factor erythroid-2 related factor-anti-oxidant response element) pathway on uremic serum-mediated endothelial dysfunction in human aortic endothelial ceils.[Methods] Human aortic endothelial cells were incubated in endothelial cell medium containing 10％ normal serum,10％ non-diabetic nuremic serum or 10％ diabetic uremic serum respectively,and 20 μmol/L tertiary butyl hydroquinone (tBHQ) were pretreated with cells to active Nrf2-ARE pathway.The cells apoptosis rate were measured by flow cytometry,and the synthesis of NO was detected by flow cytometry and immune fluorescent confocal,while the expression of P-eNOSer1177/eNOS,and quinone oxidoreductase-1 (NQO1) were measured by western blotting.The levels of malondialdehyde,superoxide dismutase,eatalase,and glutathione in these cells were also measured with kits.[Results] Aortic endothelial cells incubated with uremic serum had a higher level of apoptosis rate and MDA (P ＜ 0.05),and a lower level of NO systhesis,P-eNOSSer1177/eNOS expression,CAT,SOD,GSH (P ＜ 0.05).Pretreated with tBHQ can reduce the apoptosis rate and MDA level (P ＜ 0.05),improve the amount of NO systhesis,the expression of P-eNOSSer1177/eNOS,the levels of CAT,SOD,and GSH in these cells (P ＜ 0.05).[Conclusion] Activation of Nrf2-ARE pathway can improve endothelial dysfunction in aortic endothelial cells induced by uremic serum,and its mechanism might be related with enhancement of the antioxidant stress.
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Objective@#To explore the effects of miR-124-ROCK1 signal pathway in the damages of glomerular endothelial cells (GEnCs) induced by high glucose.@*Methods@#Rat glomerular endothelial cells were cultured in different glucose concentrations: normal control group (NG: 5.5 mmol/L), high glucose group (HG: 30.0 mmol/L), and cells were treated with ROCK1 inhibitor Y27632, miR-124-3p mimic, miR-124-3p inhibitor. The expressions of ROCK1 activity, cell apotosis and tight junction proteins were detected by Western blot. The cell tight junction protein ZO-1 in those groups were assessed by laser scanning confocal microscope.@*Results@#High glucose significantly decreased miR-124 expression (P<0.01), ROCK1 activity (P-MYPT1/MYPT1), and cell apoptosis (Cleaved-Caspase3/pro-Caspase3) were found increased while the tight junction proteins ZO-1and Occludin were found decreased in these cells (P<0.05 all P<0.01), However, when pretreated cells with ROCK1 inhibitor Y27632, these injuries were significantly reversed. In cells transfected with miR-124-3p mimic, p-MYPT1/MYPT1 was decreased. p-MYPT1/MYPT1 was however increased in cells transfected with miR-124-3p inhibitor (P<0.05), indicating that miR-124 could directly inhibit ROCK1 activity. The increased ROCK1 activity and apoptosis, as well as the decreased tight junction proteins induced by high glucose were significantly suppressed as miR-124-3p mimic transfected in GEnCs.@*Conclusions@#According to our experiments, high glucose suppressed miR-124 in glomerular endothelial cells, consequenctly activating ROCK1 activity to damage endothelial cells. MiR-124 overexpression could ameliorate these damages induced by high glucose, suggesting that miR-124 might be a new therapeutic target to prevent glomerular endothelial cells injuries in diabetic nephropathy.
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Objective To identify the risk factors associated with cardiovascular and cerebrovascular disease (CCVD) in maintenance hemodialysis (MHD) patients. Methods We analyzed all of the patients undergoing maintenance hemodialysis in the dialysis center of the 3rd Affiliated Hospital of Sun Yat-sen University for at least 3 months from Jan 1st, 2009 to Dec 31st, 2014. Baseline and yearly interval clinical data were recorded and patients were followed up until morbidity or death of CCVD. Cox proportional hazard regression and time-dependent Cox regression were used to estimate the relative risk of outcomes associated with clinical measurements. Results There were 243 patients enrolled in the study, with a mean age of (53.2 ± 16.4) years old, and 138 of them were male (56.8%). The multivariate Cox proportional model revealed that age (HR=1.040, 95%CI:1.015-1.065, P=0.002), Erythropoietin (EPO) dose (HR=0.914, 95%CI: 0.846-0.987, P=0.022) and history of cardiovascular and cerebrovascular disease (HR=4.045, 95%CI: 2.074-7.890, P<0.001) were independent predictors of CCVD in MHD patients. After adjusting for baseline predictors, time-dependent serum phosphorus level (HR=1.722, 95%CI: 1.034-2.866, P=0.037) was significantly associated with CCVD. Conclusion Older age, decreases in EPO dose and history of cardiovascular and cerebrovascular disease were associated with increased risks of CCVD in MHD patients. Increase in serum phosphorus level was associated with increased risks of CCVD in a time-dependent manner.
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Objective To explore the relationship between reversed dipper blood pressure (BP) pattern with target organ damage in Chinese chronic kidney disease (CKD) patients. Methods A total of 1 116 CKD patients from the Third hospital of Sun Yat?sen university were enrolled from May 2010 to April 2014, all of whom carried ambulatory blood pressure monitoring (ABPM), and clinical data and ultrasonography were collected. Results Total of 23.39% CKD patients were reversed dipper BP pattern, 46.95% patients were non?dipper BP pattern, and dipper BP pattern was only 27.15%. Compared with dipper and non?dipper BP pattern group, patients with reversed dipper BP pattern had higher left ventricular mass index (LVMI), lower estimated glomerular filtration rate (eGFR) and severely damaged left ventricular diastolic function (all P<0.0083). After multiple linear regression analysis, reversed dipper BP pattern was an independent predictor for determining eGFR and LVMI. Age, lower hemoglobin and combination of diabetes were independently associated with reversed dipper BP pattern. Conclusion Reversed dipper BP pattern is common in Chinese CKD patients, which is closely related to renal damage and cardiovascular injuries.
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Objective To analyze the impact factors for early renal damage in type 2 diabetic patients by the classification tree model.Methods A total of 601 patients with type 2 diabetes were enrolled.According to glomerular filtration rates and urine albumin quantification,the patients were divided into type 2 diabetes group (418 cases) and early diabetic renal damage group (183 cases).The clinical data of the patients were recorded to analyze the main influential factors for the microalbuminuria of type 2 diabetic patients using the Exhaustive CHAID classification tree algorithm.Results Six important explanatory variables were screened out by the classification tree model from the 34 candidate variables related to early renal damage,including fibrinogen,history of hypertension,retinopathy,Cys C levels,SBP and peripheral neuropathy.Elevated fibrinogen was the main factor.Conclusion The classification tree model can analyze the major influential factors of early renal damage in type 2 diabetic patients effectively,and it can help develop the prevention and treatment methods.
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Objective To explore the features and influencing factors of ambulatory blood pressure in chronic kidney disease (CKD) patients.Methods A total of 540 CKD patients from May 2010 to May 2012 in our department were enrolled in this study.Ambulatory blood pressure monitoring was carried out.Blood pressure (BP),proteinuria and other clinical parameters were measured regularly.Ultrasonography was used to evaluate cardiac structure and function,carotid intima-media thickness and plaque.Univariate and multivariate analysis were used to examine the association between BP and clinical parameters.Results 63.9％ of CKD patients was non-dipper BP pattern,and 36.1％ was dipper BP pattern.As compared to dipper BP patients,those with non-dipper BP had higher ratio of nighttime/daytime proteinuria (0.51±0.29 vs 0.42±0.21,P ＜ 0.01),lower estimated glomerular filtration rate (eGFR) [(56.2±48.2) vs (75.5±56.5) ml· min 1 · (1.73 m2)-1,P ＜ 0.01],higher serum cystatin C[(2.8±2.0) mg/L vs (2.1±2.0) mg/L,P ＜ 0.01],higher left ventricular mass index [(53.7±23.2) vs (45.1± 16.3) g/m2,P ＜ 0.01] and severely damaged left ventricular diastolic function and higher carotid intima-media thickness [(0.7±0.3) vs (0.6±0.2) mm,P＜ 0.01].Nighttime blood pressure was independent predictor for proteinuria,eGFR and left ventricular mass index.Conclusions Nondipper blood pressure pattern is very common in CKD patients.Nighttime pressure is closely associated to renal damage and cardiovascular injuries.
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Objective To analyze the prevalence,risk factors of kidney disease in type 2 diabetic patients with KDIGO classification of chronic kidney disease,also to study cardiovascular and cerebrovascular diseases and death in these patients,so as to investigate the significance of the KDIGO classification system.Methods One thousand six hundred and forty-five type 2 diabetic patients who were in hospitalization from June 2008 to December 2012 were grouped according to the KDIGO classification of chronic kidney disease and the incidence of vascular disease was analyzed based on the classification.Clinical features were compared between patients with or without kidney disease.The risk factors of kidney disease and the death of diabetic patients were also investigated.Results There were 915 male and 730 female,aged a median (57.86±12.54) years with (6.35±6.30) years duration of diabetes mellitus among the 1645 cases,and 37.2％ of patients had concomitant kidney disease.According to the classi fi cation of CKD,patients in CKD group 3a,group 3b and CKD group 4-5 accounted for 5.7％,3.5％ and 7.6％,while 33.4％ of patients had proteinuria,among which 19.5％ with microalbuminuria,13.5％ with macroalbuminuria.On complications,patients with hypertension accounted for 49.5％,hyperlipidemia 67.7％,diabetic retinopathy 27.4％,cardiovascular and cerebrovascular diseases 18.5％ (coronary artery disease 16.5％,cerebrovascular diseases 8.8％).Statistical difference was detected in the incidence of diabetic retinopathy,coronary artery disease and cerebrovascular diseases between CKD group 3a and 3b (P ＜ 0.05).The duration of diabetes,concomitant hypertention especially with elevated systolic blood pressure,diabetic retinopathy and hyperuricemia were the independent risk factors for type 2 diabetic patients with kidney disease.Age,Scr,complicating cardiovascular and cerebrovascular diseases and advanced CKD stage were the independent risk factors for the death of type 2 diabetic patients with kidney disease.Conclusion KDIGO classification of chronic kidney disease enables better staging of kidney diseases in diabetic patients for management and prognosis.Diabetic patients have a higher prevalence of renal diseases and cardiovascular and cerebrovascular events than the general population.Early control of factors such as blood pressure and serum uric acid can delay the progression of kidney disease,and the predictive role of diabetic retinopathy should be emphasized.
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Objective To investigate whether high glucose can induce endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells and the role of TGF-β in the process.Methods Rat glomerular endothelial cells were divided into five groups:normal glucose (NG,5.5mmol/L),high glucose (HG,15,30 mmol/L),TGF-β inhibition (HG+ LY36,30 mmol/L glucose + 10 μmol/L LY364947),hyperosmotic control (M,5.5 mmol/L glucose+25.5 mmol/L mannitol) and solvent control (D,5.5 mmol/L glucose + 1 ml/L DMSO).Western blotting was performed to detect relative protein quantities of endothelial marker claudin 5 and mesenchymal marker α-smooth muscle actin (α-SMA).TGF-β1 and TGF-β2 mRNA levels were measured by real-time PCR.Vascular endothelial marker VE-cadherin and mesenchymal marker α-SMA were detected by immunofluorescent stain and observed by confocal microscopy.Results Compared with NG,the expression of claudin5 protein in HG (15 or 30 mmol/L) was up-regulated while expression of α-SMA protein was down-regulated (P ＜0.05).Both TGF-β1 and TGF-β2 mRNA levels increased as well (P ＜ 0.05).However,when compared with HG,the claudin 5 levels increased while α-SMA decreased in TGF-β inhibition group.No significant changes were observed in hyperosmotic or solvent control group.Confocal microscopy showed the transformation of cells from a cobblestone-liked shape to a spindle one,and a decreasing expression of VE-cadherin while an increasing α-SMA in HG group (P ＜ 0.05),whereas TGF-β inhibition partly attenuated those changes in both morphological and protein levels.Conclusions High glucose treatment of glomerular endothelial cells results in an increase in the level of TGF-β1 and TGF-β2 mRNA and leads to endothelial-mesenchymal transiton.Inhibition of TGF-β partly prevents this process,indicating that TGF-β plays a crucial role in high-glucose-induced glomerular endothelial-mesenchymal transiton.
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Objective To explore the effect of high glucose on the renin-angiotensin system (RAS) in rat glomerular endothelial cells and its probable mechanism.Methods Rat glomerular endothelial cells were stimulated by culture medium containing 5 mmol/L or 30 mmol/L glucose (with or without pre-treatment of captopril and chymostatin) for 12 h,24 h,48 h,72 h.ELISA,real-time PCR,Western blotting and confocal immunofluorescence microscopy were employed to examine the follows:the angiotensin Ⅱ (Ang Ⅱ ) concentration in cell lysate and the culture medium; the mRNA levels of angiotensinogen and renin; the protein levels of angiotensin Ⅱtype 1 receptor (AT1R),angiotensin Ⅱ type 2 receptor (AT2R),renin and angiotensinogen in cell lysate; localization of intracellular AT1R,AT2R and renin.Results Exposure to high glucose for only 12 h or 72 h resulted in a significant increase of Ang Ⅱ levels in the culture medium compared with control cells (P＜0.05),but only exposure to high glucose for 72 h resulted in a significant increase of Ang Ⅱ levels in the cell lysate compared with control cells (P＜0.05).However,exposure to high glucose for 24 h or 48 h had no effects on Ang Ⅱ levels in the cell lysate or culture medium.The captopril and chymostatin were able to antagonize high glucose induced Ang Ⅱ generation when exposure time was 72 h but not 12 h.Exposure to high glucoseincreased the mRNA level of angiotensinogen,but reduced the level of renin mRNA,meanwhile angiotensinogen protein increased,and AT1 protein reduced,but protein levels of AT2R and renin were unchanged.However,the transformation of AT2R from the cell nucleus to cytoplasm was observed.Conclusions High glucose can activate the local renin-angiotensin system in rat glomerular endothelial cells,and the probable mechanism may contribute to ACE and non-ACE pathways.The effects of high glucose on glomerular endothelial cells may also involve in the substrate and receptors of Ang Ⅱ.
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Objective To investigate the effect of advanced glycation end products (AGEs) on the disruption of tight junctions in rat glomerular endothelial cells (rGEnCs) and the role of renin-angiotensin system (RAS) in this pathological procedure.Methods Primary cultured rGEnCs were incubated with AGEs at concentrations of 20 mg/L,40 mg/L and 80 mg/L,for 6 h,12 h and 24 h respectively.The cells were treated with captopril (1 mmol/L) or valsartan (10 μ mol/L)to block RAS.The endothelial permeability was investigated by transendothelial electrical resistance and the flux of fluorescein isothiocyanate-conjugated bovine serum albumin.The expression of AGEs receptor (RAGE),tight junction proteins [occludin,claudin-5,junctional adhesion molecules A (JAM-A) and zona occludens-1 (ZO-1)]and RAS components [angiotensinogen,renin and angiotensin Ⅱ type 1 receptor (AT1)]were detected by Western blotting.Immunofluorescence was used to demonstrate the disruptions of the tight junction proteins.The activity of angiotensin converting enzyme (ACE) was evaluated by UV spectrophotometry.Angiotensin Ⅱ (Ang Ⅱ ) was measured by enzyme immunoassay.Results The monolayer permeability,the expression of RAGE,the activity of ACE,the concentration of Ang Ⅱ and the expression of AT1 of rGEnCs were increased after induced by AGEs.Meanwhile,AGEs decreased the expression of occludin,claudin5 and JAM-A and induced disruption of tight junction proteins.Pretreatment with anti-RAGE antibody (100 mg/L),captopril or valsartan could attenuate the detrimental effect of AGEs.Conclusion The changes of permeability induced by AGEs in glomerular endothelial cells are partly mediated by RAS through RAGE.
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Objective To present the baseline characteristics of serum uric acid level in patients with chronic kidney disease(CKD)in single.centre nephrology clinic and judge the risk factor for decreased renal function of CKD Datients.Methods A cross-sectional study on CKD patients in clinic was carried out for 9 months.Results 780 CKD cases were enrolled in the study.The top four causes of CKD in these patients were primary glomerular disease(59.0%),essential hypertension(7.6%),lupus nephritis(6.4%)and diabetic nephropathy(6.3%).The average age was 41.9.The distribution of CKD stage was 47.8%of CKD1,18.7%of CKD2,14.0%of CKD3,8.1% of CKD4 and 11.4%of CKD5.Multivariate Logistic regression regression analysis indicated that age,proteinuria,hypertension were independently correlated with decreased renal function.Conclusion This is the largest cross-sectional study of CKD in China,which will help to determine the basic status of Chinese CKD patients,laying a basis for further followup.