Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration.2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI). Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). A linear regression model was developed to analyze the factors which determine eGFR and TKV changes.To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222) and higher TKV (r = 0.134).The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3±10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline logThis large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression. PKD1 and PKD2) are known to cause ADPKD PKD1 gene which encodes the ciliary protein polycystin-1 are responsible for 85% of the cases, and mutations in PKD2 encoding polycystin-2 are responsible for the remaining 15% of the cases PKD2 gene mutations generally lead to milder disease than PKD1 gene mutations Autosomal dominant polycystic kidney disease (ADPKD) is a distinct genetic disease which occurs with variable frequency in all parts of the world Although the clinical description of ADPKD is well known, it remains difficult to predict the clinical course and the occurrence of complications. Therefore longitudinal cohorts have been established to document the long-term clinical course of the disease and to identify parameters which predict progression. The best characterized cohort (n = 241) with the longest follow-up is the cohort of the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) in the United States which has provided important information regarding the main predictors of renal disease progression Here we describe the clinical characteristics and the factors which predict disease progression in a unique longitudinal cohort of Chinese patients (n = 541) with ADPKD. These data will be useful to design future clinical trials which endeavor to define therapies which retard disease progression in ADPKD.The study protocol and consent form were developed, reviewed and approved by the Kidney Institute of PLA. The study was approved by the Ethics Committee of the Second Military Medical University . Chinese patients with an established diagnosis of polycystic kidney disease were identified by a nationwide search in mainland China. All patients were recruited at a single nephrology center at Changzheng Hospital . Recruitment started in June 2009, and is ongoing. Informed written consent was obtained from each potentially eligible subject or his legal representative prior to enrollment.2 according to the CKD-EPI formula for adults or the Schwarz equation for children. Patients on dialysis treatment or having received a kidney transplant were excluded.Patients had to have an established diagnosis of autosomal dominant polycystic kidney disease (ADPKD) as defined by the criteria of Pei Subjects were ineligible to participate if they were unable to undergo breath-held magnetic resonance imaging (MRI), or had contraindications for MRI such as having a cardiac pacemaker, metallic foreign bodies or aneurysmal clips. Patients were also excluded if they had systemic diseases other than hypertension that could potentially affect renal function. Female patients who were pregnant, lactating or less than 6 months postpartum were also excluded.Medical histories were taken and physical examinations were performed at the time of screening and enrollment at Changzheng Hospital in Shanghai. Enrolled subjects were scheduled for a 2-day evaluation visit, and were then seen at 6 months intervals. Blood and urine samples were collected at each visit. Abdominal MRI scans were obtained at baseline and at each follow-up visit, using a previously described protocol All medical data were anonymized and transferred to a spreadsheet. Descriptive analyses were performed for all baseline data . Female and male patients were compared with a two-tailed Fisher’s exact test for nominal variables and with a two-tailed Mann-Whitney U test for quantitative variables. For the correlation analyses, the Pearson product-moment correlation coefficient or Spearman’s rho was calculated.P = 0.105).A multiple linear regression was run with yearly eGFR change or yearly TKV growth (%) as dependent variable, and the following independent variables: age, sex, observation time, history of hypertension, intake of antihypertensive drugs, SBP, DBP, episodes of macrohematuria, baseline eGFR, protein/creatinine ratio, baseline TKV and baseline thrombocyte count. A total of 279 patients aged >18 years and ≤60 years with valid data for all variables of the model were included. For the variables SBP, DBP, episodes of macrohematuria and thrombocyte count, missing values were imputed by data from the next following visit. Overall, the missingness of data was dependent on observation time, i.e., patients with fewer visits and thus shorter observation time had more missing data. Except for observation time, Little’s test indicated that data were missing completely at random , a regression with robust standard errors was run.For predictor selection, a stepwise forward and backward selection using the exact Akaike Information Criterion (AIC) was performed. In the model with yearly eGFR change as dependent variable, baseline eGFR was also included as additional controlling variable. Nonlinearity was evaluated with component plus residual plots, normality was checked with a Q-Q plot for studentized residuals. Homoscedasticity was evaluated with a studentized residuals versus fitted values plot and with the non-constant error variance test. The outlier test and Cook’s D plot were used to check for outliers and influential points. Several measures had to be taken to meet the assumptions of linear regression. A normal distribution of the residuals was achieved by windsorizing the dependent variable. Linearity was reached by logAll analyses were done using SPSS Version 20 except for the regression, which was performed in R version 2.15.2.The Chinese ADPKD cohort represents an ongoing longitudinal study. In the present interim report, we analyzed 541 patients who were enrolled between June 2009 and December 2011. Patients were followed up every six months. The mean follow-up duration was 14.3±10.6 months .P<0.001), were less often hypertensive (P<0.001), had slightly more often liver cysts (P = 0.444) and more pain (P = 0.311), but less often macrohematuria (P = 0.035). Frequency distributions for age, antihypertensive drugs, diastolic blood pressure (DBP), systolic blood pressure (SBP), eGFR, and TKV are shown in the The recruitment strategy of the cohort subjects was designed to allow for the inclusion of a broad age range of patients with ADPKD, including children. 2-microglobulin was found with increasing age. Likewise, the eGFR (creatinine-based CKD-EPI formula) showed a steady decrease in these four age categories. Correlation analysis confirmed that age was negatively correlated with eGFR (see below). Of note, the yearly eGFR decline became more pronounced with increasing age, amounting to –3.5 ml/min/1.73 m2 per year in the age category of 51 to 60. Furthermore, the urine protein/creatinine ratio also increased with age, whereas the urine specific gravity (1.016±0.007 g/cm3) and the urine pH (5.69±0.50) did not change substantially in the different age groups. Table S1 in 10-transformed TKV and positively with eGFR , and a lower yearly TKV growth rate .The mean TKV for the entire cohort amounted to 1265±1002 cmper year . The larr = 0.902), between RCV and LCV (r = 0.857), and between TKV and TCV (r = 0.951). The Tables S3 and S4 in 3. In r amounted to –0.596 (p<0.001). TKV correlated best with eGFR in the age group 19–30 (r = –0.622) and was least in the age group 51–60 (r = –0.382). As mentioned above, age correlated positively with log10-transformed TKV (r = 0.439) and negatively with eGFR (r = –0.645)  . However –0.645) .10 protein/creatinine ratio and also baseline log10 TKV with the yearly decrease of eGFR. Age and thrombocyte count were also significantly associated. At first sight the influence of history of hypertension and intake of antihypertensive drugs on eGFR change seems complicated. When developing the model we found that the association between the unadjusted estimate of history of hypertension and the yearly eGFR change was negative. When controlling for intake of antihypertensive drugs the association turned into a positive one. Since the intake of antihypertensive drugs may reflect a higher disease severity, the addition of this latter parameter to the model seems to be justified.10 protein/creatinine were significant predictors for yearly TKV change. Although the dependent variable already accounted for baseline TKV insofar it represents the percental increase, baseline TKV was also retained in the regression model. Paradoxically, a lower diastolic blood pressure was associated with a higher yearly TKV change. It is however difficult to estimate the true effect of blood pressure on TKV change since in most hypertensive patients, blood pressure is controlled by antihypertensive drugs. The regression model for TKV change was hampered by heterogeneity of variance, which could be reduced considerably by introducing observation time into the model.th or 6th decade of life PKD1, male sex, early onset hypertension and macrohematuria, baseline GFR, albuminuria, renal cyst volume and uric acid are among the most important factors which predict more severe disease progression and an earlier onset of ESRD A majority of patients with ADPKD reach end-stage renal disease (ESRD) in the 5Large cross-sectional and retrospective studies of ADPKD cohorts have provided fundamental information on the clinical course and the predictive factors, but their value has been limited by the lack of prospective data for GFR decline and cyst growth. Thus it is only recently – and particularly in association with the advent of CT- and MRI-based radiological techniques that allow precise measurement of renal volume changes – that truly prospective cohorts have been set-up to elucidate the characteristics of polycystic kidney disease progression. The invaluable CRISP cohort has been established between 2001 and 2005 and represents the most detailed cohort of 241 patients with ADPKD Here we describe a large longitudinal clinical cohort of 541 Chinese patients with ADPKD. Our data allow not only verification but also extension of the data from CRISP 3 and a 5.3±3.9% yearly increase of TKV 3 and an extrapolated yearly TKV growth of 5.4±9.5% 3 and an average yearly TKV growth of approximately 5.2% in the age category between 19 and 40 years. Furthermore the baseline eGFR and the yearly eGFR changes seen in CRISP and SUISSE ADPKD were similar to the Chinese patients in the respective age categories. Taken together this suggests that the impact of the Chinese ethnicity on ADPKD is negligible. As a consequence, clinical trials in Chinese ADPKD patients might rely on similar assumptions regarding the definition of clinical endpoints.In agreement with the CRISP and the SUISSE ADPKD results, our data confirm that ADPKD is more severe in male than in female patients, and that there is an age-dependent decrease of eGFR and increase in TKV which extends to older patients. Consistent with the two other cohorts we found similar values for eGFR and TKV and the yearly changes thereof in their respective age range. Thus at a mean age of 32.4±8.9 years, CRISP reported a baseline TKV of 1076±670 cm3. For reasons not yet well understood it appears that the predictability of the change in TKV is as difficult as the predictability of changes in eGFR. This is also illustrated by the poor correlation between the yearly eGFR and TKV changes in our cohort, and by the data in Earlier prospective studies in patients with ADPKD have shown that GFR and kidney volume correlate 10 protein/creatinine ratio, log10 baseline TKV and age. On the other hand the linear regression analysis with percental yearly TKV change as dependent variable revealed that the intake of antihypertensive drugs, male sex, lower thrombocyte count and higher log10 protein/creatinine were associated with this variable. The fact that the TKV change was dependent on observation time implicates that the variance is larger for patients with short observation periods and decreases with longer observation periods. This might possibly be explained by the fact that bursting cysts lead to lower TKV at shorter observation periods but less so when the observation time is longer. With increasing observation time, the trend towards a steady TKV growth might get clearer. Consequentially and as stated above, it is essential for the study of TKV growth to maximize follow-up times in order to reduce the “noise” caused by ruptured cysts.The linear regression analysis revealed that the yearly decrease of eGFR was significantly associated with higher logAn important finding which has not been described in other cohorts was the identification of a reduced thrombocyte count in older age groups. Although there is a small decrease of the thrombocyte count with increasing age in the normal population, we found a 32% lower thrombocyte count (–71 G/l) in the oldest age group when compared with the youngest cohort patients. Furthermore we found a positive correlation between thrombocyte count and eGFR, and a negative correlation with TKV. Bath et al. also described a reduced number of thrombocytes in ADPKD patients (average age 31 years) in comparison with matched control subjects (–63 G/l), in addition to an increased platelet volume (median 8.4 vs 8.0 fl), suggesting that there is enhanced platelet consumption in ADPKD 10-transformed TKV and protein/creatinine ratio significantly predicted eGFR loss and were associated with TKV growth. Furthermore we identified the decreased thrombocyte count as a novel parameter which is associated with more advanced renal impairment, higher TKV and higher TKV growth. The Chinese cohort provides an important data source for the understanding of ADPKD disease progression and the design of future clinical trials in China.In conclusion, we describe the clinical characteristics and the factors that predict disease progression in a large cohort of Chinese patients with ADPKD. Among the progression factors we found that logFigure S1Frequency distributions for different categories. A) frequency distributions for age (years) (n = 541); B) frequency distributions for number of prescribed antihypertensive drugs (n = 522); C) frequency distributions for diastolic blood pressure (DBP) in mm Hg (n = 403); D) frequency distributions for systolic blood pressure (SBP) in mm Hg (n = 403); E) frequency distributions for estimated glomerular filtration rate (eGFR) in ml/min/1.73 m2 (n = 502); F) frequency distributions for total kidney volume (TKV) <5000 in cm3 (n = 529).(TIF)Click here for additional data file.Figure S2Correlations between baseline TKV and yearly TKV growth. A) Baseline TKV (cm3) lined up in ascending order, with corresponding yearly TKV growth (cm3) depicted in the graph above. B) Yearly TKV growth (cm3) lined up in ascending order with corresponding baseline TKV (cm3) depicted in the graph above. Only patients >18 years and ≤60 years are included (n = 393).(TIF)Click here for additional data file.File S1Supporting Tables. Table S1: Table shows the eGFR and the yearly changes of the eGFR, stratified by age categories. The eGFR was calculated according to the CKD-EPI formula in adults and according to the Schwarz formula in children. Table S2: Data show mean ± standard deviation. Table S3: Table reports baseline kidney volumes in cm3. RKV, right kidney volume; LKV, left kidney volume; TKV, total kidney volume. Table S4: Table reports baseline cyst volumes in cm3. RCV, right cyst volume; LCV, left cyst volume; TCV, total cyst volume.(DOC)Click here for additional data file.


Angiotensin II receptor antagonists (ARBs) have a protective effect in patients with chronic kidney disease (CKD) by suppressing progression, possibly by controlling hypertension. One marker of progression in such patients is the degree of proteinuria.We aimed to retrospectively examine the protective effect of ARBs  on CKD patients without a history of diabetic nephropathy.Data were retrieved from medical records of patients with a diagnosis of CKD (serum creatinine [Cre] <3.0 mg/dL [265.2 μmol/L] and urinary protein of 0.3–3.5 g/g Cre) who were treated with ARBs and those with diabetic nephropathy were excluded. Blood pressure, serum Cre, urinary protein, urinary Cre, and estimated glomerular filtration rate were measured before the research began and at 1, 3, 6, 12, and 24 months after the ARB treatment was started.P < 0.05), and after 2 years, it was greater than for losartan (P < 0.05). Diastolic blood pressure decreased in all patients; this decrease was significantly greater with olmesartan 1 month after treatment started than with candesartan (P < 0.05). Olmesartan significantly decreased daily urinary protein compared with that with the other ARBs during follow-up. This decrease 1 month after starting ARB treatment was greater for olmesartan than losartan, valsartan, and candesartan , and after 2 years, this effect was still significant .Forty-four patients completed the research protocol. Of these, 10 took olmesartan, 13 took losartan, 9 took candesartan, 9 took valsartan, and 3 took telmisartan. Systolic blood pressure was decreased in all cases. The extent of this decrease 1 month after starting ARB treatment was greater for olmesartan than for candesartan (Olmesartan is more effective in reducing urinary protein than other ARBs, suggesting that the renal protective effects of olmesartan may be better than those of other ARBs. Angiotensin II receptor antagonists (ARBs) confer protection in patients with renal insufficiency, delaying progression in patients with managed hypertension. Most reported cases have been in patients with diabetic mellitus (DM) and related kidney disease.The current research examined the protective effects of various ARBs in patients with nondiabetic related chronic renal failure.We used a computerized database of all patients admitted from 2004 to June 2010 for this retrospective review. Patients included in this review were those in whom chronic kidney disease (CKD) had been treated with ARBs and whose diagnosis was made by renal biopsy or their clinical history and results of laboratory investigations. We aimed to exclude patients with nephritic syndrome whose urine protein was >3.5 g/g creatinine (Cre). Internal medicine physicians specializing in diabetes examined patients with diabetic nephropathy earlier than those specializing in the kidney in our hospital. However, they did not examine urine Cre concentrations in those patients. When patients consult internal medicine physicians specializing in the kidney in preparation for dialysis therapy, their CKD is already beyond stage 4 (with a serum Cre concentration >3.0 mg/dL). Because these Cre concentrations were outside the range of our research, those with diabetic nephropathy were excluded. Patients with serum Cre concentrations of 3.0 mg/dL (265.2 μmol/L) and a urine protein of 0.3–3.5 g/g Cre when ARB treatment was started were included in the analysis. To evaluate the effect of each ARB and to ignore the effect of concomitant drugs, when a research patient was taking other drugs , they were not excluded, provided that they continued to take these drugs after ARB treatment was started and continued to take the same doses during the research period. An arbitrary choice of ARB was not made in any of the patients when they started treatment with an ARB, and each patient took only 1 ARB during the research period. The research was approved by the institutional review board, and informed consent was waived because of the retrospective analysis design.2] = 194 × Cre−1.094 × age−0.287, female eGFR: [ml/min/1.73 m2] = 194 × Cre−1.094 × age−0.287 × 0.739).Blood pressure, serum Cre concentrations, urinary protein concentrations, urinary Cre concentrations, and estimated glomerular filtration rate (eGFR) were measured before the ARBs were started and then at 1, 3, 6, 12, and 24 months and were analyzed retrospectively. All urine and blood Cre concentrations were measured using the creatinase sarcosine oxidase peroxidase method in our hospital. This method for measuring urine and blood Cre concentrations was used throughout this research. The eGFR was calculated using the Japanese Kidney Society method . Changes in systolic and diastolic blood pressure and daily urinary protein loss after starting ARB treatment did not follow a normal distribution on a histogram. Because it was assumed that they would closely fit a log-normal distribution, these changes were logarithmically transformed to obtain a normal distribution. The intergroup variation from the start of treatment for hypertension and urine protein concentrations was analyzed using Dunnett’s post hoc test. Comparisons between olmesartan and each ARB  for hypertension and urine protein concentrations were analyzed using the Bonferroni adjustment. Multigroup analysis of the 4 groups  for hypertension and urine protein concentrations was performed using repeated-measures ANOVA, assuming a 2-sided 5% significance level and a power of 80%. Statistical analysis was performed using Microsoft Excel 2010 software.2, serum potassium concentrations were 4.5 (0.5) mEq/L, and urine protein concentrations were 1.24 (0.86) g/g Cre. The mean (SD) time from the onset of CKD to starting ARB treatment was 9.5 (9.5) years (The research protocol was completed by 44 patients with a mean (SD) age of 52.8 (13.4) years; and 20 patients were men. When ARB treatment was started, the mean (SD) systolic blood pressure was 145.3 (22.7) mm Hg and the mean (SD) diastolic pressure was 85.2 (13.4) mm Hg. Mean (SD) serum Cre concentrations were 1.1 (0.6) mg/dL, eGFR was 58.25 (25.2) mL/min/1.73 m5) years . A renalP < 0.05)  mg olmesartan, 28.8 (9.0) mg losartan, 6.7 (1.9) mg candesartan, 48.9 (16.6) mg valsartan, and 33.3 (9.4) mg telmisartan. Because only 3 patients took telmisartan and only 1 completed 2 years of follow-up, those taking telmisartan were excluded from the research. In all patients, the doses remained the same throughout the research period. When ARB treatment was started, there were no significant differences in mean age, systolic and diastolic blood pressure, concentrations of serum Cre, eGFR, serum potassium, and urine protein in any of the groups of patients . The onl < 0.05) .In all patients, there were no significant changes in the concentrations of serum Cre and serum potassium and eGFR.P < 0.05) (P < 0.05)  among the 4 groups. However, we did observe a time-dependent difference in the decrease in blood pressure between olmesartan and 2 of the ARBs using a 2-group analysis. Systolic blood pressure was decreased in all cases , but the < 0.05) , and aft < 0.05) .P < 0.05)  .There were no significant differences in urinary protein by multigroup analysis (ANOVA) among the 4 groups.P < 0.01, P < 0.01, and P < 0.05, respectively), and after 2 years, this difference was still significant   .P < 0.01, P < 0.05) (P<0.01)  . Olmesar(P<0.01) .P < 0.01]; all ARBs, achievement group [n = 27]: −0.56 [0.16] g/g Cre vs the nonachievement group [n = 14]: −0.42 [0.22] g/g Cre [P < 0.05]).We evaluated daily urinary protein in the subpopulation who achieved the ARB blood pressure goal of 130/80 at 1 year after starting ARB treatment versus those who did not achieve this blood pressure goal. Urinary protein was decreased in the group who achieved the blood pressure goal compared with the group who did not  and block the action of angiotensin II. In addition, the receptor itself depends on inverse agonist activity inhibiting mechanical stress caused by the stretching of cells, which is to be expected in organs such as the heart and kidney.Olmesartan has a double-chained domain consisting of carboxyl and hydroxyl groups, which can strongly combine with the ARB type 1 . Therefore, another limitation of this analysis is that it was underpowered. The prescription of ARBs was not influenced by the evaluation team. This is also a limitation in that the prescribing physicians could have been biased in their determination of which ARB to use for a given patient.Therefore, to determine whether olmesartan has a renal protective effect other than an antihypertensive protective effect, a prospective, randomized, large-scale study is necessary.


We assessed left ventricular structural alterations associated with chronic kidney disease (CKD) in Congolese patients with type 2 diabetes.2), moderate (CrCl 30–60 ml/min per 1.73 m2) and severe CKD (< 30 ml/min per 1.73 m2). Left ventricular hypertrophy (LVH) was indicated by a LV mass index (LVMI) > 51 g/m2.7 and LV geometry was defined as normal, or with concentric remodelling, eccentric or concentric hypertrophy, using relative wall thickness (RWT) and LVMI.This was a cross-sectional study of a case series. We obtained anthropometric, clinical, biological and echocardiographic measurements in 60 consecutive type 2 diabetes patients  aged 20 years or older from the diabetes outpatient clinic, University of Kinshasa Hospital, DRC. We computed creatinine clearance rate according to the MDRD equation and categorised patients into mild (CrCl > 60 ml/min per 1.73 mp ≤ 0.001), a greater proportion of LVH  and longstanding diabetes . Their left ventricular internal diameter, diastolic (LVIDD) was , LVMI was  and proportions of concentric  or eccentric  LVH were also greater. Severe CKD was associated with increased interventricular septum, diastolic (IVSD) , posterior wall thickness, diastolic (PWTD) , relative wall thickness (RWT)  rate of LVH , and elevated proportions of concentric remodelling  and concentric LVH  in comparison with patients with moderate CKD. In multivariable adjusted analysis, hyperuricaemia emerged as the only predictor of the presence of LVH in patients with CKD .Compared to patients with normal kidney function, CKD patients had higher uric acid levels (450 ± 166 vs 306 ± 107 μmol/l; In keeping with a higher rate of cardiovascular events usually reported in patients with impaired renal function, CKD patients exhibited LVH and abnormal LV geometry. Prevention of cardiovascular disease (CVD) requires early detection and correction of predisposing conditions and risk factors in susceptible subjects.2Several reports have indicated that chronic kidney disease (CKD) is independently associated with the presence of LVH on echocardiography, suggesting that CKD might be related to LV mass index (LVMI).7Such an association holds more risk for black people, whose high propensity to diabetic nephropathy has often been documented.We enrolled in the present study consecutive type 2 diabetes subjects aged 20 years and older attending the outpatient clinic at the University of Kinshasa Hospital. Ethical approval was obtained from the institutional ethics review board and informed consent was obtained from the study participants. Exclusion criteria included ischaemic heart disease (IHD), acute coronary syndrome (ACS), congestive heart failure , valvular heart disease, cerebral infarction or transient ischaemic attack (TIA).2 and ≥ 30 kg/m2, respectively. Central obesity was categorised as waist circumference > 102 cm in men and > 88 cm in women.Self-reported physical activity, alcohol use and smoking habits, known duration of diabetes mellitus, current treatments and measures of adiposity [body mass index (BMI) and waist circumference] were obtained in all patients. Overweight and obesity were classified as BMI ≥ 25 kg/mBlood pressure (BP) was measured in the supine position using a mercury sphygmomanometer with an appropriate cuff on the left arm; the average of two readings was used for statistical analysis. Pulse pressure (PP) calculated as systolic blood pressure (SBP) minus diastolic blood pressure (DBP) was considered increased when > 60 mmHg.A 12-hour overnight fasting venous blood sample was collected for measurement of total cholesterol and its sub-fractions [low-density lipoprotein cholesterol (LDL-C) high-density lipoprotein cholesterol (HDL-C)], triglycerides (TG), plasma glucose, serum uric acid and creatinine levels. LDL-C was calculated according to the Friedewald formula.According to the NCEP-ATP III guidelines,2; it was stratified into mild (CrCl > 60 ml/min per 1.73 m2), moderate (CrCl: 30–60 ml/min per 1.73 m2) and severe (CrCl < 30 ml/min per 1.73 m2).We computed glomerular filtration rate [creatinine clearance (CrCl)] using the MDRD equation.Echocardiographic examination was performed with the patient in the partial left lateral decubitus position using an Acuson 128XP/10˝ machine with a 3.5-MHz transducer. Two-dimensional guided M-mode measurements were obtained as recommended by the American Society of Echocardiography (ASE).132.2.17We used the Devereux modified cubed formula to calculate left ventricular mass (LVM).t-tests were used for comparing categorical and normally distributed continuous variables, respectively.Data are expressed as mean ± standard deviation (SD) or relative frequency in per cent. The distribution of duration of hypertension and triglyceride levels being positively skewed, the non-parametric Mann-Whitney test was used for these variables. Chi-square and Student p-value ≤ 0.5 was considered statistically significant.Multiple regression models and the likelihood ratio method were performed with LVH as the dependent variable for the assessment of the strength and independence of association with risk factors. Adjusted odds ratio (aOR) were calculated for each variable from a model which included all these variables; the resulting aOR allowed the direct comparison of the independent effects of these variables to decide which variable has the greater effect on LVH. All statistical analyses were performed with SPSS for Windows, version 18.0. A 2, 95 ± 12 cm, 148 ± 26 mmHg, 84 ± 13 mmHg, and 8.10 ± 3.31 mmol/l, respectively. Diabetes was frequently associated with other CV risk factors, among which hypertension (80%) was the commonest. Clustering of risk factors into the metabolic syndrome was observed in 58% of patients.2 or higher. Compared to those with normal renal function, the duration of diabetes was longer , the proportion of patients on current antihypertensive drugs greater  and the level of uric acid higher  in CKD patients. The two subgroups were similar for the other variables.Besides antidiabetic therapy, 97% of patients were receiving BP-lowering drugs. CKD was observed in 32 patients (53%), 20 of whom (62%) had a CrCl rate of 30 ml/min per 1.73 mp ≤ 0.001), LVMI  and higher proportions of LVH ; they also showed higher proportions of concentric  and eccentric  LVH. Compared to patients with moderate CKD, those with severe CKD had increased interventricular septum thickness, diastolic (IVSD) , RWT  and higher proportions of LVH . Concentric remodelling  and concentric hypertrophy  were the geometric patterns most frequently encountered in patients with severe CKD. Between groups, systolic function indices did not differ.In multivariable adjusted analysis, the probability of LVH among CKD patients was increased by hyperuricaemia  for the presence versus the absence of hyperuricaemia.The key finding of the study was that the elevated prevalence of chronic kidney disease in our diabetic patients was associated with abnormal cardiac structure. The alteration in renal function was moderate in the majority of cases. Left ventricular mass index, the frequency of left ventricular hypertrophy and uric acid levels were higher in CKD patients in whom multivariable adjusted analysis indicated uric acid as the only predictor of LVH.The elevated prevalence of moderate to severe CKD has been reported in 15 to 23% of diabetic patients in whom it predicts the occurrence of CVD.23Alteration in kidney function predominated in patients with a longer duration of diabetes, enhancing the effect of both chronic hyperglycaemia and the ageing process.272.4The high prevalence of LVH in CKD patients found in our study agrees with that of other studies.LVH has been reported to predispose to ischaemic heart disease, arrhythmias and congestive heart failure.33et al. reported greater systolic, diastolic, pulse and mean blood pressure among patients with concentric hypertrophy in comparison with those with normal geometric patterns.34Moderate CKD and a high proportion of hypertension could explain the pre-eminence of concentric hypertrophy observed in the present study. In Nigerian hypertensive patients, Aje In our study, hyperuricaemia emerged as the only predictor of LVH in CKD patients. The mechanisms that could account for increased uric acid levels in CKD include overproduction to counteract oxidative stress and endothelial dysfunction, the severity of diabetes and/or hypertension, impaired renal uric acid clearance, and insulin resistance/hyperinsulinaemia-induced proximal renal tubular reabsorption of sodium and urate.38The interpretation of the results of our study is confounded by some limitations. The cross-sectional design of the work precludes any causal relationship between CKD and associated risk factors. Moreover, the sample size did not allow sufficient power to detect additional associations. One wonders to what extent the conclusions of this clinic-based study could be extrapolated to the general population, given the bias in the referral of patients. The findings of our study bear, however, some clinical implications for CKD identification, treatment protocol and estimated prognosis in hypertensive patients.This study has shown that LVH is common among type 2 diabetes patients with CKD. Concentric LVH was the geometric LV pattern most frequently encountered and its frequency increased with the decline in renal function. Hyperuricaemia emerged as the unique independent predictor of the risk of LVH


Background. The association between outcome and elevated admission blood pressure (BP) remains uncertain in acute stroke patients. The aim of the present study was to examine the association between admission blood pressure and outcome in ischemic stroke patients treated with tissue plasminogen activator (tPA). Method. This study included patients treated with tPA within 4.5 hours after symptom onset. Four quartiles based on the admission BP values were defined. BP development of the first 12 hours was compared to outcome parameters defined as NIHSS 24 hours after tPA and mRS after 3 months. Results. 265 patients were included. A trend with worse short- and long-term outcome was present in the quartiles with the lowest and highest admission BP compared to the quartile with admission values at 140–160 mm Hg systolic. BP in quartile 1 was insignificantly decreased after 12 hours while the BP in quartiles 3 and 4 remained above recommended levels. Conclusion. Admission BP is associated with short- and long-term outcome after stroke. Low- or high-admission BP indicates cardiac comorbidity or preexisting hypertension, where close monitoring and further examinations are requested to prevent poorer outcome. The relation between acutely elevated blood pressure and stroke severity and outcome in acute stroke fuels the continued debate whether the increase in blood pressure shall be seen primarily as a pathological mechanism or a physiological stress indicator.A U-shaped relation between the level of acute elevation in blood pressure and outcome has been introduced defining a middle area with better prognosis than patients with high as well as low blood pressure [1–3]. High blood pressure is observed in the majority of patients admitted with acute stroke , 5. SeveThe aim of the present study was to examine the association between admission blood pressure levels and the subsequent development in outcome in ischemic stroke patients treated with tissue plasminogen activator (tPA).This prospective cohort study included consecutive patients treated with tPA within the first 4.5 hours after symptoms onset from April 2009 to December 2011 at Copenhagen University Hospital, Bispebjerg, which has a catchment area of 1.7 million on even dates. Inclusion criteria included reported admission values for systolic blood pressure, admission NIHSS, and prehospitalization mRS, but missing values of diastolic blood pressure, follow-up NIHSS, and mRS after 3 months were accepted due to a random pattern of undecipherable values.On admission, patients underwent standard neurological and radiological workup including clinical scoring , biochemistry, and monitoring.Radiological workup contained noncontrast computed tomography (CT) and CTA from the arcus aorta to the vertex cranium on a 64-slice MDCT scanner (Phillips).tPA treatment decision was based on clinical and radiological findings and post-tPA follow-up included 24 hours monitoring, CT-C, and NIHSS evaluation on day 2. After discharge all patients were followed up at 3 months by telephone or in the outpatients' department. Patients' data regarding ability to be self-reliant after discharge were collected and described with modified Rankin Scale (mRS).On admission nurses measured the blood pressure manually using standard automated OMRON sphygmomanometers with fitting cuff and the patient in a supine position and subsequent monitoring included repeated measurements 12 hours post-treatment.Clinical data was collected prospectively from the patient files regarding relevant blood pressure measurements, biochemistry, NIHSS, and medical history. Likewise the presence of relevant risk factors including hypertension, diabetes mellitus, hypercholesterolemia, prior myocardial infarction, atrial fibrillation (AFIB), smoking, and alcohol consumption was noted. Hypertension was defined either by registration of the diagnosis in previous medical charts, use of antihypertensive medication, or 3 blood pressure measurements ≥140/90 mm Hg taken 1 hour apart and at least 24 hour after stroke onset. Diabetes mellitus was defined by use of antidiabetic medication, fasting p-glucose ≥ 9 mmol/L, or HgA1c ≥ 6.5. Definition of hypercholesterolemia was use of lipid-lowering medication or p-cholesterol ≥ 5.0 mmol/L. Prior myocardial infarction or coronary bypass surgery defined ischemic heart disease and AFIB was defined by previous AFIB or ≤30 seconds or documented at ECG in 12 leads. Smoking was defined as current use of tobacco and former smoker was defined with a history of at least 3 pack years. Consumption of alcohol to an excessive amount was defined with ≥14/21 units of alcohol weekly, respectively, for women and men. We divided patients into the four quartiles of systolic and diastolic blood pressure values on admission. The blood pressure change at 12 hours was also calculated for these groups. Admission blood pressure levels as well as their degree of subsequent decline (after 12 hours) were compared to outcome parameters, which were defined as NIHHS development 24 hours after thrombolysis and 3 months outcome (mRS). A good outcome was defined as mRS ≤ 2 and a poor outcome as mRS > 2.The presence of risk factors was compared between groups concerning significant differences.P value ≤0.05 defined a significant difference between the compared variables. Statistics were calculated in SPSS, version 19.0. Demographic variables, risk factors, NIHSS, and mRS were compared in the four blood pressure groups with the Kruskal-Wallis test and Pearson Chi-Square test. The study was approved by the Danish Data Protection Agency, file number 2010-41-5205.n = 265) and the excluded group (n = 65) concerning mean age, being 68 years (SD 13.7) versus 66 years (SD 13.8), respectively. Also no difference was found regarding NIHSS at admission, being 8.5 (SD 6.6) versus 8.6 (SD 5.9) and post-thrombolysis NIHSS, being 5.6 (SD 6.6) versus 4.5 (SD 5.4), respectively.Seven hundred and sixty patients were admitted and evaluated for thrombolysis treatment in the study period. Two hundred and sixty five (app. 35%) were treated with tPA and had decipherable systolic blood pressure values on charts . These pA trend towards a negative influenced short and long-term outcome was seen in both ends of spectrum concerning admission blood pressure. Low (group 1) as well as high (groups 3 and 4) admission blood pressure thus presented poorer outcome parameters compared with the group who showed admission values between 140 and 160 systolic (group 2) . This trPatients with low admission blood pressure (group 1) were alone in experiencing nonsignificant drop in systolic and diastolic blood pressure values during the first 12 hours after ictus . This isOpposed to these, patients with admission blood pressure values between 140–160 systolic (group 2) experienced a moderate decrease in systolic and diastolic blood pressure values and showed levels closest to the normal spectrum after 12 hours. This tendency was associated with better short and long-term outcome Figures  and 4.Patients with mRS at 3 months of 0–2 experienced an average systolic decrease in admission blood pressure, which was 10 mm Hg higher than patients with mRS 3–6.The presence of cardiac premorbidity in the group with low admission BT was significantly higher than in the other groups . PreexisIn the present study we demonstrated both a trend towards poorer short- and long-term outcome in groups with low as well as high admission blood pressure. A trend with a higher decrease in blood pressure after 12 hours in the quartile group with values interpretable as resulting from a physiological stress response was also found. Poor outcome in patients with low admission blood pressure has previously been identified as resulting from cardiac comorbidity inhibiting elevation of acute blood pressure levels , 13, 14.A number of factors influence the outcome after thrombolysis and among these blood pressure levels are only one among many. In accordance with this, we describe the findings in the present study as an association and not a stand-alone causal factor.The possible presence of differences between factors, such as age, between the different groups with accentuated admission blood pressure, has been examined. No significant difference between the median age of the patients in the four blood pressure groups was observed and very broad confidence intervals were present. A slight tendency towards increasing age could be observed with increasing admission blood pressure, but this was not confirmed by statistical comparison between the groups.The strength of this study is the homogeneous study population of stroke patients with symptoms within the first 4.5 hours. All patients were evaluated by the same neuro-radiological and neurological senior consultants and were monitored closely in an advanced stroke care unit. This study has limitations mostly due to missing values, which however can be contributed to random error why the study population remains representative. However, a comparison between the 65 excluded patients and the 265 included patients regarding median age, admission NIHSS, and postthrombolysis NIHSS showed no significant difference—or trends—between patients in the analysis and patients with missing values.Results from the present study suggest what previously has been reported about the need for an extensive workup for stroke patients with a low admission blood pressure and suspected cardiac comorbidity . LikewisAdditional studies regarding this complicated area are needed like the presently ongoing trial, ENOS, aiming to investigate the effect of blood pressure decrease in hypertensive stroke patients within the first 7 days after symptoms debut .Admission blood pressure co-variates with the short- and long-term outcome after stroke. Especially a low or high admission blood pressure can indicate a cardiac comorbidity or preexisting hypertension, where close monitoring and further examinations are requested to minimize poorer outcome. Interventional trials especially the ENOS trial will help clarifying if active blood pressure reduction affects patients' outcome significantly.


This study aims to observe the impact of the temperature of blood transfusion and infusion toward the perioperative cerebral oxygen metabolism and the postoperative cognitive recovery.n = 40) and control group (n = 40). The changes of nasopharyngeal temperature, middle cerebral artery blood flow, CERO2, and SjVO2 of the two groups were recorded at each time point for the assessment of the postoperative overall quality of recovery and cognitive recovery situation.Eighty patients of knee replacement under epidural and general anesthesia were randomly divided into warming blood transfusion and infusion (WBI) group (P < 0.05). The CERO2 values of the two groups at T3 were significantly higher than at T1, while the SjVO2 values were significantly decreased (P < 0.01).The nasopharyngeal temperatures of the two groups at different time points after transfusion were significantly lower than that at T1, and there was a significant difference between the two groups (The WBI can significantly reduce the occurrence of the perioperative hypothermia, while it has no significant effect toward cerebral oxygen metabolism, postoperative overall recovery, and recovery of cognitive function. Postoperative neuropsychological dysfunction is a common complication in elderly patients after joint replacement surgery. Some data indicated that  the inciLow temperature has been identified with positive effects toward cerebral protection both in animal experiments and clinical practice. Ohnishi et al.  studied n = 40) and control group (n = 40). WBI group used infusion fluid heating apparatus  to warm the infusion blood and fluid up to 37°C. In the control group, the infusion blood and liquid were kept at room temperature (24°C) for 15–20 min before the direct infusion without warming treatment. Except for the researchers, the subjects, the surgeons, and the serum biochemical parameter detectors did not know the patient's grouping situation. This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of General Hospital of Ningxia Medical University. Written informed consent was obtained from all participants.The study was a prospective, randomized, single-blind, and controlled trial, and 80 patients who undergone single knee replacement surgery from Mar. 2012 to Feb. 2013 in the Department of Osteology, General Hospital of Ningxia Medical University were enrolled. The patients aged 60–75 years old, without gender limitation. The patients would be excluded if they were with a preoperative history of cerebrovascular disease and external injuries; episode of thrombotic event; coagulation disorders; knee infection complicated by systemic infection; educational attainment <7 years; severe visual or hearing impairment, unable to cooperate the completion of cognitive function test; secondary emergency surgery; and when they refuse to sign the informed consent. The patients were randomly divided into WBI group (2), and continuous invasive arterial blood pressure , the patient had undergone L3-4 epidural catheterization, then intravenously administered with midazolam 0.05 mg/kg , fentanyl 2–3 μg/kg , propofol 2 mg/kg , and rocuronium 0.8–1.0 mg/kg  for the general anesthesia induction, with mechanical ventilation by endotracheal intubation. The anesthesia status was maintained with the inhalation of 0.5%–1.5% isoflurane, and propofol was continuously infused at 2–4 mg/kg/h with micropump, with intermittent boluses of fentanyl . The respiratory parameters were set as follows: tidal volume as 8–10 ml/kg, respiratory rate as 10 to 12 times/min, maintaining the end-tidal carbon dioxide (ETCO2) at 35–45 mmHg . The intraoperative inspired-oxygen concentration was 100%, and the intraoperative blood pressure fluctuation should be ensured not to exceed 20% of baseline values. The fluid infusion of all patients started with 500 ml compound sodium chloride, followed by the infusion demand at crystal/gel ratio 2:1 and at the speed of 5–8 ml · kg-1 · h-1. Lower extremity tourniquet was used during the surgery, with the inflation pressure at 350–400 mmHg. The patients of the two groups were infused allogeneic or preoperative autologous blood through the peripheral vein 10 min before removing the tourniquet, with the speed as 15 ml/min. During the surgery, the amount of blood loss was calculated by the aspirator volume and gauze weighing. The postoperative wound drainage was recorded hourly; the drainage device could be removed until 48 h after the surgery. The postoperative patient-controlled epidural analgesia was performed, with 0.2% ropivacaine  2 ml/h for 72 h, followed by oral non-steroidal anti-inflammatory analgesics. The surgeons and the anesthesiologists of all patients were the same group of people.All patients were given epidural and general anesthesia. Before anesthesia, the patient was intravenously injected with 10 mg dexamethasone and 0.5 mg atropine; the patient who had rapid heart rate would be given 0.3 mg scopolamine instead of atropine. Under the monitoring of electrocardiogram, saturation of pulse oxygen (SPO2) and cerebral extraction rate of oxygen (CERO2) monitoring: the patient was in supine position, with head in neutral line and parallel to the bedside. After local anesthesia, the internal jugular vein paracentesis was performed from the spot slightly outside the carotid pulse and parallel to the lower edge of thyroid cartilage, and along the ipsilateral external ear direction. After the success of paracentesis, 5F bi-cavity deep vein catheter was directed inside, with the catheter tip in the equivalent position of external ear canal . The catheter was sealed with heparin saline, and the radial arterial blood and jugular bulbar blood were extracted synchronously at T0–T5 for the blood gas analysis, respectively; the SjVO2 value was monitored and CERO2 calculated. (4) Assessment of the postoperative recovery quality and the cognitive function: the Post-operative Quality Recovery Scale (PQRS) of all subjects were tested preoperatively, 15 and 40 min after extubation, postoperative 1 and 3 days, respectively . (3) Jugular venous oxygen saturation , but the difference between the two groups at all time points was not statistically significant (P > 0.05). The RI of control group at T2 was significantly higher than at T1 (P < 0.05), while the difference between the two groups at different time points was not statistically significant . However, the CERO2 and SjVO2 at each time point had no statistically significant difference between the two groups  could cause chills, coagulation disorders, cardiovascular dysfunction, metabolic abnormalities, etc. ,16. Low In this study, transcranial Doppler instrument was used to monitor the indicators which could reflect the cerebral blood flow velocity (CBFV) in the middle cerebral artery, including Vs, Vd, and Vm (mean blood flow velocity), among which Vs represented the highest blood flow velocity in systolic period, reflecting the highest MCA flow velocity during entire cardiac cycle; Vd represented the highest MCA blood flow velocity at the end of cardiac cycle, reflecting the vascular resistance; RI mainly reflected the cerebrovascular resistance condition. If there was no significant change in vessel diameter, the above indicators would increase with the CBFV, and the cerebral blood flow (CBF) would also increase; but when the vascular spasm or strong contraction happened, through CBFV would increase, CBF might have no change or even decrease; while the vasodilation at this time would make CBFV reduce, CBF would increase or exhibit no change. In this study, the Vs of the two groups decreased immediately after the transfusion and still decreased 30 min after the transfusion; it might probably be because of the relief of tourniquet pressure, the lower limb blood vessels could dilate, causing the CBF slow down. The intergroup comparison exhibited no significant difference, indicating that compared with the control group, the WBI had no effect on cerebral blood flow velocity of elderly knee replacement patients; it might partially be because the transfusion volume in this study was relatively small and the degree of hypothermia did not break 35°C.2 and SjVO2 were simultaneously monitored for the comprehension of the balance of perioperative cerebral oxygen supply and demand. Under normal circumstances, when the CBF is constant, CERO2 would reduce as the temperature decreases, while SjVO2 would relatively increase. In this study, the CERO2 of the two groups 30 min after transfusion were significantly higher than those before the transfusion, and SjVO2 were significantly lower than those after anesthesia while before transfusion, but they were still within the normal ranges. We considered the above situation might be because of the insufficient cerebral blood supply, which was induced by the acute bleeding in short time after the tourniquet was released. Because the major organ reservation and the compensatory function of elderly patients significantly reduce, the biotransformation and elimination rates of liver and kidney toward the narcotic drug would significantly prolong, resulting in the poor quality of postoperative recovery, even the occurrence of POCD [In this study, CERO of POCD . Althoug of POCD  indicateAlthough studies have shown  that theThe objects of study are patients with knee replacement surgery, and the intraoperative blood transfusion amount is less than normal. In addition, the follow-up of postoperative overall recovery quality and cognitive function restoration is performed just for three postoperative days, without long-term follow-up (6 months or 1 year). These are the limitations of this study. Next, based on results of this study, the research objects should be patients with large blood transfusion in surgery. The change of perioperative cerebral oxygen metabolism and overall recovery quality and cognitive function restoration in one postoperative year will be observed. The objective is to decide performing WBI or not, and guide clinical reasonable blood transfusion.It is found that the blood transfusion is a risk factor for postoperative early cognitive dysfunction in elderly patients. Whether intraoperative infusion of preoperative autologous blood or allogeneic blood will influence the postoperative cognitive function to a certain degree, and this mainly depends on the amount of infused blood. More than 1,000 ml of infused blood is considered as the independent risk factor for postoperative delirium . In thisFor elderly patients treated by single knee replacement surgery, intraoperative WBI can reduce the occurrence of perioperative hypothermia, which is not contrary to the concept of cerebral protection by low temperature. The intraoperative WBI has no significant effect on the perioperative cerebral oxygen metabolism or cognitive function recovery. In addition, sometimes the WBI device cannot be used, for saving medical resources and reducing expense of patients and medical burden of society.POCD: postoperative cognitive dysfunction; RI: resistance index.The authors declare that they have no competing interest.XN and CW designed this paper and performed critical revision of the manuscript. YY and YC performed data collection. YW analyzed the date. XN wrote the manuscript. All authors read and approved the final manuscript.


Diabetes prevalence is increasing and current methods of management are unsustainable. Effective approaches to supporting self-management are required. The aim of this randomized controlled trial is to establish whether supported telemetric monitoring of glycemic control and blood pressure results in reductions in glycosylated hemoglobin  and secondary outcomes of blood pressure and weight among people with poorly controlled diabetes compared to a control group receiving usual care.Design: multi-center, randomized controlled trial with embedded qualitative study.Setting: primary care in Lothian, Kent, Glasgow and Borders regions in the UK.Participants: people with type 2 diabetes and confirmed HbA1c >7.5% (58 mmol/mol).Intervention/comparison: randomization to intervention or control groups will be performed by the Edinburgh Clinical Trials Unit. Participants in the intervention group will be shown how to use blood glucose and blood pressure monitors and weighing scales which use Bluetooth wireless technology to transmit readings via modem to a remote server. These participants will be asked to provide at least twice weekly measurements of morning and evening blood glucose and weekly measurements of weight and blood pressure. Measurements will be checked at least weekly by practice nurses who will contact the patients to adjust therapy according to guidelines and reinforce lifestyle advice. Participants in the control group will receive usual care. All participants will receive an individual education session.Follow-up: measurements will be performed at practices 9 months after randomization by research nurses blinded to allocation. The primary outcome measure is HbA1c and secondary outcomes measure are daytime systolic and diastolic blood pressure, weight and cost per quality-adjusted life year.Analysis: intention-to-treat analyses will be performed. The sample size of 320 participants allows for 20% drop-out and has 80% power at 5% significance to detect a 0.5% absolute (6 mmol/mol) fall in HbA1c in the intervention group. The qualitative study will explore the experiences of patients and professionals using the intervention.ISRCTN71674628Trial registration number  The prevalence of diagnosed diabetes is increasing across the world and, in Scotland, has increased from 3.9% to 4.7% in people of all ages between 2006 and 2011 according to the annual Diabetes Survey .The current medical model for managing diabetes does not necessarily engage individuals in a self-management approach, is expensive and often not very effective partly because therapeutic inertia may result in reluctance to change treatments. Effective chronic disease management should not only reduce costs but also improve quality of care. A study in the US has found that providing healthcare professionals with current patient information improved care and reduced costs . SystemaAs described previously in the protocol for a trial of telehealthcare among people with chronic obstructive pulmonary disease from our group , severalThe Telescot diabetes trial is a randomized controlled trial of supported telemetric monitoring of glycemic control, blood pressure and weight of 9 months duration with a primary outcome of HbA1c, a measure of long-term glycemic control. Secondary outcomes include blood pressure and weight and will be measured by research nurses blinded to allocation group. The setting for the trial is primary care in Lothian, Kent and Borders in the UK. Participants will have poorly controlled type 2 diabetes (defined as HbA1c>7.5% (58 mmol/mol)), be over 17 years of age, have a mobile telephone signal available at their home and each participant will have given informed consent. People with very high blood pressure (>210/135 mmHg), who have hypertension or renal disease managed in secondary care, have had treatment for a cardiac event, or other life-threatening illness within the past 6 months or have had major surgery within the last 3 months, are unable to use self-monitoring equipment, have atrial fibrillation that has not been successfully treated or are pregnant will be excluded. Approval of the trial, which will be conducted to comply with the Declaration of Helsinki, has been obtained from the South East Scotland ethics committee 2 (reference number: 10/S1102160).We will recruit socially diverse practices to the trial using both the Scottish and English Primary Care and Diabetes Research Networks. We will make use of the network of practices in Lothian we have established during a previous blood pressure trial, who are familiar with the technology and have already expressed a willingness to take part. We will also use the networks and contacts provided by our grantholders to extend recruitment beyond Lothian to Kent and Borders. Training for the practices will be provided by the research team.Diabetes registers in participating practices will be searched to identify potential participants with HbA1c>7.5% (58 mmol/mol). Potentially eligible patients will be sent the study materials by their general practice with a covering letter and asked to contact the researcher if they are interested in participating. Once a patient has indicated interest in participating they will be invited to a clinic in their general practitioner’s (GP’s) surgery run by a research nurse. At the initial appointment the nurse will go through the study information with the patient, take written informed consent , check potential eligibility, ask the patient to complete a short questionnaire on their demographic characteristics, past and current self-monitoring of blood pressure and blood glucose, collect a blood sample for HbA1c and cholesterol measurement, a urine sample for sodium:creatinine ratio and initiate ambulatory blood pressure monitoring using the Spacelab Ambulatory Blood Pressure Monitor (ABPM) . The nurAll patients will be loaned an ABPM with which they can monitor their blood pressure for 14 hours. However, if they wish they can delay collecting ABPM data until after the result of their HbA1C is available and their eligibility is confirmed. Once the HbA1c result is available, any ineligible patients will be telephoned to let them know that they do not need to return for a second appointment to gather baseline measurements. Patients’ ABPM results will be released to the practice.At their second appointment, prior to randomization, participants will have the following baseline measurements taken: smoking history, height and weight, and exhaled carbon monoxide. In addition they will be asked to complete a range of questionnaires to collect information on anxiety/depression , qualityRandomization will be carried out remotely at the Edinburgh Clinical Trials Unit to ensure adequate concealment. We will use minimization with a random element based on age (<70 or ≥70 years of age), sex, location  use of two or more diabetes drugs, use of three or more hypertension drugs and glucose self-monitoring history in order to make sure that these factors are distributed equally between intervention and usual care groups. The allocated treatment code will be generated by the Edinburgh Clinical Trials Unit over the internet (with a telephone back-up option if required). The participant will then be informed about the arm of the trial to which they have been assigned and given appropriate information and demonstration of equipment if allocated to the intervention group. All randomized participants will be included in the intention-to-treat analysis. All participants, regardless of allocation group, will be seen by a healthcare professional from the practice trained in the management of type 2 diabetes who will assess current control, optimize management in line with Scottish Intercollegiate Guidelines Network and National Institute of Health and Clinical Excellence (NICE) guidelines and deliver a one-to-one standardized education session.It is not possible to blind clinicians or patients to the allocation group but baseline data collection will be undertaken by the research nurses before randomization takes place. Patients will be requested not to reveal their allocation to research nurses undertaking follow-up measurements, although we recognize that inadvertent references by the patients or in their primary care record may reveal their allocation. The use of objective outcomes  will also reduce the possibility of bias. Patients will be asked not to reveal which group they are in or to return their equipment until the final monitoring has been carried out. The research nurses will be asked to record unblinding prior to the final assessment.Patients in the intervention group will be given blood pressure and blood glucose monitors and weighing scales which use Bluetooth to transmit readings via a (supplied) modem to a remote server. The user may securely access their record on the server at any time . Their GP and practice nurse will also be able to access this record via the Internet. Users will also receive regular (monthly) feedback based on their blood pressure and blood glucose over the past 10 readings which will be sent by post or email according to the patient’s wishes.Participants will be trained in use of the equipment and the demonstration will be backed up by written information. The written information pack will also contain leaflets about initiating or maintaining lifestyle changes and how long it is likely to be before any lifestyle or medication change will have an impact on their rolling average blood pressure or blood glucose. The suggested lifestyle changes will include weight control, reducing salt in the diet and increasing physical activity.The user will also be given contact details for the practice nurse and encouraged to make contact by email or by telephoning at specified times if their blood pressure or blood glucose remains high, to discuss their treatment. In the event of a very high blood pressure (>220 mmHg) or very high blood glucose levels (>15 mmol/l) patients will be asked to repeat the measurements and, if they remain high, to contact their practice urgently for advice. Patients recording very low blood glucose (<4 mmol/l) will be advised to eat or take a glucose drink and, if hypoglycemia persists, to contact the practice. Practice nurses will be encouraged to review the readings they are sent about patients whose blood pressure or blood glucose remains high or persistently low or who have not checked their blood pressure or blood glucose within the agreed timeframe on a weekly basis. Practice nurses may choose to contact the patient to offer further treatment or support and will be asked to record such contacts in the normal practice electronic record. The nurses will also be asked to transfer the current average blood pressure and blood glucose into the primary care record.Patients will be encouraged to check their blood pressure 10 to 20 times over the first seven days to establish a reliable average and then about 4 times a month if their average blood pressure is at or below the target of 130 mmHg. If blood pressure is above the target and any changes to lifestyle or medication are made, the users will be asked to undertake another more intensive period of monitoring (10 to 20 readings over seven days) after an appropriate time  in order to establish the impact on the rolling average blood pressure. The guidance will not be restrictive as this tool is being provided for patients to use in order to understand their blood pressure better and to better manage their own health.Patients in the intervention group will be asked to provide at least twice weekly measurements of morning and evening blood glucose and weekly measurements of morning weight. These measurements will be automatically forwarded to the study website and checked at least weekly by the practice nurse. Patients with high readings will be highlighted by the software for easy identification. The nurses will contact the patients by telephone, text or email to adjust therapy and reinforce lifestyle advice on the need for more or less intensive monitoring. Antihypertensive drug treatment may be altered every 4 to 6 weeks until mean blood pressure based on the last 10 readings is at or below the target of 130 mmHg. Treatment for diabetes will be altered according to the protocol based on guidelines every 4 weeks with the aim of maintaining consecutive fasting blood levels between 4 and 6 mmol/l. Patients who require the addition of insulin to their treatment during the course of the trial will be jointly managed by the practice nurse and GP along with specialist diabetes nurses at the local hospital (if appropriate) according to local practice, all of whom will have access to the telemetric data for patients in the intervention group. Algorithms for glucose and blood pressure management are given in the appendices.Patients in the control group will receive leaflets with lifestyle advice and usual care, that is attending the practice nurse or GP for appointments as normal. They will be asked about their use of self-monitoring of blood pressure and blood glucose at baseline and follow-up. Patients with uncontrolled blood pressure in our recent audit saw the nurse or doctor three or four times on average in 6 months and we would anticipate a similar number of attendances for patients with both uncontrolled glycemia and blood pressure. Patients requiring insulin during the course of the trial will be managed jointly as above with specialist diabetes nurse support. Throughout the trial, patients will be reviewed according to clinical need by their normal clinical advisors. Clinical care in both groups for patients in Lothian will be in accordance with NHS Lothian protocols which are based on the recommendations of national and international guidelines, and in other areas according to NICE guidance. Therapeutic algorithms for both controls and intervention will follow guidelines, based upon the NICE guidelines  using a Participants will be seen by a researcher/research nurse blinded to their allocation at their GP practice 9 months after randomization. The follow-up appointment will include completion of questionnaires to collect information as at baseline, other than ethnicity, blood sample collection for HbA1c and cholesterol and fitting of the ABPM. Participants will be asked to return the ABPM the following day. Use of healthcare resources  and adverse events will be extracted from the participant’s electronic record by the researcher or research nurse at the follow-up appointment. Electronic records will be retrieved and analyzed for compliance with monitoring. The baseline measures (excluding height) will be repeated at the end of the 9 month follow-up period.Records will be kept of the numbers of practices and patients that were approached to participate in the study and the numbers and proportions of practices and patients that consented or declined to take part. Data from participating individuals will be entered from questionnaires and paper records by the researcher to a database. A random 10% sample will be checked for accuracy by independent trial staff. If we detect systematic errors we will re-enter all the data. Every attempt will be made to collect complete data on all of the participants.Data analysis will be carried out by the Edinburgh Clinical Trials Unit. Data will be analyzed on an intention-to-treat basis, that is by allocation group regardless of compliance with the intervention. In the primary analysis we will remove patients with missing outcome data, but will perform sensitivity analyses to investigate the effect of this. Binary outcomes will be presented both as relative and absolute risk reductions. For HbA1c and blood pressure, and other normally distributed measurements that are taken at baseline and follow-up, adjustment for baseline measures will be performed using analysis of covariance. For the primary outcome, subgroup analyses will be performed based on sex, tertiles of age and socio-economic status (based on the Scottish Index of Multiple Deprivation derived from postcode) and tertiles of baseline HbA1c, home self-monitored systolic blood pressure and body mass index. These factors may all reasonably be hypothesized to influence the effect of the intervention. Subgroup analyses will be performed by adding any interaction between these factors and treatment into the analysis of covariance model and observing whether the fit of the model is statistically significantly improved. No interim analysis is planned.There were 4440 people with type 2 diabetes, an HbA1c of >7.5% and systolic blood pressure of ≥135 mmHg on the Lothian diabetes register in 2008. This group reflects approximately 16% of people on the register with type 2 diabetes. Their mean (standard deviation) HbA1c was 8.8% (1.4%) and their mean (standard deviation) systolic blood pressure was 149 mmHg (13 mmHg).Using these values, we calculate that a randomized controlled trial with 125 people completing each arm with no change in values in the control group at the end of the trial would have 80% power at 5% significance to detect a 0.5% absolute fall in HbA1c and a 5 mmHg fall in systolic blood pressure in the intervention group. In an earlier trial of telemetric monitoring of blood pressure, 60% of patients on a practice hypertension register agreed to take part and 82% were retained within the trial ; we antiThe health economic analyses will assess the cost-effectiveness of the tele-supported self-monitoring compared to usual care. A cost-utility analysis  will be performed. The perspective will be the NHS. The benefits will include health outcomes measured in terms of quality-adjusted life years which will be derived from the responses to the EQ-5D . Health A sub-sample of participants in the randomized controlled trial will be recruited to the nested qualitative study. Up to 20 participants from the intervention group will be recruited for semi-structured interviews plus a further 10 to 12 for two focus groups. The purpose of the focus groups will be to allow the group to explore shared ideas and experiences relating to type 2 diabetes and hypertension and their experiences in managing it. The interviews with individuals will cover similar subjects but will allow private discussion of issues such as not using medication in the prescribed way (which people may not be willing to discuss in a public situation). A maximum variation sample in relation to age, social class, ethnicity (if ethnicity varies sufficiently between participants) and severity of type 2 diabetes and hypertension, plus level of use of the system will be sought.Up to 20 professionals participating in the trial will be interviewed (face-to-face or by telephone according to the preference of the clinician). This will include the specialist diabetes nurses providing the support services, long-term condition nurses, and representatives of primary and secondary care services.The initial guide for semi-structured interviews with patients will be based on the themes identified from the literature and the on-going studies, but the guide will be reviewed and refined iteratively as data are gathered and analyzed and new themes arise. Participants will therefore be encouraged to give their views on the usefulness of the systems in general and then tell their own story about managing their own long-term conditions and the impact of the systems.Interviews with professionals will seek to investigate perceptions of the benefits (or otherwise) of the intervention, experiences of implementing and maintaining it and the barriers and facilitators they have experienced.The interviews and focus groups will be fully transcribed. The Framework method will be used to classify and organize data according to key themes, concepts and emergent categories . Data wiThe proposed trial will provide additional information on the cost-effectiveness and feasibility of supported telemetric monitoring of two common, chronic conditions, diabetes and hypertension, whose prevalence is expected to continue increasing across the world. Limitations of the trial include the potential for unblinding of research nurses undertaking follow-up measurements to allocated group and the inability to identify whether the intervention may be more effective in patient sub-groups, for example people with newly diagnosed diabetes or who may shortly require insulin treatment. In addition the assumption that outcome measures among the comparison group will remain unchanged may not hold which will either strengthen or weaken the power of the study depending on the direction in which change occurs. The study design also precludes investigation of whether effectiveness of the intervention would be influenced by separate monitoring of blood pressure and glycemic control in different groups as this would require a factorial design. The standard limitation of all health services research that it is difficult to generalize the findings regarding feasibility to other settings also applies to this work, but the effectiveness of the intervention may have wider application to other populations.Ongoing. Recruitment started in August 2011 and follow-up is expected to be complete by April 2014.ABPM: Ambulatory blood pressure monitor; GP: General Practitioner; HbA1c: glycosylated hemoglobin; NICE: National Institute of Health and Clinical Excellence.The authors declare that they have no competing interests.SW drafted the manuscript on the basis of the study protocol. BM and JH conceived the study. All authors participated in study design and have read and approved the final manuscript.


Calcium-channel blockers (CCBs) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) formulation are the most studied of the once-daily CCBs. Amlodipine has an inherently long pharma-cokinetic half-life, whereas, in contrast, nifedipine has an inherently short half-life but in the GITS formulation the sophisticated delivery system allows for once-daily dosing. This article is derived from a systematic review of the published literature in hypertensive patients. The following search terms in three main databases  from 1990 to 2011 were utilized: amlodipine, nifedipine, sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine and heart rate. More than 1500 articles were then screened to derive the relevant analysis. As markers of sympathetic nervous system activation, studies of plasma norepinephrine concentrations, power spectral analysis, muscle sympathetic nerve activity and norepinephrine spillover were reviewed. Overall, each drug lowered blood pressure in hypertensive patients in association with only small changes in heart rate (i.e. < 1 beat/min). Plasma norepinephrine concentrations, as the most widely reported marker of sympathetic nervous system activity, showed greater increases in patients treated with amlodipine than with nifedipine GITS. The evidence indicates that both these once-daily dihydropyridine CCBs lower blood pressure effectively with minimal effects on heart rate. There are small differences between the drugs in the extent to which each activates the sympathetic nervous system with an overall non-significant trend in favour of nifedipine GITS. Calcium-channel blockers (CCBs), comprise three distinct subgroups: benzothiazepines (e.g. diltiazem), dihydropyridines  and phenylalkylamines (e.g. verapamil). Despite this diversity, they are often referred to as a single, homogeneous class of pharmacological agents. Furthermore, even within the dihydropyridine group, there are numerous drugs and formulations  with different pharmacokinetic profiles, clinical uses and responses, and different dosing requirements.Despite these various pharmacokinetic differences, arterial vasodilatation is the fundamental response to calcium-channel blockade with a dihy-dropyridine CCB. Peripheral arterial vasodilatation leads to a reduction in blood pressure and coronary artery vasodilatation leads to increased blood flow to the myocardium. However, it has long been known that potent arterial vasodilators evoke a barorecep-tor-mediated reflex increase in heart rate that is mediated via the sympathetic nervous system. This holds for both arterial vasodilators, such as nifedipine and hydralazine , and forInsights into the balance between these positive and negative effects became apparent in the results of the early studies with nifedipine in its immediate release formulation: two clinical outcome studies indicated that in patients with unstable angina  and postIn a later review, Grossman & Messerli  suggesteDespite obvious differences between drugs, between classes or subgroups or formulations, CCBs are often indiscriminately grouped together. They are often summarized as a single entity in reviews of outcome trials and when reviewed by formulary committees and by funding organizations. This raises obvious questions about the most appropriate method of considering the interchangeability of different CCBs and, for this reason, we decided to conduct a detailed review of the literature on two of the most commonly used dihydropyridine CCBs, amlodipine and nifedipine GITS, with specific regard to their effects on sympathetic activation.sympathetic nervous system, sympathetic response, sympathetic nerve activity, noradrenaline, norepinephrine, heart rate, hypertension. We included only articles published in the English language. If a study was published in more than one journal, efforts were made only to include the data once from whichever article was most complete in study details and data. The primary focus was on full manuscript publications and not abstracts. However, if an abstract was published but a full paper was not subsequently found, the abstract was used if there were data on number of patients, dose of drug, duration of treatment and relevant measurement values. More than 1500 articles were screened and only those in which treatment lasted for at least 1 week were included in the analysis.The MEDLINE (Pubmed), Embase, Derwent Drug File, Biosis and Science Citation Index databases were searched for articles published between 1990 and April 2011 on amlodipine and nifedipine using the terms (1)plasma norepinephrine  concentrations;(2)muscle sympathetic nerve activity recordings;(3)power spectral analyses of low-frequency and high-frequency activity.The following measurements of sympathetic nervous system activity/sympathetic activation were evaluated:All plasma concentration values for norepineph-rine were converted to pg/ml and changes were calculated as percentage (%) values. Sympathetic activation values were included for patients at rest as distinct from those stimulated by mental stress, handgrip, standing or cold pressor tests.Generally, data were reported for patients in the supine or sitting position. For the blood pressure measurements, office- or clinic-based values are incorporated and average daytime values if ambulatory blood pressure readings were used. If the final blood pressure, heart rate or other measurement was not given as an absolute value but as a change from baseline, the end of measurement value was calculated by simply adding the mean change value to the initial/baseline value. To make allowances for different baseline values, different study designs, different methodologies etc., percentage changes from baseline to the end time point have been calculated. If measurements were made at multiple time points within one published study, the longest duration of treatment was chosen and if multiple doses were reported, or dose titration occurred, the final dose of drug or the most-used dose is reported.Only one study permitted a direct statistical comparison . It was Measurement of plasma norepinephrine concentrations was the most commonly reported index of sympathetic activity and activation. Twenty-three  studies The changes in blood pressure (BP) and heart rate were similar with the two drugs. With amlodipine, systolic blood pressure (SBP) decreased by 10.2±0.9%, diastolic blood pressure (DBP) by 10.4±0.8% and heart rate increased by 0.6±0.8% . With niIn summary, plasma norepinephrine increased by 21.7±4.3% after amlodipine and by 17.1±5.7% after nifedipine GITS .Measurement of muscle  sympathetic activity was the second most commonly used method and was employed in five amlodipine studies and in one study with nifedipine GITS. In the amlodipine studies, a total of 70 patients with an average age of 52 years were evaluated . For nifThe changes in SBP, DBP and heart rate were 8.4±1.0%, 6.7±1.0% and 0.4±2.2%, respectively, in the amlodipine studies and the corresponding values were 3.8±3.0%, 4.5±3.5% and 3.0±0.1% in the nifedipine studies.In summary, the increase in muscle sympathetic nerve activity was 21.4±8.5% for amlodipine and 6.7±1.8% for nifedipine GITS .This methodology involves continuous measurement of the ECG to tease out R–R interval variations using fast Fourier transformation and autoregressive algorithms . The lowIn the amlodipine-treated patients, the decreases in SBP, DBP and heart rate were 13.5±1.8%, 10.8±1.0% and 1.0±1.3% . The lowThe activity of the sympathetic nervous system is essential for the moment-to-moment regulation of the cardiovascular system but “overactivity” has been implicated in both the genesis of, and the complications of, cardiovascular disease ,11. WithIn the earlier review by Grossman & Messerli , long-acUnfortunately, there is only one study that directly compares amlodipine and nifedipine GITS: the conclusion of this single study was that chronic treatment with amlodipine was associated with sympathetic activation, whereas no such activation occurred with nifedipine GITS. This finding is consistent with the overall trend in this present analysis albeit there was no statistical significance. However, the changes in baseline for plasma norepinephrine do not appear to be directly related to the blood pressure lowering effect, since the blood pressure decreases were very similar between the two drugs with, if anything, a marginally greater decrease with nifedipine GITS. Furthermore, the heart rate changes were comparable with the two drugs at approximately 0.6 beats/min.Thus, the main finding of this overview is that amlodipine  caused a small but significant activation of the sympathetic nervous system, as assessed by multiple markers. It is also noteworthy that, for measurements of plasma norepinephrine and assessment of muscle sympathetic activation, the percentage increases are coincidentally almost identical . In turn, the ratio of low to high frequency from the power spectral analysis suggests that the sympathetic activation component overall is greater than the parasympathetic component after amlodipine administration. Therefore, there is consistency in three different surrogate measures for sympathetic activation, suggesting that amlodipine increases activity of the sympathetic nervous system in hypertensive patients.A detailed explanation for the apparent differential effects of amlodipine and nifedipine GITS on the sympathetic nervous system is not readily apparent. However, in studies of spontaneously hypertensive rats (SHR), Huang & Leenen  concludeNotwithstanding the above observations and discussion, the results of this overview must be taken in proper context. The data are compiled from studies spanning some 20 years with patients of varying durations of hypertension, severity of disease, baseline blood pressures, conditions for sampling or measurements, time of day, body posture, dose of drug, age of patient etc. Moreover, no formal statistical analyses were conducted because of varying methodologies and study characteristics, and widely varying results. All of these are potentially complicating and confounding factors when trying to compare drugs. Ideally, a study comparing the two drugs in a head-to-head manner with proper randomization and assessment should provide more robust data. To date, only one such study was found, that by de Cham-plain et al. . In thatChronic activation of the sympathetic nervous system has been implicated in the pathogenesis of hypertension and its cardiovascular complications. However, both amlodipine and nifedipine GITS have positive outcome data in the treatment of hypertensive patients . Thi


Aims. Patients with diabetic nephropathy are reported to have a high prevalence of leftventricular structural and functional abnormalities. This study was designed to assessthe determinants of left ventricular mass index (LVMI) and left ventricular ejectionfraction (LVEF) in diabetic patients at various stages of chronic kidney disease(CKD). Methods. This cross-sectional study enrolled 285 diabetic patients with CKD stages 3to 5 from our outpatient department of internal medicine. Clinical andechocardiographic parameters were compared and analyzed. Results. We found a significant stepwise increase in LVMI (P < 0.001), LVH (P < 0.001), and LVEF <55% (P = 0.013) and a stepwise decrease in LVEF (P = 0.038)corresponding to advance in CKD stages. Conclusions. Our findings suggest that increases in LVMI and decreases in LVEF coincidewith advances in CKD stages in patients with diabetes. Diabetic nephropathy is one of the major complications of diabetes mellitus (DM) and one of the major reasons for renal replacement therapy . The lea There are a number of hemodynamic and metabolic disturbances that affect the structure and function of heart in patients with diabetic nephropathy. The major factors that contribute to further heart failure in diabetic patients include cardiac microangiopathy, neuropathy of the cardiac autonomous nervous system, disturbed metabolism, and fatty degeneration of the myocardium . These p2) of 30 to 59, 15 to 29, and <15, respectively, as recommended in the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines [The study was conducted in a regional hospital in southern Taiwan. In total, 285 diabetic patients with CKD stages 3 to 5 were enrolled consecutively from our outpatient department of internal medicine from January 2007 to May 2010. Patients with evidence of kidney damage lasting for more than 3 months were classified into CKD stage 3, 4, or 5 groups based on estimated glomerular filtration rate (eGFR) level (mL/min/1.73 mE), and peak late transmitral filling wave velocity (A). Left ventricular mass was calculated using the Devereux-modified method [2 and 110 g/m2 for men and women, respectively [E/A ratio; a value of <1.0 was considered diastolic dysfunction.The echocardiographic examination was performed using VIVID 7 , with the participant respiring quietly in the left decubitus position. The echocardiographers were blind to patient data. Two-dimensional and two-dimensional guided M-mode images were recorded from the standardized view points. The echocardiographic measurements included aortic root diameter, left atrial diameter (LAD), left ventricular internal diameter in diastole (LVIDd), and left ventricular internal diameter in systole (LVIDs), LVEF, peak early transmitral filling wave velocity , and comorbid conditions, were garnered from medical records or interviews with patients. Study subjects were defined as having DM if their fasting blood glucose levels were greater than 126 mg/dL or they were taking hypoglycemic agents to control blood glucose levels. Similarly, participants were defined as having hypertension if their systolic blood pressures were ≥140 mmHg or diastolic blood pressure ≥90 mmHg or they were taking antihypertensive drugs. Coronary artery disease was defined if they had a history of typical angina with positive stress test, angiographically documented coronary artery disease, and old myocardial infarction or they had undergone coronary artery bypass surgery or angioplasty. Cerebrovascular disease was defined if they had a history of cerebrovascular incidents such as cerebral bleeding and infarction. Congestive heart failure was defined based on the Framingham criteria. Body mass index was calculated as the ratio of weight in kilograms divided by square of height in meters. Blood and urine samples were obtained within 1 month of enrollment. Laboratory data were measured from fasting blood samples using an autoanalyzer . Serum creatinine was measured by the compensated Jaffé  method in a Roche/Integra 400 Analyzer  using a calibrator traceable to isotope-dilution mass spectrometry . The valP value less than 0.05 was considered significant. All statistical operations were performed using SPSS 12.0 for Windows .Data are expressed as percentages or mean ± standard deviation or median (25th–75th percentile) for triglyceride. Multiple comparisons among the study groups were performed by one-way analysis of variance (ANOVA) followed by post hoc test adjusted with a LSD correction. The relationship between two continuous variables was assessed by a bivariate correlation method (Pearson's correlation). Linear regression analysis was used to identify the factors associated with LVMI and LVEF. Significant variables in univariate analysis were selected for multivariate analysis. As can be seen in As seen in In the present study, we evaluated the determinants of LVMI and LVEF in diabetic patients with various stages of CKD. We found a significant trend for a stepwise increase in LVMI and the prevalence of LVH and LVEF < 55% and a stepwise decrease in LVEF corresponding to advancement in CKD stage.Patients with diabetic nephropathy have a high prevalence of LVH and left ventricular systolic dysfunction, two disorders that contribute majorly to increased risk of cardiovascular death –4. StrucDM, hypertension, and dyslipidemia are traditional cardiovascular risk factors. In addition to these traditional risk factors, patients with CKD may have other risk factors for increase cardiovascular risk such as inflammation, oxidative stress, anemia, metabolic disorders, calcium-phosphorous disorders, hypervolemia, and structural and functional abnormalities of heart, which may help to explain the high cardiovascular morbidity and mortality in such patients –25. LVH, Low serum albumin level has been regarded as indicator of malnutrition. Malnutrition may worsen the outcome of CKD by aggravating existing inflammation and heart failure . HypoalbOne limitation of this study was that it had a cross-sectional design, and thus the predictors of cardiovascular events could not be evaluated. Further prospective studies are needed to confirm our findings.In conclusion, our results found a significant trend for a stepwise increase in LVMI and the prevalence of LVH and LVEF < 55% and a stepwise decrease in LVEF corresponding to advancement in CKD stage in diabetic patients.The authors have no financial interest in the information contained in the paper.