Emotional distress has been associated with cardiovascular disease (CVD) in Africans. Cortisol and brain-derived neurotrophic factor (BDNF), as markers of emotional distress, increase cardiometabolic risk. We therefore aimed to investigate associations between cardiometabolic risk markers and the cortisol-to-BDNF ratio (cortisol:BDNF).A cross-sectional study included a bi-ethnic gender cohort (n = 406) aged 44.7 ± 9.52 years. Ambulatory blood pressure (ABPM), ECG, fasting serum cortisol and BDNF levels and cardiometabolic risk markers were obtained.Africans had increased incidence of hyperglycaemia and 24-hour silent ischaemic events, and elevated 24-hour blood pressure (BP) and cortisol:BDNF ratios compared to Caucasians. Forward stepwise linear regression analysis underscored a similar trend with associations between hyperglycaemia, 24-hour BP , silent ischaemia  and cortisol:BDNF levels in Africans, mostly in the men.Attenuated cortisol levels in this group may be indicative of emotional distress and if chronic, drive the cortisol:BDNF ratio to desensitise BDNF. Desensitised cortisol:BDNF may sustain cardiometabolic risk and induce neurodegeneration in African men via silent ischaemia. Compensatory increases in blood pressure to increase perfusion and maintain homeostasis may increase coronary artery disease risk. Cardiovascular disease (CVD) is a major concern throughout the world.5Prolonged exposure to a taxing emotionally stressful environment, such as an urban lifestyle, disrupts homeostasis, which can lead to chronic stress.Mineralocorticoid-based hypertension is associated with an excess of extracellular fluid as a result of increased sodium and water retention.3Brain-derived neurotrophic factor (BDNF), a protein complex and part of the neurotrophin family, is synthesised and secreted by the central nervous system and plays a major role in brain plasticity and survival of the developing neurons.11The down-regulation may reduce neuroplasticity and ultimately lead to neurodegeneration. As the reduction by itself may not be enough to lead to destruction of hippocampal neurons, it may lead to an increased vulnerability to neuronal damage, especially during times of emotional distress.BDNF circulates systemically and supports the notion that BDNF may play an important role in cardiometabolic morbidity.This sub-study is part of the Sympathetic Activity and ambulatory Blood Pressure in Africans (SABPA) study carried out in 2008–2009 and described elsewehere.Exclusion criteria included tympanum temperature above 37.5°C, the use of anti-depressants, α- and β-blockers, and blood donors or individuals vaccinated within a period of three months prior to data collection. Additionally we excluded cortisone users (n = 3), and the final sample comprised 406 individuals.Participants were fully informed with regard to the study procedure and signed an informed consent form. The study was approved by the Ethics Review Board of the North-West University (NWU-00036-07-S6).During the 48-hour clinical data-collection process, ambulatory blood pressure (ABPM), electrocardiogram  and accelerometer measures were obtained . The BP apparatus was fitted before 09:00, with an appropriately sized cuff on the non-dominant side of the participant. The participants were asked to record abnormalities such as nausea, feeling stressed or having a headache on a 24-hour diary card. The apparatus was pre-programmed to measure blood pressure every 30 minutes (08:00–22:00) and hourly (22:00–06:00).The ABPM and ECG data were analysed using the CardioVisions 1.19 Personal Edition software (Meditech). An average 24-hour systolic blood pressure (SBP) of ≥ 130 mmHg and/or diastolic blood pressure (DBP) of ≥ 80 mmHg were used as the criteria to define hypertension.16Silent ischaemia was assessed by two-channel ECG recordings (Cardiotens CE120®) for 20 seconds at five-minute intervals. An ischaemic event was defined according to the following criteria: horizontal or descending ST-segment depression of 1 mm, duration of ST-segment episode lasting for one minute, and a one-minute interval from the preceding episode.15At 16:30, participants were transported to the North-West University’s Metabolic Unit Research Facility where they were introduced to the experimental procedures. They completed psychosocial questionnaires under supervision of a registered clinical psychologist. They received a standardised dinner and were advised to go to bed at 22:00 and to fast overnight. At 05:45 they were woken, and the devices were removed after the last ambulatory recording at 06:00. Anthropometric measurements and fasting blood samples followed.The participant’s daily physical activity was monitored over 24 hours, considering resting metabolic rate, with the Actical® activity monitor . Gamma-glutamyl transferase (γ-GT) and cotinine levels were used to assess alcohol intake and smoking habits.2) was calculated according to the Mosteller formula. The mean of three measurements was used to ensure accuracy. Inter- and intra-observer variability was found to be less than 10%.Anthropometric measurements were done in triplicate by level two-accredited anthropometrists using calibrated instruments . Body mass and height of the participants were measured while remaining in underwear, for accuracy. Body surface area (BSA) (in m1c levels (glycated haemoglobin) .Fasting blood samples were obtained from the ante-brachial vein branches with a winged infusion set using standardised protocol, and were stored at –80°C until batch assay. Sequential multiple analysers analysed serum gamma-glutamyl transferase, high-sensitivity C-reactive protein (hsCRP) (low-grade inflammation was defined when hsCRP was > 3 mg/l), cotinine and HbAQuantikine colorimetric-sandwich immunoassays from R & D Systems  were used to determine serum BDNF levels with an intra-assay and inter-assay precision of 3.8–6.2% and 7.6–11.3%, respectively. Serum cortisol samples were obtained before 09:00, avoiding the cortisol awakening responses (CAR),Data analysis was done using Statsoft (Statistica V.12). The Shapiro–Wilks test ascertained normality of data, and skewed data were log normalised . Multiple comparisons were not done and a priori hypotheses for all tests were performed.2) tests computed proportions and prevalence. The raw data are presented as mean ± standard deviation in the descriptive table  for all cardiometabolic variables independent of a priori confounders . There after ANCOVAs, using least-square means, compared bi-ethnic gender groups while adjusting for a priori confounders.1c level, 24-hour BP, silent ischaemia and cortisol level, as well as cortsol:BDNF, independent of a priori covariates. Forward stepwise linear regression analyses determined associations in several models between dependent variables: HbA1c level, blood pressure, ischaemia and the independent variables: cortisol, cortisol:BDNF and a priori covariates in the separate ethnic gender groups.Pearson and partial correlation analyses determined unadjusted and adjusted associations between HbASensitivity analyses: forward stepwise linear regression analyses were repeated after excluding HIV-positive status teachers, and hypertension and diabetes medication users. Significant values were noted as p ≤ 0.05.1c) levels, lower BDNF levels (p < 0.001), larger cortisol:BDNF ratios (p = 0.012) and a higher mean 24-hour hypertensive state. Caucasians were more physically active compared to the Africans. Both ethnic groups’ cortisol levels were within the normal range of 138–635 nmol/l but the Africans’ cortisol levels showed a tendency towards lower levels (p = 0.093) than their Caucasian counterparts.In In Pearson correlations showed inverse associations between silent ischaemia and cortisol:BDNF  in the African male cohort but not in any of the other ethnic gender groups (data not shown). When considering a priori covariates , 4, forw1c level, and 24-hour BP with a tendency for silent ischaemia (p = 0.07) in the African men only. No change in the outcome was demonstrated after adjustment for HIV-positive status, hypertension and diabetes medication use.Cortisol level was positively associated with HbA1c level, ambulatory BP and silent ischaemia in a bi-ethnic gender cohort. Overall, African men showed a poorer cardiometabolic profile accompanied by lower cortisol levels when compared to their Caucasian counterparts. Attenuated cortisol levels therefore seem to act as the driving force in the cortisol:BDNF ratio and may ultimately down-regulate BDNF.Our objectives were to investigate associations between cortisol, the cortisol:BDNF ratio and cardiometabolic risk markers, specifically HbAThe novel ratio of cortisol:BDNF may sustain cardiometabolic risk and induce neurodegeneration. Cardiometabolic morbidity further increased in the African men as their reduced coronary perfusion, as evidenced in the number of 24-hour silent ischaemic events, would increase BP as a compensatory mechanism to maintain homeostasis.1c concentration and coronary artery calcification. A hyperglycaemic state therefore predisposes to cardiometabolic morbidity in the presence of emotional distress markers such as cortisol:BDNF.Despite the fact that a pre-diabetic state was demonstrated in the African gender cohort, it was not directly associated with cortisol:BDNF ratio. In another SABPA sub-study, chronic hyperglycaemia was shown to facilitate endothelial dysfunction and susceptibility to stroke risk in the African male cohort.A profile of blunted cortisol and norepinephrine metabolite responses were associated with structural wall remodelling in a depressed SABPA African male cohort.20Attenuated BDNF levels in Africans might also induce decreased neuroplasticity, vulnerability to depression and cardiovascular risk20Indeed, we have confirmed that chronic depression in the SABPA African teachers’ cohort was associated with microvascular dysregulation and perfusion deficits.The cortisol:BDNF ratio in African men suggests a susceptibility to increased cardiometabolic risk. Indeed, cortisol:BDNF is associated with silent ischaemia in African men and impairs central autoregulation, explaining the compensatory increases in blood pressure to maintain homeostasis.19During chronic stress, sympathetic hyperactivity and increased norepinephrine and cortisol levels will elicit vasoconstrictive responses and reduce perfusion in the coronary circulation.Cortisol can further induce or exacerbate down-regulation of BDNF during chronic stress conditions.Susceptibility to emotional distress may be an underlying factor in the observed differences in the bi-ethnic gender cohort. We suggest that attenuated cortisol levels may act as the driving force to downregulate BDNF, increasing cardiometabolic risk and reducing coronary perfusion during psychological distress.One limitation of the study is that a very specific population was studied and results may vary across populations, depending on similar lifestyle and behavioural factors. Another limitation is the cross-sectional nature of the study where causality cannot be inferred. ECG assessment of silent ischaemia showed a sensitivity of 68% and a specificity of 77%,25 therefore further studies are needed to support silent ischaemic events, such as troponin T determinations, in order to confirm reduced blood supply to the heart. We recommend prospective analyses to underpin downregulation of the cortisol:BDNF pathway, as well as the use of a validated depression score to substantiate chronic emotional distress and its relationship with cortisol:BDNF ratio.Central neural dysregulation may mediate cortisol levels as the driving force in the cortisol:BDNF ratio, as it seemingly disturbs BDNF levels during chronic stress. A possible down-regulation may lead to neurodegeneration and add to cardiometabolic risk in Africans. The combined impact of cortisol and BDNF levels associated with silent ischaemia may increase future coronary artery disease risk via compensatory increases in blood pressure.


The surge in arterial pressure during arousal in the waking period is thought to be largely due to activation of the sympathetic nervous system. In this study we compared in SHR the effects of chronic administration of the centrally acting sympatholytic agent rilmenidine with an angiotensin converting enzyme inhibitor perindopril on the rate of rise and power of the surge in mean arterial pressure (MAP) that occurs with arousal associated with the onset of night. Recordings were made using radiotelemetry in 17 adult SHR before and after treatment with rilmenidine (2mg/kg/day), perindopril (1mg/kg/day) or vehicle in the drinking water for 2 weeks. Rilmenidine reduced MAP by 7.2 ± 1.7mmHg while perindopril reduced MAP by 19 ± 3mmHg. Double logistic curve fit analysis showed that the rate and power of increase in systolic pressure during the transition from light to dark was reduced by 50% and 65%, respectively, but had no effect on diastolic pressure. Rilmenidine also reduced blood pressure variability in the autonomic frequency in the active period as assessed by spectral analysis which is consistent with reduction in sympathetic nervous system activity. Perindopril had no effect on the rate or power of the arousal surge in either systolic or diastolic pressure. These results suggest that the arousal induced surge in blood pressure can largely be reduced by an antihypertensive agent that inhibits the sympathetic nervous system and that angiotensin converting enzyme inhibition, while effective in reducing blood pressure, does not alter the rate or power of the surge associated with arousal. Hypertension is an important risk factor for predicting cardiovascular disease but it is the morning period that is the period of greatest risk of stroke and myocardial infarcts –6. DurinPower” which is the product of the rate and the amplitude of the BP morning surge [Power and rate of rise but not at all the MBPS [Power would be most susceptible to attenuation with pharmacological agents that target the sympathetic nervous system such as centrally acting antihypertensive agents. We have extensive experience with rilmenidine and moxonidine which are second generation agents of this class that have mixed actions on α2-adrenoceptrors and imidazoline receptors [Power nor whether this is simply due to a reduction in BP itself.While the rate of rise in BP is clearly important, the magnitude of the rise also hasconsiderable influence on the impact of the rise in pressure. Indeed most measures such as that developed by Kario and colleagues have used an estimate of the morning change in BP within a specified period of waking . Termed ng surge . BP poweng surge  and may ng surge . We recethe MBPS . Thus weeceptors . The prieceptors  and thiseceptors –19. Rilmeceptors . We haveeceptors . HoweverPower during night onset arousal. We also compared the findings with an angiotensin converting enzyme inhibitor perindopril to determine the effect of reducing BP but not affecting the SNS.Hence, the aim of the present study was to apply the new logistic curve fitting procedure to BP recordings from rats in order to determine the effects of chronic administration of the central sympatholytic agent rilmenidine on telemetry recordings of BP, HR and locomotor activity in spontaneously hypertensive rats (SHR). In particular we tested the hypothesis that the sympatholytic agent rilmenidine would attenuate the rate of rise in BP and the BPAll procedures were approved by the Alfred Hospital/Baker Heart & Diabetes Institute Animal Ethics Committee and were carried out according to guidelines set by the National Health and Medical Research Council of Australia. Eighteen male 12–14 week old SHR were obtained from the Baker Heart & Diabetes Institute, weighing 341 ± 11g at the onset of the experiments.In an initial operation, the rats were instrumented with a radio-telemetry probe  as previously described . The ratThe radio transmitter, once implanted and turned on by a magnetic switch, provided a continuous measure of the arterial pressure wave form as well as a measure of locomotor activity . The AM After 1–2 weeks of post-operative recovery, the rats were housed in individual boxes with a 12-hour light-dark rhythm . From the BP signal, an algorithm was used to detect systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and pulse interval . Mean arFollowing an initial 3-day control monitoring period, rats were administered with chronic antihypertensive therapy or vehicle (no treatment) via their drinking water for a period of 2 weeks. The anti-hypertensive agents used were perindopril (1mg/kg/day), or rilmenidine (2mg/kg/day), which we have shown to have antihypertensive properties , 23–25. P1 represented the 'high' plateau, i.e. data obtained during the dark period and P2 represented the data range, i.e. the difference between the calculated 'high' plateau and 'low' plateau. The difference between P1 and P2 then gives the 'low' plateau which indicates data obtained predominantly during the light period. The transition between 'low' and 'high' plateaus was determined as P3 and P5 which are rate of change coefficients. These reflect the steepness of transition from 'high' to 'low' and 'low' to 'high' plateaus, respectively, are independent of the absolute level and can be used to compare different physiological parameters. P4 and P6 are the calculated times at which the respective transitions reach 50%. The method does not assume that the plateau during the day or night is of any particular length and so they can be quite short. In this way the model can cope with data that slowly increase or decrease over several hours or with data that show a particularly short peak or trough which occasionally occurs in some animals.Data for BP, HR and behavioral activity were averaged over 10 minute periods using a specially written analysis and fitting program (CIRCAD version 2003). The data corresponding to each heart beat was initially filtered in order to reject individual data points that exceeded 2.5 times a running standard deviation. The values were then binned into hourly values and fitted to a double logistic curve with the equation:1 and P2 were established with an initial 'square wave' fit of the data which determined the mean values and standard deviation (SD) for the 'light time' and the 'dark time'. The ‘dark time' mean + 2SD was taken as y max, and the 'light time' mean—2SD was taken as y min. The constraints for P1 and the range P2 were such that the following was true i) y min < = P1 < y max ii) P2 > 0 and iii) y min < = (P1+P2) < y max. Constraints for the curvature parameters P3 and P5 were such that the entire transition between plateaus was at least 30 minutes which meant that at least 10-minute data points must be included in the slope portion. After fitting the 6 parameters of the equation, derived variables were obtained such as slope which is the rate of transition between the 'high' and 'low' plateau. Maximum slope is defined as (P2*P3)/4 for the transition between the 'high' (dark period) plateau and the 'low' (light period) plateau and as (P2*P5)/4 for the transition between the 'low' and 'high' plateau. The formula for the slope is the same as that used for single logistic curve fitting as applied to baroreflex function curves [The program CIRCAD uses an iterative least-squares fitting procedure based upon the Marquardt algorithm  with stan curves .The power of the transition was calculated as the first derivative of the logistic curve multiplied by the amplitude which is the day night difference between plateaus y^=P2×P2The maximum power at the midpoint peak of the curve can be calculated as in At the end of 2 weeks of treatment, beat-to-beat data from 72-hour recordings were analyzed separately to calculate power spectra using a program written in Labview . The autData are presented as mean ± standard error of the mean (S.E.M.) of the between-animal variation. All parameters except P3 and P5 satisfied the normal distribution. For the latter we performed a log transform which normalised the distribution in all cases. Differences between curve parameters for a given physiological measure or between physiological measures for a given curve parameter were compared within groups with a two-way repeated measures analysis of variance (ANOVA) followed by post hoc paired t tests and between group comparisons were made using a one-way ANOVA. Familywise error was accounted for by the Bonferroni procedure. Differences were considered significant when P<0.05.The main effect of chronic treatment with rilmenidine was to reduce SAP, MAP and DAP by -7.5 ± 1.9 mmHg, -7.2 ± 1.7mmHg and -6.2 ± 1.7 mmHg respectively P<0.01, , “Fig 1”2/h which is a ~65% reduction (P<0.01) and the rate by ~50%  but had little effect on the rate of change or power of SAP during the transition from dark to light . Thus there was no change to the diurnal day night difference  “”. The maP<0.001) and 87% greater in perindopril treated SHR (P<0.001) than that observed during the day inactive period. However, we did not observe a day night difference in rilmenidine treated SHR  period, MF MAP power was 105% greater in vehicle treated SHR (During the dark (active) period, LF and HF MAP power in vehicle treated SHR were similar to those recorded during the inactive period “”. RilmenMF HR power was 76% greater in the dark active period compared to the day inactive period in vehicle treated SHR (P = 0.001) but baroreflex gain was similar in the day and night periods “”. PerindThe duration of the complete experiments ranged from 5–14 weeks. The aging of animals during this time had no effect on MAP in that the initial control values did not differ from those observed during the recovery from treatment period .In this study we have shown that chronic treatment with rilmenidine and perindopril reduced BP in SHR but rilmenidine was the only treatment to very strongly limit the arousal induced surge in BP that occurs with the onset of the dark period when the rats become active. Presumably the greater effect of rilmenidine in the active period reflects the greater sympathetic vasomotor drive during this time as is reflected in the selective reduction in the MF power. The MF has been shown to be related to sympathetic drive in mice  and rabbOne of the interesting and perhaps unexpected finding was that the attenuation of the rate and power of the arousal surge in BP by rilmenidine was only observed in SAP and not in DAP. The rate and power of the rise in BP reflect the activation of the SNS and changes in a range of other hormones such as increasing catecholamine plasma concentrations, glucocorticoids such as cortisol (in humans) and components of the renin angiotensin system . ImportaOne possibility is that the nocturnal pattern of SAP changes in SHR are mediated more by the SNS but not those involving the DAP changes. This is unlike the BPH/2J mice where the SNS contributes equally to both measures of BP. Doxazosin, an alpha-adrenoreceptor antagonist, is most effective in reducing morning hypertension particularly if administered at bedtime . SimilarOne of the strengths of the current study was to include another type of antihypertensive agent that is very effective in lowering BP in SHR but that doesn’t appear to affect the sympathetic nervous system, namely perindopril . The dosIn conclusion the present study suggests that the arousal associated with hypertension can be specifically targeted by a centrally acting sympatholytic agent such as rilmenidine at doses that produce a modest hypotension. This contrasts angiotensin converting enzyme inhibitors which are very effective antihypertensive agents but do not alter the circadian pattern of BP variability. These studies suggest that centrally acting drugs may be ideal to counter the cardiovascular risk associated with the morning surge in patients. Clearly only a long term outcome study would be able to determine the effectiveness of this strategy.S1 File(XLSX)Click here for additional data file.


Asthma and COPD are both highly prevalent chronic lung diseases with a high personal and economic impact. Asthma usually starts at young age with variable symptoms of wheezing, cough, dyspnea, and bronchial hyperresponsiveness. The airflow obstruction in asthma is often fully reversible after treatment with a bronchodilator. In contrast, COPD usually starts after the age of 40 years in smokers and ex-smokers who develop chronic symptoms of dyspnea, cough and sputum production and display chronic airflow obstruction that is not fully reversible after bronchodilator treatment. In their pure forms, it is easy to distinguish between asthma and COPD. However, it is well recognized in clinical practice that many patients have features compatible with both diseases. To describe this, international asthma and COPD guidelines have recently introduced the term ACOS (Asthma COPD overlap syndrome). Thus far, the underlying mechanisms of ACOS and its appropriately treatment remain largely unclear, because these patients have been systematically excluded from clinical studies.On the long-term, a subset of up to 20% of asthma patients develops a fixed airflow obstruction. Interestingly, Fabbri et al demonstrated that the type of inflammation in asthma patients with fixed airway obstruction differs from that seen in COPD :418–24). They showed that asthma patients irreversible airflow obstruction had significantly more eosinophilic inflammation measured in blood, sputum and bronchoalveolar lavage fluid compared to patients with COPD with a similar degree of airflow obstruction. Interestingly, patients with asthma and irreversible airflow obstruction had a greater rate of lung function decline compared to an asthmatic control group with fully reversible airflow obstruction during a follow-up period of 5 years. Their rate of decline was similar to that observed in COPD. Importantly, higher sputum eosinophil counts predicted lung function decline in patients with asthma and irreversible airflow obstruction, whereas increased numbers of sputum neutrophils were associated with lung function decline in COPD. Currently, these adult asthmatics with irreversible airflow obstruction are often labeled as COPD and unjustly denied treatment with ICS. The introduction of ACOS will lead to a better recognition of these patients so that this is now prevented. In addition, a better phenotyping in COPD may help to identify those COPD patients who benefit from ICS treatment, for example those with bronchodilator reversibility, bronchial hyperresponsiveness or eosinophilic airway inflammation.1 after 8 weeks’ treatment with fluticasone/salmeterol 250/50 μg b.i.d. was significantly greater in COPD patients with (n=161) versus without (n=197) bronchodilator reversibility :682–8.). This is in agreement with the findings of Kitaguchi et al who found a significantly larger improvement in FEV1 after 2–3 months of ICS treatment in COPD patients with versus without bronchodilator reversibility, their mean improvements in FEV1 being 359 ml and 168 ml respectively :1742–52.). Two further studies did not demonstrate a difference in ICS responsiveness between COPD patients with and without bronchodilator reversibility, but these studies were small and hampered by a lack of power.Although bronchodilator reversibility and bronchial hyperresponsiveness are frequently considered to be hallmarks of asthma, they can occur in up to 50% of patients with COPD as well). Bleecker et al showed that the improvement in post-bronchodilator FEV1. However, this does not appear to be the case, since it was shown in a multivariate regression analysis that a more severe BHR in COPD is independently associated with airway inflammation as reflected by the number of neutrophils, lymphocytes and macrophages in induced sputum and bronchial biopsies. One small study showed that COPD patients who exhibited BHR to the indirect stimulus mannitol (n=7) had a significantly greater improvement in FEV1 after 3 months’ treatment with ICS compared to COPD patients without BHR to mannitol (n=30). However, this contrasts with the findings of Rutgers et al who did not find any improvement in FEV1 after 6 weeks’ treatment with budesonide 1600 μg daily in COPD patients with BHR to both methacholine and another indirect stimulus, adenosine 5’-monophosphate :880–6.).It has been argued that BHR is not of pathophysiological importance in COPD as it would merely reflect a lower pre-challenge FEV1, at least over a period of up to 12 months. In this context, our recent findings are also of interest. We evaluated genes, previously reported to be associated with Th2-high asthma in two independent cohorts of patients with COPD. The 100 genes most up-regulated in the airway epithelium in Th2 high asthma as compared to Th2 low asthma/ healthy controls were summarized into a single Th2 composite score using a principal component analysis (PCA) projection algorithm. COPD patients with a higher Th2 composite score had a more severe airflow obstruction and displayed asthmatic features, i.e. increased eosinophilic inflammation in their blood and bronchial biopsies, and bronchodilator reversibility. Moreover, they had a favorable treatment response: after both short-(6-month) and long-term (30-month) treatment with inhaled fluticasone with or without added salmeterol: they experienced more improvement in hyperinflation, measured with body plethysmography. These findings are promising as they show that the presence and extent of ‘Th2-driven eosinophilic inflammation’ is a useful biomarker to guide the diagnosis of asthma, COPD, or ACOS. Future longitudinal studies are now needed to better define the clinical implications of ACOS with respect to the long-term outcome and treatment of ACOS and its sub-phenotypes compared to only asthma or COPD.Finally, there is an increasing amount of evidence that the presence of eosinophilic inflammation in sputum and blood predicts a favorable response to ICS treatment in COPD with fewer exacerbations and improved in FEV


Background/Aims. Subclinical atherosclerosis and long-term glycemic variability have been reported to predict incident chronic kidney disease (CKD) in the general population. However, these associations have not been investigated in patients with type 2 diabetes with preserved kidney function. Methods. We prospectively followed up 162 patients with type 2 diabetes  and assessed whether carotid intima-media thickness (IMT) measured by B-mode ultrasound and visit-to-visit HbA1c variability are associated with deterioration of CKD (incident CKD defined as estimated GFR [eGFR] < 60 mL/min/1.73 m2 and progression of CKD stages) over a median follow-up of 6.0 years. At baseline, 25 patients (15.4%) had CKD. Cox proportional hazards regression models were used for identifying associated factors of CKD deterioration. Results. Estimated GFR decreased from 75.8 ± 16.3 to 67.4 ± 18.2 mL/min/1.73 m2 (p < 0.01). Of 162 patients, 32 developed CKD and 8 made a progression of CKD stages. Multivariate Cox regression analysis revealed that carotid IMT  and coefficient of variation of HbA1c  were predictors of deterioration of CKD independently of age, mean HbA1c, urinary albumin/creatinine ratio, baseline eGFR, uric acid, and leucocyte count. Conclusions. Subclinical atherosclerosis and long-term glycemic variability predict deterioration of chronic kidney disease (as defined by incident or worsening CKD) in type 2 diabetic patients with preserved kidney function. Chronic kidney disease (CKD) has been consistently and independently associated with longitudinal risk for cardiovascular disease and heart failure. Progression towards end-stage renal disease exposes CKD patients to an increased risk of development of vascular disease and cardiovascular morbidity and mortality , 2. EstaThese overlapping risk factor patterns lead us to hypothesize that atherosclerosis may be an important mechanism leading to declines in kidney function. Prospective studies have shown a positive correlation between increased carotid artery intima-media thickness (IMT), a subclinical marker of atherosclerosis and cardiovascular disease, and the risk for kidney function decline and incident CKD in the elderly , 10. In The setting for this observational study was the same as previously reported . We repoFor each subject on each monthly visit, waist circumference, weight, and BP were measured by registered nurses. As previously reported in detail , blood wIntrapersonal mean and coefficient of variation (CV) of HbA1c, fasting and postmeal plasma glucose , and serum TG  taken during the first 12 months after enrollment were calculated and their means ± SD were shown in 2 after 6.0 years in participants with an eGFR > 60 mL/min/1.73 m2 at baseline. Linear regression was used to estimate changes in eGFR using a median of 52 creatinine measurements (interquartile range: 31–60) over 6.0 years of follow-up in each patient. Patients were staged according to the level of eGFR in mL/min/1.73 m2: G1: >90, G2: 60–89, G3a: 45–59, G3b: 30–44, and G4: 15–29 [Urinary albumin was measured once in random urine samples obtained during the first 3-4 months after enrollment using a turbidimetric immunoassay and expressed as albumin/creatinine ratio (ACR). Normoalbuminuria, microalbuminuria, and macroalbuminuria were defined as ACR < 30 mg/g, ACR between 30 and 299 mg/g, and ACR ≥ 300 mg/g, respectively . Serum aIMT was measured by a well-trained medical technologist of Sadamitsu Hospital using ultrasonic diagnosis equipment  that was programmed with IMT software  as previously described . Carotidt-test and frequencies of conditions by chi-square tests. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of deterioration of CKD. Results were expressed as hazard ratio (HR) with their 95% confidence intervals (CI). A two-tailed p < 0.05 was considered statistically significant. All calculations were performed with SPSS system 15.0 .Data were presented as means ± SD unless otherwise stated. Differences between 2 groups were analyzed by The baseline characteristics of 162 participants are shown in p = 0.001) there was no difference in the proportion of patients with microalbuminuria . Consequently, patients with CKD tended to have higher proportion of ACR ≥ 30 mg/g (p = 0.06). There was no difference in glycemic variables and carotid IMT between the 2 groups.As compared to patients without CKD, those with CKD at baseline were older and had longer duration of diabetes and higher proportion of patients on BP-lowering agents . Urinary 30 mg/g . Diastol2 at baseline to 67.4 ± 18.2 mL/min/1.73 m2 after 6.0 years of follow-up (p < 0.01) with an annual decline of 1.11 ± 2.94 mL/min/1.73 m2. Proportion of patients with CKD (eGFR < 60 mL/min/1.73 m2) increased from 15.5% (n = 26) at baseline to 32.7% (n = 55) after follow-up whereas proportion of patients with stage G2 decreased from 63.6% (n = 107) to 54.7% (n = 92) and proportion with G1 decreased from 20.9% (n = 35) to 12.5% (n = 21).The level of eGFR decreased from 75.8 ± 16.3 mL/min/1.73 m2) occurred in 32 patients. Progression from stage 3A to stage 3B and stage 4 occurred in 7 patients and 1 patient, respectively. In total deterioration of CKD occurred in 40 patients . Maximum IMT and CV HbA1c were significant predictors of CKD deterioration. Leucocyte count and baseline eGFR were associated with CKD deterioration, but the relations were of borderline significance. In a model which included mean IMT instead of maximum IMT, CV-HbA1c , mean IMT , baseline eGFR , and leucocyte count  were independent predictors of CKD deterioration.Cox proportional hazard regression models were used for identifying associated factors of deterioration of CKD . IndepenThis study demonstrates in type 2 diabetic patients with preserved kidney function and relatively good glycemic, lipid, and BP control at baseline that the presence of CVD measured as subclinical carotid atherosclerosis was a predictor for deterioration of CKD. In addition, a nontraditional risk factor, namely, visit-to-visit variation in HbA1c, was found to be a risk factor of CKD deterioration.Cross-sectional associations between reduced kidney function and IMT thickening are reported in patients with type 2 diabetes , 18, hypLong-term glycemic variability has been suspected to be a major factor of diabetic complications . We haveThere were no differences in BP between patients whose kidney function deteriorated and those whose kidney function did not in the present study. This may be in line with observation that BP control of 138/86 or 132/78 mmHg appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period , as progThe strength of the current study is that mean and CV of HbA1c and other traditional and nontraditional risk factors shown in Measurements of carotid IMT and visit-to-visit HbA1c variability retain predictive power with respect to CKD progression even after traditional and nontraditional risk factors for kidney disease progression have been taken into consideration. These results suggest that type 2 diabetic patients with subclinical carotid atherosclerosis should be recognized as a group at high risk for CKD progression. In addition, these findings also raise the issue of whether aggressive treatment of traditional risk factors for subclinical carotid atherosclerosis might, in fact, decrease progression to renal replacement therapy. Further studies are needed to confirm the association in other ethnic groups with more patients.


The purposes of this review are to identify population characteristics of important risk factors for the development and progression of diabetic kidney disease (DKD) in the United States and to discuss barriers and opportunities to improve awareness, management, and outcomes in patients with DKD.The major risk factors for the development and progression of DKD include hyperglycemia, hypertension, and albuminuria. DKD disproportionately affects minorities and individuals with low educational and socioeconomic status. Barriers to effective management of DKD include the following: (a) limited patient and healthcare provider awareness of DKD, (b) lack of timely referrals of patients to a nephrologist, (c) low patient healthcare literacy, and (d) insufficient access to healthcare and health insurance.Increased patient and physician awareness of DKD has been shown to enhance patient outcomes. Multifactorial and multidisciplinary interventions targeting multiple risk factors and patient/physician education may provide better outcomes in patients with DKD.The online version of this article (10.1007/s11892-018-0980-x) contains supplementary material, which is available to authorized users. Diabetes mellitus is the major cause of chronic kidney disease (CKD) and end-stage renal/kidney disease (ESRD/ESKD) in the United States • and glo2) and/or increased urinary albumin excretion (> 30 mg/g creatinine), a marker of kidney damage, that persist ≥3 months in the presence of longstanding diabetes and exclusion of other causes of CKD [Approximately 25% of individuals with diabetes have diabetic kidney disease (DKD) . DKD is s of CKD , 8. In ts of CKD .Based on data from the United States Renal Data System (USRDS), the overall prevalence of CKD stages 1–5) in the United States was 15% from 2011 to 2014, with stage 3 CKD being the most prevalent  , which iReferences for this review were identified through a search of PubMed for English language articles published from January 2011 to August 2017 by use of the term “diabetic kidney disease” alone and in combination with “progression” and “risk factors.” Articles pertaining to CKD and DKD epidemiology, management, albuminuria, socioeconomic factors, and patient/physician education and awareness were retrieved and reviewed. Relevant references cited in retrieved articles were also reviewed. Note, in this review, the terms African American, Black, and Non-Hispanic Black are used interchangeably based on how persons were characterized in the literature. The same holds true for the terms Hispanic and Latino.In patients with CKD, the rate of decline in GFR is variable , and theN = 266,975) at high risk for CKD , there was a graded and independent increased risk for all-cause and cardiovascular mortality with increasing albuminuria and decreasing eGFR below 60 mL/min/1.73 m2 [Chronic kidney disease is often asymptomatic, especially in its early stages. Yet, the risk for CVD is increased even in individuals with stages 1–2 CKD compared with those without CKD . In an a/1.73 m2 . Other sImproved communication with patients of the importance of risk factors associated with diabetes and DKD may improve management of the risk factors and the clinical outcomes. In the United States, the high prevalence of obesity (35%)  and metaThe need to treat multiple risk factors increases the challenge of controlling DKD progression. An analysis of the NHANES database (2007–2010) found that only 52% of adults with diagnosed diabetes achieved HbA1c < 7%, 51% achieved blood pressure < 130/80 mmHg, and approximately 56% achieved LDL cholesterol < 100 mg/dL . HoweverA more detailed discussion of these and other risk factors can be found in the Results from the Diabetes Control and Complications Trial (DCCT)  and its The ADA recommends target blood pressure < 140/90 mmHg for most patients with diabetes , 41•, anLipid abnormalities are common in patients with diabetes and typically include elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, and elevated low-density lipoprotein (LDL) cholesterol . AlthougAlbuminuria is both a marker of kidney disease and a risk factor for CKD progression and cardiovascular events . It is i2 and/or albuminuria > 30 mg/g creatinine in the presence of longstanding diabetes and no other causes of CKD [As noted earlier, DKD is commonly diagnosed by an eGFR < 60 mL/min/1.73 ms of CKD . Howevers of CKD . Therefos of CKD , 47, 48.s of CKD  and reins of CKD , 51. Nevs of CKD , 52. TheA key problem associated with CKD and DKD is a lack of awareness of the disease Fig. a.Effective management of DKD is multidisciplinary and requires heightened awareness of DKD by healthcare providers and patients as well as effective communication and collaboration between healthcare providers, specialists, and their patients. Additional barriers exist affecting the successful management of DKD, including socioeconomic factors, access to healthcare and health insurance, and education and awareness of DKD. Unfortunately, populations at highest risk of T2DM, DKD, and ESRD  •, 4 are Data related to patient-specific barriers for DKD are limited; thus, we present data for overall CKD, recognizing that these data should be applicable to DKD as well. Data supporting the discussion of patient-specific barriers can be found in Supplemental Table The greater awareness of CKD among men may be because men normally have higher serum creatinine than women, and physicians may view them as being at higher risk for CKD than women . HoweverBoth the extent of educational attainment and socioeconomic status have been shown to be associated with barriers to care in CKD patients. A variety of studies have demonstrated that income and level of education are associated with risk factors for and progression of CKD , 62. BecIn general, poor health literacy  is associated with more hospitalizations and emergency room use, lower use of preventative services, and poorer adherence to medications, and may partially explain racial disparities in healthcare service utilization and outcomes .In the United States, individuals with CKD and no health insurance were less likely to receive treatment for risk factors associated with the progression of CKD, such as hypertension, diabetes, and obesity, than individuals with CKD and health insurance . A smallPrimary care physicians appear to have a low awareness of CKD and DKD. In a multicenter observational study in 466 primary care practices, only 47% of primary care providers (PCPs) identified CKD in their patients with T2DM, primarily because of underutilization of screening assessments, such as urinary albumin/protein excretion . ImportaSome studies suggest that screening for albuminuria in patients at risk for DKD may be underused in primary care , 66. UnsDiabetes care professionals commonly cite lack of available time as a barrier for effective communication with patients . The int2) to a nephrologist was associated with better preservation of renal function and better control of blood pressure, when compared with continued treatment by PCPs alone [In a prospective cohort study of patients from primary care, referral of patients with T2DM and early DKD  [The finding that nephrologists deliver better CKD-related care to patients with early CKD than PCPs is not unexpected, but there is not a sufficient nephrology workforce in the United States  and globatinine)  or acuteatinine) , 77.The critical need for referral is further highlighted by a report from Gillespie et al.  who examTreatment of diabetes and CKD is complex, both for the provider and patient. Clinical inertia, or the failure to intensify treatment when a patient is not at recommended goals, is of particular concern. In a retrospective analysis of people with T2DM, some patients remained in poor glycemic control for up to 7 years before intensification of treatment . SimilarPatients with CKD usually have multiple comorbidities and may be prescribed more than 20 medications . Thus, sThe first barrier to overcome for optimal DKD care is to ensure the understanding of the significance and limitations of appropriate laboratory testing . AdditioMultiple barriers to DKD care exist at the community level, especially in high-risk communities, and include low health literacy, being un- or under-insured, difficulty in accessing quality care, limited availability of CKD information, lack of readiness to learn, lack of trust in the health system, and other factors , 88, 89.The reviewed literature herein suggests that patients’ and healthcare providers’ knowledge and awareness of CKD and DKD can be improved. Many patients with CKD or ESRD do not feel engaged , and many do not receive patient-centered care . HealthcEducational efforts aimed at patients and healthcare providers have been shown to improve clinical outcomes. For example, brief physician-led educational discussions with patients improve their CKD awareness and understanding of the severity of their disease . Many paThe burden of PCP workload superimposed with patient struggles with inadequate health literacy, coping with new diagnoses, and implications of a possible poor prognosis conspire to limit effective communication. There are tools currently available to help foster such communication. Educational programs are available for patients  , and theThe United States Preventative Services Task Force concluded that there was insufficient evidence to assess the benefits and harms of screening for CKD in asymptomatic adults . By contConcerns about total population screening include inappropriate disease labeling impacting insurability as well as false-positive results with attendant unnecessary testing and treatment. Also, false-negative results create an unwarranted sense of assurance and can delay needed interventions when the actual disease is present , 105.Modeling and other studies have generally found that screening for CKD may be cost-effective only in non-Hispanic Blacks  or in olCurrent guidelines from the ADA  and the 2 and every 3 months if eGFR is 30–44 mL/min/1.73 m2 [In patients with known DKD, eGFR should be monitored more frequently; every 6 months if eGFR is 45–60 mL/min/1.73 m/1.73 m2 . Serum c/1.73 m2  either b/1.73 m2 , althoug/1.73 m2 .Early detection and treatment of DKD delays progression to ESRD . MethodsOwing to the complex nature of DKD and associated comorbidities, the care of patients with DKD is often divided among PCPs, specialists, nurses, and other healthcare providers. Multidisciplinary care consisting of an integrated team of physicians, nurses, dietitians, and educators has been shown to slow the decline in kidney function and the progression to ESRD . For exaAs noted earlier, a multidimensional educational support program can improve HbA1c levels, albuminuria, and physical activity in patients with DKD . SimilarTreatment guidelines and pharmacotherapy recommendations for diabetes, DKD, and CKD are beyond the scope of this review but can be found in publications from the ADA  and NatiDiabetic kidney disease remains a major healthcare issue. Awareness of DKD is low among both patients and their healthcare providers. Although many barriers exist, diagnostic tools needed to increase awareness are readily available, and programs that increase disease awareness have been demonstrated to be both clinically effective and effective in reducing the use of healthcare resources. DKD disproportionately affects minorities, and those with more limited education, lower socioeconomic status, and reduced access to healthcare and health insurance. Progressive policy changes are needed to address these social determinants of health.Given the strong association of increasing levels of albuminuria and clinical outcomes, albuminuria should be reported as a continuous variable, rather than the more limited terms microalbuminuria and macroalbuminuria. This will promote more attention at the health system and provider levels to each patient’s risk status and can help to guide response to therapy. Novel strategies to improve DKD outcomes Table , Fig. 2 ESM 1(DOCX 176 kb)


Self-measurement of blood pressure is a priority strategy for managing blood pressure.The aim of this study was to evaluate the reliability and validity of blood pressure and heart rate following the European Society of Hypertension’s international validation protocol, as measured with the QardioArm, a fully automatic, noninvasive wireless blood pressure monitor and mobile app.A total of 100 healthy volunteers older than 25 years from the general population of Ciudad Real, Spain, participated in a test-retest validation study with two measurement sessions separated by 5 to 7 days. In each measurement session, seven systolic blood pressure, diastolic blood pressure, and heart rate assessments were taken, alternating between the two devices. The test device was the QardioArm and the previously validated criterion device was the Omron M3. Sessions took place at a single study site with an evaluation room that was maintained at an appropriate temperature and kept free from noises and distractions.The QardioArm displayed very consistent readings both within and across sessions . The QardioArm measurements corresponded closely to those from the criterion device (r>.96) and mean values for the two devices were nearly identical. The QardioArm easily passed all validation standards set by the European Society of Hypertension International Protocol.The QardioArm mobile app has validity and it can be used free of major measurement error. Blood pressure (BP) plays a major role in the development of cardiovascular disease, which is the leading cause of premature death worldwide . For patSuccessful BP management depends to a large extent on the patient’s willingness and capacity to make certain lifestyle changes . As demoTherefore, increased use of self-measured BP in the care of patients with arterial hypotension or hypertension could be beneficial. Recent clinical practice guidelines identified several indications for self-measured BP, which may provide for more standardized measurement of BP -17. TodaIn a recent market study of mobile phone apps for managing hypertension, most were focused on health management. Only 14% of these Android and iPhone apps transformed a mobile phone into a BP measuring device . QardioASelf-measured BP devices are only useful and beneficial to the extent that they are user-friendly and accurate ,11,13,14We examined the concordance between two European Community-certified devices for measuring BP and HR in a study involving repeated measurements conducted in the city of Ciudad Real, Spain, between May and August 2016. The Clinical Research Ethics Committee of Hospital Clínico San Carlos in Madrid, Spain, approved this study (number 16/179-E). This study complies with the ethical principles of the Declaration of Helsinki , includiWe recruited 125 participants from the general population of Ciudad Real using snowball sampling, from May to August 2016. A total of 100 participants completed the study; 25 participants did not return for the second measurement. According to the ESH International Protocol , a minimInclusion criteria:Demographic: men and women aged at least 25 years. Of the total number of participants, at least one-third must be men and one-third must be women.Temporal and geographic: healthy adult volunteers able to attend assessments in Ciudad Real.Clinical: ideal BP range of 90 to 180 mm Hg for systolic blood pressure (SBP) and 40 to 130 mm Hg for diastolic blood pressure (DBP), and arm circumference of 220 to 320 mm.Exclusion criteria:Clinical: sustained arrhythmia, circulatory problems in which the use of a cuff is contraindicated, and/or pregnancy.Cognitive impairment that leads to inability to follow instructions.All participants gave their written informed consent to participate in this study.Before recruitment, we calculated with the GRANMO sample size calculation program  that a sample size of 125 would give 80% statistical power (α=.05) and two-tailed test to detect a difference equal to or greater than 0.9 mm Hg in BP. This calculation was based on the assumptions of a standard deviation of 3.2 mm Hg  and a loParticipants visited the study site for two measurement sessions separated by 5 to 7 days. The first author (VMP) collected all the data. Both BP and HR were measured in the left arm. The central portion of the cuff was placed at heart level, with the bottom edge 1 to 2 cm above the elbow.During the first session, each participant reported his/her sex and date of birth. Measurements were taken of the participant’s weight , height , and arm circumference (with a tape measure at the midpoint between the acromion and olecranon). The participant then relaxed for 10 minutes before baseline BP and HR were measured with the criterion BP monitor Omron M3  . Next, BThe rest of the first session involved seven BP and HR measurements, alternating between the criterion and test devices, with 2 to 3 minute intervals between measurements. The first, third, fifth, and seventh measurements were made with the criterion device; the second, fourth, and sixth measurements were made with the test device. The second measurement session involved the same series of seven measurements, with identical procedures carried out by the same researcher, which occurred on the same day of the week and at the same time after lunch, in the same room with identical conditions, as far as it was possible.During measurements, participants were calm and quiet while sitting with their feet parallel and flat on the floor, their legs uncrossed, and their left hands resting palm side up on a flat surface. The room was maintained at an appropriate temperature and kept free from noises and distractions during the sessions ,34.Of the 125 participants who completed the first session, 100 also completed the second session. Our analysis focused on data from just these 100 participants.The Omron M3 Intellisense was the criterion device used as a benchmark in our study. It has CE 0197 certification and has been validated by the ESH between the Omron M3 and a different criterion device with mean 1.7 (SD 3.2) mm Hg for systolic and mean –0.9 (SD 2.6) mm Hg for diastolic .The Omron M3 is a fully automatic BP monitor operating on the oscillometric principle. It has a range of 0 to 299 mm Hg for BP and 40 to 180 beats per minute (bpm) for HR. The cuff is inflated using an electric pump and deflated by means of a pressure release valve.After each measurement, the SBP, DBP, and HR are shown on the Omron M3’s LCD screen. The device can also display a symbol on the screen indicating an irregular heartbeat, which is detected during measurement of SBP and DBP.The QardioArm app for mobile phones and tablets was the test device in our study. It has CE 0734 certification and is a fully automatic, noninvasive wireless BP monitor for measuring SBP, DBP, and HR in adults. The QardioArm also operates on the oscillometric principle and has an inflatable cuff, which is placed around the upper arm. The cuff is inflated automatically and deflated using a controlled pressure release valve. The cuff is suitable for an arm circumference of between 22 and 37 cm. The measuring range is 40 to 250 mm Hg for BP and 40 to 200 bpm for HR..The QardioArm has an automatic screen with graphics and visuals to facilitate interpretation of the data. The monitor connects to the free Qardio app on any device with Bluetooth 4.0 that runs iOS 7.0 or later or Android 4.4 or later. It can be used with iPhones, iPods, iPads, Apple Watches, and Android mobile phones and tablets. The data are stored on the mobile phone or tablet and therefore the pattern of values over time can be viewed. The app can be configured to issue reminders and warnings, and the measurements and progress can be shared in real time with other users The QardioArm weighs approximately 310 g without batteries and measures 6.8 cm in width, 3.8 cm in height, and 14 cm in length, with the cuff closed. It requires four AAA batteries.P<.05.All data were analyzed using SPSS version 19 . Statistical significance was set at We computed univariate summary statistics on participants’ characteristics. Body mass index (BMI) was defined as weight in kilograms divided by height (in meters) squared. To assess whether the BP and HR variables were normally distributed, we conducted one-sample Kolmogorov-Smirnov tests, applying the Lilliefors significance correction. Significant probability values in this test indicate nonnormality.To evaluate the reliability of the QardioArm, we computed the intraclass correlation coefficient (ICC) for comparing measurements taken within the same session (intrasession) and in different sessions (intersession) . The parWe interpreted ICC values with the guide proposed by Landis and Koch : ≤0.20=st tests.We also calculated the standard error of measurement (SEM) for each intrasession and intersession primary variable. SEM values indicate the degree of error, with low values indicating low error. We used the SEM formula of the standard deviation multiplied by the square root of (1–ICC). To identify systematic error over time, we also compared first and second session means on each primary variable with paired-sample Student t test. Following the ESH protocol [To determine the validity of the QardioArm, we compared the QardioArm measurements with those made by the Omron M3, using both the ESH’s International Protocol for the validation of BP measuring devices and the Student protocol ,34, we cprotocol ,34. If tWe compared the observed number of differences (out of 300: three paired differences for a variable × 100 participants in a session) falling into these categories with the standards specified in the ESH International Protocol. There were two phases of this comparison. If a test device did not pass during the first session, the validation process was terminated. If it passed during the first session, the second session was started.t test for independent samples to check whether there were differences between devices in BP and HR measurements. For these tests, we used the mean values of the three study variables obtained from both sessions for the different devices. We also compared the mean intersession differences for the two devices. Furthermore, we calculated the Pearson correlations between the devices for the mean participant values on the three primary variables [In addition to following the ESH International Protocol, we computed Student ariables .Finally, we produced Bland-Altman plots  to displP<.001), height (P<.001), and BMI (P=.009), but no differences in age (P=.10) and arm circumference (P=.08). The Kolmogorov-Smirnov tests showed that SBP (P=.14), DBP (P=.20), HR (P=.20), as well as weight (P=.17) and BMI (P=.20) were normally distributedThe QardioArm is recommended by dabl Educational Trust, which is an organization that provides an interpreted one-page BP report for the medical team and patient , but theWe evaluated the reliability and validity of the QardioArm device for self-measured BP with 100 participants in two measurement sessions. The QardioArm displayed very consistent readings both within and across sessions. The QardioArm measurements corresponded closely to those from the previously validated criterion device, the Omron M3. The QardioArm easily passed all validation standards set by the ESH International Protocol. Therefore, the QardioArm can be recommended for clinical use in individuals with similar characteristics to those who participated in this study, such as adults aged 48 to 56 years with a BMI between 25 and 29, not pregnant, and without cardiac arrhythmia, vascular problems, or arteriovenous fistulas in the arm.There are several limitations of the ESH International Protocol and, thus, our study. The ESH International Protocol uses the same validation requirements  for both SBP and DBP, even though the magnitude of diastolic values is usually half that of systolic measurements.Also, HR as a parameter is not considered in any version of the ESH International Protocol despite the fact that automatic sphygmomanometers produce measurements of HR as well as BP. We have not found any studies of HR validation attempts in the literature that follow the ESH International Protocol ,45-49. TMoreover, the recommendations made in the ESH International Protocol regarding the populations to which validation results can be applied may not be followed faithfully in clinical practice. The ESH International Protocol imposes certain gender requirements and limits validation studies to individuals older than 25 years who have BPs and arm circumferences within specific ranges. Because these subgroups represent only a portion of the large heterogeneous population with BP abnormalities, extrapolation of ESH validation results to other specific populations could be considered unsafe. Additional validation studies are needed if the product is to be used in other subpopulations, such as pregnant women, obese individuals, children, or individuals with particular conditions, such as arrhythmia.The ESH International Protocol also does not indicate the number of validation studies needed to confirm the accuracy of the device. According to experts, at least two validation studies should be performed in different centers and in different populations . The proThere is a high concordance between the measurements made with QardioArm, both intrasession and intersession. The QardioArm mobile app has validity and there is a direct linear correlation between QardioArm measurements and the previously validated Omron M3 measurements, so it can be used without the risk of major measurement error.


Background. IgA nephropathy is the most common cause of primary glomerulonephritis in China, and Traditional Chinese Medicine (TCM) is a vital treatment strategy. However, not all doctors prescribing TCM medicine have adequate knowledge to classify the syndrome accurately. Aim. To explore the feasibility of differentiation of TCM syndrome types among IgA nephropathy patients based on clinicopathological parameters. Materials and Methods. The cross-sectional study enrolled 464 biopsy-proven IgA nephropathy adult patients from 2010 to 2016. The demographic data, clinicopathological features, and TCM syndrome types were collected, and the decision tree models based on classification and regression tree were built to differentiate between the syndrome types. Results. 370 patients of training dataset were 32 years old with serum creatinine of 79 μmol/L, estimated glomerular filtration rate (eGFR) of 97.2 mL/min/1.73 m2, and proteinuria of 1.0 g/day. The scores of Oxford classifications were as follows: M1 = 97.6%, E1 = 14.6%, S1 = 50.0%, and T1 = 52.2%/T2 = 18.4%. The decision trees without or with MEST scores achieved equal precision in training data. However, the tree with MEST scores performed better in validation dataset, especially in classifying the syndrome of qi deficiency of spleen and kidney. Conclusion. A feasible method to deduce TCM syndromes of IgA nephropathy patients by common parameters in routine clinical practice was proposed. The MEST scores helped in the differentiation of TCM syndromes with clinical data. Similar to several other developing countries, alternative therapies are considered as pivotal and general treatment strategies for IgA nephropathy in China, especially the decoction and the patent medicine of TCM [IgA nephropathy has been recognized as the most common form of primary glomerulonephritis –5 and ise of TCM –11. In fe of TCM –15.The experience of 3000 years and modern researches show that Chinese Medicine must be applied with syndrome classification under the direction of TCM theory. Only in this way could the effectiveness be significant and the adverse events be avoided . Syndrom370 biopsy-proven IgA nephropathy patients from 1 January 2010 to 31 December 2014, in Guangdong Provincial Hospital of Chinese Medicine and Shanxi Provincial Hospital of Chinese Medicine, and 94 from 1 January 2015 to 30 June 2016, in Guangdong Provincial Hospital of Chinese Medicine, were enrolled in the present study after excluding patients below 14 years of age and those with Henoch-Schönlein purpura, systemic lupus erythematosus, and cirrhosis. The patients were categorized into two sets: training dataset and validation dataset. The training dataset included 370 patients during 2010–2014, while the validation dataset consisted of 94 patients during 2015-2016.The standard process of interpreting renopuncture tissues included light microscopy, immunofluorescence, and electron microscopy. For light microscopy, all specimens were stained with hematoxylin and eosin (H&E), Periodic acid–Schiff, Masson's trichrome, and Jones' methenamine silver. Renal biopsies were scored according to the Oxford MEST scoring system  by two pThe evaluation of TCM syndromes was performed according to the Guiding Principle of Clinical Research on New Drugs of Traditional Chinese Medicine  for the t-test or Kruskal-Wallis test for continuous variables and chi-squared test or Fisher's exact test for categorical variables. All the mentioned tests were two-tailed, and a P value < 0.05 was considered statistically significant. The analyses were conducted by SPSS 17.0 statistics software . The decision tree was built by R with packages of rpart and rpart.plot based on the data from 390 patients biopsied between 1 January 2010 and 31 December 2014. Variables involved in modeling included gender, age, mean arterial pressure, disease course, macroscopic hematuria or not, eGFR, uric acid, serum albumin, hemoglobin, proteinuria, and urinary red blood cell. The MEST scores were added to the model to explore whether pathological parameters would increase the accuracy of the model. Positive predictive value (PPV), negative predictive value (NPV), integrated discrimination improvement (IDI), and net reclassification index (NRI) were calculated to evaluate the improvement in predicting QDSK of the model with MEST scores.Continuous data with normal distribution were presented as the mean and standard deviation (SD), and those with abnormal distribution were presented as a median and interquartile range. The ranked data with equal intervals were expressed as median and interquartile range, and those with unequal intervals were expressed as counts and percentages of each rank. The categorical variables were expressed as counts and percentages. Comparisons between groups were conducted using independent-samples μmol/L, and eGFR was 97.2 (67.2–120.5) mL/min/1.73 m2. The scores of Oxford classification were as follows: M1 = 97.6%, E1 = 14.6%, S1 = 50.0%, and T1 = 52.2%/T2 = 18.4%.P = 0.025), the pairwise comparison did not reach a significant level. Any statistical difference was not observed in gender, disease course, and inducement among the three types of fundamental symptoms. The systolic blood pressure, diastolic blood pressure, and mean arterial pressure (MAP) of different types did not exhibit a significant difference; however, patients in OTs category showed a higher rate of hypertension than DBQY (P = 0.008). Although patients of QDSK seemed less likely to acquire macroscopic hematuria than OTs (P = 0.015) and some difference was seen in urinary red blood cell (P = 0.015), a pairwise test could not figure out the difference. Moreover, no obvious difference was observed in hemoglobin, proteinuria, uric acid, serum albumin, serum IgA, and C3 among those three types. For the renal function, the serum creatinine of patients with DBQY was <QDSK (P = 0.019) and OTs (P < 0.001). The eGFR of those with DBQY was > QDSK (P = 0.014) and OTs (P < 0.001), and the eGFR of OTs was <QDSK (P = 0.012). When dividing the patients' eGFR to different levels according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of CKD [P < 0.001) and QDSK (P = 0.005), primarily because the percentage of patients with an eGFR lower than 60 mL/min/1.73 m2 in OTs (41.9%) was significantly larger than that of those with DBQY (7.6%) and QDSK (20.5%). With respect to the pathological features, the three syndrome types seemed to have some differences in M scores (P = 0.032); however, the pairwise analysis did not show a sufficient difference, and a statistical difference was not observed in E, S, and T scores and the ratio of crescents.273 (73.8%) patients got QDSK, 66 (17.8%) patients got DBQY, and 31 (8.4%) patients were categorized as OTs. Although some difference was found in age , diastolic blood pressure (P = 0.001), and MAP (P < 0.001) of the validation dataset were larger compared to the training dataset (P < 0.001) and serum creatinine (P < 0.001) and the lower eGFR (P < 0.001) implied that kidney injury was more severe in the validation dataset. However, the M score (P < 0.001) and T score (P < 0.001) were smaller in the validation dataset. We analyzed the eGFR of each T score  patients had yin deficiency of liver and kidney or yang deficiency of spleen and kidney. A cross-sectional study surveyed 1148 Chinese IgA nephropathy patients' clinicopathological features . The stuTo our knowledge, this is the first report differentiating TCM syndromes by building models with objective indexes in IgA nephropathy. In other diseases, some model has been developed to diagnose patients' syndromes –40. SomeThe classification and regression tree has several advantages of its own, irrespective of the management decision and statistical method. One obvious advantage is that the logic and operation are easily understood, making it intuitive and clear. The advantage is prominent when compared to the method with an opaque mechanism of weight and prediction, such as neural networks. Another advantage is the way of handling the missing data that can make full use of the data. The most common approach to handling missing values is deleting missing observations, but classification and regression tree only deletes the observations with missed dependent variables, while the observations with missed independent variables would be reserved. This method also exhibits adequate stability and versatility, because the dividing basis of variables is dependent on the rank of value instead of the numeric size, and thus even some outliers appearing in the dataset would have little influence on the result. The result is less affected by choice of variables than multiple regression analysis, as the addition and elimination of variables would not affect the result unless the variables were involved in the tree. Compared to the simple regressions, the classification and regression tree also eliminates the trouble in selecting variables, because, during the process of constructing the tree, the optimal cut-off point of each involved variable will be automatically selected.Several limitations should be considered while interpreting our study. This is a retrospective study; thus, the types of TCM syndromes were not strictly classified by identical criteria, and necessary postreclassification was performed. Except for the combined type of OTs, only 2 syndromes, QDSK and DBQY, entered into the statistical analysis, making the generalization of the findings to other TCM syndromes uncertain. The precision of classifying OTs was much less than 1/3, which might be due to the type mixed with several types, and the characteristic of each original type was confused. The clinicopathological parameters of training and validation datasets were quite different, especially in renal function and pathological features. The limited sample size limitedly represented the population of all IgA nephropathy patients.In conclusion, the decision trees on the basis of clinical indexes can help classify the types of TCM syndromes, and the pathological features may slightly improve the precision. Similar studies based on larger sample size or prospective studies would be useful for further exploration.


Data on the prevalence of persistent symptoms in the first year after preeclampsia are limited. Furthermore, possible risk factors for these sequelae are poorly defined. We investigated kidney function, blood pressure, proteinuria and urine sediment in women with preeclampsia 6 months after delivery with secondary analysis for possible associated clinical characteristics.From January 2007 to July 2014 all women with preeclampsia and 6-months follow up at the University Hospital Basel were analyzed. Preeclampsia was defined as new onset of hypertension (≥140/90 mmHg) and either proteinuria or signs of end-organ dysfunction. Hypertension was defined as a blood pressure ≥ 140/90 mmHg or the use of antihypertensive medication. Proteinuria was defined as a protein-to-creatinine ratio in a spot urine > 11 mg/mmol. Urine sediment was evaluated by a nephrologist. Secondary analyses were performed to investigate for possible parameters associated with persistent symptoms after preeclampsia.2 (range 59.7–142.4 mml/min/1.73m2) . 20.3% (41/202) had a blood pressure of 140/90 mmHg or higher (mean 143/89 mmHg) or were receiving antihypertensive medication . Proteinuria was present in 33.1% (66/199) (mean 27.5 mg/mmol). Proteinuria and hypertension was present in 8% (16/199). No active urine sediment (e.g. signs of glomerulonephritis) was observed. Age and gestational diabetes were associated with persistent proteinuria and severe preeclampsia with eGFR decline of ≥ 10 ml/min/1.73m2.Two hundred two women were included into the analysis. At a mean time of follow up of 172 days (+/− 39.6) after delivery, mean blood pressure was 124/76 mmHg  and the mean serum-creatinine was 61.8 μmol/l (33–105 μmol/l) . Mean estimated glomerular filtration rate using CKD-EPI was 110.7 mml/min/1.73mHypertension and proteinuria are common after 6 months underlining the importance of close follow up to identify those women who need further care. Preeclampsia is a pregnancy related disease defined as new onset of hypertension and either proteinuria or signs of other end-organ dysfunction . Preeclampsia occurs in approximately 5% of pregnancies , and is To identify those with chronic hypertension or proteinuria after delivery, it is important to know the usual time of resolution of these symptoms. Guidelines state that blood pressure should normalize in the first 3 months  and refe2. Urine sediments were evaluated by a staff nephrologist. For secondary analyses, a multivariate logistic regression model was applied. Univariate analysis was conducted in all variables with at least 15 observations and variables with a p-value < 0.2 were added to the model. Wilcoxon Mann Whitney test was used to compare medians due to skewed distribution of the baseline characteristics in the subgroups; chi-squared test was used to compare frequencies. Different denominators in the results section are due to missing data in a few patients.From January 2007 to July 2014 all women with preeclampsia at the University Hospital Basel referred to our nephrology clinic were included into the study. As by our hospital policy, all patients with preeclampsia are referred for nephrology follow-up after 6 months. Patients were closely followed by their family doctor or obstetrician and referred earlier if necessary. Preeclampsia was defined as new onset of hypertension (≥140/90 mmHg) after the 20th gestational week or worsening hypertension  in patients with pre-existing elevated blood pressure and either proteinuria or other signs of end-organ dysfunction. The gynaecology department of the University Hospital of Basel had been in the practice of defining preeclampsia without the proteinuria requirement, as was later confirmed by the ACOG 2013 guidelines . DeclineOf the 225 women referred to our nephrology clinic, 23 were lost to follow-up 10%). Two hundred two were included in the analysis. The mean time of the follow up visit was 172 days (+/− 39.6) after delivery. Mean age of the 202 women was 32 years (18–45 years). 58.2% (117/201) were pregnant for the first time (primigravida). In 22.2% (43/194) of the patient’s preeclampsia occurred before 34 weeks of gestation. Severe preeclampsia was observed in 67% (132/197) and eclampsia as the most severe form was seen in 2% (4/198). 90.1% (181/201) had no pre-existing diseases before pregnancy . Baseline characteristics are shown in Table 0%. Two h2 (59.7–142.4 ml/min/1.73m2) . 20.3% (41/202) had a blood pressure of 140/90 mmHg or higher (mean 143/89 mmHg) or received antihypertensive medication . Proteinuria was present in 33.1% (66/199) . Proteinuria and hypertension were present in 8% (16/199)  with persistent hypertensive values ≥ 150/100 mmHg at follow-up, but not persistent proteinuria or eGFR decline.In our study, 20% of women were hypertensive after 6 months. In the study by Berks et al., 39% of women had hypertensive blood pressure values after 3 months and 18% were still hypertensive after 2 years . These f2. Only one woman had an eGFR below 60 ml/min/1.73m2. Thus, a reduced eGFR early after preeclampsia is uncommon. Our results correspond well with an analysis from Vikse et al. that showed a 0.1% risk of ESRD after preeclampsia after 30 years [Data on kidney function in the first months to years after preeclampsia are limited. In the study by Shahbazian et al.  the mean30 years . The imp2, which was present in 27 women. The clinical significance of this decline is difficult to interpret. Since physiologic glomerular hyperfiltration is still present at the end of pregnancy, the reported “decline” could really be a return to baseline before pregnancy. On the other hand, it was only present in a minority of patients and significantly associated with severe preeclampsia, both arguments against a physiological process. However, although a signifcant difference (p < 0.00) in medians in eGFR in women with a decline in eGFR (103 ml/min/1.73m2) and women without (114 ml/min/1.73m2) was present, both were within normal range. Furthermore, as mentioned above the risk of ESRD after preeclampsia is far lower than the 13% (27/197) of women with an eGFR delcine in our study, thus the clinical significance remains unclear.We arbitrarily defined kidney decline as a decrease in kidney function by ≥10 ml/min/1.73mOur study has several strengths. To the best of our knowledge, this is the largest study on short term sequelae of preeclampsia. Furthermore, information on urine sediments has not been reported in this setting before. Due to a standardized protocol for follow-up after preeclampsia at our clinic, a low number of patients were lost to follow-up. The collection of several baseline characteristics allowed for secondary analysis for risk factors.There are also several limitations. Being designed as a cohort study, there is no control group as a reference. We did not have information on GFR during pregnancies, since there were no routine blood tests before preeclampsia symptoms occurred with mostly initiation of delivery short thereafter. An analysis on possible sociodemographic differences between the patients lost to follow-up and the patients included in our study would have been of interest, but was not possible due to unavailability of sociodemographic data. There seems to be a selection bias with a high incidence for severe preeclampsia (67%), most likely due to our hospital being a tertiary center with referral of more complicated deliveries. Additionally, even though all patients with preeclampsia in our center are supposed to be referred for nephrology follow-up after 6 months, we cannot exclude that some patients with mild forms of preeclampsia were not referred for follow-up leading to a higher incidence of severe preeclampsia.Given the high frequency of sequelae 6 months after preeclampsia, this study underlies the importance of close follow-up. To identify those women at risk for persistent symptoms, knowing what features of preeclampsia are associated with these short-term sequelae would be important. We identified age and gestational diabetes as risk factors for proteinuria and severe preeclampsia for a decline in eGFR. However, further studies are need to define the clinical relevance of these findings.


The cases of donation after brain death followed by circulatory death (DBCD) and donation after cardiac death (DCD) have been increased year by year in China. Further research is needed to understand in the outcomes and risk factors of delayed graft function (DGF) in order to minimize the risk of DGF and ameliorate its potential impact on long-term outcomes. This study was to explore the differences in outcomes between DBCD and DCD transplant and the main risk factors for DGF in DBCD.Retrospective analysis of the clinical data of 367donations after citizens’ death kidney transplant procedures (donors and recipients) between July 2012 and August 2015 at our center.p = 0.002). The 1-year percent freedom from acute rejection (AR) was significantly higher in DBCD group compared with it of DCD group . Multivariate logistic regression analysis of the kidney transplants revealed that the high risk factors for DGF after renal transplantation in DBCD were history of hypertension , low blood pressure (BP < 80 mmHg)  and serum creatinine of donor  before donation.During the study period, the donation success rate was 25.3%. 164 cases of DBCD and 35 cases of DCD had been implemented and 367 kidneys were transplanted. The incidence of DGF in DBCD group were significantly lower than that of DCD group (12.0% vs. 27.0%, The outcomes of DBCD could be better than DCD in DGF and AR. The main risk factors for DGF in DBCD kidney transplants are donors with a history of hypertension, low blood pressure, and serum creatinine of donor before donation. Donation after cardiac death (DCD) and donation after brain death (DBD) are two processes for organ donation. Transplant technology and experiences with DCD and DBD resources are now highly advanced, and the transplantation outcomes of both organ resources processes are well explored . AlthougIn 2012, Dr. Qiu and his colleagues summarized the introduction of DBCD in China as a new protocol for deceased donations, which responded to brain death not being legally recognized in China . AdditioDelayed graft function (DGF) is an early complication after deceased donor kidney transplantation with significant adverse effects on graft outcomes. One of the major concerns of kidneys from DCD donors is the high incidence of DGF observed after transplantation. The harmful impact of DGF on graft outcomes in DBD transplant is well documented , 7–9. HoIn China, the cases of DBCD and DCD have been increased year by year. Further research is needed to understand in the outcomes and risk factors of DGF in the DBCD transplants, so that to minimize the risk of DGF and ameliorate its potential impact on long-term outcomes. The aim of this study was to compare the outcomes of DBCD transplants with those of DCD transplants, and explore the risk factors of DGF among patients with DBCD kidney transplantation.This was a single-center, retrospective cohort study conducted at the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China. Data were obtained from the registry system of organ donation database, which collects all data prospectively. All patients who received a deceased-donor kidney-only transplant from July 2012 to August 2015 were included in this study. Recipients were regularly followed up post transplant. The follow up time points were the first month, the second months, the third month, the sixth month, 1 year after kidney transplantation, then once a year. The median follow up time was 317 days, range from 1 day to 700 days. Recipients were divided into two groups based on the type of donor DBCD and DBD. End points studied were patient survival and uncensored graft survival. Other end points included DGF, AR, and infection in the first year.A Donation after Citizens’ Death flow chart for donors in China is briefly shown in our previous study . AcceptaThree hundred sixty seven kidney transplant cases derived from 199 donors were completed in our center, in accordance with the donation after citizens’ death standard implementation at our local organ procurement organization (OPO). The family members  of the donors agreed to the organ donation after cardiac death, and signed a voluntary organ donation form and other related documents. Organs were recovered after removal of the donor from mechanical ventilation and 2 ~ 5 min after confirmation of cardiac death. All kidneys were preserved by hypothermic machine perfusion . A kidney transplantation would not be performed if machine perfusion parameters showed that a flow rate < 80 mL/min and/or resistant index >0.4. The characteristics of the donors and recipients were reported in Tables High-resolution HLA typing  was performed using sequence-specific oligo nucleotide probes . HLA types A, B, and DR (three pairs and six antigens) are used for matching before kidney transplantation. All of the recipients were complement-dependent-cytotoxicity-crossmatch negative and therefore considered to be at low risk of early AR.All of the recipients were given a triple immunosuppressive regimen with calcineurin inhibitors (CNIs), enteric-coated mycophenolate sodium , and prednisone. The CNIs included cyclosporine A  and tacrolimus . The initial dosages of CsA, TAC, EC-MPS, and prednisone were 4.0-4.5 mg/kg/day, 0.06-0.08 mg/kg/day, 1080–1440 mg/day, and 10–20 mg/day, respectively. All of the recipients were treated with rabbit anti-thymocyte globulin  at a dosage of 1–1.25 mg/kg/day as induction therapy during the surgery, and for a total of 4–6 days after kidney transplantation.Anti-infective prophylaxis included oral intake of sulfamethoxazole/trimethoprim for 6 months and intravenous administration of valganciclovir for 2 weeks, which was initiated immediately and after 2 months post-transplantation, respectively. This was followed by maintenance therapy with oral ganciclovir for at least 3 months, depending on donor and recipient cytomegalovirus (CMV) serological status.DGF was defined as a serum creatinine concentration at postoperative day 7 of >2.5 mg/dL or the need for dialysis during the first week after transplantation.AR was identified on biopsy and classified according to the Banff’07 classification and its subsequent updates . AR was The infections within the first year of kidney transplantation were also explored in this study, including pulmonary infection, urinary tract infection, and incision infection.Serum concentrations of total bilirubin, alanine aminotransferase, albumin, blood urea nitrogen, and serum creatinine were measured using an automatic biochemistry analyzer . The blood trough concentrations of CsA, TAC and Mycophenolic acid (MPA) were measured regularly using an enzyme multiplied immunoassay . The PRA and donor-specific antibody (DSA) were screened using the Luminex 200 system .U test or Student’s t test, as appropriate. Kaplan-Meier non-parametric methods were used to determine the one-year freedom from the events  after kidney transplantation. Log rank tests were used to compare the difference in them between DBCD and DCD patients. Univariate and multivariate logistic regression analyses were performed to identify risk factors of DGF in the DBCD group. Variables with P values <0.1 in the univariate analyses were entered into the multivariate logistic regression models. Odds ratios (ORs) were presented with their 95% CIs. P < 0.05 was considered statistically significant.Data were analyzed by SPSS® version 17.0. Categorical data were compared using the Chi-square tests or Fisher’s exact tests, while continuous data were analyzed using Mann–Whitney p < 0.001) and BMI of recipients was a little higher in DBCD group compare it of DCD group . Other clinical characteristics were not found significantly different between DBCD and DCD groups.Among the 786 families in our study, 587 families did not give consent to donate organs of potential donors, while the remaining 199 families provided consent. Donation success rate was 25.3%. The conditions of 164 (82.4%) donors complied with the standard of DBCD. The other 35 cases were complied with DCD. The average ages of the donors and recipients were 39.6 ± 16.1 and 36.2 ± 10.5 years, respectively. There are 159 (79.9%) male out of 199 donors and 248 (67.6%) male out of 367 recipients. A comparison of donors and recipients characteristics between DBCD patients and DCD patients is displayed in Tables p = 0.002), and one-year percent freedom from AR was higher in DBCD group compared with it of DCD group , respectively  , and one-year percent freedom from infection   and other diseases  had higher risk of developing DGF compared with the recipients whose donors died from craniocerebral injury. Higher serum creatinine of donor’s  before donation, longer cold ischemic time , processes of CPR , history of hypertension  for donors were found associated with higher risk of DGF. Donors experienced in hypotension would increase the risk of DGF for recipients . If a donor used vasopressor agents, the recipient of the kidney would have lower risk of DGF after the kidney transplantation .Results of univariate analyses for the risk factors of DGF were reported in Table p = 0.002), hypotension , and serum creatinine of donors before donation  were risk factors of DGF occurrence (Table p = 0.008) was benefits factor for DGF in our study.In multivariate logistic regression analysis, history of hypertension  before donation was risk factors of DGF occurrence, which was identical with others reports.The incidence of DGF after renal transplantation in the present study was 27% in recipients whose grafts were recovered from donors with a history of hypertension of at least 5 years. For such donors, it is necessary to learn more about their history of anti hypertensive treatment and treatment outcomes, whether they suffered complications of hypertension, and its influence on renal function. The donor’s final serum creatinine value was one of important proposed risk factors for DGF . MultivaP < 0.1 in the univariate analyses were included in one multivariate model, it could be due to lack of power. In brief, both univariate and multivariate analysis showed the lower of the blood pressure, the higher of the DGF risk. The vasopressor agents used in our study were vascular active pharmaceutical  to stabilize the donor’s blood pressure. All of the pharmaceuticals have minimal impact on renal function. On the other hand, the vasopressor agents ensure the sufficient blood in organs before donation, which is benefit for the function recovery of graft after transplantation.Kidney is an organ of hypertransfusion and very sensitive to ischemia, while Low blood pressure results the insufficient of kidney blood flow volume, which will induce ischemia/reperfusion injury on kidney and clinically present as the DGF. In our study, the data of univariate analysis showed that donors experienced in hypotension (BP < 100 mmHg) would increase the risk of DGF for recipients. However, multivariate analysis data showed hypotension experience with blood pressure less than 80 mmHg became significant after all variables with It was showed that cold ischemia time has a critical effect on the development of DGF. The two most widely used preservation buffers, University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions, show similar efficacy in terms of DGF rates for most donor types , 22. MacLimitations of our study include, first, it’s a retrospective study and some information of donors and recipients are collected incompletely, which could influence the occurrence of DGF and graft outcomes. Second, a variety of other clinical factors may also increase the risk of DGF, such as marked body mass index of the donor and recipient, potential drug nephrotoxicity, surgical problems and/ or hyperimmunization of the recipient . It shouIn conclusion, the clinical outcomes of DBCD kidney transplantation is better than DCD kidney transplantation. Successful implementation of DBCD and subsequent kidney transplantation requires an accurate and timely assessment and maintenance of the function of the donated organs. The main risk factors of DGF are donors who have a history of hypertension, serum creatinine of donor before donation, and low blood pressure of donor before donation.