Rationale: Anemia, a common feature in chronic kidney disease (CKD), has multiple contributors to its pathogenesis. Besides the well recognized erythropoietin and iron deficiencies, hydration status might be involved.Objective: To assess the prevalence and correlations of anemia, iron deficiency and overhydration in patients with stage 2 to 5 CKD.Methods and Results: This cross-sectional study enrolled 125 erythropoietin and iron therapy naïve non-dialysis CKD patients, without a identifiable cause of anemia.Parameters of hematological, iron, inflammatory and nutritional status were measured. The overhydration parameter (OH) assessed by bioimpedance spectroscopy was used to characterize hydration status.p=0.008). Fluid overload (OH >1L) and lower serum albumin (<40g/L) were more common in stage 5 versus stage 3 CKD , suggesting a potential dilutional reduction in serum proteins. Conversely, decreased iron stores (ferritin <100mcg/L) and iron availability  were similarly prevalent irrespective of kidney function decline.The prevalence of decreased hemoglobin (Hb) <110g/L increased along CKD stages from 0% to 40% (Hemoglobin was positively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and transferrin saturation, but inversely with OH. However, in a model of multiple linear regression which explained 32% of hemoglobin variation, only eGFR and overhydration remained the independent predictors of anemia.Discussion: As fluid overload is a common denominator for hemoglobin and TSAT levels, and is closely related to the declining kidney function, it should be considered in the management of renal anemia, at least in advanced CKD. Anemia is common in the course of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), due to either disturbances induced by the glomerular filtration rate (GFR) decline  or the underlining disease or various chronic therapies . DecreasConsequently, erythropoiesis stimulating agents (ESA) and iron are widely prescribed to correct anemia in CKD, but both approaches were related to unwanted side effects . Large iNational Kidney Foundation defines anemia as hemoglobin (Hb) <135g/L (13.5g/ dL) in men and <120g/L (12g/dL) in women  were also seen in advanced CKD: more subjects in stage 5 CKD had fluid overload than those in stage 3 and 2 CKD , and lower serum albumin versus stage 3 CKD (p=0.02). A higher prevalence of overhydration was found even in stage 4 as compared to stage 3 CKD (p=0.01)  in accordance with the Renal Association updated guideline , was 24%(p=0.01) .In the whole group, the prevalence of decreased iron stores [ferritin <100mcg/L (100ng/mL)] and iron availability for erythropoiesis [ferritin >100mcg/L (100ng/mL) and TSAT <0.20 (20%)] were 32% and 33%, respectively, without differences across CKD stages.Subjects with anemia had lower eGFR and TSAT, but higher OH and more prevalent diabetes mellitus .p<0.001) and double than in euvolemic  subjects.In addition, when divided according to the hydration status, more patients with hypervolemia  had anemia as compared to both euvolemic  and hypovolemic  subgroups. The prevalence of anemia in patients with higher OH was five times as much as in hypovolemic  and serum albumin , but inversely with overhydration , only overhydration and eGFR were retained as the independent predictors of anemia .Chronic kidney disease is a growing public health problem since it affects in average one out of ten persons worldwide. A recent epidemiologic study in our country reported an overall CKD prevalence of almost 7% , so one As presumed based on the pathophysiology of renal anemia and in accordance with data from the literature ,16, highHowever, the novel and most interesting finding in this study is the trend of volume overload prevalence which runs almost parallel that of the anemia along the CKD stages. The seriousness of hyperhydration is from long-time well known in ESKD patients , but morThe fact that as higher the hydration status parameter is the hemoglobin is lower, points to the need of make the distinction between the true anemia and the influence of hemodilution even in CKD patients without overt signs of volume overload.Despite the strength resulted from the inclusion of subjects never before treated with ESA and intravenous iron, the current study has limitations. Firstly, the cross-sectional design does not allow any causality speculations, and the small sample size and single center character hamper the possibility of generalizability. Another drawback is the lack of data about the dietary salt intake and diuretic treatment. However, the association between anemia and fluid overload can be argued, and this warrants further studies.In conclusion, as fluid overload is a common denominator for serum hemoglobin and transferrin saturation, and is closely related to the reduction in kidney function, it is an important factor to consider in the management of renal anemia, at least in advanced chronic kidney disease. In other words, it is advisable for clinicians to carefully assess hydration status during the diagnosis work-up for renal anemia whenever the GFR is below 0.50mL/s (30mL/min) and to decide the prescription of antianemic medications only after correction of the “dilutional” component of the anemia.The authors confirm that there are no conflicts of interest.


Analysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system. Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU’s.TI and KTE) were calculated.Infants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV. Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured. Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (KP < 0.01). QI was significantly lower than QE , and KTI:KTE ratio was 1:1.04 (1:0.59–1.42).We included 16 patients, of median age 2.5 (1–5.8) months. Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities. Measured respiratory pressures were PIP 29 (26–31), PPL 24 (20–26), tPEEP 9 [8–11] cmH2O. Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP – PEEP)  contains supplementary material, which is available to authorized users. Respiratory infections are the leading cause of childhood mortality and morbidity worldwide. Bronchiolitis, the most common lower respiratory infection in infants, continues to be a major pediatric public health problem , 2. ReseBronchiolitis is usually a self–limited disease, but some children may develop respiratory failure with increased work of breathing (WOB), hypoxemia and hypercarbia requiring mechanical ventilation (MV) in addition to usual supportive measures , 8. ReseModern ventilators are thought to be not only a supportive machine, but also a bedside monitoring tool. Respiratory mechanics are the expression of lung function trough measures of pressure and flow. When positive pressure is applied to the respiratory system, advance analysis of respiratory mechanics can discriminate the different elements of WOB according to equation of motion: resistive component (the resistance to displacement of a determined gas flow), elastic component (elastic opposition to a determined change of volume) and a threshold load. The threshold load refers to the amount of work required to commence inspiratory flow and it is determined by autoPEEP –12. InteBronchiolitis is usually considered an airway obstructive disease based on physical exam, although bronchodilator therapy has been proven to be ineffective. Groundbreaking studies 50 years ago described increased respiratory rate and decreased lung compliance in spontaneously breathing children with bronchiolitis . A betteWith these facts in mind, we designed this study to examine the analysis of respiratory mechanics in infants on MV due to severe bronchiolitis. Our aim was to describe the work of breathing in this group of patients, analyzing the different components of the respiratory mechanics: the resistive and elastic forces, as well as threshold.This prospective observational study was conducted in 2 PICU’s: Centro Hospitalario Pereira Rossell is a 20 bed mixed medical surgical pediatric intensive care unit located in Montevideo, Uruguay, that covers all PICU pathologies except cardiosurgery; Hospital El Carmen de Maipú is a 6 bed polyvalent unit and a referral center for acute respiratory failure in Santiago, Chile.T), consolidation or atelectasis greater than 2 quadrants on Antero-Posterior chest x-ray, bronchodilator administration 1 h before measurement at the time of measurement were excluded due to possible interference with data acquisition.Between May 1st and August 28th, 2015, children younger than 1 year old with clinical diagnosis of bronchiolitis requiring MV due to acute respiratory failure were screened for the study. Patients were excluded if they had uncorrected congenital heart, pre-existing lung or airway disease, chronic respiratory failure requiring long–term MV and tracheostomy. Additionally, patients with spontaneous breathing effort, endotracheal tube air leak >20% of tidal volume (VPL), extrinsic PEEP (PEEP), total PEEP (tPEEP), driving pressure (∆P = PPL–tPEEP), expiratory VT (VTE), inspiratory time (IT), and respiratory rate (RR)], maximum inspiratory and expiratory flow (QI and QE), and arterial blood gases before the measurement were registered and PaO2/FiO2 (PF) ratio and Oxygenation Index (OI) were calculated.We registered demographics at admission, clinical information, Pediatric Index of Mortality 2 (PIM 2) and outcome. Patients were ventilated on Volume Control mode. Ventilator parameters , but no significant differences were found between KTI and KTE [0.18 (0.12–0.30) v/s 0.18 (0.13–0.22) s]. However, RawI and RawE were not statistically different [38.8 (32–53) v/s 40.5 (22–55) cmH2O·L−1·s−1]. RawI was higher than RawE in 37.5% of cases and KTI:KTE ratio was 1:1.04 (1:0.59–1.42).Comparison between inspiratory and expiratory parameters showed that QI was significantly lower than QE [5 (4.27–6.75) L·minE and CRS  , mean airway pressure  and RawI .There was a significant inverse relation between RawIn this study, we measured pulmonary mechanics at bedside in infants requiring MV due to severe bronchiolitis, using the measurements provided by two conventional contemporary mechanical ventilators. Data obtained from these measurements show that the elastic component of the respiratory system  and not the airway resistance is the main determinant of the work imposed upon MV. We calculated that almost three fourth parts of the total workload is generated to overcome the elastic component of the respiratory system. In addition, we found that the calculated resistance and time constant were similar during the expiratory and inspiratory phase, showing that an increase in expiratory resistance is not the main alteration in patients with severe bronchiolitis under mechanical ventilation.RS in spontaneous breathing infants with bronchiolitis when compared with healthy infants. More recent studies found the same alteration in CRS, most of the time attributed to significant air trapping and lung hyperinflation [RS of infants without significant respiratory disease, patients of our study had consistently a decreased of CRS [These findings may seem unexpected and contradictory with the current understanding of severe bronchiolitis as a primarily obstructive airway disease with an increase in expiratory resistance, but they are supported by the observation done over a half century ago by Krieger et al. . They obnflation . We werenflation , 14. Thrnflation . When cod of CRS .TI:KTE ratio in children with bronchiolitis was higher than normal subjects (mean 1:1.1). They stated that this finding could be explained by Otis’ theory of the equality of time constants (which are the product of compliance and resistance) in a system with different airway’s caliber , and flow is rapid in such a system, measured value of resistance would be the one of the larger airways [PL changes [2O when children were ventilated with moderate to high VT (10–15 ml·kg−1) [T can also require longer expiratory times to allow the passive expiration, increasing the risk of air trapping and decreasing compliance due to hyperinflation. One of the strengths of our study is that MV settings were standardized and compatible with current standard of care: VT and PPL were limited and low QI were applied. This could have caused the low resistance to expiratory flow observed in our cohort. Normal values of RawE for this specific age group are scarce, but our patients’ RawE was lower than data from premature newborns without significant respiratory disease on spontaneous breathing [Conflicting data exist with regard to the resistive airway component during severe bronchiolitis. Krieger et al. found that there were not clinical significant differences between inspiration and expiration in infants during bronchiolitis; even more, the latter was shortened. In that study measured K airways . It is i changes . A cliniml·kg−1) . An augmreathing . Anotherreathing .RS and RawE. As previously reported in patients with ARDS, this observation shows that lungs with lower CRS had higher elastic recoil [T era and contemporary care of acute respiratory failure, it is difficult to compare both case series. Surprisingly the duration of MV was greater than 14 days, compared to ours that was close to 5 days. We have to acknowledge that current PALICC consensus [An interesting finding was the inverse correlation between Cc recoil . This fic recoil , 22. It onsensus  definitiIt is important to emphasize that most bronchiolitis, even the most severe forms, do not require invasive mechanical ventilation with the contemporary care . In our RS. A single set of measurements, very close to intubation, was done, because we did not want to use long term or multiple doses of neuromuscular blockade. Also, patients were on controlled MV without respiratory muscle activity, can influence in the low Inspiratory resistance and measured autoPEEP, because patient efforts may increase the lung volume, facilitating hyperinflation [I, RR, I:E ratio), but we tried to standardize the ventilatory setting during measurements.Our study has some limitations. Our infants had a single disorder and the age range was large, thus our findings cannot be generalized to infants or children who have other disorders such as asthma, chronic lung disease or congenital heart disease. Reference values for healthy children in this age group has not been specifically reported and we did not include a control group, so comparisons and increments of the different components are only estimates. As previously commented, due to small size of patients we did not measure pleural pressure, so we could not determine the contribution of the chest to Cnflation , being fDespite these limitations, we consider our findings in infants under mechanical ventilation with severe bronchiolitis are important in terms of the pathophysiological approach to this condition. Our analysis shows that the elastic component of the working pressure predominates rather than the airways resistance component. Future epidemiologic multicentric studies should address the different components of working pressure in severe bronchiolitis. A better understanding of respiratory system mechanics during mechanical ventilation may lead to change the traditional pharmacological and ventilatory approach to severe bronchiolitis as a predominant airway resistance disease.Analysis of respiratory mechanics measurements of infants with severe bronchiolitis receiving controlled MV shows that the preponderant constituent of the working pressure of the respiratory system is the elastic component. The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases. A better understanding of the pathophysiology may lead to improve the traditional pharmacological and ventilatory approach of severe bronchiolitis as a predominant airway resistance disease.Additional file 1: Table S1.Formulas for estimation of lung mechanics in quasi - static conditions. (DOCX 16 kb)Additional file 2: Figure S1.RS: respiratory system compliance; RawE: expiratory airway resistance.) (TIFF 19195 kb)Correlation between respiratory system compliance and expiratory airway resistance measured in children on mechanical ventilation due to severe bronchiolitis. (Abbreviations: C


Hypertension is a major risk factor for cardio-cerebrovascular disease. Songling Xuemaikang capsules (SXC), a formulation of Chinese herbal patent medicine, has been used as a complementary medicine with conventional western medicine to treat patients with hypertension since 1994 in mainland China. However, the efficacy of treatment with SXC alone against hypertension remains unclear.This is a multicenter, placebo-controlled, double-blinded, randomized controlled clinical trial. A total of 570 patients with low-to-medium risk hypertension are randomized in a 1:1 ratio to receive SXC or placebo three times daily for eight weeks. The primary outcomes are 24-h average systolic blood pressure and average diastolic blood pressure. The secondary outcomes are daytime average blood pressure, night-time average blood pressure, fluctuation of blood pressure, hypertension control rate, traditional Chinese medicine (TCM) syndrome scores, and quality-of-life scores.This is the first multicenter trial conducted to evaluate the efficacy and safety of TCM in patients with low-to-medium risk hypertension. Our study will provide evidence-based results of a complementary preventive measure for hypertension.ChiCTR-IPR-17011383. Registered on 12 May 2017.Chinese Clinical Trial Registry, The online version of this article (10.1186/s13063-019-3308-5) contains supplementary material, which is available to authorized users. Hypertension is the leading risk factor for cardio-cerebrovascular disease and premature death in China . Recent Pueraria lobata, and pearl powder. Studies have shown that puerarin, the main active ingredient of P. lobata, can reduce renin-angiotensin levels, dilate coronary and cerebral arteries, improve microcirculation, reduce vascular remodeling and ventricular hypertrophy, and exhibit anti-platelet aggregation, resulting in the promotion of endothelial cell function and the regulation of vasoactive factors [Conventional antihypertensive agents are usually associated with many adverse effects. Chinese patent medicines, which are important components of traditional Chinese medicine (TCM), have been increasingly accepted by patients with hypertension. Songling Xuemaikang capsules (SXC) are a formulation for oral intake produced by Chengdu Kanghong Pharmaceutical Co. Ltd., with official approval from the China Food and Drug Administration (ratification document number: Sinopharm Z10960023). It comprises fresh pine needles,  factors –11. Acti factors , 13. The factors . Several factors , 16; howThis study aims to determine the efficacy of SXC in patients with low-to-medium risk hypertension.This multicenter, double-blind, randomized, placebo-controlled parallel-group, superiority trial is registered in the Chinese Clinical Trials Registry (ChiCTR-IPR-17011383). It complies with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all patients before their participation in this study; the recruited patients will be randomized to either the SXC group or the placebo group. We will rigorously follow the Consolidated Standards of Reporting Trials (CONSORT) recommendations when reporting the results [The trial will be conducted in seven centers in China. A total of 570 participants will be recruited. After we acquire their consent, the participants will be enrolled in the trial, which consists of a two-week run-in period and an eight-week treatment period.A completed SPIRIT checklist is available as a supplement . The secondary outcomes include daytime average blood pressure, nocturnal average blood pressure, fluctuation of blood pressure (24-h ambulatory blood pressure), fluctuation degree of systolic and diastolic blood pressure, control rate of hypertension (control rate of hypertension = hypertension control number/hypertension number × 100%), TCM syndrome scores, and the 36-item Short Form Health Survey score. The other outcomes include levels of vasoactive substances , four hormones related to hypertension , inflammatory mediators, and blood lipids. Safety outcomes, which include complete blood count, routine urine test, liver and renal function tests, and electrocardiograms, will also be monitored periodically. All adverse events (AEs) will be followed from randomization to the end of the trial. Items to be measured and the time window of data collection are shown in Fig. AEs are defined as negative or unintended clinical manifestations following treatment. Patients will be asked to report to the investigators any abnormal reactions occurring at any time during the trial. In addition, investigators will collect information about abnormal reactions monthly. All details of related and unexpected AEs, such as time of occurrence, degree of AE, and suspected causes, will be recorded on case report forms (CRFs). Moreover, there is a data safety monitoring board to oversee the trial.The schedule for all study procedures for all evaluations is shown in Fig. Participants are randomized in a 1:1 ratio using a computer-generated, site-stratified, block randomization schedule. The study capsules will be labeled with sequential randomization numbers and each patient will be assigned the lowest number available at each participating center. All patients, care providers, and attending physicians will be blinded to treatment assignment until the study is completed. Duplicated blinding codes will be given to the main research institution and the manufacturer; the blinding codes cannot be revealed during the trial.http://www.xyedc.com/). To maintain the quality of data, we will adopt valid measures to ensure information accuracy, integrity, and authenticity. First, computer logic checks will be run to identify items such as inconsistent data, missing data, and questionable values. After that, the supervisor will perform source data verification to check the consistency of the original data. Queries may be issued by the supervisor, which will be answered by the site investigators. Second, manual checks will identify more complicated and less common errors. Third, the supervisor will conduct site visits to compare the electronic database with the source documents. Identified errors will be resolved to ensure data quality. Fourth, the Data Coordination Center will be in charge of data validation.CRFs are being used for data entry and data from all participating centers will be imported into the clinical data management system (P < 0.01) and diastolic blood pressure (DBP)  compared with that by antihypertensive drugs alone [2 = 49, type I error rate (α) = 0.05, and a power of 90% (type II error rate (β) = 0.1), the sample size for one arm needed to be 258, resulting in n = 2 × 258 = 516 . Considering a dropout rate of 10%, a total of 570 patients needed to be allocated to attain the required number of patients for the efficacy analysis.The sample size was calculated based on the expected reduction in hypertension. A meta-analysis has showed that SXC combined with antihypertensive drugs is more effective in lowering both the systolic blood pressure (SBP) .For all analyses, In this trial, we will assess the efficacy and safety of SXC in treating patients with low-to-medium risk hypertension. The present study is designed as a multicenter, double-blind, randomized, placebo-controlled, parallel-group superiority trial that will provide high-powered evidence regarding the efficacy and safety of SXC in treating patients with low-to-medium risk hypertension.A previous study showed that pine needle extract has pharmacological properties that modulate hippocampal excitotoxicity-derived memory impairment under severe stress conditions . In saltFor patients with low-to-medium risk hypertension, the current domestic and foreign guidelines generally recommend lifestyle improvement and monitoring of blood pressure and other risk factors 1–3 months before deciding whether to carry out drug treatment. Therefore, 10 weeks of follow-up monitoring and placebo therapy will not cause irreversible damage to the individuals .There are certain limitations to this study. First, because the study is being performed in Beijing, China, it is uncertain whether the relative effects of the trial drugs would be similar in other ethnic groups. Second, the follow-up period is relatively short.Nevertheless, this trial aims to evaluate the efficacy and safety of SXC for the treatment of patients with low-to-medium risk hypertension.The trial was initiated in July 2017 and is currently open for enrolment; thus far, 120 patients have completed the 10-week follow-up. However, no analysis has been conducted since the commencement of the trial. No serious AEs have occurred to date.Additional file 1:SPIRIT Checklist. (DOC 124 kb)


This study aimed to evaluate the effectiveness of hypertension management and analyse the factors associated with blood pressure reduction within China’s primary healthcare system.Hypertension is one of the leading risk factors for global disease burden and is strongly associated with cardiovascular diseases. In China, hypertension is a serious public health problem, but few studies have evaluated the effectiveness of hypertension management in China’s primary healthcare system.The study sites were 24 primary healthcare institutions, selected using multistage stratified random sampling method. In each institution, hypertension patients aged at least 35 years who agreed to participate and had no disabilities or mental health problems were enrolled for hypertension management. Participants received comprehensive interventions in the primary healthcare system via a team. After a one-year intervention, data from 6575 hypertension patients were analysed to check the effectiveness of hypertension management and examined factors associated with hypertension control.P < 0.05). Education level and baseline SBP showed a significant positive association (P < 0.05).There was an overall mean reduction of 4.5 mmHg in systolic blood pressure (SBP) and 1.9 mmHg in diastolic blood pressure (DBP). The blood pressure reduction after one year was greater in rural patients than in urban patients, 6.6 mmHg versus 3.4 mmHg for SBP and 2.6 mmHg versus 1.6 mmHg for DBP, respectively. The hypertension control rate also increased more in rural areas (22.1%) than in urban areas (10.6%) after the one-year intervention. Age, body mass index, region and being in an urban area had a significant negative association with the reduction of SBP (Community-based hypertension management by general practitioners was feasible and effective. The effectiveness of hypertension management in rural areas was greater than in urban areas. Intervention strategies should pay more attention to patients in rural areas and western China. In the second stage, one urban and one rural area were randomly selected from each province, based on their social and economic development levels and populations. In the third stage, equal numbers of primary healthcare institutions in urban and rural areas were recruited, consisting of township hospitals in rural areas and community health centres in urban areas. Finally, 24 primary healthcare institutions were selected as the study sites. In each institution, hypertension patients aged at least 35 years who agreed to participate and had no disabilities or mental health problems were enrolled for hypertension management. The sample size in the study was powered to detect clinically meaningful differences in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 2 mmHg after a one-year hypertension management programme. We assumed a normal approximation to compare two independent means. The sample size provided 95% power to detect differences, and the assumed SDs for SBP and DBP were both 10 mmHg. We used a two-sided α of 0.01 and a 75% response rate to estimate the sample size and enrolled 8139 hypertension patients. In total, 6778 patients finished the one-year management programme, and 203 did not have a blood pressure measurement after one year, giving a total of 6575 hypertension patients for analysis. A flow chart of patient from recruitment to inclusion was shown in Figure Study participants received comprehensive interventions in the primary healthcare system via a team of GPs, nurses and public health doctors. The intervention included one physical examination and at least four face-to-face follow-ups with GPs in the course of the year. Further interventions were offered depending on the outcome of the follow-ups. Figure All the participating GPs, nurses and public health doctors received training before the intervention. The training included hypertension screening, treatment and management, follow-up visits and health education.2. Lean, normal weight, overweight and obese were defined in line with the Chinese standard criteria for weight for adults (WS/T 428–2013) as BMI < 18.5, 18.5 to < 24, 24 to < 28 and ≥ 28 kg/m2.At baseline information collection, GPs collected information from all patients about their socio-demographic characteristics, medication and whether they had diabetes or coronary heart disease. During the baseline physical examination, patient height and weight were measured, and BMI was calculated in kg/met al., A trained nurse used a mercury sphygmomanometer to measure blood pressure three times on the patient’s right arm in a seated position after 5 min of rest. The mean of the three measurements was used for analysis. Patients were also advised to avoid alcohol, smoking, coffee and tea, and exercise for at least 30 min before their BP measurement. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defined hypertension as SBP ≥ 140 mmHg and/or DBP ≥ 90 mm Hg, and/or use of antihypertensive medication , sex, education level, area , region , medication, reduction in BMI (as a continuous variable), and others. All statistical tests were two-tailed, with P < 0.05 considered statistically significant.Statistical analysis used SPSS for Windows, Version 15.0 . Socio-demographic characteristics of the participants were analysed using descriptive statistics. The average reductions in SBP and DBP in different subgroups were given as the mean and 95% confidence interval (95% CI). The average reductions in SBP and DBP through the one-year programme were calculated using a paired A total of 6575 hypertension patients (mean age: 64.6 ± 10.4 years) were eligible for analysis in the study. Of these, 40.7% were men, over 36% had received at least middle school education, 38.5% were overweight and 14.3% were obese. In total, 64.2% were from urban areas and 43.9%, 22.4% and 33.7% were from the eastern, central and western regions of China. Medically, 63.5% were on medication and 13.3% had diabetes as a comorbidity  after the one-year intervention. The control rate rose in all three regions, from 57.3% to 68.9% (east), from 44.1% to 57.1%  and from 26.4% to 48.8% (west). Table P < 0.01), and reduction in DBP was higher among younger patients, those with higher levels of education, and from the western region or rural areas (P < 0.01). There was no significant difference in SBP reduction between male and female patients (P > 0.05). However, the reduction in DBP was higher in men than women. Medication and concurrent diabetes showed no significant effect on the reduction in SBP and DBP (P > 0.05). There were significant differences between urban and rural areas in SBP and DBP (P < 0.01) [mean SBP and DBP reduction 6.6 mmHg (95% CI: 6.1–7.1 mmHg) vs 2.6 mmHg (95% CI: 2.2–2.9 mmHg)]. Similarly, region  was also significant for both SBP and DBP.Table P < 0.05). However, having a level of education of at least middle school and baseline SBP had a positive association (P < 0.05). Age, BMI and living in the eastern region or an urban area were significantly associated with a reduction in DBP (P < 0.05), while a level of education of at least middle school and baseline DBP had a significant positive association with DBP reduction (P < 0.05). Sex and medication were not significantly associated with reductions in either SBP or DBP (P > 0.05).Table et al., et al., The one-year hypertension intervention in this study generally reduced the SBP and DBP of the hypertension patients by a mean of 4.6 and 1.9 mmHg. The hypertension control rate increased from 44.4% to 59.1%. These results therefore show the intervention’s efficacy. There were several reasons for these results. First, the implementation of the national essential public health services required the GPs to establish health records for hypertension patients. Second, the primary healthcare centres offered annual health examinations and four sessions of face-to-face follow-up. This community-based hypertension management and support for blood pressure control is critical for hypertension patients. Some studies have shown that even a small reduction in blood pressure could markedly reduce the risk of coronary artery disease events (Staessen et al., et al., et al., et al., et al., Health resources are unevenly allocated in China between urban and rural areas, and among the eastern, central and western regions. Patients in rural areas tend to be poorer than those in urban areas, have little professional medical contact and lack management strategies for chronic disease (Ross et al., et al., et al., et al., et al., et al., This study found that age and BMI were independently associated with better hypertension control. Hypertension is known to increase with age, so one possible explanation is that older people made more effective changes to their lifestyle, perhaps because of their poor self-perceived health status. Numerous studies have found that being overweight or obese is significantly associated with hypertension and poorer blood pressure control (Shuqiong In China, industrialization, urbanization, population aging and lifestyle changes are accelerating. The numbers of people with chronic diseases are also rapidly increasing each year. This poses a challenge for the primary healthcare system. This study found that a community-based health intervention for hypertension was associated with significantly improved blood pressure control. Our data will be helpful in designing and implementing future primary healthcare programmes for hypertension control and management.This study found that community-based hypertension management conducted by GPs was both feasible and effective. This suggests that implementing essential public health services could improve long-term health outcomes for chronic disease. Our data will be helpful in designing and implementing future primary healthcare programmes for hypertension control and management. The effectiveness of hypertension management in rural areas was greater than in urban areas. Intervention strategies should pay greater attention to patients in rural areas and western China.The study had a few limitations. First, it did not have a comparative control group. This was because hypertension management had been improved in the national primary healthcare system. Second, we did not collect information about some important factors related to hypertension control, such as the duration and severity of hypertension, and comorbidities. We therefore could not calculate to what extent the intervention was responsible for improved blood pressure control. Third, our analysis focused on blood pressure reduction as the successful outcome of hypertension management in the primary healthcare system. We were unable to estimate the effects of factors such as lifestyle changes, medication, and hypertension complications, which would be useful information for public health policymakers. We also could not analyse the cost and cost-effectiveness of hypertension management, although this would also be useful for policymakers. Despite these limitations, the strengths of this study included regional representative data and an evidence-based rationale for control and management of hypertension at a population level.


Severe alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma.A cross-sectional cohort study of 648 patients with HDM allergic asthma was carried out. Demographic, clinical and analytical variables were collected. PI*S and PI*Z AAT deficient alleles of the SERPINA1 gene were assayed by real-time PCR.Asthma was intermittent in 253 patients and persistent in 395 patients . One hundred and forty-five asthmatic patients (22.4%) with at least one mutated allele (S or Z) were identified. No association between the different genotypes and asthma severity was found. No significant differences in all clinical and functional tests, as well as nasal eosinophils, IgA and IgE serum levels were observed. Peripheral eosinophils were significantly lower in patients with the PI*MS genotype (p = 0.0228). Neither association between deficient AAT genotypes or serum ATT deficiency (AATD) and development of severe asthma, or correlation between ATT levels and FEV1 was observed.In conclusion, the distribution of AAT genotypes in HDM allergic asthmatic patients did not differ from those found in Spanish population. Neither severe ATTD or deficient AAT genotypes appear to confer different clinical expression of asthma. SERPINA1, are associated with low serum AAT levels. The most common deficient alleles are protease inhibitor PI*S and PI*Z, being PI*M the normal variant. Pi*ZZ individuals have severe AAT deficiency, with only 10% of normal serum levels as compared to Pi*MM subjects. Individuals homozygous for the Pi*S (Pi*SS) alleles have approximately 60% of normal serum ATT levels [Alpha-1 antitrypsin (AAT) is a serine proteinase inhibitor (PI) that protects alveoli against the destructive effects of neutrophil elastase, proteinase 3 and cathepsin G, which cause destruction of pulmonary parenchyma . Alpha-1T levels , 5. AlthT levels . NowadayT levels , 9.Worldwide, AATD has been frequently related to chronic obstructive pulmonary disease (COPD), premature emphysema and liver failure –13, but The aim of this study is to analyze the distribution of the most common ATT genotypes in a cohort of asthmatic patients sensitized to house dust mites (HDM). Furthermore, this study attempts to investigate the influence of ATTD and the presence of certain genotypes on the severity of allergic asthma.A cross-sectional cohort study of HDM-sensitive asthmatic patients (skin prick test and specific immunoglobulin E) was carried out. Asthmatic subjects were recruited through the Allergy Clinic of the “Hospital Universitario de Gran Canaria Doctor Negrín” (Canary Islands). All of them were Caucasian, aged over 12. They all had a diagnosis of asthma, with or without rhinitis or other allergic conditions, and complained of typical asthma symptoms such as wheezing, dyspnea and/or other symptoms which they had suffered from over the previous two years. Patients were divided into four groups , according to the severity of their disease and following the Spanish asthma guideline—GEMA4.0 . Written® Aerocrine).Asthma was diagnosed on the basis of a history of asthma symptoms and clinical examination , and a significant reversibility of their forced expiratory volume in one second (FEV1), as measured with a spirometer  upon treatment with bronchodilators, at least in one visit during the patient follow-up . FractioDermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, Acarus siro, Lepidoglyphus destructor and Tyrophagus putrescientae) from ALK Abelló, Spain. A positive skin-prick test was defined as a mean wheal diameter of at least 3 mm or larger than that of the negative control following current guidelines [Skin-prick tests were performed with several dust mite allergens  were determined. ATT serum levels were measured by nephelometry .In all subjects, blood eosinophils and neutrophils, and total serum immunoglobulin A (IgA), immunoglobulin E (IgE) and specific IgE to ATT genotypes were determined by using real-time polymerase chain reaction (PCR) and LigthCycler 2.0 for the detection of the mutation according to the technique previously described .Statistical analysis was performed using the nonparametric Kruskal–Wallis test for quantitative variables and Chi square or Fisher tests for qualitative variables. Binary logistic regression was used to determine the association between genotypes and the presence or absence of severe persistent asthma, adjusting for age, smoking habit, significant comorbidity, previous treatment received and some analytical values. The possible correlation between the serum levels of ATT and bronchial functional test parameters was evaluated by Spearman's rank correlation coefficient. A value of p < 0.05 was considered to be statistically significant. All analyses were performed using the R Project (Version 1.0.153) .During a period of 22 months, 648 asthmatic patients over 12 years (median age 29 years) who were allergic to HDM were recruited into the study. Four hundred and twenty-five (66%) were females and 54 (8%) were smokers. Demographic and clinical characteristics of the patients are listed in Table −12) as has been previously reported [According to the GEMA4.0, 253 asthmatic patients were classified as intermittent and 395 as persistent . Patients with severe asthma were significantly older (p = 1.72reported . In addi9/L (0.2–0.5). Median percentage of eosinophils found in the nasal cytology was 37.5% (10–70), with no significant differences among all stages of disease severity. The median serum IgE was high, 255 IU/ml (117–563) as compared to the normal value (< 100 IU/ml), but there was no significant difference among asthma groups. The values of specific IgE were quite similar among all groups. IgA serum levels were significantly higher in patients with severe asthma  as compared to the other groups  (p = 0.00024).Median blood eosinophil count was 0.3 × 10Median AAT value was 134 mg/dl (118-154), within normal range (100–200 mg/dL), and no significant difference was observed according to the severity of the disease. Sixty-six (10.2%) asthmatics had serum AAT levels below the lower limit of normal (< 100 mg/dl) and only three (0.5%) had severe deficiency (< 57 mg/dl) .One hundred and forty-five patients (22.4%) had a deficient AAT genotype. No individual with severe AAT deficiency genotype (PI*ZZ) was identified in our series.−25). Analytical and functional respiratory test variables are illustrated in Table Demographic and clinical characteristics according to PI genotype are shown in Table Many authors have suggested an increased risk of asthma with some AAT genotypes. Eden et al.  showed tD pteronyssinus, such as group 1 allergens (Der p 1), can activate different routes that alter the immune system [The balance between normal lung inflammation and repair is a complex process that involves pro- and anti-inflammatory cytokines and the accumulation of inflammatory and immune effector cells . In thise system . Other ae system . It is ee system .D pteronyssinus, such as Der p 1, has already been proven [ATT inhibits neutrophil serine proteases and can regulate the chemotaxis of neutrophils in two different ways: inhibition of IL8-CXCR1 interaction and modulation of ADAM17 activity impeding FcγRIIIb release . The inan proven . The majn proven . Neithern proven . What wen proven . That isWe have also assessed the distribution of different AAT genotypes in our series, which does not differ from the general population in our country , 36. FurIn contrast to previous reports , we haveWe recognize that our study has some limitations. First of all, we did not predict the required sample size by power calculation, but we strongly believe that this sample of patients truly reflects what happens to the asthmatic population. Moreover, our series is the largest sample studied at the moment. Secondly, we could not find any patient heterozygous for Z allele but this genotype is extremely uncommon and less prevalent in Spain. Finally, we only measured serum ATT levels and we do not know if the local production of ATT by pulmonary epithelial cells and macrophages may balance the low serum ATT levels.To conclude, we could not find any association between AATD and asthma severity among patients sensitized to HDM. Our findings support what has been reported by others in smaller series of asthmatics. The proportion of asthmatics with deficient AAT genotypes in our series is similar to the proportion in the general population. Although the blood count and nasal eosinophils values seem to be different among the different genotypes, more studies are needed to confirm this due to the scarcity of asthmatic allergic populations with alleles PI*Z.


Atherosclerosis is the primary etiological factor associated with acute coronary syndrome (ACS). Kidneys have a highly arterial vascular structure and are therefore commonly affected by atherosclerosis, including those affecting the coronary arteries. Renal shear wave elastography (SWE) is an ultrasonographic method, which provides reliable information regarding the condition of the renal parenchyma.We investigated the relationship between SWE findings and the severity of coronary atherosclerosis.We calculated the following: the renal cortical stiffness (rCS) evaluated via SWE, the renal resistive index, the renal pulsatility index, the acceleration time, and the mean Syntax score (SS). Patients with a mean SS <12 were categorized into a low-risk (LR) and those with a mean SS ≥12 were categorized into the high-risk (HR) group.Our study included 132 patients—76 in the LR and 56 in the HR group. Creatinine, high-sensitivity C-reactive protein (hs-CRP), and rCS were significantly higher, but the glomerular filtration rate (GFR) was significantly lower in the HR group. The Hs-CRP (odds ratio [OR] 1.220), GFR (OR 0.967), and rCS (OR 1.316) were observed to be independent predictors for the HR group. The cutoff value of rCS using receiver-operating characteristic curve analysis was 4.43 for the prediction of HR patients and showed 60.7% sensitivity and 57.9% specificity (area under the curve 0.642).SWE which shows renal parenchymal injury and atherosclerosis in renal vessels may give an idea about the severity of coronary atherosclerosis. Atherosclerosis is a systemic inflammatory process that can affect nearly all arteries in the human body. Cholesterol crystal deposition and local inflammation between the arterial intima and media layers play a primary role in the development of atherosclerosis. Following the onset of atherosclerosis, arterial wall elasticity diminishes in the presence of accompanying risk factors like hypertension, diabetes mellitus, and smoking with the eventual development of tissue oxygen supply imbalance.,5Coronary artery disease (CAD) is becoming increasingly widespread globally. Acute coronary syndrome (ACS) can show poorer prognosis than that observed with other forms of CAD in the absence of appropriate treatment.,7 Atherosclerosis causes important anatomical and functional changes in the kidneys.,8 These functional changes can be monitored via the estimation of blood levels of electrolytes, blood urea nitrogen, creatinine, and urine osmolarity. Abnormalities in these laboratory parameters suggest the onset of irreversible damage to the kidneys. It has been shown that ultrasonographic (USG) methods can predict the development of such damage before such irreversible renal parenchymal impairment actually occurs. Renal shear wave elastography (SWE) is an ultrasonographic method, which provides reliable information regarding the condition of the renal parenchyma  evaluated using SWE is related to several types of renal parenchymal disease and fibrosis.–13The brain and the kidneys have a highly arterial vascular structure and are therefore affected by atherosclerosis like the coronary arteries.yma Fig. A and B.[ The SYNTAX score is an independent predictor of cardiac mortality in patients with ACS. Atherosclerosis can develop simultaneously in the coronary and the renal arteries. Renal atherosclerosis can cause renal parenchymal deterioration. The association between rCS and coronary atherosclerosis remains unclear in the literature.The Synergy Between Percutaneous Coronary Intervention With Taxus and Coronary Artery Bypass Graft Surgery (SYNTAX) score (SS) is a comprehensive scoring system used to assess the severity of CAD.We aimed to investigate the association between rCS and the severity of coronary atherosclerosis.22.1We investigated consecutively hospitalized patients in the coronary intensive care unit with STEMI or NSTEMI between January 2017 and January 2018. The study protocol was approved by the Ethics Committee of the Cukurova University, Faculty of Medicine. Informed consent was obtained from each patient. This study protocol conforms to the Ethical Guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institutional Human Research Committee. Patients with functional and anatomical renal disorders, disorders of hepatic function, previous percutaneous coronary intervention, or a history of coronary artery bypass surgery were excluded. Demographic data of patients were recorded.2.2Blood samples were obtained in a routine manner, and the following were evaluated: blood glucose level, complete blood count, renal function tests, glomerular filtration rate (GFR), creatinine clearance (CrCl), lipid parameters, high-sensitivity troponin T (hs-TnT), creatine kinase-myocardial band (CK-MB), high-sensitivity C-reactive protein (hs-CRP), and uric acid level.2.3The ejection fraction was recorded echocardiographically .2.4Renal USG was performed in all patients 48 hours after hospitalization. A high-resolution Doppler ultrasound system (Philips EPIQ 7) equipped with a high-resolution convex probe (2–5 MHz)  was used. All patients had at least a 6-hour fast and a 20-minute rest before undergoing the USG. Gray scale abdominal USG was initially performed and quantitative Doppler parameters were subsequently recorded. Doppler USG measured the peak systolic velocity (PSV), end-diastolic velocity (EDV), and the acceleration time (AT) from both interlobular renal arteries at the intercostal window. The Doppler angle was maintained between 30 and 60 degree. After recording the PSV and the EDV, the spectral waveform was traced manually, and the renal resistive index (RRI) was calculated using the formula: PSV-EDV/PSV. The renal pulsatility index (RPI) was measured using the spectral waveform tracing and the PSV-EDV/mean flow rate formula. AT was defined as the time between the beginning of the systolic upstroke and the first systolic peak. All parameters were measured thrice in both kidneys. The mean RRI, RPI, and AT values were recorded. The probe was maneuvered in a steady manner with minimal compression. Patients were instructed to hold their breath in full inspiration for a few seconds to minimize motion of the kidney. The patient was placed in the left and right lateral decubitus positions, and measurements were obtained after the preliminary identification of a target region of interest (ROI) on a conventional ultrasonographic image. The ROI was placed perpendicular to an area of the renal cortex that did not contain any detectable vasculature or cysts. The main axis of the ROI was set parallel to the axis of the renal pyramids (perpendicular to the surface of the kidney). Minimal transducer pressure was applied during imaging to avoid mechanical compression of the kidney. The examination procedure was repeated for the contralateral kidney. We obtained 6 accurate measurements in each kidney in each patient, and a median value was calculated. If measurement reliability was low, the result was recorded as 0.00 kPa. The result was expressed in kPa.SWE was performed using 2 to 5 MHz convex probes that utilized the ElastPQ software based on acoustic radiation force impulse imaging-based technology. All measurements were performed as described earlier.2.5 After this, either 180-mg ticagrelor or 600-mg clopidogrel were given, or patients were redirected to coronary angiography (CAG) laboratory. Coronary angiography (CAG) was performed through femoral or radial access using the Judkins technique. Two cardiologists individually evaluated the CAG images. The left main coronary artery and other coronary artery occlusions were categorically recorded. The SS and clinical SYNTAX score (cSS) were calculated after including vessels with a diameter >1.5 mm and >50% stenosis determined using CAG images (http://www.Syntaxscore.com). Culprit lesion was predilated, and an appropriately sized stent was implanted. Thrombolysis in myocardial infarction (TIMI)-3 flow was achieved in all patients. Tirofiban  or abciximab (0.25 mg/kg IV bolus over at least 1 minutes and 0.125 μg/kg/min IV continuous infusion for 12 hours) infusion was given to patients with high thrombotic burden. As in previous study , the mean and median SS values were calculated for all patients. Patients with a mean SS <12 were categorized into a low-risk (LR) and patients with a mean SS ≥12 were categorized into a high-risk (HR) group.Patients were administered with 70 to 100 U/kg heparin bolus and 300 mg acetylsalicylic acid (ASA) initially at the time of diagnosis.2.6χ2 test was used to analyze categorical variables. Continuous variables were expressed as means ± standard deviation. The Kolmogorov-Smirnov test was used to determine whether the continuous variables were normally distributed. Normally distributed variables were analyzed using the independent samples t test. Nonnormally distributed variables were analyzed using the Mann-Whitney U test. Independent predictors for HR patients were determined using binomial logistic regression analysis using P < .05 variables. Receiver-operating characteristic curve (ROC) analysis was used to calculate the cut-off, sensitivity, and specificity values for predictors of HR. The SPSS for Windows Program software version 20.0  was used for statistical analysis. A P value <.05 was considered statistically significant.Variables were classified into the categorical and continuous groups. Categorical variables were expressed as numbers and percentages. The 3P = .022) and hs-CRP (P = .001) were significantly higher and GFR was significantly lower (P = .001) in the HR group, and other variables did not show statistically significant differences (Table P = .006). A comparison of angiographic findings revealed that the HR group showed a significantly higher frequency of 2- and 3-vessel disease, SS, and cSS and that the LR group showed a significantly higher frequency of single-vessel disease . We observed that hs-CRP , GFR , and rCS  were independent predictors for the HR group (Table P = .006) , and the HR group included 56 patients (mean age 63.4 ± 11.9 years). No statistically significant intergroup differences were observed in terms of demographic variables , GFR values were significantly higher , uric acid and hs-TnT were significantly lower . So, we excluded these patients from the study.The kidneys have a rich vascularized structure. They show anisotropic anatomy owing to a dual-compartment structure comprising the renal cortex and the medulla.,21 The RRI is a hemodynamic parameter, which can show rapid alterations. All patients undergoing the study should have at least a 6-hour fast and 20 minutres of rest before undergoing USG. The sensitivity of this evaluation is arguable to us because of its changeable nature by other parameters. We observed similar RRI values in our groups. Both groups in our study showed higher RRI values than those reported by other studies. Our study included patients with NSTEMI and STEMI. Therefore, the high RRI could be attributed to acute stress. Perhaps we might not have observed this difference in RRI if we had performed this evaluation after discharge.Recent studies show that the RRI obtained using Doppler USG was closely related to the severity of CAD.4.12; thus, obtaining clear images of the kidneys was difficult. SWE performed using acoustic radiation force impulse imaging technology shows limited efficiency in kidneys that are located deeper than 5 cm. All our patients were diagnosed with CAD. This kind of study should ideally have been performed initially in patients with subclinical atherosclerosis. Further studies are warranted to support our hypothesis.Our study has relatively small and nonhomogeneous population (STEMI vs non-STEMI). USG evaluation of the kidneys is difficult owing to their retroperitoneal location. Moreover, evaluation is difficult in patients with obesity. All patients in our study showed a body mass index >25 kg/m5A close relationship is observed between the severity of CAD and rCS. Increased rCS values indicate a higher possibility of HR CAD.Conceptualization: Abdullah Orhan Demirtas.Data curation: Abdullah Orhan Demirtas, Atilla Bulut.Formal analysis: Abdullah Orhan Demirtas, Atilla Bulut.Funding acquisition: Abdullah Orhan Demirtas.Investigation: Abdullah Orhan Demirtas.Methodology: Abdullah Orhan Demirtas, Atilla Bulut.Project administration: Abdullah Orhan Demirtas.Resources: Abdullah Orhan Demirtas.Software: Abdullah Orhan Demirtas, Atilla Bulut.Supervision: Abdullah Orhan Demirtas.Validation: Abdullah Orhan Demirtas.Visualization: Abdullah Orhan Demirtas.Writing – Original Draft: Abdullah Orhan Demirtas, Atilla Bulut.Writing – Review & Editing: Abdullah Orhan Demirtas, Atilla Bulut.Abdullah Orhan Demirtas orcid: 0000-0003-4768-0536.


The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03,  IgA nephropathy (IgAN) remains the most common type of primary chronic glomerulonephritis worldwide . Its preCurrently, IgAN is diagnosed by renal biopsy which is often performed to confirm causes of mild urinary abnormalities, particularly hematuria; however, biopsies are invasive procedures  that carRecently, the Kidney Injury Test (KIT) Assay was developed by our group as a noninvasive test to measure kidney injury and function in the context of chronic kidney disease , nephrolSixty-nine spot urine samples were collected from 34 enrolled patients in the IgAN clinical trial over the study follow-up of 1 year . PatientAs concluded by the original study, and as shown in p < 0.0001). Receiver–operator characteristic curves . We then investigated whether midpoint (0.5 year prior to progression determination) and baseline (1 year prior) urinary biomarkers could predict progression status. We found that the KIT-IgA score could predict progressor status with 100% accuracy at both time-points . For both the baseline and midpoint predictions, the cfDNA values were the most important predictors, with chi square likelihood ratios of 25.92 and 141.98, respectively, and with p < 0.0001 for both. However, neither baseline nor midpoint proteinuria alone could predict progression (p < 0.0001) (ROC AUC = 1.00).We further investigated whether the KIT Assay biomarkers and the KIT-IgA score could distinguish progressors versus non-progressors. Progression was assessed based on a composite clinical evaluation of changes in proteinuria and eGFR from baseline (>50% increase in proteinuria and/or a 25% reduction in eGFR) and, as such, was dependent on both urine and serum biomarker values. We first sought to investigate whether urinary biomarkers alone could be used to classify progressor status. Looking at the 1-year endpoint biomarkers A, progregression B. As theclinicaltrials.gov [2. To establish continued risk, baseline proteinuria needed to be >1000 mg/day while on stable doses of angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or renin inhibitor therapy for at least 2 months. However, patients who were on dual therapy with agents that inhibit angiotensin II required a lower proteinuria threshold of >500 mg/day. Baseline BP was controlled to <130/80 mmHg. Patients with secondary forms of IgAN, such as cirrhosis, were excluded, although subjects with Henoch–Schönlein purpura nephritis (HSPN) could be included. Patients were excluded if they had previously received Rituximab, were receiving other immunosuppressive therapy, or had ever received >6 months of prednisone or other systemic corticosteroid therapy in the past. There was no corticosteroid exposure within 3 months of study initiation. Randomization was done centrally by a random assignment by prefilled envelopes. The protocol was approved by the institutional review board of each participating center. The study was registered with clinicaltrials.gov, protocol NCT00498368. Informed consent was obtained before all study procedures, and the study adhered to the Declaration of Helsinki.Samples were those from a study done in 2017 (NCT00498368) and the study was registered with ials.gov  was recoials.gov ) or measThe primary outcome measures were the change in proteinuria and the change in eGFR from baseline to 12 months. The secondary outcome was safety related, comparing overall adverse events and monitoring for potential intervention-specific complications, such as infusion-related reactions, hypogammaglobulinemia, and infections. Progression was defined as a >50% increase in proteinuria and/or a 25% reduction in eGFR at the one-year time-point. Results showed that treatment with Rituximab resulted in statistically insignificant changes in proteinuria or partial remissions that could not be distinguished from the response to supportive therapy alone.n = 64) who had no evidence of kidney disease or injury as assessed by both absence of proteinuria and eGFR greater than 120. Demographics of this cohort include a median age of 24 (range 2 to 64), median weight of 57.5 kg (range 13.7 to 120.2), 53.1% female, 9.4% African American, and median eGFR of 132 (range 120 to 213).For the healthy control cohort, urine samples were collected from healthy controls . Urinary creatinine was measured using the Creatinine Assay Kit  as a method for urinary concentration and hydration status normalization. Briefly, cell-free DNA (cfDNA), methylated cell-free DNA (m-cfDNA), CXCL10, Clusterin, (Dimethylamino)iminomethyl-ornithine (DMAIMO), and (Methylamino)(methylimino)methyl-ornithine (MAMIMO), were measured using the KIT Assay , a set of in-house developed ELISA assays. Microwell plate readings were measured using a SpectraMax iD3 Multi-Mode Microplate Reader . All assays were run in duplicates.Measurement of the KIT Assay biomarkers was performed as previously described . Total pU test. Comparisons involving three groups were performed using the nonparametric Kruskal–Wallis test with Dunn’s post-hoc multiple comparisons correction. The IgA risk score was determined using a Bootstrap Forest ensemble model by averaging numerous decision trees each fit to a bootstrap sample of the training data. The final prediction is the average of the predicted values over all the decision trees. Specifically, six trees were used in the forest, with a minimum of ten splits per tree and a minimum size split of five. The number of splits for trees 1–6 were 9, 17, 15, 7, 13, and 11 respectively. The top contributing biomarkers as based on G2 were total protein, MAMIMO, creatinine, and DMAIMO, with G2 values of 36.02, 21.12, 9.72, and 6.74 respectively. The overall statistics for the Entropy R2 was 0.7422, Generalized R2 was 0.8568, and Root Mean Square Error (RMSE) was 0.1996.Comparisons involving two groups were performed using the nonparametric Mann–Whitney Modeling of progressor status was done using nominal logistic regression. All analyses were performed using either GraphPad Prism 8.0.2  or JMP 14.3 .In this study, we used urine samples from IgA nephropathy (IgAN) patients to evaluate the predictive capacity of the KIT Assay biomarkers to discriminate IgAN from healthy controls as well as predict progression of renal functional decline. Our results show that these urinary biomarkers could distinguish between healthy control patients and those with IgAN better than urinary protein alone. Furthermore, the biomarkers could predict progressor status up to one year in advance of status determination while urinary protein could not.Such findings are important because IgAN is the most prevalent chronic glomerular disease worldwide , with diThe multi-hit hypothesis for the pathogenesis of IgA nephropathy is the leading theory behind the mechanism of progression . In thisWe had previously validated the utility of the biomarkers comprising the KIT Assay in chronic kidney disease , chronicWe have discussed the rationale of the KIT Assay biomarkers previously , with seFurther, proteinuria alone was not a significant predictor for progression at one-year of treatment duration measured at either the baseline or midpoint time-points. It is notable that the cfDNA values at baseline and midpoint were the strongest predictors of progression at the one-year timepoint. Urinary cfDNA has been previously reported to be a sensitive indicator of kidney injury and reflects ongoing damage to the kidney prior to functional changes or decline ,32,33. TIn summary, our data indicate that the non-invasive KIT Assay panel of urinary biomarkers can distinguish between healthy controls and patients with IgAN. Furthermore, this panel could monitor progression of disease and changes in kidney function. We believe that the KIT-IgA score would have great utility in (1) screening for IgAN in patients with hematuria, as a replacement for biopsy as done in many Asian countries; (2) diagnosis; (3) monitoring efficacy of treatment; and (4) predicting progression and monitoring disease activity. While our sample size is limited by the small size of the parent study, these results add to a growing body of evidence of the generalizability and utility of the KIT Assay biomarkers in renal disease and beyond. Additionally, while all comparisons in this study were between healthy control and IgAN patients, we have planned additional studies where we will include samples from patients with other types of renal diseases so that we can assess the performance of these and other biomarkers in discriminating IgAN from other nephropathies. Future studies using additional kidney disease cohorts will clarify whether there is a specific pattern among these biomarkers to discriminate one disease from another. Future multi-center, prospective studies are planned to further build on the clinical utility of these observations to assess serial performance of the KIT assay in IgAN patients as a non-invasive tool to monitor disease progression and evaluate the efficacy of new reno-protective therapies for IgA disease.


Previously it has been reported that at clinically used doses of sevoflurane, cerebral vasoreactivity is maintained. However, there are no data how sevoflurane influences systemic and cerebral circulation in parallel. The aim of our study was to assess systemic and cerebral hemodynamic changes as well as cerebral CO2 for 5 min respectively. At the end of each period, transcranial Doppler and hemodynamic parameters using applanation tonometry were recorded.Twenty nine patients undergoing general anesthesia were enrolled. Anesthesia was maintained with 1 MAC sevoflurane in 40% oxygen. Ventilatory settings  were adjusted to reach and maintain 40, 35 and 30 mmHg EtCO2 levels were reached. Both cerebral autoregulation and cerebral CO2-reactivity was maintained at 1 MAC sevoflurane.Systemic mean arterial pressure significantly decreased during anesthetic induction and remained unchanged during the entire study period. Central aortic and peripherial pulse pressure and augmentation index as markers of arterial stiffness significantly increased during the anesthetic induction and remained stable at the time points when target CO2-reactivity is preserved at 1 MAC sevoflurane. Cerebrovascular effects of anesthetic compounds have to be assessed together with systemic circulatory effects.Cerebral autoregulation and COhttp://www.clinicaltrials.gov, identifier: NCT02054143, retrospectively registered. Date of registration: February 4, 2014.The study was registered at  The most important vasoregulatory mechanisms determining brain circulation are cerebral autoregulation and cerebral vasoreactivity. Cerebral autoregulation is the inherent ability of the brain circulation to maintain constant cerebral blood flow during alterations of systemic blood pressure and cerebral perfusion pressure. Cerebral vasoreactivity is responsible for enabling to change the blood flow  according to the metabolic needs of the brain tissue . IdeallyDuring induction and maintenance of general anesthesia different systemic and cerebral effects of the anesthetic agents have to be taken into account to have a global view on the anesthetic’s effect and for the interpretation of the results. Thus, in the present study we aimed to assess changes in cerebral circulation and peripheral systemic hemodynamic changes in parallel during induction and maintenance of anesthesia with sevoflurane and the effect of different hypocapnic levels.Applanation tonometry, a new, non-invasive method has been recently reported to be accurate for non-invasive intraoperative assessment of systemic hemodynamic changes during general anesthesia . In lineWhat is the effect of anesthetic induction and reaching the steady state sevoflurane anesthesia on systemic hemodynamics and cerebral blood flow measurements?Is cerebral autoregulation maintained at normocapnic steady state 1 MAC sevoflurane anesthesia?What are the cerebral and systemic hemodynamic effects of induced hypocapnia at 1 MAC sevoflurane?We aimed to answer the following study questions:http://www.clinicaltrials.gov, identifier: NCT02054143, retrospectively registered. Exclusion criteria were age < 18 years or > 60 years, severe cardiovascular disease, severe carotid artery stenosis, cerebrovascular disease, smoking, diabetes mellitus, renal disease, hyperlipidemia, left ventricular hypertrophy and severe alteration of the preoperative pulmonary function, characterized as FEV1 < 70% and FEV1/FVC ≤70% of the predicted value.After approval from the local Ethics Committee , written informed consent was obtained from 35 ASA I-II patients scheduled for varicectomy and inguinal hernial repair surgery. The study was registered at For applanation tonometry SphygmoCor  device was used. During applanation tonometry the sensor was placed on the patient’s skin over the radial artery. This placement applies pressure on the radial artery and the pressure of the sensor flattens  the radial artery. Under optimal ‘applanation conditions’, the transmural pressure of the radial artery wall is zero and the intraluminal applanation tonometry can be recorded by the sensor. In the present study applanation tonometry parameters were recorded at the left radial artery. Using applanation tonometry we registered systolic and diastolic aortic pressure, aortic pulse pressure, peripherial pulse pressure, augmentation pressure, augmentation index normalized on actual heart rate (Alx@HR) and ejection duration. All measurements were performed by the same experienced operator (DP).Transcranial Doppler (TCD) measurements were performed using Rimed Digilite transcranial Doppler sonography . The temporal window was used for insonation of the middle cerebral artery at 45–55 mm depth, depending on the best signal. A fixed probe was used to register systolic, diastolic and mean blood flow velocities; pulsatility indices were calculated by the device.− 1 propofol and 2 μg.kg− 1 fentanyl. Intubation was facilitated by administration of 0.6 mg.kg− 1 rocuronium. Fentanyl and rocuronium were repeated as needed. Anesthesia was maintained with sevoflurane in 40% oxygen. The concentration of sevoflurane was titrated to a target Bispectral Index (BIS) between 40 and 60  and it was targeted at 1 MAC. Neuromuscular block was monitored with acceleromyography . Standard monitoring included five-leads ECG, NIBP, core temperature at the tympanic membrane, and pulse oximetry. Normothermia was maintained with forced-air system .Preoperative measurements were recorded one hour before anesthetic induction in supine position in quiet environment. Patients were then premedicated with 7.5 mg midazolam orally 60 min before entering the operating room. Anaesthesia was induced with a combination of 2 mg.kg− 1 TV, 5 cmH2O PEEP, 2 L.min− 1 fresh gas flow and with a respiratory rate adjusted to reach and maintain 40 mmHg EtCO2 .Patients were ventilated using volume-controlled square-wave flow pattern ventilation with 6–8 mL.kgAfter induction of general anaesthesia and intubation, lungs were ventilated in supine position for 20 min as described above. At this stage, hemodynamic, transcranial Doppler, applanation tonometry and ventilatory parameters were simultaneously recorded.2. After 5 min stabilisation period all measurements were repeated.In the second phase of the study minute ventilation  was changed to reach and maintain 35 mmHg EtCO2 After a 5 min stabilisation period, applanation tonometry and transcranial Doppler measurements were repeated. The flow chart of the study is summarized in Fig.At the next stage of measurement series ventilatory settings were again changed to reach and maintain 30 mmHg EtCO2), heart rate, systolic and diastolic blood pressure, bispectral index values, systolic, diastolic and mean blood flow velocities and pulsatility indices in the middle cerebral artery, systolic and diastolic aortic pressure, aortic pulse pressure, peripherial pulse pressure, augmentation pressure, Alx@HR, ejection duration and operation index were registered.During each measurement pulse oxygen saturation (SpOThe entire study and its interpretation follows the CONSORT guidelines.2-reactivity at 1 MAC (primary end point). Based on our previous study performed among non-anesthetized individuals, we found that hyperventilation lasting for 1 min results in a decrease of PCO2 by 7 mmhHg, accompanied by a 26.7 cm/s decrease of the middle cerebral artery mean blood flow velocity [2 results in a 3.84 cm/s change in blood flow velocity. As per protocol we intended to decrease CO2 by 10 mmHg in 2 steps, we calculated with a 38.4 cm/s (30 cm/s standard deviation) change, with a power of 0.9 and with an alpha of 0.01. Our power calculation indicated that 12 patients need to be included to test our hypothesis. As both registration methods may be operator-dependent, for sake of clarity we decided to include 30 patients. The normality of distribution of data was tested by Shapiro–Wilks test. Thereafter, differences were analyzed with the Repeated Measures Analysis of Variance (ANOVA) with Bonferroni post hoc correction. Values of p < 0.05 were accepted as statistically significant. Data are presented as mean (SD). MedCalc Statistical Software version 18.2.1.  was used for statistical analy.Before starting the study, a power analysis was performed to calculate the necessary number of patients to be included. We hypothesized that sevoflurane will not affect cerebral COTwenty-nine patients were enrolled aged 19–58 (mean 37), 17 female, 12 male. 7 patients underwent inguinal hiatal repair surgery, while 22 varicetomy. 1 patient was excluded due to inapproriate temporal window for TCD.2 . Accordingly, there were significant differences in values of tidal volumes, respiratory rates. BIS values were stable during the entire procedure indicating adaequate depth of anesthesia . However, mean blood flow velocity values measured during EtCO2 35 and 30 mmHg were significantly different form each other as well as from preoperative and values measured at EtCO240 .Preoperative middle cerebral artery mean blood flow velocity values were not significantly different from values measured at steady state sevoflurane stage under normocapnic conditions EtCO2 0 mmHg. H2 (40 mmHg). As shown in Fig. We assessed the percent change between mean arterial pressure and middle cerebral artery mean blood flow velocity before anesthetic induction and 20 min after anesthesia was induced and a steady state of sevoflurane anesthesia was reached at normocapnic PCO2 - thus influencing flow-metabolism coupling of the brain tissue. The main actors of this systemic and cerebral effects are cerebral arterioles, that are responsible for autoregulatory reactions during changes of cerebral blood flow and vasoreactivity related to metabolic changes [Anesthetic agents may have various effects on systemic circulation determining the cerebral perfusion pressure. Additionally, whyle using some agents, direct cerebral effect has also to be taken into account. Both effects are dose-dependent and are exerted through vasodilation or vasoconstriction of the cerebral vessels (medium-size vessels and arterioles), as well as through decreasing CMRO changes . ConsequPrevious reports indicated that sevoflurane between 0.5–1.0 MAC has minimal direct vasodilatory effect on the brain arteries , 9 and hWe found that reaching the stady state under sevoflurane anesthesia resulted in a decrease of the mean arterial pressure leading to non significant change in the cerebral blood flow velocity. Cerebral autoregulation is defined as the inherent ability of the brain circulation to maintain a constant cerebral blood flow during changes of cerebral perfusion pressure . In line2. In previous volunteer studies it has been demonstrated that forced hyperventilation lasting for 60 s results in a 38% percent decrease of the middle cerebral artery mean flood flow velocity compared to the resting BFV [2-reactivity is 2–5 cm/s/mmHg [2 from 40 mmHg to 35 mmHg resulted in an average decrease of mean blood flow velocity of 4 cm/s/mmHg, whereas to 30 mmgHg PCO2 resulted in a decrease of 8 cm/s/mmHg. These values correspond to the previous observations and indicate preserved CO2-reactivity during sevoflurane anesthesia at MAC 1 concentrations.Carbon-dioxide reactivity of the cerebral circulation is defined as the change in cerebral blood flow velocity per mmHg change in PCOting BFV . The accm/s/mmHg . In the Both cerebral autoregulation and cerebral vasoreactivity are multifactorially determined defending mechanisms of the brain that aim to optimize global and cerebral circulation according to the actual metabolic needs. The main actors of these two mechanisms are cerebral arterioles, roughly 200 μm in diameter . The pat2-reactivity toward hypocapnic direction. This was done intentionally, as in the usual practice normocapnia is maintained during anesthesia and in specific neuroanesthetic cases only induced hypocapnia is used as the part of the intracranial pressure decreasing strategy.Finally, we have to mention the limitations of our study. The methodological limitations are that transcranial Doppler does not measure cerebral blood flow, only changes of the blood flow velocities are proportional to cerebral blood flow values. Applanation tonometry that was used for monitoring the systemic hemodynamic effect is operator-dependent procedure. Therefore all measurements were performed by the same, experienced physician (DP). And finally, in the present study we only tested COSevoflurane at clinically administered doses does not have any significant systemic hemodynamic effects and does not influence static cerebral autoregulation and cerebrovascular reactivity.


Chronic Kidney Disease (CKD) is a worldwide public health problem. The prevalence of CKD is rising especially in elderly, as consequence of population-ageing related to socioeconomic development and better life expectancy. There are scarce studies evaluating CKD progression and its associated factors in elderly patients.2/year, respectively).This is a retrospective observational study including 340 patients (≥ 65 years old) CKD stages 3a–5 non-dialysis, incidents in an outpatient CKD clinic, followed by 2.1 years. CKD progression was assessed by the slope of eGFR calculated by CKD-EPI and BIS 1 equations. The patients were divided in progressor and non-progressor groups  vs. 76 (69–80) years; p = 0.02]; had higher proportion of diabetic nephropathy, higher serum phosphorus  and proteinuria [0.10 (0–0.9 vs. 0 (0–0.3)] g/L; p = 0.007)] at the admission. In the logistic regression analysis adjusted for gender and eGFR, proteinuria was independently associated with CKD progression [OR (Odds Ratio) ].Kidney function declined in 193 (57%) patients. In this group, the progression rate was -2.83 (-5.1 / -1.1) mL /min /1.73 mCKD progression was observed in the majority of elderly CKD patients and proteinuria was the most important factor associated to the decline of kidney function in this population. Chronic Kidney Disease (CKD) is a worldwide public health problem. CKD is one of the leading causes of non-communicable diseases and its prevalence is rising especially among older adults, as a consequence of socioeconomic development and better life expectancy .The estimated glomerular filtration rate (eGFR) in elderly people has been a challenge. The 2012 Clinical Practice Guidelines KDIGO , were su2 and achievement of end stage renal disease (ESRD) . The patients were classified into ‘progressor’ and ‘non-progressor’ groups  were calculated for each variable, as appropriate. The Kolmogorov-Smirnov statistical test was used to investigate the variable distribution. Comparisons of continuous variables were performed using Student’s t-test and the Mann-Whitney U-test, for normal and skewed data, respectively. Comparisons of proportions were performed using chi-squared analysis or Fisher’s exact test, as appropriate. Multiple imputations were performed for missing data using MICE package of software R. This approach was applied only to variables with up to 25% missing data. Thus, all the patients were included for the logistic regression analysis. A stepwise multivariate model was constructed to test the variables associated with CKD progression. This method selected variables with p < 0.10, adjusted for gender and CKD-EPI at the admission. Cox proportional hazards model was used to investigate the impact of the occurrence of death on the CKD progression. Values of p < 0.05 were considered statistically significant. All analyses were performed using a standard statistical package .2. During the follow up eGFR declined in 193 (57%) patients  vs. 73 (69–79) years; p = 0.01], had higher prevalence of diabetic nephropathy  and higher eGFR 1 . The other variables were similar in both groups.In the progressor group, 49 out of 193 (25%) patients were fast progressors and their median eGFR slope was -6.9 (-8.4 / -5.6) mL/min/1.73 m In the present single center retrospective observational study, regardless the equation used to estimate GFR, almost 60% of the elderly patients showed a decline in kidney function over a median of two years of follow-up. CKD progression was related to younger age, diabetic nephropathy, higher serum phosphorus and proteinuria.2 /year) used in the study, once we and other authors [2 /year and found higher rates of progression. Unexpectedly, 43% of the patients presented some increase of eGFR during the study. The reasons why there was an improvement in the kidney function remain to be clarified. One could hypothesize that the implementation of the treatment could have had a beneficial impact in the eGFR. Moreover, some of the patients could have experienced an acute renal insult before the admission in the program. Of note, similar to our findings some authors also observed in prospective studies that 30% and 48% of the patients maintained or improved kidney function during the follow up [It has been reported a rate of CKD progression varying from 13% to 70% , 12, 13.2 [Several factors could be related to CKD progression, such as baseline eGFR, age, presence of proteinuria, and diabetes among others. Older age has been associated with the occurrence and higher progression of CKD , 15, 16.2 , 12. A m2 . This fa2 . Differe2 .The presence of proteinuria, the major marker of kidney damage, is the best-known risk factor for CKD progression. Several studies observed that proteinuria was associated with a faster rate of kidney function decline and achievement of ESRD , 19–21. Another important risk for CKD progression and faster decline of renal function is the presence of diabetes, in general , 22 and Some limitations of this study should be address: a single center and retrospective study, a relatively small follow up and proteinuria evaluated by spot urine sample. Despite that, using the two currently recommended equations for estimate GFR, this study was able to identify CKD progression in the majority of elderly patients.In conclusion, CKD progression was observed in the majority of elderly CKD patients and proteinuria was the most important factor associated to kidney function decline in this population.