Although renin-angiotensin II-aldosterone system inhibitor (RASI) use for renal protection is well-documented, adherence to RASI therapy in the pediatric population is unclear. This study aimed to evaluate patient characteristics associated with adherence to chronic RASI use in patients with childhood chronic kidney disease (CKD).Childhood CKD was identified using ICD-9 codes in the population-based, Taiwan national health insurance research database between 1997 and 2011. Patients continuously receiving RASIs for ≥3 months without interruption > 30 days after CKD diagnosis were defined as incident users. Medication adherence was measured as the proportion of days covered (PDC) by RASI prescription refills during the study period. Multivariate logistic regression was employed to assess the odds for adherence (PDC ≥80%) to RASI refills.n = 215) had PDC ≥80%. Compared to the group with PDC < 80%, patients in the high adherence group more often had proteinuria , anemia , and time to start of chronic use > 2 years . Odds of being non-adherent were increased by hypertension and older ages (comparing to < 4 years) at start of chronic use, 9–12 years , 13–17 years ,≥18 years  and males .Of 1271 incident users of RASI chronic therapy, 16.9%  contains supplementary material, which is available to authorized users. Childhood chronic kidney disease (CKD) increases the risk of renal replacement therapy, cardiovascular disease, and premature death in the pediatric population. Randomized controlled trials have shown that renin-angiotensin II-aldosterone system inhibitors (RASIs), including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), may control blood pressure , reduce Medication adherence refers to the degree to which patients take their medications as prescribed , as well as whether they continue to take a prescribed medication . Non-adhMedication adherence in children and adolescents has been examined for childhood CKD, but limited in a short term (recent 7 days) time frame , 12. MedA population-based cohort study was conducted using the National Health Insurance Research Database (NHIRD), which includes 99% of the 23 million persons enrolled in the Taiwan National Health Insurance (NHI) program . BrieflyFollowing Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for diagnosis of childhood CKD, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify individuals who had CKD diagnoses on at least 2 occasions , which is defined as the number of follow-up days covered with medication, divided by the total number of days in follow-up. The PDC truncates any oversupply during a specific observation period and is widely used in health care setting as a tool to measure health care quality . The PDCDemographics, including gender and age were assessed on the index date. Baseline CKD-related comorbid conditions , includip values less than 0.05 were considered statistically significant. Operationalized definitions of all diagnosis, procedure, and medication codes are included in Additional file Demographic and clinical characteristics were reported using the median (interquartile range [IQR]) for continuous variables and the frequency (percentage) for categorical variables. Patients with PDC ≥80 and < 80% in the study period were compared with respect to baseline characteristics, groups of medications used, and comorbid conditions. A multivariate logistic regression analysis was conducted to assess baseline patient and medication-related factors  associated with high adherence (PDC ≥80%). Two-sided Of the 51,846 children diagnosed as having CKD, 7174 (13.84%) children who were ever prescribed a RASI and 1271 other children met inclusion and exclusion criteria for chronic use  varied over the entire study period. The percentage of patients using ≥3 classes of medications increased from the RASI index period (including the prior and post 6 months covering the index date), slowly decreased to 3.29% at 5.5 years, and then gradually increased to 5.24% at 10.5 years, during the 11 years of follow-up , anemia , and late RASI initiation . On the other hand, patient age 9–12 years , 13–17 years  and ≥ 18 years , male , and presence of hypertension-related disease at baseline  were associated with decreased odds of being adherent to chronic RASI therapy. In the same model, older age at the start of chronic RASI therapy was associated with 20% less  likely to be adherent.In multivariate analysis including baseline patient and clinical characteristics Table , 3 factoThe study used a population-based claims database to investigate prescription patterns and adherence to RASI for childhood CKD. The findings revealed that overall adherence to chronic RASI therapy was low and was highly correlated with the presence of CKD-related comorbid conditions among children and adolescents with CKD. Adherence to RASI therapy can be partially explained by clinical factors, such as advanced aggressive comorbidities, time since CKD diagnosis, and patient age and gender. However, the time to adherence with chronic therapy was not fully supported by guidelines, suggesting that more research on childhood CKD is needed to increase medication adherence.The rate of ACEI/ARB use in our study was consistent with previous registry and claims database studies on childhood CKD  or childHowever, our finding of a low rate of adherence to chronic RASI treatment in children with CKD concurs with few studies. ACEIs and ARBs have been shown to decrease systemic and glomerular pressure and reduce proteinuria more effectively than other antihypertensive medications . In patiAdherence to RASI therapy might be influenced by adverse drug reactions and tolerability concerns , which may lead to treatment interruption. For example, patients treated with ACEIs or ARBs should be monitored for hypotension, early decrease in glomerular filtration rate, and hyperkalemia . AlthougThere is a paucity of research examining time to ACEI/ARB initiation and its impacts on treatment adherence and persistence in clinical practice. However, a cross-sectional study suggested that CKD duration had no effect on medication adherence, although only the prior 7 days of adherence were evaluated .CKD and associated comorbidities impose a substantial pill burden on children and adolescents. It explains that a longer time since CKD diagnosis, which implies a more advanced stage of kidney disease, is more likely to be associated with adherence than a shorter duration of CKD in the present study. But, ACEI/ARB (18%) was one of the most frequently reported not being taken prescription  in a childhood CKD cohort . In thatn = 744) in multiple pediatric nephrology clinics in Taiwan [n = 202) in a registered US pediatric cohort [Growing evidence has shown that hypertension is undertreated in pediatric populations. For example, almost half of all children and adolescents with CKD had uncontrolled hypertension: 44.1%  are not available in the NHI dataset. This limitation was addressed by using the proxy of the number of medication classes at 3-month intervals. Second, medication adherence was determined by indirect measurement using pharmacy prescription filling data. Accurate medication adherence is difficult to examine, and is a challenge at both individual and population levels . PharmacAdherence to chronic RASI therapy in children and adolescents with CKD was heavily influenced by age and comorbid conditions related to progressive kidney disease in the present study cohort. Further research on understanding of the role of demographics , the CKD care delivery process, and socioeconomic determinants of prescribing is imperative for the design of effective intervention strategies to improve management of hypertension and related chronic complications in childhood and young adulthood.Additional file 1:Table S1. ICD 9 codes for disease conditions in the study. Table S2. Medications used to treat chronic kidney disease and its related comorbid conditions. (DOCX 21 kb)


Community-based blood pressure (BP) monitoring plays an important role in national hypertension management in China. However, the utilisation of this service, together with its associations on hypertension treatment and BP control has not been fully investigated.The study population was from the China Health and Retirement Longitudinal Study (CHARLS) in 2015. Cross-sectional data of 2487 hypertensive persons were included as subjects. Stratified sample households were selected from 450 villages or communities of 150 counties from 28 provinces. Finally, 21,097 individuals were interviewed successfully. The main outcome was hypertension control (having average BP under 140-90 mmHg). The main independent variable was utilisation of community-based BP monitoring service (having BP examination once a season or more). The mediators were hypertension treatment (currently taking any antihypertensive medicine) and lifestyle factors . We performed chi-square and binary logistic regression to analyse associations of BP monitoring with hypertension treatment and blood pressure control. The mediation model was examined by the Sobel test.P < 0.01, OR = 3.52, CI = 2.467–5.030), and BP control . Medication treatment played a complete mediating role between monitoring and hypertension control in this study . Those who underwent BP monitoring tended to be those who did not finish primary school education , had poorer household income , and lived in rural areas rather than in urban areas .Mean age of the population was 64.2 (0.24). The percentage of males was 42.8%. Prevalence of community-based BP monitoring was 32.1%. Patients who used this service had higher odds of hypertension treatment (β = 1.259, Although the use of BP monitoring service had no direct effect on BP control, it had a positive effect on BP control through the full mediation effect of hypertension treatment. Termly BP monitoring by community-based health expertise among hypertensive persons, for instance, once a season, can be recommended to public health policymakers for BP control through instructions on medication treatment and health behaviours. Hypertension is one of the major non-communicable diseases (NCDs) in the world that defined as one’s systolic blood pressure (SBP) above 140 mmHg or diastolic blood pressure (DBP) above 90 mmHg without taking any antihypertensive medicine. Hypertension is associated with higher risks of cardiovascular diseases (CVD) accounting for 17 million deaths in 2013 worldwide . In ChinBlood pressure of hypertensive persons is controlled if BP < 140-90 mmHg with or without medication. The major hypertension treatment is to take antihypertensive medicine. As the main cause of uncontrolled BP, hypertension is lack of treatment in most countries. Burden of the hypertension management was severe in many countries including China. A study across four Middle Eastern countries  presented that 47% of persons with hypertension were treated and only 19% had controlled BP . The stuIn addition to inadequate medication treatment, uncontrolled hypertension is also attributed to unhealthy lifestyle behaviours including smoking, drinking and lack of exercise. In a study identified latent classes of hypertensive persons’ lifestyle risk factors including physical activity, smoking habits, and blood pressure control, about 85% of hypertensive persons were categorized in an intermediate to high-risk class of lifestyle . In ChinConventionally, hypertensive persons are encouraged to control the symptom by long-term BP monitoring, medication use as well as establishing healthy lifestyle behaviours . InterveUtilisation of community-based BP monitoring service was defined as receiving free blood pressure examination at least 4 times annually in the study. In 2009, a national program, Essential Public Health Services (EPHS) was launched in China as part of the new Health Care System Reform . ChronicIt is believed that patients could achieve a better outcome of BP control if they follow health expertise advice on hypertension treatment and healthy lifestyles in terms of exercising properly , avoidinThis is a cross-sectional study based on data from the China Health and Retirement Longitudinal Study (CHARLS) 2015. This study is designed to explore the association of community-based BP monitoring utilisation with hypertension control. CHARLS respondents were followed using a computer-aided personal interview every 2 years. A structured questionnaire with several main sections was used to collect data from each subject. One section was used to record height, weight and blood pressure. Each subject’s systolic and diastolic blood pressures were recorded three times by a trained nurse using a HEM-7112 electronic monitor . The mean values for each subject were then calculated. The interviewees were asked face-to-face if they were taking any form of anti-hypertensive medication and how often they had blood pressure examination by village or community doctors in the last year.CHARLS is a nationally representative survey of individuals over age 45 in China. The 2015 survey was the fourth to be conducted in the country. Information about community-based hypertension management was only provided in the recent investigation of this wave. Stratified sample households were selected in 450 villages or communities of 150 counties from 28 provinces. In total, 12,241 households were selected for the survey. 21,097 individuals were interviewed successfully. The de-identified database was publicly available online.The members of the selected households aged over 45 years old were chosen as subjects. If a selected household had more than one member aged 45 years or older, one such member – randomly chosen – and his or her spouse if also aged 45 years or older were selected as subjects of the survey. Overall, 21,097 respondents were interviewed in 2015. Subjects were selected for this study if they were identified as hypertensive and provided information about community-based BP monitoring.This study is based on a secondary data analysis. The primary data collection of China Health and Retirement Longitudinal Study (CHARLS) was conducted in 2015. The data request of 2015 CHARLS was approved in May 2018. The study sample selection was conducted from May to August 2018. Data analysis was accomplished from September to October 2018.A four-stage, stratified, cluster sampling was used to select primary participants in the baseline CHARLS survey 2011. In the first stage, 150 county-level units from 28 provinces were selected to give a mix of urban and rural settings and a wide variation in the level of economic development. Three primary sampling units – administrative villages in rural areas or communities in urban areas – were then chosen in each selected county-level unit. All of the dwellings in each selected primary sampling unit were then outlined on Google Earth maps using the “CHARLS-GIS” software package that was specifically designed for the survey. Finally, 24 of the mapped households in each primary sampling unit were randomly selected.n = 15,247). A subject was considered hypertensive if he or she had a mean systolic blood pressure of ≥140 mmHg, a mean diastolic blood pressure of ≥90 mmHg or was already taking anti-hypertensive medication. Among all subjects provided blood pressure biomarker, 5884 respondents were identified with hypertension, and 3498 of them provided information about community-based BP monitoring. 2487 of subjects provided complete data for this study.In this study, the eligible sample was selected from subjects who had provided BP measures (n = 5884).Inclusion criteria: Subjects were included if blood pressure biomarker provided  and identified as hypertensive (n = 5050), missing values of whether who used community-based monitoring service (n = 2386), diagnosed comorbidities of stroke (n = 268) or chronic kidney diseases (n = 456), and missing values of comorbidities (n = 661).Exclusion criteria: Subjects were excluded due to missing values of biomarker (The variable of BP control was chosen as the dependent variable. Hypertensive persons with SBP (systolic blood pressure) under 140 mmHg and DBP (diastolic blood pressure) under 90 mmHg were considered to be controlling their hypertension well. According to it, the variable of BP control was categorized by yes and no.Mediators included one variable of hypertension treatment and three variables of lifestyle behaviours. Hypertensive persons who claimed to be receiving any form of anti-hypertensive medication were considered to be treated. Hypertension treatment was categorized by yes , and no (for those who are not taking any medicine). Three lifestyle behaviours related variables included alcohol intake, physical activity level and smoking. Alcohol intake was categorized by often (drink more than once a month), occasionally (drink less than once a month) and never (never drink) according to the question “How frequent do you drink?” Physical activity level was divided as plenty level (more than 300 min moderate exercise or 150 min vigorous exercise weekly), adequate level (150–300 min moderate exercise or 75–150 min vigorous exercise weekly), light level (less than 150 min moderate exercise or 75 min vigorous exercise weekly) and no exercise at all. Smokers were categorized by yes and no according to the question “Do you currently smoke?”The independent variable of interest was utilisation of community-based BP monitoring service. Subjects were identified as BP monitored if they received EPHS-covered BP examination once a season . The variable was categorized by yes (those who had BP examination once a season or more) and no (those who had BP examination less than once a season) according to their answers to the question “How often did you have blood pressure examination by community/village doctors?”2 (m2). Subjects who had previously received a doctor’s diagnosis of diabetes, cancer, stomach diseases, or arthritis in CHARLS were considered with diagnosed chronic diseases.Covariates were respondents’ sociodemographic characteristics, including age , sex, educational attainment , annual household income , administrative registration status , cohabitation status (living with spouse or cohabitated), insurance status, BMI (body mass index) and diagnosed chronic diseases. The four groups of household income categories were defined based on the 25th, 50th, and 75th percentiles of annual household income of the subjects. The rural or urban administrative registration status is based on the National Bureau of Statistics definition where a primary sampling units is defined as urban if it is located in a city, suburb of a city, a town, suburb of a town, or other special areas where nonfarm employment constitutes at least 70% of the workforce, such as a special economic zone, state-owned farm enterprise. BMI was defined as weight (kg) divided by heightSocio-demographic characteristics were performed as percentages. A complex sampling plan was constructed according to stratification, cluster, and weights of this survey for chi-square test and binary logistic regression. The Chi-square test was used to compare socio-demographic characteristics, 4 mediators, and hypertension control between respondents monitored by community-based BP examination and those who did not. We also used Chi-square test to examine BP control for independent and mediation variables. To examine the association of BP monitoring with BP control and significant mediators in Chi-square test, we used logistic regression which can take hypertension treatment into consideration. The Sobel test was conducted to examine the mediation effect of medication treatment between independent BP monitoring variable and dependent BP control variable with their coefficients of three regression models above. All models were adjusted for age, gender, educational attainment, household income, cohabitation status, residential region, working status, insurance status, BMI, and chronic diseases diagnosis. Statistical analysis was implemented by using SPSS 13.0 .Table Table The reach of the community-based BP monitoring service varied largely between different regions (from 16 to 69%), as well as the BP control rate from 23 to 76%). Among 28 provinces of China, the percentage of BP monitoring patients was the largest in Qinghai and Gansu provinces in western China, while the smallest in Heilongjiang and Hunan province in the central and eastern China. The rate of BP control was the highest in the west of Xinjiang and Chongqing provinces and the lowest in the Fujian and Guizhou Province . Patients who were more likely to use antihypertensive medicine tended to be females, living with spouse or cohabitated and with diabetes.A binary regression analysis was conducted to investigate factors affected the hypertension treatment. Null hypothesis was βP < 0.05, OR = 1.246, CI = 1.035–1.499). Subjects more likely to control their BP tended to be female and with higher level education (Table A binary logistic regression was conducted to investigate factors affected BP control. As shown in Table P = 0.816). It indicated the use of BP monitoring service had no direct effect on BP control. The effect of independent variable BP monitoring on dependent variable BP control was completely mediated by the intermediate variable of hypertension treatment. Hypertension treatment played a perfect mediation role between monitoring and hypertension control. The Sobel test was conducted to further confirm its mediation effect . The final mediation model of the independent variable (community-based BP monitoring service utilisation), the mediator variable (medication treatment) and the dependent variable (hypertension control) was shown in Fig. As community-based BP monitoring service utilisation significantly predicted both the dependent variable of hypertension control and the mediator variable of hypertension treatment but not healthy lifestyle behaviours, the mediation model was adjusted based on our original hypothesis in Fig. Based on a nationally representative data from CHARLS, this study explored the association between utilisation of community-based BP monitoring service and BP control among hypertensive adults aged above 45. The prevalence of community-based BP monitoring service use was 32% among hypertensive persons in 2015. It showed an improvement in EPHS utilisation of hypertensive persons compared with a previous estimate in China (vs 8.1% in 2013) [Though improvement had been achieved over time, less than half of the hypertensive persons had their BP regularly examined by the community or village doctors. Percentage of hypertensive persons had their BP examined at least once annually was reported about 54–58% in 2011 and 51–65% in 2013 in China . A similThis low reaching of community-based management may be due to several reasons. First, it is likely that many patients are unaware of this service in the community and consequently do not avail it . FurtherOn the other hand, utilisation of this service showed a development of hypertension management in grass-roots institutions, especially for the disadvantaged population . CommuniAt the same time, this service has made a difference since an improvement of hypertension management was realized in less developed areas of China. In rural, patients used this service more than urban ones. Those patients from the western provinces where is the most underdeveloped area in China were mostly monitored and had controlled BP. It was possibly because of the local scarcity of multiple health facilities in these areas. It also takes longer to travel to higher level institutions from the rural . It is nSelf or home monitoring of BP had been proved effective on increase hypertension treatment and BP control , whereasMeanwhile, Studies had shown intervention program ran by grass-root institutions could effectively achieve higher BP control rate by improving not only medication use but also healthy lifestyle behaviours . But a rThis study has four limitations. Firstly, hypertension diagnosis was not done by 24-h ambulatory blood pressure monitoring, which could be the best diagnosis way but would take a long time and not be cost-inefficient in a national survey . SecondlThe use of BP monitoring service had no direct effect on BP control. Utilisation of national community-based BP monitoring service is positively associated with BP control through a full medication effect of hypertension treatment. This study emphasized that through improving antihypertensive medication use among hypertensive persons, the national community-based BP monitoring could be an effective way to achieve hypertension control. Termly BP monitoring by community-based health expertise among hypertensive persons, for instance, once a season, can be recommended to public health policymakers for BP control through instructions on medication treatment and health behaviours. It was suggested that awareness of EPHS service and primary health care workforce should be enhanced to increase utilisation of community-based BP management. Education about healthy lifestyle behaviours in EPHS should be bolstered in the future.


To investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes and to compare detection rates of thrombophilias between standard blood tests and a novel genetic test.This is a case-control prospective study performed in Hospital Sant Joan de Déu in Barcelona, Spain. Cases had a history of intrauterine growth restriction requiring delivery before 34 weeks gestation, placental abruption before 34 weeks gestation, or severe preeclampsia. Controls had at least two normal, spontaneously conceived pregnancies at term, without complications or no underlying medical disease. At least 3 months after delivery, all case and control women underwent blood collection for standard blood tests for thrombophilias and saliva collection for the genetic test, which enables the diagnosis of 12 hereditary thrombophilias by analyzing genetic variants affecting different points of the blood coagulation cascade.The study included 33 cases and 41 controls. There were no statistically significant differences between cases and controls in the standard blood tests for thrombophilias in plasma or the TiC test for genetic variables. One clinical-genetic model was generated using variables with the lowest P values: ABO, body mass index, C_rs5985, C_rs6025, and protein S. This model exhibited good prediction capacity, with an area under the curve of almost 0.7 (P <0.05), sensitivity of almost 67%, and specificity of 70%.Although some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in subsequent pregnancies. MTHFR) gene mutation; and hyperhomocysteinemia[Thrombophilia describes a tendency to develop thromboses because of inherited or acquired disorders of blood coagulation or fibrinolysis, which lead to a prothrombotic state , 2. Caussteinemia.The hemostatic system appears to play an important role in both establishing and maintaining pregnancy. Development of the placental circulation is ensured by structural modifications of the spiral arteries and a pregnancy-induced hypercoagulable state resulting from an increase in procoagulant factors and a decrease in anticoagulant factors and fibrinolysis ,3, 4. ThThere has always existed much controversy about the association between inherited thrombophilias and the possibility of adverse pregnancy outcomes due to uteroplacental thrombosis , 7. A nuNevertheless, many current guidelines do not recommend screening unless a personal or strong family history of venous thromboembolism is present. Some reasons can be found against screening women with a history of adverse pregnancy outcome. First of all, some studies fail to demonstrate a strong association between hypercoagulability and pregnancy outcomes. And moreover, most pregnant women with inherited thrombophilia have normal pregnancy outcomes .Anticoagulants and aspirin are the best studied and most commonly used therapeutic agents to prevent pregnancy complications in thrombophilic women , 15, andIn addition to conventional thrombophilias , novel thrombophilias have been recently investigated and also appear to potentially affect pregnancy outcomes . It is aThe aim of this study was to investigate the incidence of inherited thrombophilias in patients with adverse obstetric outcomes  and to compare detection rates of thrombophilia between standard blood tests and the genetic test, with the goal of improving prediction of patients who could benefit from anticoagulant therapy in subsequent pregnancies.This is a case-control prospective study performed in Hospital Sant Joan de Deú in Barcelona, Spain. The study protocol was approved by the Institutional Review Board of Sant Joan de Déu University Hospital. Written informed consent was obtained from each participant.Cases and controls were recruited over a 12-month period from women above age 18 (22–45 years old) attending the outpatient clinic in the obstetrics department of the Hospital Sant Joan de Déu and who also gave birth in the same hospital. Gestational ages for all cases and controls were determined by measuring the crown-rump length during the first trimester .Women were eligible for inclusion as cases in this study if they met the following criteria:th percentile with an abnormal uterine arterial Doppler study (pulsatility index >95th percentile [th percentile [Intrauterine growth restriction: birth weight <10rcentile ) or cerercentile ), which Placental abruption before 34 weeks gestation.Systolic BP ≥160 mm Hg and/or diastolic BP ≥110 mm Hg measured on two occasions separated by 6 h, with the patient at rest. Systolic BP >180 and/or diastolic BP >120 mm Hg on two separate occasions in 30 min.Persistent symptoms of eclampsia, including one or more of the following: hyperreflexia with clonus, severe headache, visual disturbances, stupor, epigastric or right upper quadrant pain, nausea, or vomiting.Oliguria: ≤500 mL in 24 h or <100 mL in 3 h, or evidence of renal insufficiency (serum creatinine >1.2 mg/dL or blood urea nitrogen >40 mg/dL).Acute pulmonary edemaHepatic dysfunction3)Thrombocytopenia  by analyzing genetic variants affecting different points of the blood coagulation cascade.A bivariate table was constructed to show the distribution of population characteristics between cases and controls. Normally distributed variables are described as mean and standard deviation and were analyzed using the Student’s t-test. Continuous non-normally distributed variables are presented as median and interquartile range and were analyzed using the Kruskal-Wallis test. Categorical variables are shown as absolute frequency and percentage and were analyzed using the chi-squared test (or Fisher’s exact test when the expected cell frequency was <5). Multivariate logistic regression analysis was performed to explore the relationships between potential risk factors and adverse obstetric events.The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive performance of multivariate logistic models. Sensitivity, specificity, and positive and negative likelihood ratios were based on the point of the curve that maximized the Youden index. All calculations were performed using R statistical software (version 3.1.3) . P values <0.05 were considered statistically significant.A total of 33 patients were identified as cases and 41 as controls. The incidence of thrombophilias in women with adverse obstetric outcomes (cases group) was 15.2% versus 18.2% in controls. There were no significant differences between both groups.No significant differences in the results of any standard blood test for thrombophilia were observed between cases and controls . Lupus aWe analyzed multivariate prediction models that considered only thrombophilic variables of usual clinical practice or only genetic variables. None of these models were individually predictive of pregnancy complications. We then generated one clinical-genetic model combining variables with the lowest P values Tables  and 5. TOver the past years, there has been much debate regarding the association between inherited thrombophilias and the risk of placenta-related adverse obstetric outcomes. Many case-control studies and systematic reviews –27 have Similar to our results, other studies failed to confirm an association between inherited thrombophilias and adverse obstetric outcomes –32, and Because of discrepancies in the literature regarding the importance of thrombophilias in placenta-related adverse obstetric outcomes, an even larger controversy has recently arisen regarding the use of screening for inherited thrombophilias in women with a history of adverse pregnancy outcomes or loss . The ultWe note limitations to our study. The main limitation was the small sample size, which may have rendered our study underpowered to evaluate differences in detecting inherited thrombophilias between groups. Another limitation is that sticky platelet syndrome was not included in the evaluation of thrombophilias, on one hand because it is an expensive and operator-dependent test and on the other hand because the vast majority of published studies on hereditary thrombophilias do not consider it.In conclusion, our study shows that, although some association may exist between hypercoagulability and pregnancy outcomes, no significant direct correlation was observed between adverse obstetric outcomes and inherited thrombophilias when analyzed using either standard blood tests or the genetic test. Future studies with a larger sample size are required to create a clinical-genetic model that better discriminates women with a history of adverse pregnancy outcomes and an increased risk of poor outcomes in following pregnancies.


Renal dysfunction following intraoperative arterial hypotension is mainly caused by an insufficient renal blood flow. It is associated with higher mortality and morbidity rates. We hypothesised that the intraoperative haemodynamics are more stable during xenon anaesthesia than during isoflurane anaesthesia in patients undergoing partial nephrectomy.We performed a secondary analysis of the haemodynamic variables collected during the randomised, single-blinded, single-centre PaNeX study, which analysed the postoperative renal function in 46 patients who underwent partial nephrectomy. The patients received either xenon or isoflurane anaesthesia with 1:1 allocation ratio. We analysed the duration of the intraoperative systolic blood pressure decrease by > 40% from baseline values and the cumulative duration of a mean arterial blood pressure (MAP) of < 65 mmHg as primary outcomes. The secondary outcomes were related to other blood pressure thresholds, the amount of administered norepinephrine, and the analysis of confounding factors on the haemodynamic stability.P = 0.002). However, the cumulative duration of a systolic blood pressure decrease by > 40% did not significantly differ between the groups (P = 0.51). The periods with a systolic blood pressure decrease by 20% from baseline, MAP decrease to values < 60 mmHg, and the need for norepinephrine, as well as the cumulative dose of norepinephrine were significantly shorter and lower, respectively, in the xenon group. The confounding factors, such as demographic data, surgical technique, or anaesthesia data, were similar in the two groups.The periods of an MAP of < 65 mmHg were significantly shorter in the xenon group than in the isoflurane group. The medians [interquartile range] were 0 [0–10.0] and 25.0 [10.0–47.5] minutes, for the xenon and isoflurane group, respectively  contains supplementary material, which is available to authorized users. P = 0.001), in particular, a higher incidence of intraoperative hypotension requiring catecholamine therapy (P = 0.003), were found in the isoflurane group. The intraoperative hypotension was not predefined in the PaNeX study; rather, it was based on the attending anaesthetist’s judgement. Therefore, we have performed a predefined secondary analysis of the particular haemodynamic differences between the two study groups of the PaNeX study. We hypothesized that the patients undergoing xenon anaesthesia would exhibit significantly better haemodynamics during the surgery, as defined by the recommendation of the DGAI ), tachycardia (defined as heart rate > 100 bpm), and the relative heart rate deviation (decrease and increase) by 20% from the baseline values. The heart rate was recorded every 5 min from the start of the monitoring in the operating room until the transfer to the post-anaesthesia care unit. The proportion of the study treatment duration represented by all aforementioned heart rate deviations was also analysed.Other outcome measures included the analysis of the effect of the confounding variables on the patients’ haemodynamics. These confounders comprised the anaesthetic concentrations (recorded every 5 min), the amount of administered norepinephrine and opioids, and anaesthesia depth . Furthermore, we analysed the influence of a pre-existent arterial hypertension on the need for a haemodynamic support with norepinephrine and the influence of the epidural anaesthesia on the applied opioid amount.p-value of < 0.05 was considered statistically significant. GraphPad PRISM®  was used for figure creation.Statistical analysis was performed using SPSS software . After testing for normality using the Shapiro Wilk Test, the continuous data were explored using the Mann-Whitney U test and the dichotomous variables were analysed using Fisher’s exact test. A n = 31). Both study groups were comparable with regard to the sex, age, weight, and the pre-existing chronic diseases [The results of the main PaNeX study are presented elsewhere . For thidiseases . The basP = 0.51 ] were 5.0 [0–35.0] and 2.5 0–12.5] minutes for isoflurane and xenon, respectively, 2.5 minutP = 0.55. Nevertheless, the duration of MAP of < 65 mmHg was significantly longer in the isoflurane group, P < 0.01 . The overall time effect was also significant (P < 0.001 each) for both models (MAP and systolic blood pressure). In contrast, the group-by-time interaction effect was not significant for the MAP (P = 0.546), neither for the systolic blood pressure (P = 0.183).In an additional sensitivity analysis, we compared the group differences for both MAP and systolic blood pressure, using two mixed-models (repeated measurements ANOVA). For each model, the results showed a significant difference between the groups  (Table P = 0.086 (Table The mean (SD) intraoperative heart rates were 65.2 (9.1) bpm and 61.6 (13.2) bpm in the isoflurane and xenon group, respectively . AlthougMoreover, the episodes of tachycardia, as well as the cumulative duration of a relative decrease or increase of the heart rate by > 20%, were similar in the two groups (Table P = 0.897). Furthermore, there was neither a significant main effect for time nor for the group, with P = 0.250 and P = 0.447, respectively.An additional sensitivity analysis of the heart rate using a mixed-model repeated measures ANOVA did not show a statistically significant interaction between the time and groups  and 19 (83%) patients, in the isoflurane and xenon group, respectively  antagonist before surgery (xenon (11 of 12), isoflurane (7 of 12)). The ACE/AR antagonist therapy was discontinued for all patients 24 h before the surgery in accordance with our SOP.This secondary analysis showed that the proportion of patients with pre-existent hypertension, bradycardia, and tachycardia did not differ between the groups Tables  and 3. HP = 0.702, P = 0,248, and P = 0.361, respectively. Volatile anaesthetics were administered according to the MAC values in the clinical routine and quantified by BIS. The patients received a mean (SD) of 0.8 (0.1) Vol.%, 0.7 MAC isoflurane, and 51.1 (2.5) Vol.%, 0.8 MAC xenon. The BIS values were comparable  between the groups. Four patients in the isoflurane and one patient in the xenon group underwent a total nephrectomy due to an unforeseen intraoperative decision, based on the tumour extent and the urologic SOP. The mean (SD) study treatment duration was 197 (60) minutes in the isoflurane and 166 59) minutes in the xenon group. The groups showed a similar fluid balance; crystalloid and colloid infusions, and total blood loss showed no significant differences with 9 minutesThe present secondary analysis of the PaNeX study evaluated the haemodynamics during xenon anaesthesia in patients undergoing partial nephrectomy. The xenon group showed a significantly better intraoperative haemodynamic stability, with a lesser need for norepinephrine and no major differences in the heart rates, compared to the isoflurane group.In contrast to our findings, previous studies have reported an absent or minimal negative impact of xenon on the peripheral vascular resistance or cardiac inotropy –28. IsofThere is still no consensus regarding the lowest acceptable absolute or relative intraoperative blood pressure threshold and its tolerable maximum duration , 12. TheSeveral confounders on the patients’ haemodynamics were analysed in detail and showed no difference in their appearance between the groups. Hypovolaemia is known to be an important additional cause for postoperative renal failure , 4; howeThe usually applied lateral position of the patient during open partial nephrectomy might induce haemodynamic and respiratory changes, but there were no differences regarding the positioning. The anaesthetics exposure times, and the surgical technique, duration and team were similar in our study.Renal hypoperfusion is known to activate the renin-angiotensin-aldosterone system (RAAS) with a consecutive sympathetic response . About hThis secondary analysis included all enrolled patients, irrespective of a successful conduction of the partial nephrectomy. Even though there were no statistical differences between the groups regarding the pathological results, there was a difference in the number of patients with an unexpected total nephrectomy. The data on the effects of the unilateral nephrectomy on the levels of blood pressure and RAAS showed no difference before and after the nephrectomy . TherefoSince most of the anaesthetics are cardiodepressants, the anaesthesia depth might influence the intraoperative haemodynamics. In both groups, the anaesthesia was performed according to the SOPs. The MAC as well as the BIS values were in the recommended range, therefore a comparable anaesthesia depth could be expected. The higher blood pressure in the xenon group might indicate an insufficient analgesia, which induces sympathetic stimulation with tachycardia and hypertension. However, the tendency for lower heart rates argues against this postulation. The analgesic properties of xenon are controversial . Xenon mThe heart rate is one further important factor on the haemodynamic stability. Though not significant, we confirmed the observations of more pronounced intraoperative heart rate decrease with xenon , 43–45. What renders our study novel, however, is that we used xenon in a partial nephrectomy setting and had already predefined this secondary analysis. Therefore, we could analyse the prospectively collected data for all patients and we possessed clearly documented baseline blood pressure values. This enabled us to quantify the haemodynamic stability directly via calculation of the cumulative times below different blood pressure thresholds as well as individual relative blood pressure drops from baseline. This is in contrast to other studies, which have only indirectly analysed the haemodynamics via the catecholamine consumption as a surrogate indicator , 47.First, the blood pressure was not measured by invasive methods but non-invasively every five minutes, which likely had an influence on our results .Second, the attending anaesthetists could not be blinded for safety reasons. Due to the nature of our study, norepinephrine was applied for hypotensive therapy after an inadequate respond to fluid administration, according to the clinical routine in our hospital. The anaesthetists had to adhere to our SOPs for partial nephrectomy. Nevertheless, it might reflect a “real world” situation , that thmaximum postoperative GFR decrease. It was not powered to analyse the blood pressure differences.Third, this study was a secondary analysis of a prospective trial with the primary outcome Fourth, it may be questionable whether the reduced need for vasopressors and more stable intraoperative haemodynamic with xenon represents a better preservation of renal function apart from facilitating the haemodynamic management. The PaNeX study could only show a tendency to better postoperative renal function with xenon . The undWe acknowledge several limitations in this secondary analysis:The patients undergoing partial nephrectomy under xenon anaesthesia presented a more stable haemodynamic profile, with a significantly lesser need for norepinephrine than those under isoflurane anaesthesia. The tendency of a better-preserved renal function after partial nephrectomy under xenon anaesthesia might be explained by a better renal perfusion.Additional file 1:aP-values were derived using Fisher’s exact test  or the Mann-Whitney U-test (quantitative data). The data are presented as median (interquartile range) or number (proportion). ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; IDDM, insulin dependent diabetes mellitus; n, number; NIDDM, non-insulin dependent diabetes mellitus; NYHA, New York Heart Association; PAOD, peripheral artery occlusive disease. (DOCX 94 kb)Patients’ baseline characteristics. Modified table according to . aP-valuAdditional file 2:aP-values were derived using Fisher’s exact test  or the Mann-Whitney U-test (quantitative data). The data are presented as median (interquartile range) or number and percentage. AKIN, Acute Kidney Injury Network; GFR, Glomerular filtration rate; Min, minutes; n, number; PBRC, packed red blood cells; y/n, yes/ no. (DOCX 22 kb)Important outcomes. Modified previously published data . aP-valu


The ASTRAL trial showed no difference in clinical outcomes between medical therapy and revascularization for atherosclerotic renal vascular disease (ARVD). Here we report a sub-study using echocardiography to assess differences in cardiac structure and function at 12 months.ASTRAL patients from 7 participating centres underwent echocardiography at baseline and 12 months after randomisation. Changes in left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left atrial diameter (LAD), aortic root diameter (AoRD), E:A, and E deceleration time (EDT) were compared between study arms. Analyses were performed using t-tests and multivariate linear regression.p = 0.05), δLVM − 2.9 ± 33 versus − 1.7 ± 39 g (p = 0.9), δLAD 0.1 ± 0.4 versus 0.01 ± 0.5 cm (p = 0.3), δAoRD 0.002 ± 0.3 versus 0.06 ± 0.3 cm (p = 0.4), δE:A − 0.0005 ± 0.6 versus 0.03 ± 0.7 (p = 0.8), δEDT − 1.1 ± 55.5 versus − 9.0 ± 70.2 ms (p = 0.6). In multivariate models, there were no differences between treatment groups for any parameter at 12 months. Likewise, change in blood pressure did not differ between arms .Ninety two patients were included . There was no difference between arms in any baseline echocardiographic parameter. Comparisons of longitudinal changes in echocardiographic measurements were: δLVEF medical 0.8 ± 8.7% versus revascularization − 2.8 ± 6.8% (This sub-study did not show any significant differences in cardiac structure and function accompanying renal revascularization in ASTRAL. Limitations include the small sample size, the relative insensitivity of echocardiography, and the fact that a large proportion of ASTRAL patient population had only modest renal artery stenosis as described in the main study. The presence of atherosclerotic renovascular disease (ARVD) in patients with chronic kidney disease (CKD) presents an increased risk of cardiovascular morbidity compared to other causes of CKD. ARVD is typically associated with extensive extra-renal atherosclerosis and significant cardiovascular comorbidities; 91% of ARVD patients have hypertension, 38% have clinical heart failure, and 67% have coronary artery disease .As a result of these overlapping cardiovascular risk factors, cardiac structural remodelling is almost ubiquitous in ARVD. At least three-quarters of ARVD patients have left ventricular hypertrophy and diastolic dysfunction on echocardiography . PatientTwo large clinical trials failed to show clinical benefit of renal artery revascularization when used as first line therapy for ARVD. The primary outcome measure of the ASTRAL  trial was longitudinal change in renal function, while that of the CORAL  trial was a composite of death or major morbidity from cardiovascular or renal causes , 6.Although revascularization does not benefit most patients, there are many documented cases of significant clinical and cardiac structural changes soon after intervention , 8. ThesFlash pulmonary oedema is however the presenting feature in only 12% of cases of ARVD , meaningHere we present findings from an echocardiographic sub-study of the ASTRAL trial. The primary aim of this study was to evaluate whether the addition of renal artery revascularization to standard medical therapy led to improvements in the cardiac structural and functional abnormalities associated with ARVD, as found on echocardiography, compared to standard medical therapy alone. A secondary aim was to quantitatively describe the natural progression of cardiac abnormalities in an ARVD cohort, irrespective of therapy, and specifically in patients for whom revascularization is not already indicated.. Ethical approval for ASTRAL was granted by the West Midlands Multicentre Research Ethics Committee, UK and the ethics committee relevant to each individual participating study centre. Ethical permission for the echocardiographic sub-study was obtained separately. Support for the main ASTRAL trial was received from the Medical Research Council UK, Kidney Research UK, and Medtronic.The detailed method of patient selection and intervention for ASTRAL has previously been published . In summPatients were eligible for ASTRAL if they had at least one renal artery with an atherosclerotic lesion suitable for percutaneous revascularization and their managing clinician was not convinced that revascularization was essential. Patients were excluded if revascularization was already indicated as per guidelines, if the patient had undergone previous revascularization, or if the stenosis was not atherosclerotic in origin. No patients on haemodialysis were entered into the study, and because flash pulmonary oedema is a long-standing agreed indication for revascularization in ARVD, such patients were not recruited to ASTRAL.Patients from 7 centres participating in ASTRAL were approached to take part in this cardiac sub-study . Patients were randomised 1:1 into the ASTRAL study to either revascularization or no revascularization, and this also determined the randomised treatment allocation of patients in the sub-study. No specific exclusion criteria were applied to the echocardiographic sub-study, and every patient provided signed informed consent.Patients underwent a full cross-sectional transthoracic echocardiogram within 6 weeks of enrolment and, if randomised to revascularization, before they underwent the procedure. A second transthoracic echocardiography was obtained 1 year later. Scans were performed locally at each participating centre by technicians accredited for transthoracic echocardiography by the British Society for Echocardiography. Interpretation was performed by a single imaging consultant cardiologist blind to the date of each scan and the participant’s randomised treatment allocation.All image acquisitions and measurements were performed as recommended by the American Society of Echocardiography  and haveSample size calculation was based on left ventricular end diastolic diameter (LVEDD), one of the more sensitive parameters of change in cardiac function over time, or after intervention, and based upon change in LVEDD in a previous study of 79 ARVD patients (mean LVEDD 5.37 ± 0.95 cm). To detect a 0.6 cm (SD 0.95) difference between revascularization and control groups at a power of 80%, 41 patients would be needed for each group with an alpha of 0.05. At 90% power, patient numbers would be 54 per group.p-value of < 0.05 was considered statistically significant. All analyses were performed using SAS version 9.1 .The main end-points were change from baseline to follow up in each of the echocardiographic parameters listed above. The two treatment groups of medical therapy alone and medical therapy plus revascularization were compared using 2-sample t-tests. Multivariate linear regression models were then constructed to consider the effects of other pre-specified clinically relevant baseline variables on each of the echocardiographic parameters at 12 months. Alongside treatment group, the following variables were included in each model: age, presence of diabetes, history of coronary heart disease, systolic blood pressure, diastolic blood pressure, degree of stenosis to most affected kidney, renal function using eGFR, prescription of beta-blockers and renin angiotensin blockade and baseline ventricular measurement. A p = 0.9). There was no difference in baseline eGFR, calculated using the Cockroft-Gault equation: 43.0 (17.0–79.7) ml/min versus 44.7 (15.4–89.8) ml/min (p = 0.65). Similarly, there was no difference in systolic blood pressure: 152 (90–220) mmHg versus 146 (103–196) mmHg (p = 0.36). A full comparison of baseline characteristics is found in Table p = 0.04). However, serum cholesterol was no different: 4.5 (2.8–7.9) mmol/L versus 4.3 (2.3–6.5) mmol/L, p = 0.43.There were 92 patients included in the study . The two arms were broadly comparable: the age in the medical arm was 71 years (range 51–86) compared with 70 (53–86) years in the revascularization arm (p = 0.05).The baseline echocardiographic measurements were all comparable between groups, with none showing a statistically significant difference. Systolic function was well preserved overall (54 ± 10%). The complete list of baseline echocardiographic variables is found in Table p = 0.60). For diastolic blood pressure, the respective changes were 0 (− 27 to + 80) mmHg versus − 4 (− 41 to + 20) mmHg (p = 0.27).Importantly, allied to this, there was no change in blood pressure between arms during follow up. In the medical arm, the mean systolic blood pressure change during follow up was 0 mmHg (range − 56 to + 54 mmHg). This compared with a mean change of − 3 (− 61 to + 59) mmHg in the revascularization arm , for left atrial diameter was − 1.1 cm to + 1.4 cm (median 0 cm), for LVEDD was − 0.9 cm to + 1.0 cm (median − 0.1 cm), and for LV mass was -101 g to + 129 g (median 0 g).When comparing all follow up scans with all baseline scans, there was no overall significant difference between any individual parameter using paired t-test: LVEF baseline = 54 ± 10% versus LVEF at follow up = 53 ± 9%, p < 0.01.Figure p = 0.01). The distribution was parametric.In a between group comparison of dLVEF between those with preserved baseline LVEF (≥50% versus those with reduced LVEF (< 50%) at baseline, the mean change in the preserved function group was − 2.4 ± 6.4 mL versus + 5.2 ± 10.5 mL in the reduced function group  at baseline showed an improvement in diameter at follow up. The figure for baseline normal left atrium was 25%. For change in left atrial diameter against baseline reading, the correlation coefficient was − 0.16, p = 0.201).In a between group comparison of change in left atrial diameter between those with normal baseline diameter (< 4.0 cm) versus those with increased diameter (≥4.0 cm), the mean change in the normal group was + 0.1 ± 0.4 cm versus 0.0 ± 0.5 cm in the dilated group (p = 0.61) and CORAL [p = 0.58).This sub-study of a randomised clinical trial included 92 patients with ARVD and did not show any difference in longitudinal change in echocardiographic parameters between patients treated with renal artery revascularization versus those given medical therapy alone. This is consistent with the cardiovascular end point findings of the main ASTRAL  (hazard p = 0.8) [2 and well-controlled blood pressure; patients in both arms were established on multi-targeted medical therapy. Revascularization was shown to have no additional impact on cardiac structure and blood pressure control beyond optimal medical therapy. However, there was again significant equivalent improvement in blood pressure control and LVMI in both revascularized (n = 43) and non-revascularized patients (n = 41) [Our findings are consistent with two other randomised clinical trials. A recent parallel ASTRAL sub-study investigated the effects of revascularization on cardiac structure and function using cardiac magnetic resonance imaging in 18 patients treated exclusively medically and 23 patients who underwent revascularization in addition to treatment with medical therapy. Although slight improvements in cardiac structural parameters were seen in both groups at 12 months follow-up, there were no significant differences between groups  . The steIn contrast, in our study there was no overall difference in parameters at follow up compared to baseline. Previous small non-randomised studies had demonstrated improvement in left ventricular mass in patients with renovascular hypertension or haemodynamically significant stenosis. In two of these studies, this was shown to correlate with improvement in blood pressure control , 20. In Although a lack of longitudinal improvement was noted in this study, which differs from the results of ASTRAL cardiac magnetic resonance imaging sub-study and RAS-CAD , 18, thiIn view of the lack of measurable longitudinal changes observed in our study, we support the current view that optimised medical therapy is as effective as revascularization for routine ARVD therapy, except in those patients for whom revascularization is already indicated. Indeed, in the current study we provided examples of patients who showed definite improvement or stabilisation in echocardiographic parameters at 1 year, and likewise some with evidence of deterioration and this is of clinical importance. This comment is made notwithstanding the possibility that the longitudinal changes seen represent regression to the mean in a population with a broad baseline measurement in echocardiographic descriptors.Our results suggest a weak inverse correlation between baseline function and improvement at 1 year, in keeping with results from observational studies showing that revascularization only appears to be of benefit in a small subset of ‘high-risk’ patients , 21, 22.p = 0.02) and nonfatal cardiovascular events  [In our study, beta-blockade was associated with reduction in aortic root diameter. In light of the predominance of diastolic dysfunction in patients with ARVD , this is= 0.003) .In the context of non-ARVD patients with hypertension and diastolic dysfunction without a clinical diagnosis of heart failure, angiotensin-receptor blockers have been shown to reduce left ventricular mass and function and improve exercise tolerance; the changes in RWT observed in this study did not mirror this –30, but This study has limitations. Due to the slightly lower than expected number of patients, the study had 80%, rather than 90%, power to detect differences of the anticipated magnitude. Finally, as mentioned above, an important consideration is that some patients recruited into this study may have had clinical and haemodynamically insignificant RAS and so these results are not necessarily generalizable to all patients with ARVD, particularly those with severe renal artery stenosis presenting with heart failure and other high-risk clinical phenotypes .In this ASTRAL sub-study, there was no significant difference in longitudinal change in echocardiographic parameters between revascularized and non-revascularized patients, nor between baseline and follow-up scans in the study population as a whole. These results are consistent with the neutral renal, cardiovascular and mortality end-points observed in the main ASTRAL trial and in the subsequent CORAL trial.


CD36 is associated with regulation of lipid metabolism, atherosclerosis, and blood pressure. Moreover, its variation may be involved in the development of hypertension and/or coronary artery disease (CAD). The present study was conducted to investigate the possible association of CD36 rs1761667 (G > A) polymorphism with hypertension and/or CAD in the southeastern of Iran.n = 52); 2) hypertensive with CAD ; 3) CAD without hypertension ; and 4) non-hypertensive without CAD as the control group . The CD36 rs1761667 polymorphism was genotyped with PCR-RFLP method. Association between CD36 rs1761667 genotypes and the risk of CAD and hypertension was assessed using multinomial regression by adjusting for age, sex, creatinine, fasting blood sugar (FBS), systolic blood pressure (SBP) and diastolic blood pressure (DBP).The present observational study was composed of 238 subjects who were admitted for coronary angiography, and divided into four groups: 1) hypertensive without CAD . Furthermore, using a recessive inheritance model CD36 rs1761667 polymorphism was significantly associated with an increased risk of CAD with hypertension . However, using the dominant model of CD36 rs1761667 had a protective effect on H-Tens and CAD patients.In the present study, minor allele (A) frequency was 0.36. The genotype, but not allele frequency of the CD36 rs1761667 was significantly different between the four study groups (The present findings revealed an association between CD36 rs1761667 polymorphism and susceptibility to hypertension and/or CAD in a southeastern Iranian population. Cardiovascular disease (CVD) is one of the most important threats to human life around the world, and includes sub-categories such as coronary artery disease (CAD), acute coronary syndrome (ACS) and ischemic cardiomyopathy . CAD is CD36, a transmembrane glycoprotein, is a member of class B scavenger receptor family. In addition to monocytes and macrophages, it is expressed in a number of other cells, such as adipocytes, endothelial cells, and platelets. Multiple ligands are attached to this receptor and CD36 participates in many biological processes .Recently, various studies have revealed results about the relationship between CD36 gene polymorphisms and obesity on the one hand and CD36 gene polymorphisms, hypertension, and CVDs on the other. The CD36 gene with 32 kb is located on the chromosome 7 q11.2) and contains 15 exons . SNP rs1.2 and coIt is believed that CD36 polymorphisms confer susceptibility for hypertension and/or CAD due to the roles of CD36 in the regulation of lipid metabolism, atherosclerosis, and blood pressure , 15, 16.Therefore, the present study was conducted aiming to evaluate the CD36 rs1761667 polymorphism in patients with CAD and hypertension in a southeastern Iranian population.n = 52); 2) hypertensive with CAD ; 3) CAD without hypertension ; and 4) non-hypertensive without CAD as the control group  . Subject selection process was conducted as described elsewhere –19. BrieDeclaration of Helsinki regarding research involving human subjects and was approved by the Ethics Committee of Kerman University of Medical Sciences, Kerman, Iran (IR.KMU.REC.1395.261).This study conforms to the 2). Blood pressure was also measured from the right arm using an automatic sphygmomanometer during supine rest with 10-min intervals, and an average number of three blood pressure measurements were used. The criteria for occurrence of hypertension were as follow: a systolic blood pressure (SBP) ≥ 140 mmHg, a diastolic blood pressure (DBP) ≥ 90 mmHg and receiving antihypertensive medication.Interviews were conducted to gather demographic data from all participants, each of whom provided an approximate amount of 10 ml of blood, of which 5 ml was collected into vacutainer tubes containing EDTA (for DNA extraction) and 5 ml into vacutainer tubes without anti-coagulation agent. The samples were stored at room temperature and then centrifuged for serum separation. The serum samples were aliquoted and frozen at − 20 °C to be used for subsequent experiments. Fasting blood sugar (FBS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), sodium (Na), potassium (K), creatinine (Cr), and urea were determined using commercially available kits . BMI was calculated as weight divided by the square of height . It was then frozen at − 70 °C to be used for subsequent experiments. Genotypes of CD36-rs1761667 polymorphism were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method as described below.HhaI restriction endonuclease  at 37 °C for 16 h and fragments were separated by agarose gel electrophoresis (1.5% agarose) stained with ethidium bromide. Afterwards, being observed by ultraviolet light (UV Tec Cambridge Gel doc), three genotypes of CD36-rs1761667 were detected which include: GG (161 and 264 bp), GA , and AA (425 bp).The SNP was detected by PCR using following primers: 5′- CAAGGTCTGGTATCCACCTGTT − 3′ (forward), 5′- ATGAAGCTTCCCGCCTTAGAA − 3′ (reverse) and amplification was carried out using a Biometra T advanced . PCR conditions were as follows: initial denaturation at 95 °C for 5 min, followed by 35 cycles of amplification including denaturation at 95 °C, annealing at 60 °C, extension at 72 °C (each comprising 30 s), and the final extension at 72 °C for 5 min. PCR products (10 μl) were digested with p-values less than 0.05 were considered to be statistically significant. Raw p-values are reported and no correction for multiple testing was applied. Power analysis was performed using the Power and Sample Size Calculation G* Power software (version 3.1.9.2). In the post hoc power analysis, 1-beta (power) computed as a function of alpha  and the sample size(s) used in the study. The significant level was considered as 0.05.All continuous and categorical variables were expressed, respectively, in the form of mean ± standard deviation (M ± SD) and counts (percentages). The differences among groups were assessed using one-way analysis of variance (ANOVA)/Kruskal-Wallis with post-hoc Tukey/Mann-Whitney U-tests as well as Chi-square/Fisher’s exact tests. Deviation from the Hardy-Weinberg equilibrium (HWE) was tested by the Chi-square test. To examine the independent roles that the genotypes play against hypertension and CAD risk, multinomial logistic regression was carried out. The statistical analyses were performed using SPSS software version 23.0 for Windows . The p < 0.001, p = 0.012, p = 0.002, and p = 0.017, respectively). However, with regard to other factors, no significant difference was found between the four study groups. In order to eliminate the effects of confounders such as age and sex, as well as adjusting for the baseline values of the desired variables , these variables were included in regression model.Demographic and biochemical parameters of all participants are presented in Table p = 0.003). Additionally, regarding the genotype frequency of CD36 rs1761667, significant differences were observed between H-Tens and Ctrl groups (p = 0.001). Likewise, the CAD + H-Tens group showed a significant difference in the genotype distribution compared with H-Tens patients and Ctrl groups . Moreover, H-Tens patients were shown to have a significantly lower A allele frequency compared to CAD + H-Tens and Ctrl subjects . However, there were no significant differences regarding alleles between the other groups . The genotypic frequencies in control group were in accordance with HWE and other groups were not in equilibrium (P = 0.005) . Furthermore, significantly lower levels of Na and K were found in GG genotype of CD36 rs1761667 between CAD patients as compared to GA . However, regarding demographic and laboratory factors, no significant differences were observed between CD36 rs1761667 genotypes in Ctrl subjects .Table p = 0.043). However, the dominant inheritance model ((GA + AA) vs. (GG)) of CD36 rs1761667 demonstrated a protective effect among H-Tens and CAD patients .Results obtained from the multinomial regression model are presented in Table p = 0.05).According to power calculations, the sample size provided a 94% power   and healIt has been demonstrated that CD36 binds to fatty acids and is involved in the lipid metabolism . GenotypIt is noteworthy that even though the role of CD36 in multiple diseases has been revealed, it is the first study which sought to examine the genetic variation of CD36 in association with CAD and/or hypertension susceptibility.A number of limitations should be considered when interpreting the current results which included the fact that it was difficult and time-consuming to select the H-Tens group, and hypertensive subjects without any critical coronary vessel stenosis. That is, one of the significant restrictions of the study included selection of non-CAD hypertensive patients as all the CAD hypertensive ones were subjected to coronary angiography, thus presenting a challenging and difficult task to choose hypertensive patients without any critical coronary vessel stenosis. Therefore, the sample size in this study is small. Moreover, the population of the study was restricted to southeastern Iran and, additionally, the study was a hospital-based observational study, as a result of which the findings could not be generalized to other racial/ethnic groups in other parts of the globe. Although diastolic blood pressure was higher in the control group compared to the hypertensive group, this difference was not statistically significant. Furthermore, the findings were adjusted using multinomial regression model to account for cofounders and no correction for multiple testing was done, moreover, only control genotypes were in HWE and one SNP was studied. In order to eliminate the effects of confounders such as age and sex, as well as adjusting for the baseline values of the desired variables , these variables were included in regression model.The present study presented the first evidence which suggests that CD36 rs1761667 gene polymorphism might be a factor predisposing to hypertension and CAD in a southeastern Iranian population. It should be noted that the results need confirmation in further, more conclusive, and prospective studies incorporating a wide range of ethnicities with a gene expression and functional assay in the future.


Few reports of lupus nephritis (LN) from Jordan and the Middle East exist. This study assessed the demographic, clinical, and basic laboratory characteristics of Jordanian patients with LN and correlations with the histological class of LN. This was a retrospective study of all patients who underwent kidney biopsy between 2007 and 2018 at a tertiary medical center in Jordan. Patients' demographic, clinical, laboratory, and pathological data were reviewed. In total, 79 patients were included in this study . Asymptomatic proteinuria and hematuria were the most common presentations in LN patients at biopsy (59.5%). The study revealed a significant difference in frequency of nephritic syndrome (p= 0.01) between sexes . Class IV was the most common pathological class of LN [37 (46.8%)], followed by class V [15 (19%)] and class III [10 (12.7%)]. Post hoc analysis of the associations between laboratory values and histopathological patterns revealed a significant correlation between class IV lupus and renal failure (p= 0.018) and class IV lupus and anti-DNA antibodies p= 0.030). End-stage renal disease (ESRD) occurred in 25% of lupus nephritis cases. There was an increased likelihood of ESRD among men than women (45% vs. 22%). Overall mortality was 10%. Although some clinical and laboratory findings correlate with histological types of LN, clinical and laboratory parameters of Jordanian patients with LN are not predictive of the histological type, although differences with regional studies were noted. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with variable clinical manifestations. Lupus nephritis (LN) is one of the most common and serious manifestations of SLE , occurriIn Jordan, LN is the most common biopsy-proven secondary glomerulonephritis (GN), accounting for 69% of total secondary GN cases , and it This study aimed to assess the demographic, clinical, and basic laboratory data of Jordanian patients with LN and correlations with the histological class of LN according to the ISN/RPS 2003 classification. Overall outcomes of SLE patients with LN in Jordan were documented. In addition, data from this study was compared with those from neighboring countries.This retrospective study was approved by the institutional review board (IRB) of the Jordan University Hospital and was conducted in accordance with the latest update of the Helsinki Declaration. Diagnosis of SLE was based on the American College of Rheumatology (ACR) classification criteria for SLE . The pat2). Indications for kidney biopsy were nephrotic syndrome, nephritic syndrome, asymptomatic hematuria (defined as >5 RBCs per field), asymptomatic proteinuria (>500 mg/day), the presence or absence of other clinical abnormalities or any level of proteinuria or hematuria, and impaired kidney function that could not be attributed to another cause.The data collected included baseline clinical characteristics at time of biopsy: age, sex, duration of lupus, presence of hypertension (blood pressure >140/90 mmHg), presence of renal failure (according to Acute Kidney Injury Network (AKIN) serum creatinine criteria) , and preNephrotic syndrome is defined as nephrotic-range proteinuria with a low serum albumin level and edema. Nephritic syndrome is defined with 30% increase in the serum creatinine level from baseline with elevated blood pressure.Baseline laboratory findings were recorded, including urine analysis and 24-hour urine collection of protein or spot urine protein, to determine the urine: creatinine ratio as an evaluation of the degree of proteinuria. Other laboratory data collected included serum hemoglobin (HB); serum creatinine levels (g/dl); immunological marker levels, including anti-nuclear antibodies (ANA) (positive > 1:40) detected by indirect immunofluorescence test (IIFT) on Hep-2 cell; anti-double stranded DNA (positive at >1:20 detected by immunofluorescence assay (IFA)); serum complements C3 ( <0.9 g/l was considered low ) and C4 ( <0.1 g/l was considered low); serum albumin levels (g/dl); and serum erythrocyte sedimentation rate (ESR) (mm/hour). Anemia was defined as Hb less than 12 g/dl in females and less than 13.5 g/dl in males. All laboratory results and immunological markers were obtained at the time of kidney biopsy.All statistical analyses were performed using SPSS version 21.0 . Continuous variables  were presented as mean (± standard deviation), and other nominal variables  were presented as number (frequency).One-way ANOVA followed by Tukey's post hoc test was used to analyze the difference in histopathological type and the following continuous variables: age, SLE duration, albumin level, ESR, and Hb.We also used independent-sample t-tests to analyze the mean gender differences and continues variables. Data are presented as a mean [95% confidence interval (CI)]. p-value of <0.05 was considered statistically significant.We used the chi-square test to analyze sex versus the following dichotomous variables: frequency of nephritic syndrome, nephrotic syndrome, proteinuria, hematuria, hypertension, C3 and C4 complements level , ANA (positive and negative), Hb and ESR, in addition to end-stage renal disease (ESRD), or death. The above variables were also tested against histopathology type, using the chi-square test followed by the Z-test for proportions. All underlying assumptions were met, unless otherwise indicated. AA total of 79 patients were included in this study [mean age 29.95 years (±12.16)]. They included 11 men (13.9%), mean age 28.18 years (±13.88), and 68 women (86.1%), mean age 30.24 years (±11.95). The female-to-male ratio was approximately 6:1. Asymptomatic proteinuria and hematuria were the most common presentations in LN patients (59.5%) at time of kidney biopsy, followed by nephritic syndrome (22.8%) and nephrotic syndrome (17.7%) as shown in μl of blood and 6% of the cases were found to involve thrombocytopenia with a platelet count <140000/μl of blood. The mean white blood cell (WBC) count was 7700 cells/μl of blood at time of biopsy and 6.3% of cases were found to involve leukopenia at this point, with a WBC count <4000 cells/μl of blood.The mean platelet count at time of kidney biopsy was 277,000/ The most common histopathological type of LN in this study, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, was class IV [37 (46.8%)], followed by class V  anThe average time from development of systemic lupus to diagnosis of LN was 25.47±20.7 months. This short duration may explain the early lupus nephritis presentation in SLE patients as 75.9% of cases are identified in the first 5 years of disease. In this study, 90% of patients who developed ESRD developed renal involvement within 2 years of SLE diagnosis. As reported in previous studies, early presentation of LN in the SLE course is correlated with poor outcomes .The most common indication for kidney biopsy in this study was the presence of proteinuria and hematuria (representing around 60% of the sample). These findings could support the general clinical practices of nephrologists and rheumatologists with respect to performing kidney biopsy in asymptomatic SLE patients. The prevalence of a nephrotic range of proteinuria in our cohort was approximately 34.2%, which is more than that reported in neighboring countries such as Saudi Arabia (20.6%)  and lessWe noticed a significant sex difference in the frequency of nephritis (p= 0.01), which was higher in male than in female patients, and renal outcomes, which were worse in male than in female patients (45% vs. 22% developed ESRD); however, this was not statically significant. This is consistent with results of previous reports in which increased disease severity is more often observed in male rather than in female SLE patients .In this study, only 40.5% of cases with biopsy-proven LN patients had anti-DNA positivity, which differs from previous reports, suggesting that the correlation between renal involvement and anti-DNA levels could reach 90% . We founIn this study, class IV was the most frequent histological type, representing approximately 46.8% of the total cases, similar to levels reported in Jordan by Mustafa et al. (60%) and observed in countries including Lebanon (38%) , Saudi AWe found there is a correlation between some clinical and laboratory findings, including renal failure, anti-DNA positivity, and class IV lupus. This can aid in prediction of the pathological pattern and in initiation of treatment. However, we could not find a correlation between other demographic, clinical, and laboratory findings and histopathological type.In this study, 25% of patients developed ESRD and 80% had class IV lupus. This was higher than the expected risk of ESRD, which is 10% in 10 years . This reThe limitations of this study are as follows: first, although this study was performed in a tertiary referral center, it remains a single-center design. Second, the small sample size made the correlation of clinical and laboratory data with histopathological type difficult. The presence of different clinical and laboratory characteristics among our population and the poor renal outcomes emphasize the need to establish a registry and to conduct research allowing a more comprehensive interpretation of our results among different patients in order to understand the risk factors and pathogenesis of LN in our geographical area.In this study, the correlations of clinical manifestations and laboratory findings with histopathologic types of LN in Jordanian patients were analyzed for the first time. We found that some demographic, clinical, and laboratory findings were different from those in previous studies of LN in the same geographical area. This study revealed correlations between clinical and laboratory findings and histopathological type. This correlation may help determine the clinical and pathologic conditions of the patient, the prognosis, and the need for immediate immunosuppressive treatment. We believe that clinical manifestations and laboratory results are helpful in the prognosis and prediction of clinical course but cannot definitively determine renal histopathology; therefore renal biopsy remains the cornerstone for identifying treatment options for LN patients. This study provides more information about LN in Jordan and future clinical research is recommended.


Secondary hyperparathyroidism (SHPT) is a manifestation of chronic kidney disease mineral bone disorder (CKD-MBD). SHPT is common in patients with chronic kidney disease (CKD) and is associated with significant morbidity and mortality.A cross- sectional descriptive study involving 230 patients with CKD.2/l2 and 9.90±1.87g/dl respectively. Majority of patients had advanced CKD with 70.3% of patients in stage G5. The prevalence rates of SHPT, hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were 55.2%, 34.8%, 66.1%, 42.2% and 25.2% respectively.The mean age of the study population was 44.17±15.24 years. The median intact parathyroid hormone and alkaline phosphatase levels were 96pg/ml (range 4–953pg/ml) and 88 iu/l (range 10–800 iu/l) respectively. The mean (with standard deviation) calcium, serum phosphate, calcium phosphate product and haemoglobin levels were 2.22±0.29mmol/l, 1.8±0.62mmol/l, 3.94±1.42mmolUnivariate analysis revealed that SHPT was associated with hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase, proteinuria, anaemia, hypertension, left ventricular hypertrophy and stage of kidney disease; being worse with advancing kidney disease. Independently associated with SHPT were hypocalcaemia (OR=4.84), hyperphosphataemia (OR=3.06), and elevated alkaline phosphatase (OR=2.04).The prevalence of SHPT in CKD is high, occurs early and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase. The prevalence of SHPT also increases with worsening renal function. Chronic kidney disease (CKD) affects between 5 to 10% of the population worldwide and is associated with significant morbidity and mortality mainly from cardiovascular causesSHPT occurs in 28.9% of CKD patients in the Philippines, 45% in Iranian patients and 55% of American patientsIn this study, we hypothesise that SHPT is rare among Nigerians with CKD. We describe the prevalence of SHPT and its clinical correlates in a cross-sectional study involving CKD patients presenting in a teaching hospital in North Central Nigeria.This was a hospital based cross- sectional descriptive study, conducted between August 2011 and September 2012. It was carried out in the Nephrology and Hypertension Clinic and medical wards of the Jos University Teaching Hospital (JUTH).Patients 18 years and above attending the Nephrology and Hypertension Clinic or who were admitted into the medical wards of JUTH and confirmed to have CKD were recruited using convenience sampling technique. CKD patients already on treatment for SHPT as well as pregnant CKD patients were excluded from the study.Demographic and clinical data were entered into a case report form. Information obtained included age, sex, weight, height, aetiology of CKD, history of body weakness, pruritus, and bone tenderness. Height and Weight were measured in metres and kilograms using a stadiometer and weighing scale with patients in light clothing, without head gears and without shoes. Body mass index (BMI) was calculated using the Quetelet indexBlood samples were obtained from the forearm vein of each subject for intact parathyroid hormone (iPTH), haemoglobin, serum creatinine, albumin, calcium, phosphate, alkaline phosphatase. In addition, a 12 lead electrocardiograph tracing, abdominal ultrasonography for renal sizes, as well as spot urine protein creatinine ratio determination was performed on all patients. Estimated glomerular filtration rate (eGFR) was calculated for each patient using the chronic kidney disease-epidemiology collaboration (CKD-EPI) formulaEnzyme linked immunosorbent assay (ELISA) kits  were used for the determination of biologically active intact 84 amino acid chain of PTH. In this reaction, iPTH binds to a polyclonal antibody that has been labelled with an indicator and binds only to the biologically active 84 amino chain of PTH. The colour change by the indicator is proportional to the concentration of iPTH with absorbance read at 405nM. Concentrations of iPTH are obtained using a dose response curve of absorbance unit versus concentration.Biochemical analysis for the determination of serum calcium, phosphate, alkaline phosphatase, albumin, and serum lipids were all determined using an autoanalyser .In this study secondary hyperparathyroidism was defined as iPTH≥65pg/ml, hyperphosphataemia was defined as serum phosphate above 1.4mmol/l, hypocalcaemia was defined as corrected serum calcium level below 2.1mmol/l, elevated calcium and phosphate product (CaXP) was defined as values greater than 4.5mmolThe human research and ethics committee of the Jos University Teaching Hospital (JUTH) approved the study. All patients gave informed consent before recruitment. Data was anonymised by removing all patient identifiers. Data was kept safe until analysis.Epi - Info version 3.5.4 (CDC Atlanta USA) software was used for data analysis. Continuous variables with normal distribution were expressed as means ± SD while variables not normally distributed were expressed as median with ranges. Categorical variables were expressed as frequencies and percentages. Chi-square test was used to determine significance of association between categorical variables. Fisher exact test was used when there were less than 5 observations. Student's t- test was used to compare means. Multivariate analysis was used to identify variables independently associated with hyperparathyroidism. In this case, variables with a p value of <0.25 on univariate analysis were entered into a multiple logistic regression model to determine their independent association with secondary hyperparathyroidism with backward elimination done to adjust for confounders. The use of p <0.25 is based on documented findings that the use of p<0.05 often fails to identify all variables known to be importantA total of 230 CKD patients were enrolled for the study, one hundred and twenty six of these patients (54.8%) were males while one hundred and four patients (45.2%) were females with a male to female ratio of 1.2:1. The mean age of the study population was 44± 15 years. All patients were Black. Majority of these patients (33.5%) had hypertension as the primary cause of renal disease, followed by 30.9% with chronic glomerulonephritis and 17% with diabetes mellitus .In addition, majority of the patients had advanced renal disease with 70.3% of them in CKD G5 and 16.1% in CKD G4 . The socThe various factors associated with SHPT on univariate analysis are as shown in The prevalence of SHPT among patients with CKD in Jos was found to be high and occurred in 55.2% of subjects studied. This study also found high prevalence rates of hyperphosphataemia, hypocalcaemia, elevated alkaline phosphatase and anaemia. This is similar to that of Bhan et al2. This is perhaps drawing attention to the fact that SHPT could possibly develop much earlier than GFR less than 60 ml/min/1.73mSHPT was also found to occur early with decreasing GFR levels and CKD categories. These findings are similar to those reported by Levin and colleaguesThis study found no association between parathyroid hormone levels on the one hand and clinical features of SHPT on the other. This could be because symptoms and signs of SHPT although common are non specific. In this study, the most common symptoms reported by the patients were body weakness, pruritus and bone pains with the least common feature being history of fractures; a similar picture was described by Seck et alThe prevalence of hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were all high in this study. These were all significantly associated with secondary hyperparathyroidism on univariate analysis. All of them, with the exception of elevated calcium phosphate product were independently associated with secondary hyperparathyroidism. This concurs with the finding of Sanusi et al7To our knowledge, this the largest study on SHPT in Nigeria, which has shown that SHPT is common among our CKD patients. This study also found no association between SHPT and its clinical features, thus stressing the need for the provision of facilities for the detection of SHPT, which often is not the case in resource limited settings like ours. Our study was limited by the inability to detect skeletal and extra skeletal manifestations of SHPT as well as novel biomarkers like FGF-23.SHPT is common in CKD patients in Jos, Nigeria and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase levels. It increases with worsening renal function and occurs as early as CKD stage G3a. SHPT is not associated with its clinical features, thus it is important that facilities for the determination of iPTH be made available for the early detection and management of SHPT.