To determine the effect of clothes on blood pressure measurement.One group pretest-posttest design was used in this study. The study consisted of 162 undergraduate students studying nursing and physiotherapy at a university in Ankara, Turkey. Blood pressure was measured over the sleeve and below a rolled-up sleeve with a mercury-filled column sphygmomanometer. All blood pressure measurements were performed on the right arm during morning hours by the same nurse. Each participant’s height, weight and clothing thickness were measured.p=0.222). The median diastolic blood pressure values were 69.56 mmHg over the sleeve and 69.59 mmHg below the rolled-up sleeve. There were no statistically significant differences between measurements taken over the sleeve and below a rolled-up sleeve (p=0.572).The mean age of the participants was 20.71. The median systolic blood pressure values were 110.07 mmHg over the sleeve and 110.37 mmHg below the rolled-up sleeve. There were no statistically significant differences between measurements taken over the sleeve and below a rolled-up sleeve (It was found that clothes have no statistically significant effect on systolic/diastolic blood pressure measurements. Measuring blood pressure over a sleeve may save time. Blood pressure measurement is one of the most common practices performed by health care professionals in everyday practice. Since blood pressure is 1 of the 4 vital signs, its accurate measurement is crucial. In order to make proper decisions regarding diagnosis and treatment, blood pressure measurement should be accurate. Tomlinson2We observed that health professionals generally measure the blood pressure below patients’ rolled-up sleeves. If tight sleeves cannot be rolled up, they commonly do not want to spend the time to remove patients’ clothes, so they measure blood pressure over the sleeve. Instead of examining whether measuring blood pressure over a sleeve is accurate, healthcare professionals often focus on completing the task. In various textbooks, bare arm measurement was reported as necessary but the reason why was not usually given.We searched Scopus, Medline and CINAHL databases with no date restrictions in English using search terms “blood pressure”, “clothes” and “sleeve”. Our review of the literature found several studies for the effect of clothes on blood pressure measurement. Each study included both male and female subjects. Most of these studies included normotensive and hypertensive patients; featured wide age, body mass index (BMI), and clothing thickness ranges; and used automatic sphygmomanometers.One group pretest-posttest design was used in this study. The inclusion criterion was to be young females at least 18 years of age. The exclusion criteria were subjects who: (1) had a diagnosis of hypertension, (2) had BMI≥30, (3) had ingested caffeinated beverages and cigarettes within 30 minutes before the blood pressure measurements and 4) had an empty bladder. These criteria of inclusion/exclusion were chosen due to the fact that blood pressure is affected by factors such as age, sex, BMI, smoking, caffeine intake, and body position. had an e19This study was conducted between February and May 2013 with a total number of 185 female undergraduate students studying nursing and physiotherapy at a university in Ankara, Turkey.The students were invited to participate in this study and168 students volunteered to take part in the study. We excluded six students who had BMI≥30. However, none of the participants had been previously diagnosed with hypertension. Consequently, 162 participants were included in this study .The data were collected at the university’s a professional skills laboratory. Each participant was interviewed about their health history. Each participant’s weight, height, and clothing thickness were measured and recorded in the morning. Blood pressure was measured in accordance with an international guideline.24The participants generally dressed in clothes such as shirts, blouses, and sweaters. They were seated for at least five minutes before measurement of blood pressure. They were instructed to lean back in the seat, place their feet on the ground, and position their right arm at heart level. The participants were requested to refrain from moving and talking during the blood pressure measurement.All blood pressure measurements were performed on the right arm during morning hours by the same nurse. Blood pressure was measured 2 times for each participant using the same sequence: over the sleeve and below a rolled-up sleeve. The nurse waited 2 minutes between measurements to allow adequate circulation to return.During the planning and execution of this study, it was reported in updated guidelines that the mercury-filled column sphygmomanometer is the gold standard for measurement of blood pressure.Each participant’s clothing thickness was measured using a skinfold caliper. Participants’ height and weight were measured using a measuring tape and weighing scale, respectively, after which BMI was calculated. Socio-demographic data were collected via a questionnaire including age, smoking status, chronic diseases, and medication usage.This study was approved by Fatih University Ethics Committee and conducted in compliance with the Declaration of Helsinki. The purpose and design of the study were explained to the students. Confidentiality and anonymity were guaranteed. Verbal information was given and written informed consent was obtained from all participants. Written permissions were obtained from the head of institutions.p<0.05.Data were analyzed using Statistical Package for Social Sciences version 16.0 software . Distribution normality was assessed using the Kolmogorov–Smirnov test, which revealed a skewed distribution. The differences among each participant’s two blood pressure measurements were analyzed using the Wilcoxon test. The Mann–Whitney U test was used to compare differences between blood pressure measurements and smoking status, chronic disease, or medication usage while the Kruskal–Wallis test was conducted to compare multiple groups (such as BMI and clothing thickness). Statistical significance was defined as All of the participants were Caucasian. The mean age of the students was 20.71 (SD=2.16) ranging from 18 to 36 years old. The mean BMI was 22.08 and the mean clothing thickness was 1.00 mm. The other characteristics of participants are summarized in p=0.222). The median diastolic blood pressure (DBP) values were 69.56 (SD=8.95) mmHg over the sleeve and 69.59 (SD=9.03) mmHg below the rolled-up sleeve. There were no statistically significant differences between measurements taken over the sleeve and below a rolled-up sleeve (p=0.572).The mean and standard deviation values of systolic–diastolic blood pressure measurements in two positions is shown in p>0.05).The effect of participants’ socio-demographic characteristics on SBP/DBP measurements for both over the sleeve and bellow a rolled-up sleeve are shown in In this study, the effect of clothes on blood pressure measurements was evaluated in normotensive female subjects with a mercury-filled column sphygmomanometer. No statistical differences were determined between SBP/DBP measurements taken over the sleeve and below a rolled-up sleeve. These data are supported by the findings of previous studies.12Ki et al.Thien et al.Liebl et al.The blood pressure measurement devices and positions as well as subject sexes, hypertension status, BMI, and clothing thicknesses differed between the current study and previous studies. However, despite these methodological differences, our results support those of previous studies regarding the effect of clothes on blood pressure measurements.This study has two limitations. First, the nurse who performed the blood pressure measurements was not blinded because of the nature of the study. Second, since the clothing thickness was not more than two mm, no comparisons can be made regarding the effect of thicker clothing on blood pressure measurement.No statistically significant effect of clothes on SBP/DBP measurements was found. As such blood pressure measurement can be taken without the patient removing their clothing or rolling up a sleeve. Additionally, there was no statistical difference detected between SBP/DBP measurements and participants’ smoking status, chronic disease, medication usage, BMI, or clothing thickness. Over-the-sleeve blood pressure measurements are recommended for normotensive female with clothing up to 2 mm thick. Since the thickness of clothing was 2 mm or less in this study, future studies should investigate whether or not thicker clothing has any effect on measurements.


The present study examined the temporal trends in the management of blood pressure, glucose, and lipid levels among middle-aged and elderly patients with type 2 diabetes using data from the Korean National Health and Nutrition Examination Survey (1998–2014). A total of 3,689 patients with diabetes were included and divided into middle-aged (30–64 years old) and elderly (≥65 years old) groups. Demographic and lifestyle data were obtained using a self-reported questionnaire, and trained medical staff obtained fasting blood samples and blood pressure data. Laboratory testing was performed to determine blood glucose, cholesterol, and triglyceride levels. In the multivariable adjusted models, significant decreasing trends in the prevalences of hyperglycemia and hypertension were observed in both age groups during 1998–2014, although no trends were observed for lipid levels. Based on the most recent survey, approximately 50% of patients with diabetes had hyperglycemia, and one-third of patients with diabetes and hypertension did not appropriately manage their blood pressure. In addition, 50% of the patients in both age groups did not manage their lipid profiles, and the management of lipid profiles did not improve in recent years. These results suggest that continuous follow-up is needed to effectively manage metabolic risk factors, especially lipid profiles, among patients with diabetes. Type 2 diabetes mellitus (T2DM) is a major chronic disease that is strongly associated with aging, with increasing prevalence and incidence at older ages , 2. A naThe diagnosis and treatment of T2DM among elderly people is similar to that among younger people –9. HowevPrevious studies have demonstrated that older patients with T2DM are more likely to achieve fasting plasma glucose control and glycemic control targets –16. HoweThe KNHANES is an ongoing national cross-sectional survey in South Korea that uses a complex, stratified, multistage, probability-cluster sampling . The iniThe present study examined data sets from KNHANES I (1998) up to the second period of KNHANES VI (2014). Only patients with confirmed T2DM were considered eligible, and these cases were identified based on a self-reported medical history of diabetes (based on a physician’s diagnosis) or medical treatment using insulin or oral hypoglycemic medication. Among the 4,087 patients with T2DM who were ≥30 years old in the 1998–2014 surveys (excluding cases with missing sampling weight data), we excluded 398 women who were pregnant or breastfeeding at the time of the survey. Thus, 3,689 patients with T2DM were included in the present study .The KNHANES involve a health examination, health interview, and nutritional survey, which provided detailed data regarding age, sex, household income, smoking status, education level, alcohol intake, psychological stress, and T2DM duration. Household income was divided into quartiles, and education level was categorized as less than high school graduation or high school graduation and above. Smoking status was classified as current smoker, previous smoker, or never smoker. Alcohol consumption was calculated by multiplying the number of alcohol servings consumed in one sitting by the frequency of consumption, and categorized as <2 or ≥2 glasses per day for men and <1 or ≥1 glass per day for women. Physical activity data  were used to calculate metabolic equivalents (METs [h/week])  from the2, and the World Health Organization’s cut-off value for Asian population was used to identify individuals who were normal/underweight (BMI of <23 kg/m2) or overweight/obese (BMI of ≥23 kg/m2) [The health examination provided data regarding body mass index (BMI), fasting blood glucose concentration, blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations. All examinations were performed by professional technicians. Each participant’s BMI was calculated as kg/m3 kg/m2) .Venous blood was collected after 8 h of fasting, and the hexokinase method was used to analyze total cholesterol, HDL-C, and triglyceride levels. The analyses were performed using different equipment for the various surveys: a Hitachi 747 autoanalyzer  for KNHANES I (1998) and KNHANES II (2001), an ADVIA1650  from 2005 to February 15, 2008, and a Hitachi Automatic Analyzer 7600  after February 20, 2008. As LDL-C testing was not performed before 2008, Friedewald's formula  was used® Desk model 0320  was used for KNHANES I–V and a Baumanometer® Wall Unit 33 (0850)  was used after KNHANES V. Blood pressure data from the second and third periods of KNHANES IV were adjusted for differences in arm heights that were used during the measurements.Blood pressure was measured after a period of relaxation in the seated position using a mercury sphygmomanometer. BaumanometerThe major variables of interest were hyperglycemia (a fasting blood glucose level of ≥126 mg/dL)  and hypeP-values for trends were calculated using the median value of the prevalence of metabolic disorder as a continuous variable in each survey during the 16-year period. All analyses were performed using SAS software , and differences were considered statistically significant at a two-tailed α value of 0.05.All statistical analyses were performed considering the KNHANES’ complex survey design, sampling weights, and stratified and clustered sampling approach. Participants were categorized into middle-aged (30–64 years old) and elderly (≥65 years old) groups. The weighted frequencies of categorical variables and weighted means and standard errors of continuous variables were calculated using SAS SURVEY procedures. Potential confounding factors were considered based on previous research and the results of the descriptive analysis. In addition, effect modification in the multivariable model was tested for these factors using multiplicative terms. Multivariable generalized linear regression analysis was used to estimate adjusted mean and 95% confidence interval (CI) values for the prevalences of hyperglycemia, uncontrolled high blood pressure, hypertension, uncontrolled lipid profiles, and dyslipidemia in both age groups and for each survey. The P < 0.001). The proportions of overweight/obesity were high in both groups (72.7% in the middle-aged group and 67.4% in the elderly group). Compared to middle-aged individuals, elderly individuals were more likely to make healthier lifestyle choices, based on a lower proportion of never smoking (P < 0.001), a higher proportion of moderate alcohol consumption (P < 0.001), and greater adherence to the use of hypoglycemic agents (P < 0.001). However, the elderly group had a lower rate of physical activity than the middle-aged group (P < 0.001). The duration of diabetes was associated with age (P < 0.001), and the elderly group tended to have a longer duration of diabetes, compared to the middle-aged group.The general characteristics of the middle-aged and elderly groups are shown in P for trend <0.001, After adjusting for sex, medication use, smoking status, moderate alcohol consumption, BMI, education level, duration of diabetes, and psychosocial stress, significant decreasing trends were detected in fasting glucose and systolic/diastolic blood pressure for both age groups during 1998–2014 . However, the most recent survey (KNHANES VI) revealed that approximately one-half of patients with T2DM in both age groups had hyperglycemia, which reflects unsatisfactory management of fasting blood glucose levels.P for trend <0.001, elderly group P for trend <0.001; hypertension: middle-aged group P for trend <0.001, elderly group P for trend = 0.03)  . The preThe present study evaluated KNHANES data from 1998–2014 for patients with confirmed T2DM who were ≥30 years old, and compared the management of blood pressure, blood glucose, and blood lipids between the middle-aged and elderly participants. Overall, one-half of the patients with T2DM in both groups did not appropriately manage their blood glucose and blood lipid levels. Furthermore, during the study period, the management of blood glucose and blood pressure appears to have improved, whereas the management of blood lipids did not improve and remains poor.Previous studies have demonstrated that older adults have better management of blood glucose than middle-aged adults , 24–28, The present study revealed that blood pressure and blood lipid management levels did not differ significantly between the age groups in most survey years, although conflicting findings have been revealed in previous studies , 27. ForThe management of blood glucose levels and blood pressure among middle-aged and elderly patients with T2DM gradually improved during the study period, although the management of blood lipid profiles remained unsatisfactory. In this context, most patients with T2DM and hypertension had adequately controlled blood pressure, which was achieved using drug therapy or diet/lifestyle modification. The Korea Centers for Disease Control and Prevention have also reported that there were rapid increasing trends in the use of antidiabetic and antihypertensive drugs among patients with diabetes and hypertension, respectively. For example, the proportion of antihypertensive drug use among patients with hypertension increased from 21.9% in 1998 to 54.8% in 2007, and the proportion of insulin or oral hypoglycemic drug treatment among patients with diabetes increased from 29.7% in 1998 to 57.4% in 2007 . These cHowever, one-half of T2DM patients with dyslipidemia had not achieved appropriate management of their blood lipid profiles. Similarly, previous studies have indicated that only one-third of T2DM patients with have adequately managed cholesterol levels, including one study of 2,591 Korean T2DM patients with dyslipidemia or hyperlipidemia  and anotPatients with T2DM require better awareness of the importance of cholesterol and lipid management. Previous reports revealed that T2DM patients with dyslipidemia had poor diet/lifestyle therapy and medication adherence, even when their blood lipids were not properly controlled , 39, 40.One of the strengths of the present study is the generalizability of its results, as the KNHANES provide nationally representative survey data. In addition, to the best of our knowledge, this is the first study to evaluate the management of metabolic biomarkers among patients with T2DM according to age group, and to examine the trends in these management levels during an extended period. Thus, the results of the present study may help guide the development of education and intervention strategies for patients with T2DM.The present study also has several limitations. For example, older patients with T2DM are more likely to have a prolonged duration of disease, which is associated with management levels and personal attitudes toward diabetes. Thus, we adjusted the models for the duration of diabetes, which is a time-dependent variable, in order to minimize this bias , 43. In In conclusion, the present study revealed that older patients had better management of blood glucose levels, compared to middle-aged patients, although no significant differences between the age groups were observed in the management of blood pressure and lipid profiles. Furthermore, we detected trends towards improved management of blood glucose and blood pressure during the study period, although no improvement was observed for the management of blood lipid levels. Furthermore, one-half of patients with T2DM and dyslipidemia did not appropriately manage their lipid profiles, which is a serious cause for concern. These patients require continuous follow-up to effectively manage their lipid profiles. Moreover, older patients with T2DM should undergo a careful evaluation for their risk of diabetes complications and the presence of comorbidities, which can be used to help develop and implement appropriate self-management goals.


South Korea has experienced problems regarding poor management of symptoms of asthma patients and remarkable increases in sleep disorders. However, few studies have investigated these issues. We examined the relationship between sleep disorders and mortality in asthma patients to suggest effective alternatives from a novel perspective.We used data from the National Health Insurance Service (NHIS) National Sample Cohort 2004–2013, which included medical claims filed for 186,491 patients who were newly diagnosed with asthma during the study period. We performed survival analyses using a Cox proportional hazards model with time-dependent covariates to examine the relationship between sleep disorders and mortality in asthma patients.There were 5179 (2.78%) patients who died during the study period. Sleep disorders in patients previously diagnosed with asthma were associated with a higher risk of mortality . In addition, significant interaction was found between sleep disorders and Charlson comorbidity index.Our findings suggest that an increased prevalence of sleep disorders in asthma patients increases the risk of mortality. Considering the worsening status of asthma management and the rapid growth of sleep disorders in South Korea, clinicians and health policymakers should work to develop interventions to address these issues. Asthma is a common chronic disease largely caused by genetic and environmental risk factors such as indoor and outdoor allergens, smoking, chemical irritants in the workplace, and air pollution. Its symptoms include recurring periods of wheezing, chest tightness, shortness of breath, and coughing . In seveTo determine the optimal management of asthma patients, numerous previous studies have been conducted, revealing many risk factors related to worsening status of asthma patients including clinical, socioeconomic, seasonal, and environmental factors –10. NeveIn South Korea, sleep issues have become increasingly common. According to National Health Insurance Service (NHIS) reports, health resource utilization due to organic sleep disorders  has gradually increased in South Korea, with the number of inpatients and outpatients growing from 358,062 in 2012 to 380,876 in 2013 and 414,524 in 2014 . Now, itsi-gun-gu (city-county-ward) districts of South Korea. We classified the data based on the si-gun-gu information to take into account the regional characteristics of the community in which each patient resided (Statistics Korea) [The data used in this study were obtained from the NHIS National Sample Cohort 2002–2013 that was released in 2014. They comprised a nationally representative random sample of 1,025,340 individuals, approximately 2.2% of the entire NHIS population in 2002. The data were produced by the NHIS using a systematic sampling method to generate a representative sample of 46,605,433 Korean residents recorded in 2002. The database included all medical claims filed from January 2002 to December 2013. To investigate the association between sleep disorders and mortality in patients with diagnosed asthma, we included only patients who were newly diagnosed with asthma (ICD-10: J45) during outpatient care after 2004. We then excluded patients diagnosed with a sleep disorder (ICD-10: G47) prior to the diagnosis of asthma to limit our investigation to the effect of sleep disorders on patients who had already experienced asthma. Ultimately, the data used in this study were from 186,491 patients newly diagnosed with asthma from 2004–2013. Regional characteristics were determined from the “e-provincial indicators” published by Statistics Korea, which contained the regional demographic structures for all 253 basic administrative s Korea) .The outcome variable was mortality in patients diagnosed with asthma (ICD-10: J45). Mortality was defined as all types of death in patients with asthma during the study period. We identified the date of each patient’s first hospital visit through either outpatient care or admission during the study period, and we followed each patient after that date.The primary independent variable in relation to the mortality of patients with asthma was whether they were diagnosed with an organic sleep disorder during follow-up (ICD-10: G47). We adjusted both patient and regional variables when analyzing the effect of sleep disorders on mortality in patients with asthma. The patient variables included in the analyses were sex, age, income, insurance coverage type, year of first asthma diagnosis, disability, Charlson comorbidity index score, and average annual pharmaceutical expenditures for asthma. Age was divided into 10-year groups  to reflect any differences in the effects of sleep disorders on mortality among patients with asthma by age group. Income level was categorized into deciles based on mean household income as follows: ≤10%, 11%–20%, 21%–30%, 31%–40%, 41%–50%, 51%–60%, 61%–70%, 71%–80%, 81%–90%, and ≥91%. The types of insurance coverage were categorized as medical aid, National Health Insurance (NHI) employee insurance, or NHI self-employed insurance based on the NHI criteria. Those with NHI employee insurance included workers and employers in all workplaces, public officials, private school employees, continuously insured persons, and daily paid workers at construction sites. Beneficiaries of NHI employee insurance included spouses, descendants, siblings, and parents. People with NHI employee insurance paid a regular portion (about 7%) of their average salary in contribution payments, and the rates changed every year. The NHI self-employed insurance category included people who did not fall into the above-described group. Their contribution amount was set by taking into account their income, property, living standard, and rate of participation in economic activities. Medical aid beneficiaries were defined as patients with an income below the government-defined poverty level or a disability who were provided with free inpatient and outpatient care paid with government funds. Therefore, the type of insurance coverage represented each patient’s socioeconomic status , 18. TheThe regional variables were region, number of medical centers per 1000 residents, population size, proportion of seniors, and financial independence rate of the local government. The region types were metropolitan and other. Population size was defined as the total number of residents in each community, and the proportion of seniors was the number of elderly individuals among the entire community. The financial independence rate of the local government was an index of the finance utilization capacity of a local government with independent discretionary power. This indicator was calculated as follows: /local government budgets × 100.χ2 tests to examine the distribution for mortality according to each variable. We examined the mean and standard deviation of each continuous variable at baseline and performed t-tests or Wilcoxon-Mann–Whitney tests for each variable by mortality during the study period. Analyses were performed for both patient- and regional-level variables. Kaplan-Meier survival curves and log-rank tests were used to compare survival rates between groups. We performed survival analyses using a Cox proportional hazards model with time-dependent covariates to examine factors associated with mortality [We first examined the frequencies and percentages of each categorical variable at each patient’s baseline and performed ortality . SubgrouThe data used in the analysis were collected from 186,491 patients with asthma. Table p < 0.0001).Figure Table We performed interaction tests to further examine potential effect modification of the associations between sleep disorders and mortality by age, insurance coverage, pharmaceutical expenditures, region, number of medical centers per 1000 residents and the CCI. Except for CCI, the interaction terms between sleep disorders and the mentioned variables were not statistically significant. Nevertheless, a trend in the magnitude of the stratified HR was observed for age and insurance coverage. For age, the highest HR were observed among younger age groups. For insurance coverage, higher HR were observed for NHI self-employed insurance than for NHI employee insurance. In addition, the association between sleep disorders and mortality was stronger in non-metropolitan regions compared with metropolitan areas, and among individuals with lower number of medical centers per 1000 residents. For CCI, the interaction term between sleep disorders and CCI was statistically significant. And, higher HR were observed among higher CCI group Table .Table 3SIn the past several decades, South Korea has experienced rapid social and economic growth. The health status of South Koreans has also improved, and their lifespan has increased accordingly. Although burdens of illness due to acute diseases have decreased, chronic conditions now present new challenges . Many reOur findings suggest that the presence of sleep disorders in patients previously diagnosed with asthma is associated with an increased mortality risk. Previous studies have reported that sleep disorders affect overall quality of life and can deteriorate patients physically and psychologically –25. GiveSubgroup analyses revealed several interesting results. The increased mortality in patients with asthma and sleep disorders was greater for younger patients, those with NHI self-employed insurance, those in non-metropolitan areas, and those in regions with low healthcare accessibility. First, younger patients had more negative outcomes, which had been previously reported . This suOur study had several strengths compared to previous publications. First, we used national sampling cohort data to assess the relationship between sleep disorders and mortality risk in patients with asthma. Such data are particularly helpful for establishing evidence-based policies to effectively manage asthma patients. Next, to the best of our knowledge, this study is the first study to investigate the impact of sleep disorders on the mortality risk of asthma patients in South Korea. Other previous reports described the negative effects of sleep disorders and relationships between sleep disorders and health outcomes. However, few studies have regarded the relationship between sleep disorders and mortality in patients with asthma in South Korea. Thus, our findings could provide useful evidence for the development of policies or programs to better manage patients with asthma and sleep disorders. Finally, we made a concerted effort to reduce the limitations of secondary data by adjusting covariates for patients’ clinical and regional characteristics. We included the year of asthma diagnosis, disability, Charlson comorbidity index score, and average annual pharmaceutical expenditures due to asthma to reflect disease severity and included regional characteristics to consider differences in medical accessibility by area.Our study also had several limitations. Although several factors that affect mortality were included in this study, more detailed information such as socioeconomic factors was not available . Given tDespite these limitations, our findings suggest that sleep disorders in patients previously diagnosed with asthma are negatively associated with their health status, and in particular, mortality. Although further studies using more detailed data will be needed, these results underscore the need for health policymakers and healthcare professionals to identify effective ways to reduce the prevalence of sleep disorders in South Korea.Sleep disorders in asthma patients are associated with higher mortality. Considering the worsening status of asthma management and the rapid growth of sleep disorders in South Korea, health policymakers should consider developing effective interventions based on our findings.


Both vitamin D deficiency and hypertension are prevalent in the general population. Several observations indicate an association between vitamin D deficiency and high blood pressure. The present case-control study aimed to compare serum 25-hydroxyvitamin D (25-OHD) in hypertensive patients versus healthy controls.One hundred patients aged 30-60 years with hypertension (HTN) and 100 healthy controls without history of hypertention were compared regarding serum 25-OHD. Blood pressure was measured using standard method and the systolic and diastolic blood pressure more than140 mmHg and 90 mmHg respectively were considered as HTN. Patients and controls with coexistent morbidities, vitamin D supplementation were excluded. The serum levels of 25-OHD, PTH and calcium were measured after obtaining a written informed consent from the patients and taking their blood pressure under standard conditions. In statistical analysis, the two groups were compared using independent t test and chi-square test using SPSS Version 18.The mean age of patients and controls was comparable . Serum 25-OHD in HTN was significantly higher than controls (P=0.001). In the present study, serum 25-OHD level in hypertension was higher than controls. The results contradict with earlier studies indicating an association of HTN with vitamin D deficiency. This issue warrants further investigations in particular the follow-up of serum 25-OHD deficient and sufficient subjects with regard to the development of HTN. Vitamin D deficiency is highly prevalent in general populations across various geographical regions and its contribution in the development of many common clinical conditions is of particular importance -4. AccorToday, high blood pressure is considered as a worldwide problem and several studies have been conducted in respect to serum level of 25-hydroxy vitamin D3 and hypertension , 13. VitHowever, the relationship between vit D and blood pressure across various studies is controversial . Also boThis case-control study was conducted on 100 hypertensive patients aged 30-60 years at the teaching hospitals of Babol University of Medical Sciences and 100 age matched and sex-matched healthy subjects based on inclusion and exclusion criteria in 2013. Systolic and diastolic blood pressure greater than 140 mmHg and 90 mmHg, respectively were considered as the presence of HTN. All patients were selected consecutively according to inclusion criteria.The subjects of the control group were selected among the patient’s relatives whit no history of hypertension. Subjects with pregnancy, known as renal disease, hypertension secondary to renal disease, inflammatory arthritis, taking diuretic medications and any supplements of vitamin D and calcium supplementation in the last year were excluded.After taking the written informed consent from all subjects, blood pressure was measured under standard conditions after at least 10 minutes of rest in a quiet environment and for two occasions for at least a 15-minute interval. Serum vitamin D was assessed by measurement of 25-hydroxyvitamin D (25-OHD) level by ELISA methods. In addition, serum calcium and parathyroid hormone (PTH) were measured using the kit provided by German Merck Company according to manufacturer’s instruction. Serum vitamin D level was classified as deficient (less than 10 ng/ml), insufficient (10 to 30 ng/ml) and sufficient (more than 30 ng/ml).All data were statistically analyzed by t-test and chi-square test using SPSS Version 15, and p<0.05 was considered as significant level.All patients and controls completed the study. Gender distribution was similar in both the comparison group by 41% males and 59% females (mean age of patients and controls was comparable (53.7±6.4 and 52.3±7.4 years) respectively. There was no significant difference in the mean age of men and women between the two groups. Data according to sex in both patients and controls are presented in As shown in Proportion of serum 25-OHD deficiency, insufficiency and sufficiency in patients were 27%, 40% and 33% and in the control group 40%, 53% and 7% respectively. In In The results of this study indicate a higher level of serum 25-OHD in HTN compared with the healthy controls. These findings are inconsistent with previous studies which have shown an association between vit D deficiency and HTN -21. High Similarly, Martins et al.  in 2007 A significant inverse correlation was observed between serum vit D level and high blood pressure of white people based on the data of National Health and Nutrition Examination Survey (NHANESIII) . However, this significant relationship disappeared when the studied subjects were homogenized in terms of age. There was no significant correlation between serum vit D level and high blood pressure of black people in his study . Scragg Similar to the present study, Margolis et al over a 7-year study period found increased systolic blood pressure by taking supplemental vit D and calcium in postmenopausal women . Neverth


The objective of this study was to assess patients’ achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting.This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood pressure were evaluated according to ADA recommendations.Of the 123 patients, 81 were women and the mean age was 61.8 years. Glycemic control was abnormal in 82 (68.33%) participants, and 45 (37.50%) were unable to control their blood pressure. Lipid profile was abnormal in 73 (60.83%) participants. Only nine (7.50%) participants fulfilled ADA recommendations for glycemic, blood pressure, and lipid control.Amongst individuals with type 2 diabetes, there was poor attainment of the ADA recommendations  for ambulatory T2DM patients. Interventions are urgently needed in order to prevent long-term diabetic complications. Type 2 Diabetes Mellitus (T2DM) is a chronic disease with a growing prevalence worldwide . In 2014Metabolic control in T2DM is a critical component in diabetes care. Without well-established metabolic control, complications can arise increasing mortality rates and lowering quality of life—this represents an important burden of disease for low-middle income countries (LMICs) . AdditioLong term care of T2DM patients represents a grand challenge for health care systems around the world . In ordeIn South America, particularly in Peru, there are few studies that evaluate demographic and clinical characteristics associated with glycemic control, blood pressure, and lipid profile in a clinical setting . Such a The objectives of this study were to: (1) explore the quality of T2DM control through achievement of the American Diabetes Association (ADA) recommendations, and (2) determine whether demographic characteristics, lifestyle choices, and clinical parameters of patients in a public hospital in Peru have an impact on the quality of control of T2DM.We conducted a cross-sectional study in which participants diagnosed with T2DM were recruited between March and July 2012 from the Endocrinology clinic of Hospital Cayetano Heredia in Lima, Peru. This is a university hospital located in San Martin de Porres, a low-income district north of the Peruvian capital .The recruitment strategy was convenience sampling, with patients recruited while they were waiting for their routine clinical encounter. The inclusion criteria included a diagnosis of T2DM for more than 12 months from the recruitment day, ≥18 years old, and at least one visit to the Endocrinology clinic in the previous year. Patients were excluded if they were diagnosed with secondary or gestational diabetes, chronic non-cardio-metabolic diseases , or any mental illness or incapability. Patients who had presented with major complications of T2DM  in the previous year and those who had been hospitalized within the previous six months were also excluded due to the decline in social, physical and psychological functionality after these major complications and their added risk factors for mortality .The participants were assessed using a standardized interview and an evaluation of their medical records, using the International Physical Activity Questionnaire (IPAQ), the Scale of Adherence to Diabetes Mellitus Type 2 Treatment , and Center for Epidemiological Studies-Depression (CES-D) scale . For labTo define “poor metabolic control,” the American Diabetes Association (ADA) recommendations were used: poor glycemic control (HbA1c ≥ 7% (53 mmol/mol)), poor controlled blood pressure (BP ≥ 140/90 mmHg), and poor controlled LDL-cholesterol (LDL ≥ 100 mg/dL) . Also, wDemographic variables were also collected including gender, age (<65 years old or ≥65 years old), and marital status . The clinical data collected included: years of disease (1–10 years or ≥10 years); treatment ; body mass index (BMI), and chronic diabetic complications defined as microvascular  and macrovascular .Participant’s activity levels were assessed using the IPAQ with three categories: inactive, minimally active, and HEPA active   Table S.The scale used to measure adherence was EATDM-III, which has previously been used in Costa Rica . This scDepression was evaluated using the CES-D. A score greater than or equal to 24 is considered positive for the presence of depression. The scale was previously validated for the Peruvian population with a sensitivity of 91.4% and specificity of 96.7% .Z = 1.96). Calculated power for depression was 28% (The sample size of 123 participants was based on the DEAL study (Diabetes en America Latina) , using a was 28% .t-test for comparison of a quantitative vs qualitative variable.Statistical analyses were performed using Stata 12.0. Demographic variables , clinical criteria , lifestyle factors , and comorbidity (depression) variables were compared against glycosylated hemoglobin looking for significant associations. Chi-square was used for comparison of qualitative variables and Multivariate models were generated using Poisson regression reporting prevalence ratios (PR) and 95% Confidence intervals (CI). Crude and adjusted analyses were performed for the three models generated to evaluate the independent association between (i) glycemic control, (ii) blood pressure, and (iii) LDL-cholesterol with demographic, clinical, lifestyle, and comorbidity variables.The study protocol was approved by the Ethical Review Board of the Universidad Peruana Cayetano Heredia and Ethical Committee of Hospital Cayetano Heredia. Written informed consent was obtained from all patients.The recruitment rate was 89.78% (123/137). Of the 123 patients participating in the study, blood samples were received from 120 patients. Most participants (65.85%) were female and the mean age was 61.84 ± 11.10. In addition, majority of the patients (63.41%) were in a relationship . Mean HbA1c was 8.2% ± 2.19 (66 mmol/mol), mean LDL (mg/dL) was 107.61 ± 39.66 and mean blood pressure was 133.26 ± 19.03/ 75.64 ± 10.84 mmHg. The prevalence of uncontrolled HbA1c was 68.33%, uncontrolled LDL-cholesterol was 60.83%, and uncontrolled blood pressure was 37.50%. With regards to comorbidities, 37.40% had hypertension and 33.33% had depression. Other characteristics of the population studied are shown in p = 0.013). Good glycemic control was present in 21.92% patients younger than 65 years old and in 46.81% of those older than 65 years (p = 0.004). Those patients who were not on pharmacological treatment had better glycemic control than the patients who required pharmacologic therapy (p < 0.001). A detailed comparison between each variable and glycemic control is shown in The patients diagnosed with diabetes for 1–10 years had better glycemic control compared to those who had had a diabetes diagnosis for ≥10 years  was found in patients who were 65 years or older when compared to younger participants  and with patients who were in a relationship compared to single patients . Also, a positive association with poor glycemic control was found with more than 10 years of disease , oral antidiabetic (OAD) use plus insulin treatment , and minimal physical activity  in the crude and adjusted model in comparison with their counterparts. BMI was included in the adjusted Poisson regression model, but there was no association found with glycemic control, LDL-cholesterol, or blood pressure. We did not find an association between LDL-cholesterol or blood pressure and demographic, clinical, lifestyle  and comorbidity variables .Only 7.5% of the patients achieved the levels of glycemic control in T2DM recommended by the ADA . In Latin America, a Colombian retrospective study with a bigger sample size got a similar result of 6.9% . There ap = 0.02), cardiovascular-death hazard ratio of 0.43  and cardiovascular-events hazard ratio of 0.41 .Of all participants in this study, 68.33% had poor glycemic control, 37.50% had uncontrolled blood pressure and 60.83% had an abnormal lipid profile. These are worrisome results as achieving the ADA recommendations is pertinent in decreasing micro-vascular and macro-vascular complications and death in T2DM patients. This is shown in the Steno 2 study, which compared intensive treatment against conventional treatment in primary outcomes of T2DM patients . The outIn a systematic review of 14 studies that involved 19 countries: 55.5% of subjects had HbA1c > 7% (53 mmol/mol), 64.8% of subjects had blood pressure > 130/80, and 48.6% subjects had LDL-cholesterol > 100 mg/dL . The difInterestingly, in our study, participants who were older than 65 and in a relationship were able to achieve better glycemic control. Meanwhile having more than 10 years of disease, OAD plus insulin treatment, and doing minimal physical activity was associated with poor glycemic control. There was not a significant association between the above analyzed variables and LDL-cholesterol or blood pressure.Participants older than 65 were more likely to have good glycemic control  than their younger counterparts. Similar results were found in other studies, for example in Mexico and the United States  , where It has also been shown that the years of disease have a significant impact towards glycemic control, which may be due to decreased insulin production from decreased beta-cell function after 5–10 years of disease . In agreAnother variable associated with good glycemic control was marital status. In this study, being in a relationship was shown to have protective effects with regards to the HbA1c goals and consequently better prognosis. This is reinforced by several studies where they found that having a partner is associated with better adherence to treatment  and decrParticipants with no pharmacological treatment had better glycemic control in comparison with OAD or OAD plus insulin. Similar results were reported in the Center for Disease Control and Prevention supplement . This cap < 0.001)  compared to HEPA active patients. Similar results were found by Abdel et al., who found a statistically significant association between patients with uncontrolled T2DM and lack of activity  .According to EATDMIII scale, 56.99% patients with diabetes were adherent to non-pharmacological treatment. However, it was still beneath the rate of 66% found by Prevalence of depression in our patients with T2DM was 33.33%, which is five times the prevalence of depression reported in the general population (6.7%) . HoweverFactors significantly associated with poor glycemic control were not associated with LDL-cholesterol or blood pressure, suggesting that there are different factors that we have not explored and could be associated.This study was small and localized to a single hospital in Peru. The small sample size and single site limits our generalizability and may have limited our scope of findings. Moreover, patients who participated in the study are representative of a low-income urban area, so we are unable to generalize the results to the whole population. The socio-economic characteristics of our population may have influenced rates of adherence, physical activity, and depression symptoms .Another limitation of this study is that currently, in addition to ADA recommendations, a patient-centered approach is promoted to individualize treatment plans taking into consideration life expectancy, disease duration, complications, comorbidities, hypoglycemia, and psychological status. Unfortunately, we do not have enough information to determine the adequate HbA1c level for each participant. Despite this limitation, this study is important and highlights a challenge to improve the health system for people with T2DM to achieve a better metabolic control, keeping in mind the necessary focus on individualization of the intensity of treatment and essential security aspects. Our findings can help to direct better management of patients with T2DM. We have shown that patients are not achieving the standards recommended by the ADA and now we can try to achieve them by targeting the significant factors including: increasing physical activity, protecting relationships with psychological couple therapy, rechecking diabetes medication, and enhancing adherence. Further studies should be conducted to determine the influence of lifestyle factors in management of T2DM.The quality of control of HbA1c, LDL-cholesterol, and blood pressure was surprisingly low in patients with T2DM in this study. In comparison to similar studies, these levels are the lowest in the literature. Additionally, patients also exhibited low glycemic control. This situation cannot solely be explained by poor adherence, but it could be explained in combination with depression or low physical activity. Further studies are needed to fully understand this problem and until this is achieved, we cannot make the necessary recommendations to address this problem.10.7717/peerj.2577/supp-1Table S1Click here for additional data file.10.7717/peerj.2577/supp-2Data S1Raw data obtained from medical records, standardized interviews, laboratory measurements, International Physical Activity Questionnaire (IPAQ), Scale of Adherence to Diabetes Mellitus Type 2 Treatment  and Center for Epidemiological Studies-Depression (CES-D) used for data analysis and preparation for Click here for additional data file.


The two significant hemodynamic changes were the decrease of systemic vascular resistance index (dyn s m2/cm5) and left cardiac work index (kg m/m²)/mean ± SD from 2319.3 ± 753.3 to 2083.0 ± 526.9 and from 4.8 ± 1.4 to 4.4 ± 0.9, respectively; both p < 0.05). The observed hemodynamic changes may explain lowering blood pressure after magnesium supplementation.The objective of this study was to examine the changes of blood pressure and hemodynamic parameters after oral magnesium supplementation in patients with essential hypertension. The single-arm non-blinded intervention study comprised 48 patients  whose antihypertensive therapy was not changed for at least one month. The participants were asked to consume (daily at home) 300 mg of oral magnesium-oxide supplementation product for one month and to have their blood pressure and hemodynamic parameters  measured in the hospital before and after the intervention. Measurements were performed with impedance cardiography. After magnesium supplementation, systolic and diastolic pressures were significantly decreased (mean ± standard deviation (SD)/mmHg/from 139.7 ± 15.0 to 130.8 ± 13.4 and from 88.0 ± 10.4 to 82.2 ± 9.0, respectively; both  Magnesium is an important cation for the activity of many enzymes related to energy metabolism, e.g., serine racemase , ATP dipAn intervention study of a 6-month supplementation with magnesium aspartate hydrochloride among patients on a diuretic therapy for hypertension showed a significant reduction of both systolic and diastolic blood pressure . On the Due to conflicting results there is a lack of definitive conclusion and consensus on the effectiveness of magnesium in the treatment of hypertension. Besides blood pressure there is a need for further investigation of the effects of magnesium on other hemodynamic parameters that may explain the Mg-hypertension relationship. The aim of this intervention study was to examine the changes of blood pressure and hemodynamic parameters after oral magnesium supplementation in patients with essential hypertension. We hypothesized that magnesium supplementation would lead to lowering blood pressure and other compatible hemodynamic changes.www.irct.ir; Registration number: IRCT2017081535716N1). All subjects signed their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Clinical Center of Serbia, Belgrade (code 1322/1) and by the Ethics Committee of the Faculty of Medicine, University of Belgrade, Serbia (code 29/VII-16).This study was performed in the collaboration between the Institute of Hygiene with Medical Ecology, Faculty of Medicine, and the Multidisciplinary Center for Polyclinic Diagnostics, Assessment and Treatment of Blood Pressure Disorders, Clinic for Cardiology, Clinical Center of Serbia. The study has been registered by The Iranian Registry of Clinical Trials  were asked to consume 300 mg of oral magnesium-oxide supplementation product for one month and to have their blood pressure and hemodynamic parameters measured in hospital settings at baseline and at the end of the intervention. The participants were given a dietary supplement  which is approved by the Ministry of Health of the Republic of Serbia (Number: 1708/2011). All participants were informed how to use this product, were warned not to exceed the daily recommended dose, and were advised not to change their dietary habits. The participants did not report adverse effects that might be related to magnesium supplementation. They were not informed about the expected changes of blood pressure and hemodynamic parameters after magnesium supplementation.The eligible participants , duration of hypertension (years), hypertension in the family , physical activity of at least 30 min most days per week  and smoking habits . Data on antihypertensive treatment were obtained from patient’s medical records. Antihypertensive treatment included: ACE inhibitors ; calcium channel blockers ; thiazide diuretics ; beta blockers  and angiotensin II receptor blockers . At follow-up after one month, all participants were invited for medical examination. Despite being called several times, 20 participants did not return for check-up (8 men and 12 women), but they did not report adverse effects of magnesium supplementation as the reason. The statistical analysis revealed that the non-responders were significantly younger than the responders (mean age of the non-responders 37.75 ± 12.45 years) with non-significantly shorter duration of hypertension (mean duration of hypertension among the non-responders 5.39 ± 5.19 years). The final sample comprised 48 persons, 19 men and 29 women, aged 47.40 ± 11.30 years, range 24 to 65 years. This sample size was considered sufficient according to afore mentioned calculation.Average daily magnesium intake from food and drinks was obtained using a 24-h recall questionnaire. The participants were very carefully asked about food and drinks they consumed during 24 h prior to the interview. The questions referred to food types and amounts, time and place of consumption, how the food was prepared  and what was used to prepare the food . A trained physician conducted the interview with the participants. Magnesium intake from food and drinks was calculated from all foodstuffs consumed the previous day using Serbian food tables . Serum mParticipants had their weight and height measured by a trained physician. Body height was measured to the nearest 0.5 cm. Body weight was measured on a digital scale (TANITA Inner Scan Body Composition Monitor BC-543) to the nearest 0.1 kg. Participants were in light clothes and barefoot. Body mass index (BMI) was calculated as body weight (in kilograms) divided by squared body height (in meters).® 2000 . A cuff was placed on patient’s left upper arm.Both at baseline and at follow-up participants had their systolic, diastolic and mean arterial blood pressure measured with impedance cardiography (ICG) by CardioScreen2) and heart rate (beats per minute). The following parameters were calculated: stroke volume  and cardiac output . With reference to body surface area the following parameters were calculated: stroke index , cardiac index , systemic vascular resistance index  and left cardiac work index . DuBois formula was used to calculate the body surface area [We also used ICG for measurements of hemodynamic parameters at baseline and follow-up. ICG electrodes measure the change in thorax impedance during the flow of the alternating current through the thorax. The following parameters were measured: thoracic fluid content , acceleration index .Descriptive statistic was presented as mean values and standard deviation for numeric variables, or as percent’s (relative numbers) for categorical variables. All investigated parameters were tested by Kolmogorov-Smirnov test and almost all observed distributions corresponded to the normal distribution. The differences between men and women were tested with Student’s t-test for parametric variables and with Mann-Whitney Men and women were of similar age, and had similar body mass index, blood pressure levels, and shared smoking habits, engagement in physical activity and magnesium intake from food and water and serum magnesium concentrations. Men and women had similar duration of hypertension, and had similar family history of hypertension. These results support further analysis regardless of gender .p = 0.432). The range of serum magnesium concentrations at baseline and at follow-up was 0.74–0.94 and 0.69–0.96 mmol/L, respectively.There was no significant difference between serum magnesium concentrations at baseline and at follow-up  . AnotherAn important magnesium function, the vasodilatation of peripheral arteries , may expSerum magnesium concentration was not significantly changed after magnesium supplementation in our study. This finding is congruent with other intervention studies of a similar duration ,24. A siThere are several limitations of this study. First, a single-arm non-blinded design was chosen because of a limited pool of patients. We consider that a placebo effect was alleviated by the fact that although the patients knew they were given magnesium supplementation they were not informed about the expected changes in blood pressure and hemodynamic parameters. Second, we did not control the possible effect of thiazide diuretics on magnesium excretion in some patients. Third, we did not check for magnesium concentration in a 24 h urine sample at baseline and at follow-up. Fourth, the intervention period of our study was limited to thirty days. In further investigations it would be useful to examine the effects of different duration (shorter and longer than in our study) of magnesium supplementation on blood pressure and hemodynamic parameters. Fifth, the study was conducted in persons with essential hypertension; the hemodynamic changes in persons with diabetes or kidney diseases would be of great importance for understanding the mechanisms of action of magnesium supplementation. The strength of this study is the use of ICG, which objectively measures both blood pressure and hemodynamic parameters that may explain blood pressure changes after magnesium supplementation.In conclusion, oral magnesium supplementation probably had a positive effect on blood pressure reduction in patients with essential hypertension. The decrease in systemic vascular resistance and left cardiac work may explain the reduction of blood pressure after magnesium supplementation.


SS) rats were fed an 8% high salt NaCl diet and intravenously infused with the irreversible cysteine cathepsin inhibitor E‐64 (1 mg/day) or the vehicle (control). Both the control and E‐64 infused groups developed significant hypertension and kidney damage, and no difference of the mean arterial pressure and the hypertension‐associated albuminuria was observed between the groups. We next tested basal calcium levels in the podocytes of both control and infused groups using confocal calcium imaging. Basal calcium did not differ between the groups, indicative of the lack of a protective or aggravating influence by the cathepsin inhibition. The efficacy of E‐64 was tested in Western blotting. Our findings corresponded to the previously reported, E‐64 induced increase in cathepsin B and L abundance. We conclude that the inhibition of cysteine cathepsins by E‐64 does not have any effects on the blood pressure development and kidney damage, at least under the studied conditions of this model of SS hypertension.Cysteine cathepsins are lysosomal enzymes expressed in the kidneys and other tissues, and are involved in the maturation and breakdown of cellular proteins. They have been shown to be integrally involved in the progression of many cardiovascular and renal diseases. The goal of this study was to determine the involvement of cysteine cathepsins in the development of salt‐sensitive hypertension and associated kidney damage. In our experiments, Dahl salt‐sensitive ( Cathepsins (Cath) are proteolytic enzymes that are important in such cellular functions as the breakdown, maturation, and modulation of the bioactivity of proteins. Three major groups of Caths have been categorized: syrine (A and G), aspartic (D and E), and cysteine Caths. Cystein Caths, members of the family of papain‐like cysteine proteases, are the largest Cath family in humans that is comprised of 11 proteases   were used. Food  and water were provided ad libitum. Animals were housed in metabolic cages 7 days prior to femoral artery and vein catheterization. They were then returned to the metabolic cages and allowed to recover from surgery for 5–7 days.Chronic instrumentation of rats for venous infusion and blood pressure measurements was done as described previously. Briefly, 8‐week old anesthetized SS rats had their left femoral artery and vein catheterized. Both catheters were fixed and exteriorized from the back of the neck and the arterial line was connected to a heparinized saline infusion pump that was in line with a blood pressure transducer, and the venous line was connected to a saline infusion pump. Animals were allowed 360° movement using a tether‐swivel system. This preparation allowed chronic venous infusion and arterial blood pressure measurement in conscious, freely moving rats. A stable baseline blood pressure was obtained for 4 days prior to switching both groups to an 8.0% NaCl diet and the simultaneous addition of N‐[N‐(L‐3‐trans‐carboxyox‐irane‐2‐carbonyl)‐L‐leucyl]‐agmatine  or the vehicle  control to the venous catheter. Daily MAP was calculated by averaging MAP taken every min over the beginning 3 h period of the rat sleep cycle.By detaching the femoral arterial catheter from the swivel, 1 mL of arterial blood was collected the morning of the diet change and at every subsequent 7th day. Twenty‐four hour urine was collected with the metabolic cage apparatus on the same day as blood collections. Whole blood and urine electrolytes were measured with a blood gas and electrolyte analyzer . Albumin was measured using a fluorescent assay , read by a fluorescent plate reader , and creatinine using a Jaffé reaction‐assay using an autoanalyzer . Inorganic phosphorus was measured by chemical reduction to form a phosphomolybdate complex  and read by a fluorescent plate reader . Ammonia was quantified using an enzymatic reagent kit  and read by a fluorescent plate reader .2+]i measurements and the other half was used for Western blot analysis. The left kidney was used for histochemistry staining.Rats were anesthetized, and their descending aortas were catheterized. Kidneys were flushed via the catheter with PBS (3 mL/min/kidney) until blanched. Kidneys were excised and decapsulated. Half of the right kidney was used for glomerular podocyte basal [Caβ‐actin as was previously described  and Cath L . Kidney cortical sections were isolated and then lysed. Equal amounts of cell lysate were subjected to Western blot analysis with the Cath antibodies and 2+]i measurements were done as has been previously reported  for 40 min at room temperature. Glomeruli were adhered to poly‐l‐lysine coated glass coverslips and imaged using a confocal laser‐scanning microscope.Isolation and basal podocyte [Ca2+]i of podocytes were measured after stable fluorescence intensities were established. Only surface podocytes of glomeruli were recorded. Each experiment measured basal [Ca2+]i of 4 to 9 podocytes of at least one glomerulus imaged.Calcium imaging was performed as has been previously described  for repeated measures followed by the Holm–Sidak post hoc test. For the podocyte calcium measurements, the values of  in the first 7 days on the diet that continued through the remainder of the diet . [Ca2+] gradually decreased during the 21 day diet . However, no significant change was observed for [Na+] and [Cl−]. All measured blood electrolyte concentrations were no different between the two groups.Blood electrolyte concentrations are shown in Figure P < 0.001, two‐way ANOVA), and a steady, significant increase in albuminuria  was observed during the 21 days of the HS diet compared to day 0  , Na+, Ca2+, and Cl− excretion significantly increased after day 0 . Urinary phosphorus significantly increased after day 0   Fig. A. Of theVA) Fig. B, K+ .Taking into consideration that E‐64 inhibition of Caths has been shown to attenuate glomerular damage, histological coronal sections of the kidneys were done. Figure P < 0.01, independent‐sample t‐test). The pro Cath L abundance was not different between the groups and pro Cath B was not detected.Previously, inhibition of cysteine Caths by E‐64 has been shown to increase the half‐lives of cysteine Caths due to the requirement of functional cysteine Caths for their degradation ‐mediated sodium absorption in the collecting ducts. ENaC is the main sodium transporter in the aldosterone‐sensitive distal nephron (Staruschenko Another potential mechanism, which might modulate the development of SS hypertension by cysteine Caths, is the control of the epithelial NaWe have shown here evidence that E‐64 does not affect either the blood pressure control or kidney injury in Dahl SS rats fed a HS diet. This might indicate that cysteine Caths are not involved in the progression of SS hypertension. Alternatively, other Caths and cellular proteases may be involved in SS hypertension and kidney damage. Our findings indicate that in vivo inhibition of cysteine Caths may be an ineffective method of attenuating SS hypertension as was indicated by the increased renal Cath B and L protein levels and the lack of attenuated pathophysiology. Likewise, the interregulation of Caths may offset any beneficial inhibitory affects. Future studies using more selective Cath inhibitors may be needed to identify in vivo Cath functions in SS hypertension.There are no conflicts of interests.


The ability of antihyperuricemic therapy to exert renoprotective effects in patients with chronic kidney disease (CKD) is controversial. In the present study, we studied patient characteristics that may mask favorable impact of antihyperuricemic therapy on the progression of CKD.This was a single-center, retrospective, follow-up study. One-hundred and seventy-eight CKD patients with hyperuricemia who received febuxostat therapy were included in this study. Mean serum uric acid (mUA) level after treatment and changes in estimated glomerular filtration rate (ΔeGFR) over 6 months were measured and their correlation was examined. Patients were divided into two groups based on mUA, and their ΔeGFR were compared. These analyses were evaluated in various subgroups.r = −0.16, p = 0.019). The renoprotective effects of febuxostat were significant in the following subgroups: male patients, age < 70 years, systolic blood pressure < 130 mmHg, normal cholesterol levels, and absence of diabetes. Coexisting vascular risk factors appear to exert additive masking effects against febuxostat renoprotection.Febuxostat therapy markedly decreased UA level in any CKD stage patients without resulting in serious adverse events. eGFRs of CKD patients in the mUA < 6.0 mg/dl group were maintained, whereas those in the mUA ≥ 6.0 mg/dl group decreased. A significant inverse correlation was observed between mUA and ΔeGFR (The results of this study suggest that various vascular risk factors markedly attenuate the renoprotective effects of febuxostat.The online version of this article (doi:10.1186/s12882-017-0572-z) contains supplementary material, which is available to authorized users. Hyperuricemia has been reported to be a risk factor for kidney dysfunction –5. The mWe often find that CKD patients treated with antihyperuricemics show improved or maintained estimated glomerular filtration rate (eGFR) along with a reduction in serum UA level, whereas we also found cases showing none of the renoprotective effects. Since various risk factors for kidney dysfunction are involved in CKD progression, these factors could make it difficult to detect febuxostat-induced renoprotection.In this study, we investigated whether antihyperuricemic therapy using febuxostat exerts renoprotective effects in CKD patients and which patient characteristics influence these renoprotective effects.2 and/or urine protein was >0.5 mg/day, or both urinary blood and protein were present over 3 months. We excluded patients with acute kidney injuries (AKI), acute nephritis, or rapidly progressive glomerulonephritis from the current study. Fifteen patients discontinued the febuxostat treatment owing to adverse events during the follow-up period, and 19 patients required renal replacement therapy. Follow-up clinical data in 20 patients could not be obtained owing to change in hospital or discontinuation of attendance. A total of 178 cases could be analyzed. No patients died during the follow-up period. Among these 178 patients, 118 did not previously use any antihyperuricemic agents and 60 were switched from allopurinol or benzbromarone to febuxostat. In Japan, a low initial dosage (10 mg/day) is recommended (maximum dose 60 mg/day). Moreover, febuxostat is known to show an increased AUC in the patients with severe kidney dysfunction (GFR < 30 ml/min) [This was a single-center, retrospective, observational study. Two-hundred thirty-two CKD patients underwent antihyperuricemic therapy using febuxostat at the Department of Nephrology in Shinshu University Hospital between May 2011 and October 2014. Patients were defined as having CKD if eGFR was <60 ml/min/1.73m ml/min) , and carTo examine the effect of febuxostat therapy on changes in serum UA levels and eGFR, those parameters were measured at the time of febuxostat prescription, as well as 3 months and 6 months after therapy initiation. The correlation between mean serum uric acid level after treatment (mUA) and the change of eGFR after 6 months (6mΔeGFR) was analyzed using Spearman’s correlation. mUA was calculated as the mean serum UA level at 3 and 6 months. 6mΔeGFR was defined as the difference obtained by subtracting eGFR at treatment initiation from eGFR at 6 months. To investigate the effect of antihyperuricemic therapy for renal function lowering in CKD patients, we performed the correlation and ROC analyses using mUA and 6mΔeGFR data. Based on a calculated optimal cutoff level estimating progression of kidney dysfunction and standard goal of UA lowering therapy, the ΔeGFR was analyzed by dividing patients into mUA < 6.0 mg/dl and mUA ≥ 6.0 mg/dl groups.2), urine protein level (< 0.5 vs. ≥ 0.5 g/gCre), and antihyperuricemic naive vs. agent switching group. The patients who were using a lipid-lowering drug or showed an abnormal level of LDL or HDL cholesterol  were defined as having symptoms of abnormal cholesterol levels. The patients who were using an antidiabetic or presented above 6.2% of HbA1c (NGSP) in a blood examination were defined as diabetes mellitus.The correlation between mUA and 6mΔeGFR was analyzed in all patients or in patient subgroups based on characteristics at the start of the therapy. Each patient’s clinical data were collected from their medical records. The patient characteristics examined were sex, age (< 70 vs. ≥ 70 years), systolic blood pressure (< 130 vs. ≥ 130 mmHg), the presence or absence of an abnormal cholesterol level, the presence or absence of diabetes mellitus, eGFR  analysis software was used in this study. Differences were considered statistically significant at 2 (range: 7.3–101.7). Patient CKD stages at the start of treatment were 7% G1-2, 35% G3, and 58% G4-5. About 66% of patients had not used any antihyperuricemics previously, with the remaining 34% using allopurinol or benzbromarone. Febuxostat dose after 6 months was 10 mg/day in 58%, 20 mg/day in 34%, and 40 mg/day in 8% of patients.Patient characteristics are presented in Table There were 15 cases wherein febuxostat treatment was discontinued during the follow-up period owing to adverse events  curve using mUA and 6mΔeGFR data are shown in Additional file ΔeGFR measurements after febuxostat administration are shown in Fig. 2, urine protein levels 0.5 g/gCre, or antihyperuricemic naïve and agent switching groups (data not shown).The relationship between mUA and 6mΔeGFR showed a wide variation when all patients were grouped together, resulting in a low correlation coefficient. Therefore, the correlation was examined relative to specific patient characteristics after dividing the patients into various subgroups . In the subgroups with one to two vascular risk factors, a significant inverse correlation between mUA and 6mΔeGFR became obscure, and the correlation completely vanished in the subgroup with more than three cardiovascular risk factors.The correlations between mUA and 6mΔeGFR in subgroups divided based on the number of these vascular risk factors are shown in Additional file The changes of eGFR in each subgroup, which were further divided based on mUA levels, are shown in Fig. Attempts to control serum UA levels using previous antihyperuricemic medicines, including benzbromarone and allopurinol, in patients with kidney dysfunction, have proved difficult. Since benzbromarone is an agent that enhances urinary excretion of UA, its antihyperuricemic effect is attenuated by kidney dysfunction. Another XO inhibitor, allopurinol, is mainly excreted by urine; therefore, its serum concentration and adverse events are increased in the patients with kidney dysfunction, requiring dose reduction from an early phase of CKD and resulting in poor control of serum UA levels. Since febuxostat is excreted via dual excretion pathways, urine 49.1% and fecal 44.9% , febuxosMany studies have reported that hyperuricemia is a risk factor for the progression of kidney dysfunction in the general population, diabetes mellitus, AKI and CKD patients –5. ThereThe current subgroup analyses demonstrated that patients with parameters including male, < 70 years, systolic blood pressure < 130 mmHg, no abnormal cholesterol levels, or no diabetes mellitus are more likely to show an inverse correlation between mUA level and 6mΔeGFR, as well as amelioration of eGFR decline by UA lowering, than their opposite subgroups. This result suggests that the renoprotective effects of febuxostat differ among CKD patients. The factors masking the renoprotective effects detected in this study, including aging, hypertension, hyperlipidemia, and diabetes mellitus, are important vascular risk factors causing endothelial dysfunction and arteriosclerosis. XO activation and hyperuricemia are also thought to be vascular injury factors. XO activation increases oxidative stress, suppresses nitric oxide production, and activates the renin-angiotensin system . HyperurThe current findings do not negate the therapeutic significance of febuxostat treatment for CKD patients with various risk factors such as diabetes mellitus. Zoppini et al. reported that hyperuricemia is an independent risk factor for CKD progression in patients with type 2 diabetes [Limitations of this study include a small number of subjects from a short duration, single-center retrospective follow-up study. The analyses with small n-number and short-duration follow-up might show borderline significance values, especially in subgroup analyses. However, we believe that the findings of the current study would provide useful information for clinical studies in the future, by identifying the patient characteristics influencing the renoprotective effects of febuxostat therapy. Further clarification of the differences in the renoprotection effects by antihyperuricemic therapy among various patient subgroups will require future examination in large-scale, extended-duration, multi-center prospective studies. Second, the dosage of febuxostat in Japan differs from that in other countries due to safety assessment and the dose ranging studies. The proportions of patients with serum UA < 6.0 mg/dl were 40 mg, 56%; 80 mg, 76%; and 120 mg, 94% in the dose ranging study in USA , whereasFebuxostat therapy was effective in controlling the UA level in patients at any CKD stage and was highly safe. In the well-controlled UA level (mUA < 6.0 mg/dl) group, antihyperuricemic therapy using febuxostat may exert renoprotective effects. The effects are more likely to be detected in patients free of vascular risk factors, such as aging, hypertension, hyperlipidemia, and diabetes mellitus.Additional file 1: Table S1.Adverse events. There were 15 cases wherein febuxostat treatment was discontinued owing to various adverse events. In most patients, the adverse events developed during the initial dosing of febuxostat at 10 mg/day. (DOCX 18 kb)Additional file 2: Figure S1.n = 178). A correlation coefficient (r) and p-value (p) were analyzed using Spearman’s correlation analysis. (b) ROC analysis revealed that the calculated optimal cutoff level of mUA estimating progression of kidney dysfunction was 6.25 mg/dl . (PPTX 83 kb)Correlation between mUA and 6mΔeGFR, and ROC curve indicating mUA cutoff level estimating CKD progression. (a) Scatter plot indicating the correlation between mean serum uric acid (mUA) level and ΔeGFR after 6 months (6mΔeGFR)  vs. Women (n = 57), (b) Age < 70 (n = 107) vs. age ≥ 70 years (n = 71), (c) systolic blood pressure (sBP) < 130 (n = 95) vs. sBP ≥ 130 mmHg (n = 83), (d) normal cholesterol levels (n = 84) vs. abnormal cholesterol levels (n = 94), (e) absence of diabetes mellitus (n = 133) vs. diabetes mellitus (n = 45). A correlation coefficient (r) and p-value (p) were analyzed using Spearman’s correlation analysis. (PPTX 151 kb)Correlation between mUA and 6mΔeGFR in various subgroups. Scatter plots indicating the correlation between mean serum uric acid (mUA) level and ΔeGFR after 6 months (6mΔeGFR) in various subgroups. (a) Men , (b) one vascular risk factor (n = 55), (c) two vascular risk factors (n = 48), (d) three or four vascular risk factors (n = 45). A correlation coefficient (r) and p-value (p) were analyzed using Spearman’s correlation analysis. (PPTX 99 kb)Correlation between mUA and 6mΔeGFR in subgroups divided based on the number of vascular risk factors. Scatter plots indicating the correlation between mean serum uric acid (mUA) level and ΔeGFR after 6 months (6mΔeGFR) in subgroups divided based on the number of vascular risk factors. (a) No vascular risk factors (


Randomized controlled trials (RCT) have shown no overall benefit of renal revascularization in atherosclerotic renovascular disease (ARVD). However, 25% of patients demonstrate improvement in renal function. We used the ratio of magnetic resonance parenchymal volume (PV) to isotopic single kidney glomerular filtration rate (isoSKGFR) ratio as our method to prospectively identify "improvers" before revascularizationPatients with renal artery stenosis who were due revascularization were recruited alongside non-ARVD hypertensive CKD controls. Using the controls, 95% CI were calculated for expected PV:isoSK-GFR at given renal volumes. For ARVD patients, “improvers” were defined as having both >15% and >1ml/min increase in isoSK-GFR at 4 months after revascularization. Sensitivity and specificity of PV:isoSK-GFR for predicting improvers was calculated.30 patients (mean age 68 ±8 years), underwent revascularization, of whom 10 patients had intervention for bilateral RAS. Stented kidneys which manifested >15% improvement in function had larger PV:isoSK-GFR compared to controls . The sensitivity and specificity of this equation in predicting a positive renal functional outcome were 64% and 88% respectively. Use of PV:isoSK-GFR increased prediction of functional improvement (area under curve 0.93). Of note, non-RAS contralateral kidneys which improved (n = 5) also demonstrated larger PV:isoSK-GFR .This study offers early indicators that the ratio of PV:isoSK-GFR may help identify patients with kidneys suitable for renal revascularization which could improve patient selection for a procedure associated with risks. Calculation of the PV:isoSK-GFR ratio is easy, does not require MRI contrast agent. Atherosclerotic renovascular disease (ARVD) is highly prevalent amongst patients with CKD (up to 15% of CKD diagnoses ). SurvivHowever, many of these patients had asymptomatic or incidental renovascular disease, and others were excluded on the basis of an apparent pre-existing indication for intervention. Questions therefore remain regarding the wider applicability of the results of ASTRAL and CORAL to all patients with ARVD .It is recognised that many individuals with RAS do benefit from stenting. Observational studies demonstrate that 20–30% of patients show improvement in renal function after revascularization ,8. In adThe diversity in renal functional outcome after revascularization is thought to reflect the spectrum of the relative contributions of pre-existing parenchymal damage from long standing hypertensive, atheromatous and cytokine insult, in addition to the simple hemodynamic effects of the arterial narrowing, in the pathogenesis of the renal dysfunction , 10. In The aims of this study were: 1) to prospectively assess the validity and predictive power of the PV:isoSK-GFR measurement; 2) to observe the longterm outcome in patients predicted to improve after revascularization compared to those patients predicted to not improve. We also studied the PV: isoSK-GFR relationship in non-RAS contralateral kidneys to determine whether revascularization of a stenosed kidney can incidentally result in improvement in non-RAS contralateral kidneys as a result of change in systemic neurohumoral responses .Ethics approval was granted by South Manchester Ethics Committee UK REC ref: 07/Q1405/21 in accordance with the Declaration of Helsinki, and all patients gave written informed consent prior to inclusion. Patients presenting to our tertiary referral centre between January 2007 and December 2010 who were due to undergo renal revascularization were approached to participate in this study. The clinical decision to consider revascularization was based on: 1) clinical grounds  or 2) randomization into the revascularization arm of an ongoing clinical trial, either the ASTRAL (ISRCTN59586944) [Control patients were those attending the renal clinic in whom there had been clinical suspicion of ARVD , but who had no evidence of RAS detectable by MR or CT angiography. The purpose of this control group was to assess renal PV:isoSK-GFR changes in hypertensive patients without RAS  in order to devise an appropriate reference group for comparison of PV:isoSK-GFR.From our pilot study , kidneys51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) clearance. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy was then used to assess the differential static radioisotope uptake of each kidney. The isoSK-GFR was expressed as an absolute individual value in ml/min and not ml/min/1.73m2 as body surface area was calculated for each patient. In patients who underwent renal revascularization, isoSK-GFR was also repeated at 4 months following the procedure. The daily variation in isoSK-GFR has been shown to be 8.8% [All patients underwent baseline assessment of individual kidney function involving a standard radioisotopic methodology –16. Over be 8.8% . The criData were collected using a 3 T whole-body MR scanner . Following acquisition of scout images a 3D imaging volume was acquired using a T1-weighted spoiled gradient echo acquisition in the oblique-coronal plane. The volume encompassed both kidneys and the descending aorta and the data were obtained in a single breathhold. Gadolinium was not used for acquisition of the data. The following parameters were used for the acquistion: TR = 4.0ms, TE = 1.0ms, FOV = 400x400x80mm, flip angle = 14 degrees, 2 signal averages, parallel acquisition using a SENSE factor = 2, following interpolation in the Fourier domain matrix = 256x256x40). The parenchymal volumes were calculated from the 3D volume images using the voxel-count method as we have previously described,17.With renal damage and shrinkage, loss of cortical tissue occurs to a greater degree than that of the medulla  and hencParametric data are presented as mean±standard deviation and non-parametric data as median (interquartile range). Differences in baseline continuous variables between groups were assessed using ANOVA with natural log transformation applied to non-normal varaibles; baseline categorical variables were compared using chi-square test.To account for possible effects of regression to the mean due to the non-randomized design, between group comparison of MRI parameters of kidneys with stable, improving or deterirorating function post-revascularization was performed using analysis of covariance (ANCOVA) incorporating follow-up isoSK-GFR data in a least squared means model. Homogeneity of slopes was assessed by including a class-by-covariate interaction term and ANCOVA plots . Standard error results were calculated to compare the study population mean versus the mean of the true population.As follow up isoSK-GFR data were not obtained for control kidneys, comparison between these and revascularized kidneys was made using standard ANOVA methodology. Sensitivity / specificity analysis was performed using receiver operating characteristic (ROC) curves and integrated discrimination improvement analysis with isoSK-GFR data considered in addition to baseline renal functional parameters.st December 2015. A Cox proportional hazard model was used, adjusted for age and overall GFR at baseline. The study was not powered specifically for this survival analysis.A survival analysis was performed to compare outcome in improvers versus non-improvers. Because some patients underwent bilateral revascularization, for this analysis responders were defined as those patients with improvement in isoSK-GFR >15% of any revascularized kidney. Outcome was all-cause mortality and follow up was until death or 31In all cases statistical significance was defined as an alpha value of <0.05. Analyses were performed in SAS version 9.2  under licence to the University of Manchester with figures generated in R version 3.0.1.During the study period, 275 patients were screened for ARVD. These patients had a mean age of 68±10 years. Patient recruitment is summarised in The baseline phenotype of the study subjects is shown in Indications for revascularization were: randomized to revascularization within the ASTRAL and CORAL trials (n = 7), severe hypertension (n = 8), rapidly deteriorating renal function (n = 9), flash pulmonary oedema (n = 2), poorly controlled heart failure and chest pain (n = 1), to preserve renal mass or prevent renal artery occlusion (RAO) during planned cardiac bypass (n = 2), to enable use of renin angiotensin blockade (RAB) for treatment of hypertension and proteinuria (n = 1).There was no significant difference in baseline renal function between stented kidneys and contralateral kidneys, although contralateral kidneys which remained stable tended to have better baseline isoSK-GFR and larger volumes. Stented kidneys which improved had a mean PV:isoSK-GFR ratio 2.8 times larger than those which remained stable or deteriorated, and 3.1 times greater than controls. The PV:isoSK-GFR ratio of stented kidneys which improved was noted to decrease significantly post revascularization .Contralateral kidneys that improved had PV:isoSK-GFR ratios 1.7 and 1.5 times greater than contralateral kidneys which remained stable or deteriorated respectively, and 2.4 times greater than control kidneys.The mean change in overall radioisotope GFR from pre-stent baseline to 4 months post-procedure for the 30 patients who underwent revascularization was 1.3±12.4 mL/min. For the 40 stented kidneys, the mean change in isoSK-GFR was 1.2±10.2 mL/min and for the 20 non-RAS contralateral kidneys the mean change was 0.5±2.1 mL/min. Differences in MRI and radioisotope measurements between patients with improving / stable / deteriorating isoSK-GFR after revascularization are shown in There was no significant correlation between severity of RAS and isoSK-GFR , PV  or PV:isoSK-GFR . Male patient improver kidneys had larger volumes than female kidneys. However, there was no significant between sex difference in the PV:isoSK-GFR ratio.Control kidneys were grouped into 5 reference categories according to their baseline volumes (ml) and isoSK-GFR. The PV:isoSK-GFR ratios were calculated for each volume group . The ratThe area under the ROC curve (AUC) for baseline isoSK-GFR in predicting a >15% increase in isoSK-GFR following revascularization was 0.81. When PV:isoSK-GFR was added this increased to 0.93 with an integrated discrimination improvement of 0.27, p = 0.001 .The sensitivity and specificity of PV:isoSK-GFR ratio in predicting beneficial functional outcomes for stented kidneys were 64% and 88%, respectively . The ratOver a mean 6.1±2.6 years follow up after revascularization, there were 12 deaths in the treatment group (40%); 5 patients progressed to end stage kidney disease necessitating dialysis (28%), of whom 2 died. The estimate of mean survival time for improvers was 6.7 year (95% CI 5.3–8.2 years) compared with 5.7 (4.3–7.1) years in non-improvers, and 7.4 (6.3–8.5) years in the control group. In a Cox proportional hazard model adjusted for baseline age, GFR, gender, diabetes, blood pressure, and coronary artery disease the hazard ratio for death in improvers versus non-improvers was 0.51 (0.16–1.61), p = 0.251. Survival curves comparing improvers with non-improvers and showing control patients is found in The Cox proportional hazard model was repeated to compare those predicted to respond versus those predicted to not respond, based on isoSK:GFR. Here, the adjusted hazard ratio for death in predicted improvers versus predicted non-improvers was 0.54 (0.15–1.95), p = 0.354.To observe the potential effect of differences in blood pressure control after revascularization on outcome in improvers versus non-improvers, we compared baseline blood pressure and change in blood pressure at one month after revascularization between the two groups. The mean baseline systolic blood pressure in improvers was 159±25 mmHg compared with 158±33 mmHg in non-improvers (unpaired t-test p = 0.774); baseline diastolic blood pressures were 87±17 mmHg and 78±17 mmHg, respectively (p = 0.143). The mean changes in systolic blood pressure were -19±42mmHg in improvers and -17±63mmHg (p = 0.463) in non-improvers, and change in diastolic blood pressure was -6±18mmHg and -8±32mmHg respectively, (p = 0.865).The most important finding of this study was that a higher PV:isoSK-GFR ratio pre-revascularization is noted in patients whose renal function improves after revascularization. Stented kidneys which improved had a ratio 3 times higher than those which deteriorated or remained stable. The higher the PV:isoSK-GFR, the more specific the ratio was in determining outcome, although the sensitivity remained moderate (Sig 1). Using ROC analysis, RAS kidneys improved 94% of the time if PV:isoSK-GFR is >95% CI of the control group. In this study, 27% of kidneys improved, which is comparable to other studies that have reported on renal functional response. This emphasizes the need for suitable pre-selection criteria .Importantly, improvement was seen even in kidneys with small SK-GFR (6 revascularized kidneys had baseline isoSK-GFR <10ml/min). These kidneys would not usually have been considered suitable for revascularization by most clinicians. However, a previous twin centre study has shown that the most significant improvements in renal function may actually accompany revascularization of ARVD patients with advanced CKD , and theAnother finding of this study is that some non-ARVD, non-revascularized kidneys contralateral to the revascularized kidney also experienced an improvement in renal function if they had a larger baseline PV:isoSK-GFR. This was more likely in but not exclusive to cases where the stented kidney improved.We presume that this improvement in contralateral kidneys relates to neurohumoral changes  or sympathetic nerve activity, or changes in blood pressure control. Thus even kidneys not directly affected by RAS may have the potential for improvement, and the implication is that the PV:SK-GFR may serve as a surrogate of renal functional reserve in either kidney.The improver contralateral kidneys with larger PV: isoSK-GFR did not demonstrate a significant drop in this ratio post revascularization, unlike the stented kidneys which did. Both volume and isoSK-GFR improvements occurred in the contralateral kidneys, whereas the isoSK-GFR improvement seemed to exceed that of volume expansion in the stented kidney. One hypothesis to explain these differences could be that ‘hibernating parenchyma’ was present within the improver stented kidneys, with return of blood flow to the ischaemic tissue leading to proportionately greater improvement of GFR rather than volume, given that irreversible structural change had not occurred. In our previous pilot study , we founThe survival analysis showed a numerical but not statistical survival benefit for improvers over non-improvers. In fact, that outcome for improvers more closely matched that of the control patients than the non-improvers. This must be taken in the context of the fact that this study was not powered to a survival analysis. Nonetheless, such a trend towards improved survival in the improver group supports the hypothesis that not only can PV:isoSK-GFR predict the likelihood of a renal functional response to revascularization but that such a response is a surrogate for improved prognosis for ARVD patients. Given the neutral results of ASTRAL and CORAL indicating that revascularization should not be seen as first line therapy for the majority of patients with ARVD, a simple technique such as that described here may enhance the required screening to select those patients who should be revascularized.The key limitation of this study is the small patient numbers. This was a pilot study and not designed to provide conclusive answers. Nonetheless, it does inform us that this is an area of potential clinically utility in the future. A second limitation of this study is the two-stop nature of the diagnostic tool. A one-stop approach would benefit patients and likely be more cost-effective in day to day practice. We have previously described the use of BOLD MRI signal in predicting renal functional response to revascularization with similar sensitivity and specificity to the volume based approached described here . The useS1 Fig(XLSX)Click here for additional data file.