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High blood pressure [keywords]
- KCa3.1: a new player in progressive kidney disease. [JOURNAL ARTICLE]
- Curr Opin Nephrol Hypertens 2014 Nov 19.
Hypertension and hyperglycaemia are major risk factors that result in chronic kidney disease (CKD). Achievement of blood pressure goals, optimal control of blood glucose levels and the use of agents to block the renin-angiotensin-aldosterone system slow the progression of CKD. However, not all patients are benefited by these interventions and novel strategies to arrest or reverse the pathological processes inherent in CKD are needed. The therapeutic potential of targeting KCa3.1 in CKD will be discussed in this review.Blockade of KCa3.1 ameliorates activation of renal fibroblasts in diabetic mice by inhibiting the transforming growth factor-β1/small mothers against decapentaplegic pathway. A concomitant reduction in nuclear factor-κB activation in human proximal tubular cells under diabetic conditions has been observed. Advanced glycosylated endproducts induce both protein expression and current density of KCa3.1, which, in turn, mediates migration and proliferation of vascular smooth muscle cells via Ca-dependent signalling pathways.Studies have clearly demonstrated a causal role of chronic hyperglycaemia and hypertension in the development of CKD. However, a large proportion of patients develop end-stage kidney disease despite strict glycaemic control and the attainment of recommended blood pressure goals. Therefore, it is essential to identify and validate novel targets to reduce the development and progression of CKD. Recent findings demonstrate that genetic deletion or pharmacologic inhibition of KCa3.1 significantly reduces the development of diabetic nephropathy in animal models. However, the consequences of blockade of KCa3.1 in preventing and treating established diabetic nephropathy in humans warrants further study.
- Longitudinal change in end-digit preference in blood pressure recordings of patients with hypertension in primary care clinics: Minhang study. [JOURNAL ARTICLE]
- Blood Press Monit 2014 Nov 20.
End-digit preference (EDP) of blood pressure (BP) has been reported in both general hospitals and primary clinics worldwide. We aimed to observe the longitudinal changes in EDP of BP recordings in hypertension patients and to estimate the impact of hypertension treatment target (140/90 mmHg) on the EDP of BP in Chinese primary care clinics.A total of 318 898 BP readings from 16 433 hypertensive patients were obtained from the electronic health record of Xinzhuang town hospital in Shanghai from 1 January 2007, to 27 September 2011. The terminal digits of the recorded systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed. Zero preference was also analyzed according to the year and follow-ups, respectively.In all, 62.5% of SBP readings and 63.5% of DBP readings ended in zero. The zero preference of SBP was reduced from the 75.2% in 2007 to 55.9% in 2011. In addition, the zero preference decreased from the 78.6% at the registration to 58.7% at the 25th follow-up. Moreover, compared with other BP levels, hypertension treatment target was associated with increased preference for the eight end-digit for both SBP and DBP (P<0.001).This study showed a decrease in zero EDP in hypertension patients managed in the Chinese community. The hypertension treatment target was associated with sub-target-EDP. Future efforts should focus on comprehensive education, coupled with the use of well-calibrated electronic BP monitors.
- Safety and efficacy of outpatient biopsy in renal transplantation. [JOURNAL ARTICLE]
- Nefrologia 2014 Nov 17; 34(6):749-755.
Background: In many centers patients are hospitalised to perform a renal allograft biopsy. Aim: To evaluate the safety and efficacy of outpatient renal allograft biopsies. Methods: Since December 2011 we perform renal allograft biopsies as an outpatient procedure. Exclusion criteria for performing an outpatient biopsy included: 1.) anticoagulant treatment, 2.) thrombocytopenia <50,000/mm3, 3.) body mass index >35kg/m2 and 4.) uncontrolled hypertension. The number and severity of complications were compared with an historical cohort of 124 biopsies done between 2007 and 2011 when all patients were hospitalised for the procedure and with 42 patients biopsied during hospitalisation between 2011 and 2013. Results: Between 2011 and 2013, 210 (95%) out of 230 biopsies indicated in the outclinic were performed as an outpatient procedure (95%). The incidence of major complications (bleeding requiring blood transfusion and/or embolisation) was 0.8% between 2007 and 2011 and 2.4% in biopsies between 2011 and 2013 in hospitalised patients (p=0.475). No major complications were observed in the outpatient biopsy group. Minor complications (hematuria, hematoma or fistula not requiring transfusion or embolisation) were also not different between groups (3.2%, 7.1% and 2.7%; respectively). Sample size adequacy according to the Banff criteria was not different among groups (p=0.052). Conclusion: Ambulatory renal allograft biopsy is a safe and efficient procedure.
- Clinical, analytical and bioimpedance characteristics of persistently overhydrated haemodialysis patients. [JOURNAL ARTICLE]
- Nefrologia 2014 Nov 17; 34(6):716-723.
Background: Fluid overload is an important and modifiable cardiovascular risk factor for haemodialysis patients. So far, the diagnosis was based on clinical methods alone. Nowadays, we have new tools to assess more objectively the hydration status of the patients on haemodialysis, as BCM (Body Composition Monitor). A Relative Overhydration (AvROH) higher than 15% (it means, Absolute Overhydration or AWOH higher than 2.5 Litres) is associated to greater risk in haemodialysis. However, there is a group of maintained hyperhydrated patients. The aim of the present study is to identify the characteristics of patients with maintained hyperhydrated status (AvROH higher than 15% or AWOH higher than 2.5 liters). The secondary aim is to show the hemodynamic and analytical changes that are related to the reduction in hyperhydration status. Methods: Longitudinal cohort study during six months in 2959 patients in haemodialysis (HD) that are grouped according to their hydration status by BCM. And we compare their clinical, analytical and bioimpedance spectroscopy parameters. Results: The change in overhydration status is followed by a decrease in blood pressure and the need for hypotensive drugs (AHT) and erythropoiesis stimulating agents (ESA). The target hydration status is not reached by two subgroups of patients. First, in diabetic patients with a high comorbidity index and high number of hypotensive drugs (AHT) but a great positive sodium gradient during dialysis sessions; and, younger non-diabetic patients with longer time on hemodialysis and positive sodium gradient, lower fat tissue index (FTI) but similar lean tissue index (LTI) and albumin than those with a reduction in hyperhydration status. Conclusion: Those patients with a reduction in hyperhydration status, also show a better control in blood pressure and anemia with less number of AHT and ESA. The maintained hyperhydrated patients, diabetic patients with many comorbidities and young men patients with longer time on hemodialysis and non-adherence treatment, can profit from a constant monitoring of their hydration state as well as an individualized treatment (dialysis and drugs).
- Hypertriglyceridemia and Cardiovascular Outcomes. [JOURNAL ARTICLE]
- Am J Ther 2014 Nov 19.
Cardiovascular disease, particularly ischemic heart disease, is one of the most common causes of morbidity and mortality in the United States. Atherosclerosis, the root cause of ischemic heart disease, is promoted by risk factors like elevated plasma low-density lipoprotein, low plasma high-density lipoprotein, smoking, hypertension, and diabetes mellitus. Even 66 years after a relation between triglycerides (TG) and cardiovascular disease was first suspected, TGs still continue to be a controversial risk factor and target for therapy. Some previous studies did not show any significant positive relationship between TG and cardiovascular mortality; however, recent meta-analyses found otherwise. The role of elevated TG in patients with low low-density lipoprotein and interventions to lower TG to reduce cardiovascular mortality and morbidity is an area of active research.
- Prevalence of Co-morbidities and severity of COPD. [JOURNAL ARTICLE]
- COPD 2014 Nov 21.
Abstract We aimed at exploring whether the prevalence of co-morbidities of chronic obstructive pulmonary disease (COPD) increases with COPD severity. Analysis of medical records of outpatients with established diagnosis of COPD was retrospectively performed. The lower limit of normality (LLN) for FEV1/FVC was applied to establish the occurrence of airway obstruction in the elderly population. The prevalence of co-morbidities was calculated, and the proportion of patients with each co-morbidity along with GOLD stages was analysed by chi-square for trend. A total of 326 (M/F: 256/70) consecutive outpatients with COPD (stage GOLD I to IV), aging 71.8 ± 9.2 years, were included in the analysis. The most frequent co-morbidities in the entire sample were systemic hypertension (64.7%), diabetes (28.5%), coronary artery disease (19.9%), arrhythmias (16.6%) and congestive heart failure (13.8%). Underweight patients were 8.0% of the sample while obese patients were 22.4%. None of the analyzed co-morbidities showed a trend towards increasing prevalence with COPD severity, except for nutritional problems. The current findings suggest that the occurrence and prevalence of co-morbidities is independent from the COPD severity, and encourage to assess co-morbidities even in the early stages of the COPD.
- Association of Metabolic Syndrome with Decreased Glomerular Filtration Rate among 75,468 Chinese Adults: A Cross-Sectional Study. [JOURNAL ARTICLE]
- PLoS One 2014; 9(11):e113450.
The impact of the various elements of metabolic syndrome (MetS) on chronic kidney disease (CKD) has been conflicting. Therefore, in the present study we aimed to examine the association of MetS and its components with decreased glomerular filtration rate (GFR).A total of 75,468 urban workers who underwent annual health examinations under the auspices of the local governments between March 2010 and September 2012 at the health examination center of Xuzhou center hospital were enrolled in the cross-sectional survey. Decreased GFR was defined as an estimated GFR <60 mL/min per 1.73 m2. The definition of MetS was based on the most-recent interim joint consensus definition, requiring any three of the five components, consisting of elevated blood pressure (BP), fasting plasma glucose (FPG), or triglycerides (TG), reduced high density lipoprotein-cholesterol (HDL-c), and obesity.MetS was related to the reduced GFR with an odds ratio [95% confidence interval (CI)] of 1.43 (1.13-1.83). In multivariable analyses, individual components of MetS that were independently associated with decreased GFR were elevated BP (OR 1.34, 95% CI 1.00-1.78), low HDL-c (OR 1.88, 95% CI 1.44-2.43), and elevated FPG (OR 1.42, 95% CI 1.09-1.85). The age-adjusted population-attributable risk percent (PARP) for reduced GFR was 27.55%, 19.67% and14.31% for elevated BP, low HDL-c and elevated FPG respectively. The multivariate-adjusted odds ratios (95% CI) of decreased GFR were 1.70(1.11-2.60), 2.38(1.53-3.71), or 4.11(2.42-6.98) for those with 1, 2, or 3 critical elements (versus zero), respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of decreased GFR were 1.11(0.84-1.48) and 0.89(0.63-1.27) for those with 1 or 2 noncritical components (versus zero), respectively.We concluded that various elements of MetS and the cumulative number of MetS should not be considered indiscriminately as risk factors for reduced GFR.
- mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity. [JOURNAL ARTICLE]
- J Clin Invest 2014 Nov 21.
The epithelial Na+ channel (ENaC) is essential for Na+ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na+ and K+ transport in WT and Sgk1-/- mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na+ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K+ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na+ homeostasis through SGK1-dependent modulation of ENaC activity.
- Hypoxia-Mediated Soluble Fms-Like Tyrosine Kinase 1 Increase is Not Attenuated in Interleukin 6-Deficient Mice. [JOURNAL ARTICLE]
- Reprod Sci 2014 Nov 18.
The soluble fms-like tyrosine kinase 1 (sFlt-1), known to be increased in the serum of preeclamptic patients, is a relevant factor in causing maternal symptoms like hypertension and proteinuria. In this study, we aimed to reveal whether hypoxia is a cause of increased sFlt-1 levels and inflammation markers in vivo and whether these symptoms can be attenuated by interleukin 6 (IL-6) depletion. For this purpose, pregnant wild-type (wt) mice or IL-6(-/-) mice on embryonic day 16 were placed under either normoxic (20.9% oxygen) or hypoxic (6% oxygen) conditions for 6 hours. This led to a rise of sFlt-1 levels in maternal serum, independent of the IL-6 status of the dam. Increased maternal sFlt-1 serum levels were, however, not due to an increase in sFlt-1 messenger RNA levels in the placenta. Moreover, there was no increase in inflammatory markers in neither wt mice nor IL-6(-/-) mice. This suggests that hypoxia alone does not contribute to the induction of an inflammatory placenta. Also, the hypoxia-induced rise in sFlt-1 levels seems not to be mediated by IL-6 in vivo.
- Prevalence and Associated Factors of Hypertension among Adults in Durame Town, Southern Ethiopia. [JOURNAL ARTICLE]
- PLoS One 2014; 9(11):e112790.
To date, non-communicable diseases, such as cardiovascular diseases, are becoming severe public health challenges particularly in developing countries. Hypertension is a modifiable risk factor that contributes the leading role for mortality. The problem is significant in low- and middle-income countries like sub-Saharan Africa. However, there are limited studies in developing countries, particularly in Ethiopia. Hence, determining the magnitude of hypertension and identifying risk groups are important.A community based cross sectional study was conducted in April 2013 among adults (age>31 years) old. A systematic sampling technique was used to select a total of 518 study participants. Data were collected after full verbal informed consent was obtained from each participant. Multivariable logistic regressions were fitted to control the effect of confounding. Adjusted Odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated to measure associations. Variables having P-value <0.05 were considered as significant.The overall prevalence of hypertension in Durame town was 22.4% (95% CI: 18.8-26.0). Nearly 40% of hypertensive patients were newly screened. Male sex [AOR = 2.03, 95% CI; 1.05-3.93], age [AOR = 29.49, 95% CI; 10.60-81.27], salt use [AOR = 6.55, 95% CI; 2.31-18.53], eating vegetable three or fewer days per week [AOR = 2.3,95% CI; 1.17-4.51], not continuously walking at least for 10 minutes per day [AOR = 7.82, 95% CI; 2.37-25.82], having family history of hypertension [AOR = 2.46, 95%CI; 1.31-4.61] and being overweight/obese [AOR = 15.7, 95% CI 7.89-31.21)] were found to be risk factors for hypertension.The prevalence of hypertension is found to be high. Older age, male sex, having family history of hypertension, physical inactivity, poor vegetable diet, additional salt consumption and obesity were important risk factors associated with hypertension among adults. Community level intervention measures with a particular emphasis on prevention by introducing lifestyle modifications are recommended.