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Additional file 1: Supplementary table 1. Patients characteristics according to median eGFR value at T1.

Literature analysis suggests that chlortalidone as first-line antihypertensive agent outperforms hydrochlorothiazide.

Background-Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (gamma-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results-We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI wasmeasured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44 +/- 0.20 nmol/L for dp-ucMGP and 64 +/- 5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (55 years; P=0.016 and P Conclusions-Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.

Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (55 years; P=0.016 and P

Arterial hypotension is a frequently encountered phenomenon in clinical practice. It is responsible for multiple consultations and/or hospitalizations, mostly in elderly people. It is associated with an increased morbidity and mortality. Arterial hypotension can be constitutional, part of a syndrome, orthostatic, or secondary (drug induced, hypovolemia). The diagnosis can be done by measuring the blood pressure in the supine position, sitting and standing position, and by 24h ambulatory blood pressure monitoring. The first line of treatment is non-drug therapies . The most frequently used medical treatments are midodrine, and fludrocortisone. However specific molecules as droxidopa, pyridostigmine, erythropoietin can also sometimes be indicated.L’hypotension artérielle est une condition fréquente. Elle génère de nombreuses consultations et est responsable d’un nombre important d’hospitalisations, surtout chez les patients âgés. Elle est associée à une augmentation des risques de morbidité et de mortalité. L’hypotension artérielle peut être constitutionnelle, liée à un syndrome, orthostatique, ou le plus souvent secondaire (médicamenteuse, baisse de la volémie). Le diagnostic se fait par une mesure de la tension artérielle en position couchée/assise et debout, voire une mesure de la tension artérielle de 24 heures. Le traitement de première ligne est non pharmacologique. Le traitement médicamenteux comprend essentiellement la midodrine et la fludrocortisone. Certains traitements plus spécifiques, droxidopa, érythropoïétine, pyridostigmine peuvent avoir aussi leur place.

Background: Blood pressure (BP) response after renal denervation (RDN) is highly variable. Besides baseline BP, no reliable predictors of response have been consistently identified. The differences between patients showing a major BP decrease after RDN vs. nonresponders have not been studied so far. Aim and methods: We identified extreme BP responders (first quintile) and nonresponders (fifth quintile) to RDN defined according to office or 24-h ambulatory BP in the European Network COordinating research on Renal Denervation database (n = 109) and compared the baseline characteristics and BP changes 6 months after RDN in both subsets. Results: In extreme responders defined according to ambulatory BP, baseline BP and BP changes 6 months after RDN were similar for office and out-of-the office BP. In contrast, extreme responders defined according to office BP were characterized by a huge white-coat effect at baseline, with dramatic shrinkage at 6 months. Compared with nonresponders, extreme responders defined according to office BP were more frequently women, had higher baseline office - but not ambulatory - BP, and higher estimated glomerular filtration rate (eGFR). In contrast, when considering ambulatory BP decrease to define extreme responders and nonresponders, the single relevant difference between both subsets was baseline ambulatory BP. Conclusion: This study suggests a major overestimation of BP response after RDN in extreme responders defined according to office, but not ambulatory BP. The association of lower eGFR with poor response to RDN is consistent with our previous analysis. The increased proportion of women in extreme responders may reflect sex differences in drug adherence.

Introduction and Aims: Hyperkalaemia is a risk factor for mortality in patients with cardiovascular disease and chronic kidney disease (CKD) (Goyal, 2012; Torlen, 2012) and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi) in these patients. Sodium (or calcium) polystyrene sulfonate (SPS/CPS) has uncertain efficacy and has been associated with substantial adverse events, as well as poor gastrointestinal tolerability, and hence is suboptimal for acute use and unsuitable for chronic use (Harel, 2013; Sterns, 2010). Therefore, there is a need for a hyperkalaemia treatment that rapidly reduces serum potassium (K+) and is safe and well tolerated in these patients. ZS-9, a nonabsorbed cation exchanger designed to specifically entrap excess K +, significantly reduced K+ vs placebo over 48 hr with excellent tolerability in patients with CKD (Ash, 2013). We report acute-phase efficacy in a Phase 3 trial of ZS-9 in patients with hyperkalemia. Methods: Patients (N=753) with serum K+ 5.0-6.5 mmol/L were randomised (1:1:1:1:1) to ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo given three times daily (TID) with meals for 48 hr (acute phase), after which those with K+ ≤4.9 mmol/L (n=542) were re-randomised to ZS-9 or placebo once daily for Day 3-15. Serum K+ was measured at baseline and at predefined intervals, including 1, 4, 24, and 48 hr after the first dose. The acute-phase primary efficacy endpoint was the rate of K+ change over the first 48 hr, using longitudinal modeling to account for all post-baseline data. Results:Mean K+ at baseline was 5.3 mmol/L. Substantial percentages of patients had CKD (60%), a history of heart failure (40%), or diabetes (60%) or were on RAASi therapy (67%). ZS-9 demonstrated significant dose-dependent reductions in K+; the acute-phase primary efficacy endpoint was met for ZS-9 2.5g (p=0.0009), 5g (p

Objective:Poor adherence to drug therapy is one of the most common factor explaining a poor blood pressures (BP) control in patients with apparent resistant hypertension. Few studies have used a standardized treatment coupled to electronic adherence monitoring in patients with apparent resistant hyp

OBJECTIVE Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P

L’hypotension orthostatique, souvent sévère, est une manifestation bien reconnue dans les dysautonomies associées à des neuropathies, ou d’autres affections systémiques (diabète). Par contre, les symptômes orthostatiques à type de pré-syncope, associés à une chute relativement modeste de la pression artérielle à l’orthostatisme, sont une entité mal connue, et font non rarement l’objet de consultations. Récemment a été reconnu le syndrome de tachycardie orthostatique ajoutant à ce tableau, une tachycardie posturale et une augmentation des catécholamines plasmatiques. Nous passons en revue dans cette article les différentes causes d’hypotension orthostatique, neurogène ou non, et nous évoquons quelques mécanismes physiopathologiques ayant trait à l’homéostasie sodique rénale dans l’hypotension. En particulier, des altérations de l’homéostasie sodique rénale pourraient contribuer à engendrer et maintenir ce syndrome, et pourraient être partiellement corrigées par l’apport de sel. Enfin, nous faisons le point sur les modalités thérapeutiques.

Objective To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. Patients Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. Study design After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. Results Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). Conclusions Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

A sensitive HPLC method with electrochemical detection was developed for the determination of the polyfructosan sinistrin in human plasma and urine. Proteins and interfering components such as glucose were removed from plasma and urine samples by solid phase extraction on C18 cartridges. Chromatographic separations were achieved at 85 degrees C on a 300 mm x 7.8 mm i.d. column, using ion moderated partition chromatography with distilled water at a flow rate of 0.6 ml min-1. After post-column addition of NaOH 0.3 M (0.6 ml min-1), the electrochemical detection of the eluate was performed with a sequence of three potentials (0.05 V, -0.8 V, 0.6 V) of specific pulse duration 300, 100 and 100 ms respectively. Xylose was used as internal standard for the quantitative determinations. The calibration curves were linear (r20.992) over the working range 5-300 micrograms ml-1. This method has been characterized, validated and applied successfully in a study comparing two modes of glomerular filtration rate determination in healthy volunteers (bolus vs. constant rate infusion of sinistrin).