Objectives were to validate the new adherence scale and its prediction of hypertension control, compared to MMAS-8, and to assess adherence rates and factors. A new Lebanese scale measuring medication adherence considered socioeconomic and cultural factors not taken into account by the eight-item Morisky Medication Adherence Scale (MMAS-8). A cross-sectional study, including 405 patients, was performed in outpatient cardiology clinics of three hospitals in Beirut. Blood pressure was measured, a questionnaire filled, and sodium intake estimated by a urine test. Logistic regression defined predictors of hypertension control and adherence.p value = 0.003), unlike MMAS-8, but the scores were correlated . Stress and smoking predicted nonadherence. 54.9% had controlled hypertension. 82.4% were adherent by the new scale, which showed good internal consistency, adequate questions (KMO coefficient = 0.743), and four factors. It predicted hypertension control (OR = 1.217;  This study elaborated a validated, practical, and useful tool measuring adherence to medications in Lebanese hypertensive patients. Hypertension is an international public health burden that caused around 9,4 million deaths in 2010 , as wellMedication adherence was defined by the WHO as “the extent to which a person's behavior, taking medication, following a diet, and/or executing lifestyle changes, corresponds to agreed recommendations from a healthcare provider” . In LebaThe primary objective of this study was to validate the LMAS in Lebanese hypertensive adults, to assess its ability to predict hypertension control, and to compare it with MMAS-8. The secondary objective was to evaluate the adherence rate in Lebanese hypertensive adults, and to determine factors affecting antihypertensive adherence.The new score (LMAS) was inspired by the Morisky score, adding other variables affecting adherence, discussed by the investigators with physicians and community pharmacists in a focus group. The reasons why MMAS-8 was our source of inspiration were its simplicity and validity, as well as its common use among clinicians and researchers (in Lebanon and elsewhere) to asses antihypertensives adherence. MMAS-8 contains seven questions with dichotomic answer (yes/no) and one Likert scale question with five possibilities and measures forgetfulness, medication taking behavior, and secondary effects . The AraLMAS assessed forgetfulness by a question evaluating its frequency, inspired by merging MMAS-8's questions regarding forgetfulness which investigate the past day, the past two weeks, and the general forgetting behavior. Moreover, a question regarding the frequency of reminders'  use to increase adherence was added, knowing that social interactions take a privileged place in the Lebanese culture and that reminders might affect adherence. Also inspired from MMAS-8, we included questions evaluating adherence change if the patients felt clinically better or worse, but behavior change if laboratory exams improved was added to LMAS. Furthermore, adherence when away from home was included in the new score, with an adaptation by adding suggestions of outdoor diner or lunch. A question regarding adherence during busy periods was also included in LMAS. In addition, economic factors, like adherence when health coverage does not pay for the medicine and delay in buying a new pills box when the old one becomes empty, were included in LMAS. Besides, adherence behaviors in case of boredom, if some food items were prohibited during treatment period, or if the patient or his neighbor (because these issues could be discussed often between Lebanese patients) experienced any secondary effects, were evaluated. Likewise, adherence behavior when the patients noticed that they took a lot of pills was tested. Consequently, LMAS contained 16 Likert scale questions with four options to answer each (coded from zero (less adherence) to three (higher adherence)) and was subject to validation.An observational cross-sectional study was conducted. Patients were recruited from the outpatient cardiology clinics of three hospitals in Beirut, visited at random dates in 2016, during patients' appointments. Patients matching the inclusion criteria were invited to participate in the study, after signing a written informed consent. Their blood pressure was measured twice, at a 10-minute interval, with their right hand placed at the level of the heart , with thThe INTERSALT equation was used to assess mean sodium intake of treated Lebanese hypertensive patients, as this equation had less bias . To reduPatients included were Lebanese, aged 18 years and above, with primary hypertension diagnosed at least six months ago, treated with antihypertensives for at least the past six weeks, and having signed the informed consent. Exclusion criteria were secondary hypertension, pregnant women, being hospitalized, dement, or mentally disabled, and patients with physical disability or any infection affecting blood pressure.A ratio of 20 : 1 (number of subjects : number of items) was used to calculate sample size . This coSociodemographic characteristics of the patients were assessed. Lifestyle characteristics included BMI, physical activity (in minutes/week), stress level during the last three months, smoking status and amount , caffeiJ = maximum (sensibility + specificity − 1). [We used SPSS version 20 for data entry and analysis. To validate LMAS, an exploratory factor analysis with Varimax rotation was done, leading to the reduced dimension score (LMAS-14). Internal consistency of LMAS-14 was assessed using Cronbach alpha, which showed good internal consistency when it was >0.5. Sensitivity and specificity were shown by ROC curve, with hypertension control as a reference variable. Cut-off value was determined by Youden Index, defined as ty − 1). . Logistip value ≤ 0.2 in bivariate analysis was included in the logistic regression (backward LR method). A cut-off of 6 was admitted to classify patients as adherent (MMAS-8 score between 6 and 8) and nonadherent (MMAS-8 score < 6). A cut-off value for classifying patients for the LMAS-14 was determined by ROC curve and Youden Index.To determine the factors affecting medication adherence, the dependent variable was adherence measured by LMAS-14. Each variable with Patients' mean age was 65 years; almost half (52.2%) were females and the majority resided in Beirut (47.2%). 12.9% had no health coverage. As for lifestyle, almost half of patients (42.2%) had a moderate stress level .Mean blood pressure measured was 132.94/80.75 (±15.36/12.02) mmHg. The majority of patients (54.9%) had controlled blood pressure. MMAS-8 showed that 86.1% of the patients were adherent to antihypertensive pills, while adherence rate using the LMAS-14 was 82.4% .p value < 0.001), proving that the model was good. Anti-image correlation matrix showed positive values in the diagonals, proving that the questions were correlated; the majority of the values were above 0.8. In the principal component analysis, the used model explained 58.259% of the variance of the score's answers. Factor analysis showed a scale of four factors, with load > 0.4 . The new score, consisting of 14 questions, had a KMO coefficient of 0.743, showing adequate questions. The Bartlett test was significant  Daily Sodium Intake Estimation. Intraclass correlation coefficient between the variables was created by the estimation of INTERSALT (using urinary sodium measure) and the calculated INTERSALT was 0.807 for average measures , proving a good correlation. We used the new variable in the following analysis. Mean daily sodium intake was 3.48 (±0.78) grams in hypertensive patients. No statistically significant difference in mean sodium intake  was found between patients declaring to follow a low salt diet (mean = 3.47 g/day) and those denying it (mean = 3.5 g/day).(2) Predictors of Hypertension Control. Patients having a higher LMAS score had an OR of 1.217  of achieving controlled blood pressure. Thus, having a longer disease duration  and a higher number of comorbidities  predicted lower hypertension control .Intraclass correlation coefficient showed good concordance between MMAS-8 and LMAS-14 scales  and being a past or actual smoker  decreased the probability of being adherent to antihypertensives by LMAS-14  than another one in Beirut (77.6%) . This coStudy strengths include sample size and control for sociodemographic, lifestyle, hypertension, comorbidities, and adherence characteristics. To our knowledge, it is the first study in Lebanon that estimated daily sodium consumption and adjusted hypertension control predictors to it. We also obtained a validated scale measuring adherence, with good psychometric properties, concordant with Morisky score, and predicting hypertension control. Factors affecting adherence were also defined and were concordant with other studies.However, some limitations are to be mentioned. A potential selection bias could be due to the recruitment done in cardiology outpatient clinics of three hospitals in Beirut. An overrepresentation of the Lebanese residing in Beirut and Mount Lebanon was also noted. A potential information bias could be due to the employment of subjective methods to measure adherence, but objective ones are expensive and are not available in Lebanon. Social desirability bias could have modified the classification of adherence in patients and its association with hypertension control. White coat effect was only prevented by the surveyors' dress code excluding hospital gowns and by the measurement technique, done outside the doctor's office in the waiting area, but baseline blood pressure before presentation to the clinic was not obtained, for the majority of the patients, due to the unavailability of sphygmomanometers at their house. Finally, financial constraints did not allow the measurement of all the necessary parameters for INTERSALT calculation to all patients; consequently, its estimation was done in the majority of patients who gave spot urine samples.This study elaborated a validated, practical, and useful tool measuring adherence to medications in Lebanese hypertensive patients. Promotion of adherence to antihypertensives by physicians and public health actors is advantageous, as well as better stress management in Lebanese hypertensive patients. Further research is needed to estimate mean sodium intake in hypertensive patients and the consistence of their diets. A comparison between LMAS-14 and MMAS-8 using an objective measure of adherence might also be beneficial for future studies.


Critically ill patients are often hemodynamically unstable (or at risk of becoming unstable) owing to hypovolemia, cardiac dysfunction, or alterations of vasomotor function, leading to organ dysfunction, deterioration into multi-organ failure, and eventually death. With hemodynamic monitoring, we aim to guide our medical management so as to prevent or treat organ failure and improve the outcomes of our patients. Therapeutic measures may include fluid resuscitation, vasopressors, or inotropic agents. Both resuscitation and de-resuscitation phases can be guided using hemodynamic monitoring. This monitoring itself includes several different techniques, each with its own advantages and disadvantages, and may range from invasive to less- and even non-invasive techniques, calibrated or non-calibrated. This article will discuss the indications and basics of monitoring, further elaborating on the different techniques of monitoring. We can often manage it with regular clinical examination and monitoring of certain basic vital parameters  and urine output, but when these fail there is an increased need for hemodynamic monitoring  to guide fluid management and vasopressor/inotropic support. Over the last few decades, hemodynamic monitoring has evolved from basic monitoring of CO to sophisticated devices providing a plethora of variables. These techniques and devices can be classified in either of two ways: 1) calibrated versus non-calibrated techniques and 2) by their degree of invasiveness . In this article, we will provide an overview of the indications and limitations for hemodynamic monitoring and the available methods of doing so.Patients admitted to the intensive care unit (ICU) in general suffer from organ failure (single or multiple) or are at risk of such organ failure, which includes patients after major surgery and/or trauma. Hemodynamic instability, causing a mismatch between oxygen delivery and demand, is a major contributive factor for organ failure. Alterations in effective circulating volume (e.g. hypovolemia), cardiac function, and/or vascular tone (e.g. vasoplegic shock in sepsis) underlie hemodynamic instability2). Those who are unstable, or at risk of instability, should receive an arterial line for continuous invasive blood pressure measurement and regular analysis of arterial blood gasses. Any patient receiving vasopressors or inotropic agents requires a central venous line for drug administration and, when indicated, measurement of CVP and central venous oxygen saturation (ScvO2). When initial resuscitation fails to improve the hemodynamic and/or respiratory status of the patient, advanced hemodynamic monitoring will be required to guide medical management. Measuring CO and its components  will tell us if there is ongoing need for fluid resuscitation, vasopressors, or inotropic agents. It can be used as a diagnostic tool to determine the type of shock  according to the hemodynamic profile. Furthermore, it can be used to guide de-resuscitation, the phase after reconvalescence during which we are often confronted with fluid overload (in itself an important negative prognostic predictor)3. The clinical context  and the different possible variables provided by the monitoring method will determine which method we will use. There is, however, an important remark to be added when discussing indications for monitoring. Trials have as of yet not been able to show a significant reduction in mortality when comparing monitoring to standard of care, although there are possible benefits concerning complications7.All patients admitted to the ICU should be monitored, but the degree of monitoring can vary. Hemodynamically stable patients require maybe nothing more than continuous electrocardiographic (ECG) monitoring, regular non-invasive blood pressure measurement, and peripheral pulse oximetry  and a pulmonary artery catheter (PAC) (deoxygenated blood), respectively. This method is therefore invasive and time consuming, and although considered the gold standard it is rarely performed.In this formula, VO9. It is still the gold standard in the clinical setting to which we refer when comparing different methods of hemodynamic monitoring. These can be classified as calibrated or non-calibrated techniques or according to their level of invasiveness . There is a trend to use more less-invasive and non-invasive techniques to reduce the risks that accompany (less) invasive techniques.Several invasive and less-invasive methods have been developed during the last few decades to measure CO. The first to be used was the PAC, introduced in the 1970’s by Swan, Ganz, and ForresterRepeated calibration is performed in order to eliminate or reduce bias in continuous measurements. It refers to the act of evaluating and adjusting the precision and accuracy of the equipment. The precision of a technique is the degree to which repeated measurements (at the same time) show the same results, and the accuracy is the degree of closeness of the results to the actual true value (obtained by the gold standard method). Non-calibrated techniques try to reduce bias by implementing correction factors based on patient demographics  or calculations. However, in situations where preload, afterload, contractility, and aortic compliance can vary widely , calibration will often prove necessary.Pulmonary artery catheter . The gold standard, the PAC, is a flow-directed catheter that is placed through an introductor in the jugular, subclavian, or, more seldom, the femoral vein and that travels from the right atrium through the right ventricle just until the pulmonary artery. It allows direct simultaneous measurement of pressures in the right atrium (CVP), PAP, and PAOP or wedge pressure, which in turn is indicative of the filling pressures in the left atrium. Blood sampling from the distal port (pulmonary artery) allows measurement of SvO2, and using fiber optic reflectometry allows for continuous monitoring of the SvO2. CO is measured with thermodilution. Initially, a cold saline bolus has to be delivered through the opening in the right atrium, with a thermistor detecting the drop in temperature a few centimeters from the tip of the catheter. Later, a heating coil is incorporated in the design, negating the need for cold fluid boluses (and thus avoiding bias because of different operators). This CO measurement, however, is not a true continuous monitoring seeing as it represents the average value of the last 5 minutes, and changes in CO during alterations in preload or afterload  cannot be appreciated instantaneously. It also provides several calculated variables such as systemic and pulmonary vascular resistance, left and right ventricular stroke work, and the oxygen extraction ratio. Intracardiac electrodes allow the monitoring of electric activity, from which volumetric variables such as right ventricular ejection fraction (RVEF) and continuous assessment of right ventricular end diastolic volume (CEDV) can be gauged, providing information concerning right ventricular contractility and preload, respectively.10. The complexity of possible variations in obtained pressure tracings has led to large inter-observer variability, together with reports of very common misinterpretation of tracings11.Although PAC was the most widely used technique in the past, a clear survival benefit has not been provenThe best indication for the PAC remains when there is right ventricular heart failure or pulmonary hypertension, seeing as no other monitoring device is capable of providing direct measurement of the pressures in the right heart and pulmonary circulation.® system .1. Transpulmonary thermodilution: the PiCCO® system provides both intermittent  and continuous CO measurement. The intermittent CO is measured using a transpulmonary thermodilution technique, where a cold fluid bolus is injected through the central line. Using the Stewart Hamilton equation, the area under the thermodilution curve is then used to calculate the CO. By using an algorithm based on the analysis of the arterial pulse contour, it is possible to continuously monitor CO and stroke volume, allowing assessment of beat-to-beat variations of stroke volume and CO in changing preload conditions. SVV and pulse pressure variation (PPV) have been proposed as variables to guide fluid loading in critical care settings13, although limited to completely sedated patients under controlled mechanical ventilation and in the absence of cardiac arrhythmias 14.Using a central venous catheter and arterial line with thermistor, the PiCCO® system allows the measurement of global end diastolic volume (GEDV), intrathoracic blood volume (ITBV), and extravascular lung water (EVLW). Pulmonary blood volume (PBV), pulmonary vascular permeability index (PVPI), global ejection fraction (GEF), contractility, and systemic vascular resistance (SVR) are derived from these values. These values can be indexed to body surface area and predicted body weight.Furthermore, the PiCCOThis system has several advantages over PAC: it is less invasive, it provides a true continuous CO and rapidly available measurements allowing the assessment of fluid responsiveness, and it is supported by literature data in humans that show good correlation between intermittent and continuous transpulmonary thermodilution CO with the PAC as gold standard.Its drawbacks are the need for a specialized arterial line , a central venous line (jugular or subclavian vein), and regular calibration (three to four times a day) with cold fluid boluses (extra fluid load). The volume measurement is not automated and not continuous. It is less useful in valvulopathies, abdominal aortic aneurysm, or enlarged atria, and it is not applicable in arrhythmias or during intra-aortic balloon counterpulsation.®/EV1000® system .2. Transpulmonary thermodilution: the VolumeView The VolumeView®/EV1000® system is similar to the PiCCO® system but differs in the measurement of the GEDV, where it uses a formula implementing the maximum upslope and downslope time of the thermodilution curve, whereas the PiCCO® system employs time constants derived from the mean appearance, mean transit, and downslope of the thermodilution curve15.® system .3. Transpulmonary dye dilution: the LiDCO Instead of thermal dilution, the LiDCO® system uses lithium as an intravascular indicator injected through a central or peripheral vein which is then measured in a peripheral artery using a specialized sensor probe attached to the pressure line16. It is coupled to a pulse contour analysis system (LiDCOrapid®/PulseCO®). The only additional measured variables compared to PAC monitoring are the PPV and SVV. The data are rapidly available and provide real-time beat-to-beat variations in CO. Volume quantification, however, is not available, and the technique cannot be used in children/patients with a weight below 40 kg or patients under the influence of muscle relaxants . Little is known about possible toxic effects or accumulation with long-term use of lithium. Furthermore, the ion-selective electrode is delicate and expensive and needs to be replaced every three days.® system .4. Ultrasound flow dilution: the COstatus The COstatus® system calculates CO by using transpulmonary ultrasound dilution technology to measure changes in blood ultrasound velocity and blood flow following an injection of saline17. It requires a primed extracorporeal arteriovenous tube set (AV loop) connected between thein situ standard arterial catheter and central venous catheter where two ultrasound flow-dilution sensors are placed on the arterial and venous ends. During calibration, a small roller pump is used to circulate blood through the AV loop from the artery to the vein. The ultrasound sensors provide an ultrasound dilution curve through which CO can be calculated following the Stewart Hamilton principle. After calibration, a continuous CO can be calculated through the arterial waveform. It calculates certain volumetric indices such as total end diastolic volume (TEDV), central blood volume (CBV), and active circulation volume (ACV), and it can detect intracardiac shunts. It is validated in both adult and pediatric patients. Recalibration is necessary in unstable conditions.5. Pulse contour and pulse pressure analysis . Several devices use the technique of pulse pressure analysis to estimate CO. The difficulty is that, to estimate CO from pulse pressure analysis, one would not only need information about the heart rate and blood pressure but also have to make an estimate about the pressure-volume relationship of the aorta. Most of the techniques being used today are based on a three-element model integrating aortic characteristic impedance, arterial compliance, and systemic vascular resistance. These models work relatively well in stable patients but lack accuracy in unstable patients or when vasoactive drugs are employed18. There are several devices using pulse pressure analysis available:- ®/Vigileo®: a widely used method that uses PPV and vascular tone to calculate stroke volume and CO, although it is less useful in situations with low vascular tone (e.g. septic shock)19.FloTrac- ®/Pulsioflex®: continuously measures CO by analyzing the systolic portion of the pressure wave after an initial autocalibration (depending on patient characteristics) or manually entering a starting cardiac index; there is, however, too large a percentage error20.ProAQT- ®/pulseCO®: uses the same algorithm as in LiDCOplus with calculating a nominal stroke volume from the entire pressure waveform. It can be calibrated using other techniques. There is, however, insufficient accuracy compared with thermodilution methods21. Calibration improved this accuracy  but only for the first four hours22.LiDCOrapid- ®/pressure recording analytical method (PRAM): uses an algorithm called “pressure recording analytical method”, which is a theoretical method developed by analyzing both pulsatile and continuous flow23; only an invasive arterial catheter is needed, the implementation is easy, and it shows good accuracy in a wide range of settings.Most Care2-rebreathing (NiCO®) .6. Respiratory derived cardiac output monitoring system: partial CO Using CO2 instead of O2 as an indicator in the Fick principle (see above), the NiCO® uses a partial rebreathing method to measure the CO. The system consists of a CO2 and airflow sensor combined with a pulse oximeter. We can measure the CO2 production by multiplying the exhaled CO2 content by the respiratory minute volume. The arterial CO2 is derived from the end tidal CO2. Every three minutes, a partial rebreathing cycle should be started using a rebreathing loop, resulting in reduced CO2 elimination. By assuming CO is stable in both normal and rebreathing conditions, the difference between normal and rebreathing ratios are used to calculate CO. However, as it is dependent on stable ventilation, this can be used only in fully sedated patients with volume-controlled ventilation. Significant pulmonary disease  can interfere with the measurements. To date, insufficient data exist to support its accuracy, specifically in critically ill patients.7. Transesophageal echocardiography (operator dependent). Transesophageal echocardiography (TEE) is an important cardiovascular diagnostic tool in perioperative and critical care medicine. It uses ultrasound to provide real-time images of the cardiac structures and blood flow. The transducer is placed in the esophagus next to the heart to produce these images. It may help define pathophysiological abnormalities in patients like wall motion abnormalities, pericardial effusions, pulmonary hypertension, and valvulopathy, in conjunction with other invasive or less-invasive monitoring. Guidelines published by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists state that TEE should be used in critical care patients with persistent hypotension or hypoxia when diagnostic information expected to alter management cannot be obtained by transthoracic echocardiography (TTE) or other modalities in a timely manner24. There is, however, a significant learning curve, TEE is expensive, and continuous monitoring is not an option. There is a (low) risk of oropharyngeal bleeding and dislocation of the endotracheal tube, and its use is relatively contraindicated in esophageal pathologies and severe coagulation abnormalities.8. Esophageal Doppler (operator dependent). Using a flexible ultrasound probe, the blood flow in the descending aorta is measured to determine stroke volume and CO. This probe can be left in place for prolonged periods of time (barring dislocation) and can provide real-time CO as well as afterload data interpretation. It provides many additional measurements as well as an estimate for preload via the corrected flow time. It is a promising, easy-to-learn technique associated with reduced hospital stay and better perioperative volume optimization25.1. Transthoracic echocardiography (operator dependent). CO can be measured with TTE using pulsed wave Doppler velocity in the left ventricular outflow tract (LVOT). It can also be measured at the mitral valve annulus, ascending aorta, right ventricular outflow tract (RVOT), and pulmonary artery, but these have been less validated. Seeing as there is less influence of systemic vascular resistance (SVR), measurements over the RVOT can provide an accurate CO, but only if there is no interference due to pulmonary arterial hypertension.2. Non-invasive pulse contour systems . These systems strive to determine CO based on an arterial pulse pressure curve, which is estimated by a completely non-invasive technique.- ®: this system uses applanation tonometry  and an autocalibrating algorithm to estimate CO; it has an acceptable accuracy compared to calibrated pulse contour analysis26 but needs more validation.T-line- ®/Nexfin®/Physiocal® system: this estimates blood pressure by a cuff wrapped around the finger and photoplethysmography to constantly adjust cuff pressure to keep the arterial diameter constant, thus creating a pulse pressure curve (Peñáz principle) used to estimate stroke volume, CO, SVV, and PPV; however, its accuracy still needs improvement and declines even further in patients with low CO, finger edema, hypothermia, or a high peripheral resistance27.ClearSight- ®/VERIFY®: this uses the same technique of photoplethysmography but corrects for changes in vasomotor activity with a specific algorithm; although a high percentage of error has been reported, this is markedly lower when using precalibration with the thermodilution technique28. Further validation is needed.CNAP3. Bioimpedance . Using skin electrodes, a small electrical current is applied. Changes in voltage over the circuit are then caused by changes in impedance and/or volume of the conducting tissues. Blood has a relatively low resistivity, and changes in intrathoracic blood volume have a high impact on impedance accordingly. With this assumption, we can postulate that changes in thoracic impedance are largely dependent on three components: a baseline impedance indirectly proportional to the thoracic fluid content, tidal changes in intrathoracic blood volume caused by respiration, and small changes caused by the cardiac cycle. The latter are primarily due to changes in aortic volume, which can be used to estimate stroke volume and CO30. However, it does have important limitations. The impedance is influenced by all changes in thoracic fluid composition such as lung edema and pleural effusions. Changes in systemic vascular resistance will influence the volume changes in the aorta and will therefore interfere with CO measurements.®) .4. Estimated continuous cardiac output  .5. Ultrasonic cardiac output monitoring , and there can be a big difference between the estimated output and the calibrated reference value36.Critically ill patients are often hemodynamically unstable (or at risk of becoming unstable), and advanced hemodynamic monitoring is recommended in complex situations or in patients with shock who do not respond to initial fluid resuscitation. We are offered a wide variety of techniques that range from invasive to less invasive and even non-invasive. These techniques can be calibrated or non-calibrated. In


Calcineurin inhibitor induced nephrotoxicity contributes to late allograft failure in kidney transplant patients. Evidence points towards aldosterone to play a role in the development of fibrosis in multiple organs. Animal studies have indicated a beneficial effect of mineralocorticoid receptor antagonists preventing calcineurin inhibitor induced nephrotoxicity. Only few studies have explored this effect in humans. The objective of this study is to evaluate the effect of spironolactone on glomerular filtration rate and fibrosis in kidney transplant patients.Prospective, double-blind, randomized, clinical trial including 170 prevalent kidney transplant patients. Patients are randomized to spironolactone 25–50 mg/day or placebo for three years. Primary outcome is glomerular filtration rate evaluated by chrome-EDTA clearance. Secondary outcomes are 24-h protein excretion, amount of interstitial fibrosis in renal allograft biopsies, and cardiovascular events. As an exploratory outcome, we aim to identify markers of fibrosis in blood and urine.Long term allograft survival remains a key issue in renal transplantation, partly due to calcineurin inhibitor induced nephrotoxicity. Evidence from animal- and small human studies indicate a beneficial effect of mineralocorticoid receptor antagonism on renal function and fibrosis. This study aims to test this hypothesis in a sufficiently powered randomized clinical trial. Results might influence the future management of long term allograft survival in renal transplantation.NCT01602861. EudraCT number (05/31/2011): 2011–002243-98.ClinicalTrials.gov identifier (05/17/2012):  The introduction of calcineurin inhibitors (CNI) cyclosporine and tacrolimus as part of immunosuppressive regimens in kidney transplantation has significantly improved short term allograft survival and function , 2, but The mineralocorticoid hormone aldosterone contributes to deleterious pro-fibrotic processes in several organs, including the kidneys , 7. AldoOnly a few studies have explored the potential of MR antagonism in kidney transplant recipients. A recent randomized clinical trial included 24 pediatric kidney transplant patients with biopsy-proven chronic allograft nephropathy and did not find a significant effect of eplerenone for 24 months versus placebo regarding GFR, proteinuria and fibrosis. The study was, however, underpowered . One opeThe SPIREN trial is an investigator initiated nationwide, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to test the hypothesis that addition of the MR-antagonist spironolactone to standard therapy in prevalent kidney transplant patients will improve long term kidney function and reduce allograft fibrosis.One hundred seventy kidney transplant patients will be included from four Danish hospitals covering all Danish renal transplant centers . Patients are recruited from outpatient clinics in the Departments of Nephrology at Odense University Hospital, Kolding Hospital, Rigshospitalet, Copenhagen and Aarhus University Hospital, respectively. Eligibility criteria are listed in Table Wide eligibility criteria have been chosen to obtain a high generalizability of the results. This study includes renal transplant patients with a stable kidney function at the time of inclusion. Even in stable patients, a gradual deterioration of renal function is expected. Previous studies have found an average rate of decline of glomerular filtration rate in of 1–3 mL/min/year –26. Hencn = 50) graft biopsies will be performed at inclusion and after two years. All registrered variables are listed in Table Patients are randomized 1:1 to spironolactone (Spirix®) or placebo for three years. Initial dosage is 25 mg once daily, which is doubled after three months, if tolerated well. At inclusion and yearly hereafter a standard workup is performed including chrome-EDTA clearance, 24-h urine collection, electrocardiogram, 24-h ambulatory blood pressure measurement and blood- and urine samples  and renal fibrosis. For the latter, Masson Trichrome stained sections of kidney allograft biopsies will be used for measuring Banff chronicity scores and calculating morphologic fibrosis by point counting. Point counting provides a quantitative and reproducible estimation of the extent of fibrosis . In brieAs an exploratory outcome we aim to identify possible biomarkers of fibrosis in blood and urine. Kidney fibrosis is currently diagnosed by renal biopsy. Besides being time-consuming, it is an invasive procedure and as such, it implies a risk of complications including bleeding, pain and infection. Hence, much effort has gone into identifying non-invasive markers of fibrosis in blood or urine. The fibrotic process is a cascade of factors including inflammation, tissue hypoxia and various pro-fibrotic cytokines and growth factors . Animal Plasma potassium and -creatinine levels are monitored closely at initiation of therapy and after any dose adjustment. Sustained potassium levels > 5.8 mmol/L will result in reduction of dosage to 25 mg per day. In case of hyperkalemia on 25 mg per day, the patient will be withdrawn from the study. Potassium binding resins will only be used to handle cases of acute hyperkalemia, thus chronic treatment with resins is not allowed. Hyperkalemia is registered as an adverse event in case of an absolute increase of > 1.5 mmol/L or any increase to a level above 5.5 mmol/L. All significant increases in plasma creatinine are evaluated by study investigators, and in case of doubt of the etiology, the study drug is discontinued until renal function has stabilized. All adverse events registered throughout participation in the study will be recorded. Serious adverse events are defined according to Good Clinical Practice as events that result in death, are life threatening, require hospitalization, cause prolongation of existing hospitalization or result in persistent or significant disability/incapacity. The project safety board continuously monitors serious adverse events to identify general study safety issues.Withdrawal criteria include a sustained compliance of less than 80%, hyperkalemia despite reduction of dosage or intolerable side effects.Assuming a standard deviation in chrome-EDTA clearance of 10 mL/min, a sample size of 126 patients (63 in each group) will be able to detect a difference in chrome-EDTA clearance of 5 mL/min between the groups with 80% power and a significance level of 0.05. With an expected dropout rate of 15%, the planned total was set to 170 patients.After completing the baseline workup Fig. , patientAll data will be documented for each visit in the respective Case Report Form and subsequently entered into the SPIREN project database. Data will be secured by double entry. The project database has been developed in cooperation with the Database Unit of the Region of Southern Denmark and complies with the standards of Good Clinical Practice.All statistical analyses will be done using STATA software. All generated variables will be documented by do-files. The main analysis will be performed as intention-to-treat using last-observation-carried-forward. Sub-analyses will include per protocol analyses and “best case”/“worst case” analyses. Where appropriate, variables will be analyzed using parametric or non-parametric tests.The first patient was included in January 2013. An interim analysis was performed in September 2015 including 40 patients after two years of participation . The intLong term kidney graft survival is a key issue in transplant medicine. Chronic CNI nephrotoxicity contributes to late allograft loss . There iConcerns have been raised regarding MR antagonism in patients with impaired renal function due to the risk of hyperkalemia, which is a potentially lethal side-effect. In the wake of the Randomized Aldactone Evaluation Study (RALES) - a randomized, clinical trial investigating the effect of spironolactone in patients with congestive heart failure and serum creatinine below 221 μmol/L - there was a significant increase in hospitalizations due to hyperkalemia from 2.4 to 11.0 per 1000 patients . The risAnother concern regarding MR antagonism is the observation that plasma creatinine levels tend to increase at the initiation of therapy. This effect has also been observed in studies of MR antagonism in chronic kidney disease . In RALEDespite potential pitfalls using MR antagonists in kidney transplant patients, evidence from animal and small human studies indicate a potential for improving long term allograft function. This study is, to our knowledge, the first to investigate the effect of MR antagonism on long term allograft function in adult kidney transplant patients in a prospective, randomized fashion. Results will contribute to current evidence and possibly influence the future management of kidney transplant patients with regards to improving long term allograft survival.


E/VCO2  remained an independent predictor in multivariate analysis . Additionally, the VE/VCO2 was the most discriminatory  in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). Conclusion: SETs, particularly the VE/VCO2, appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.Introduction: The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL  registry risk score (RRRS). Methods: Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Results: Although multiple SET variables correlated with the RRRS on univariate analyses, only V Identification of prognostic factors that affect survival has been a key goal in the clinical care of patients with pulmonary arterial hypertension (PAH). The REVEAL  cohort helped identify some important independent predictors, as well as a composite scoring system—the REVEAL registry PAH risk score (RRRS)—to help in prognosticating these patients ,2. The RThe elements of the RRRS are readily available and include the patient’s WHO functional class (WHO-FC), echocardiographic and hemodynamic parameters, as well as the six-minute walk test 6MWT) as a marker of exercise tolerance. Although the 6MWT is considered a simple, noninvasive, inexpensive marker of functional status and exercise tolerance, it suffers from several limitations, including learning effect, day-to-day variability and anthropomorphic/demographic variables MWT as a .O2) and ventilatory equivalent of carbon dioxide (VE/VCO2) obtained from a CPX appear to be important predictors of survival [O2 > 15 mL/min/kg and VE/VCO2 > 55) [In comparison, the cardiopulmonary exercise test (CPX) provides more comprehensive evaluation of exercise tolerance, but has more specific measures to evaluate ventilation, gas exchange, cardiac function, as well as muscle physiology and, therefore, could be more pertinent in the management of patients with PAH. Specific to PAH, both peak oxygen consumption  ; however2 (PETCO2), a greater VE/VCO2, a reduced oxygen saturation and VO2 efficiency slope [A novel compromise on the benefits and drawbacks of both the 6MWT and the formal CPX is the submaximal exercise test (SET), which is a low-intensity, three-minute exercise test that is easier to perform than a CPX test, yet unlike a 6MWT, is able to acquire some of the key ventilatory variables that can additionally inform the clinician on the status of the cardiopulmonary system . In partcy slope ,13,14,15cy slope .Such a tool that can measure functional status, exercise tolerance and more specific hemodynamic/ventilatory markers may not only help in prognostication, but may also potentially be an important surrogate endpoint in and of itself in clinical trials and, eventually, in clinical practice, to guide the management of PAH patients. Towards this eventual goal, we first sought to determine whether the SET variables would correlate with the validated RRRS as a prognostic marker, particularly in identifying high risk patients for whom management would be escalated.Consecutive WHO Group 1 PAH patients seen by the Pulmonary Hypertension Clinic between March, 2011, and May, 2013, were eligible for the study. All subjects had received a right heart catheterization, an echocardiogram a 6-minute walk test with its distance (6MWD), WHO-FC, as well as a SET.E/VCO2, a measure of breathing efficiency defined as the linear slope of the amount of air expired per minute (VE) versus the amount of carbon dioxide produced per minute (VCO2); (2) the oxygen uptake efficiency slope (VO2/log VE), indicating the amount of oxygen that is used per unit ventilation; (3) PETCO2, reflecting the alveolar CO2 partial pressure at the end of expiration; (4) the heart rate decay during the first minute of exercise recovery; and (5) the chronotropic response index, a measure of the patient’s heart rate response to dynamic exercise. In this study, we specifically examined whether the peak VO2 (mL/kg/min), VE/VCO2 and the partial pressure of carbon dioxide at baseline and at the end of exercise  would correlate with the RRRS.The Shape-HF™  was utilized for SET in this study. Specific measures able to be obtained by this test include: (1) VE/VCO2, PETCO2-b and the PETCO2-ex was also performed to identify significant predictors of the prognostic risk based on the RRRS. Finally, to identify a potential SET variable to distinguish those with the worst prognosis (RRRS ≥ 10), we performed univariate analyses with non-parametric assumptions (Mann–Whitney test) comparing each of the SET variables between those RRRS ≥ 10 to those with RRRS < 10. We then explored potential cut-offs for the SET variable VE/VCO2 (which was the most discriminatory) by constructing a receiver-operating characteristic (ROC) curve and its area under the curve (AUC), as well as determining the sensitivity, specificity, predictive values and likelihood ratios (LHR) for the optimal cutoff. All statistical analyses were performed using JMP® Pro 9.0.1 . The study was approved and overseen by the Mayo Clinic Institutional Review Board (IRB 12-003335).Baseline characteristics are provided with descriptive statistics. For consistency, medians with their interquartile ranges (IQR) are reported for continuous variables. Non-parametric Spearman’s correlation (ρ) was computed between the raw numeric RRRS and the SET variables. A multivariate analysis to predict the RRRS from the SET variables of age, sex, VSixty-five subjects were enrolled and available for analysis. The majority were older women, with an even separation of associated PAH (APAH) from idiopathic PAH (IPAH). On average, most had moderate to severe pulmonary hypertension and were at least WHO-FC III. The specific baseline characteristics are presented in E/VCO2 . In a multivariate model with the covariates of age, sex, VO2, VE/VCO2, PETCO2-b and PETCO2-ex, the only SET variable that remained an independent predictor was VE/VCO2 with an effect size of a 0.5 increase in the RRRS for every 10 increase in the VE/VCO2 .In univariate analyses, all variables obtained from the SET were significantly correlated with the RRRS; see E/VCO2 was the most discriminatory among the SET variables. An ROC curve was generated revealing modest discriminatory ability with an AUC of 0.84; see E/VCO2 cut-off of 40.6 revealed a sensitivity of 92% and a specificity of 67%. The positive likelihood ratio or the positive predictive value is poor, but the VE/VCO2 appeared to have a strong negative predictive value or a negative likelihood ratio; see Of the 65 patients, 13 (20%) had the worst prognosis as defined by a REVEAL registry score ≥10. The SET variables were compared between these two risk categories. All SET variables proved significantly worse for those in the higher risk category; E/VCO2 showed the strongest correlation with RRRS and was the only independent parameter that remained significant in multivariate analysis. VE/VCO2 also had excellent discriminatory power at identifying patients with the highest mortality risk . In particular, the VE/VCO2 demonstrated excellent sensitivity with high negative predictive value, such that a normal or low VE/VCO2 value (<40.6) would exclude those least likely to suffer disease progression and death.The current study showed a statistically significant correlation among SET and PAH prognosis as predicted by the RRRS. On univariate analysis, VO2, work rate (WR), anaerobic threshold (AT), VO2/WR slope, oxygen (O2) pulse and a steep heart rate (HR)-VO2 response, combined, on occasion, with a submaximal HR response. The gas exchange response is more conspicuous: high ventilatory equivalents (VE/VCO2 and VE/VO2) and a low PETCO2, along with exercise-induced hypoxia with advancing disease [O2 [E/VCO2 at AT [O2 and the VE/VCO2 at AT may not be obtained during a submaximal test, an elevated breathing efficiency (VE/VCO2 slope), which can be determined from submaximal data [Formal CPX testing is a powerful diagnostic and prognostic tool for a variety of cardiopulmonary disorders, including PAH ,18. Exer disease . Of thesease [O2 ,10,20,21O2 at AT . Both ofmal data   or clinically, to guide the clinician in helping to decide who requires treatment or escalation of therapies among the growing complexity of PAH medications now available.There are significant limitations to consider when interpreting the results of this study. This was an observational, single center study at a tertiary academic center with a specific PAH clinic. Generalizability is thus limited. Furthermore, although there were no adverse events, this may be limited by the small sample size and the selection bias introduced by the clinical selection of PAH undergoing SET testing. However, by practice protocol, all suspected or diagnosed PAH patients undergo SET testing. More importantly, the ability of the SET to prognosticate was obtained, not prospectively, but through a cross-sectional comparison of the SET to a validated prognostic score, the RRRS. We did not have enough long-term follow-up to directly compare the two tools, but our findings have encouraged us to prospectively collect data (ongoing) to more directly determine whether SET will prove a superior marker of both prognosis and disease severity. Despite some of these and other limitations, the biologic plausibility, that a tool that is able to measure both exercise tolerance and disease severity should be a powerful prognostic marker, supports that the findings in this observational study is real. The consecutive collection of hemodynamically confirmed PAH and the systematic characterization of our PAH cohort are additional strengths of this study.In summary, we are encouraged to further explore prospectively the value of SET in both predicting prognosis, as well as in guiding the management of patients affected by PAH. Furthermore, given the intrinsic advantages of the SET over the 6MWT, we hope future studies will also consider its role as a principle outcome as potentially a superior surrogate biomarker than the 6MWT. If it proves to be a more robust prognostic marker, it may have significant implications, not just for clinical practice, but on the conduct, cost and efficiency of completing clinical trials.In this hypothesis generating study, SET variables correlated significantly with the RRRS. Further prospective investigations should be considered to confirm whether SET does have significant prognostic information and to test whether it might prove to be a superior surrogate marker to the 6MWT and/or the RRRS.


In the ‘Background’ section, the sentence: “…limiting effective reduction of hypertension-related morbidity and mortality rates in patients” should be corrected to read: “…limiting effective reduction of hypertension-related morbidity and mortality rates among patients”.In the ‘Background’ section, the sentence: “A cluster-randomized trial of task shifting and blood pressure in community health centers…” should be corrected to read: “A cluster-randomized trial of task shifting and blood pressure control in community health centers…”In the ‘Methods’ section, number forty-nine should be changed to forty-seven.Upon publication of this article , it was


A registry assessing the care of hypertensive patients in daily clinicalpractice in public and private centers in various Brazilian regions has notbeen conducted to date. Such analysis is important to elucidate theeffectiveness of this care.To document the current clinical practice for the treatment of hypertensionwith identification of the profile of requested tests, type of administeredtreatment, level of blood pressure (BP) control, and adherence totreatment.National, observational, prospective, and multicenter study that will includepatients older than 18 years with hypertension for at least 4 weeks,following up in public and private centers and after signing a consent form.The study will exclude patients undergoing dialysis, hospitalized in theprevious 30 days, with class III or IV heart failure, pregnant or nursing,with severe liver disease, stroke or acute myocardial infarction in the past30 days, or with diseases with a survival prognosis < 1 year. Evaluationswill be performed at baseline and after 1 year of follow-up. The parametersthat will be evaluated include anthropometric data, lifestyle habits, BPlevels, lipid profile, metabolic syndrome, and adherence to treatment. Theprimary outcomes will be hospitalization due to hypertensive crisis,cardiocirculatory events, and cardiovascular death, while secondary outcomeswill be hospitalization for heart failure and requirement of dialysis. Asubgroup analysis of 15% of the sample will include noninvasive centralpressure evaluation at baseline and study end. The estimated sample size is3,000 individuals for a prevalence of 5%, sample error of 2%, and 95%confidence interval.The results will be presented after the final evaluation, which will occur atthe end of a 1-year follow-up.The analysis of this registry will improve the knowledge and optimize thetreatment of hypertension in Brazil, as a way of modifying the prognosis ofcardiovascular disease in the country. Considering that these are all modifiable risk factors,the INTERHEART study alerted to the need for implementation of preventive strategiesthroughout Latin America.The INTERHEART study analyzed the risk factors for acute myocardial infarction (AMI)in 52 countries (six of which in Latin America), including 15,000 cases of patientswith first AMI and a similar number of control individuals.8 Considering BP values ≥ 140 /90 mmHg, 22 studies found prevalences between 22.3% and 43.9% (mean 32.5%), with ahigher prevalence in men compared with women, and in elderly individuals.9The prevalence of hypertension in Brazil is similar to that in other countries.Surveys conducted in the Brazilian population point out to a prevalence ofhypertension of approximately 30%.10 Another studyconducted in São José do Rio Preto in 1,717 individuals found aprevalence of hypertension of 25.2% and reported as associated factors the presenceof advanced age, low educational level, and obesity.11 Among the treated hypertensive individuals, 52.4%showed adequate BP control, but only 34.3% of the overall treated and untreatedhypertensive individuals had controlled BP levels.A study in which 613 patients in the city of São Paulo were interviewed byphone found a 32% prevalence of hypertension among the respondents. Of these, 89%reported current treatment for hypertension but only 35% mentioned proper control ofBP levels.1Since hypertension is multifactorial, frequent in the adult population, and commonlyassociated with other cardiovascular risk factors and/or target-organ damage, it isan important public health problem. When the diagnosis of hypertension isestablished early, and the goals of BP control are met, the treatment of the diseasemay be effective; however, when left untreated, hypertension can cause severecomplications and follow a slow and silent course.13Data from the National Health and Nutrition Examination Survey (NHANES) collectedbetween 2009 and 2012 have shown that 84.7% of the surveyed adults with hypertensionwere aware of the diagnosis of the disease and that the percentage of patientsundergoing antihypertensive treatment was 76.5%, with a 54.1% rate of BP control.These numbers demonstrate a significant improvement in the diagnosis and control ofhypertension in the American population.16 Even though consistentlyrecommended for prevention and treatment of hypertension, lifestyle modificationsare difficult to implement from the patient's perspective and, often, also from thephysician's perspective, who is frequently unable to rely on the support of amultiprofessional team.Lifestyle modifications lead to decreases in BP and cardiovascularmortality.With the objective of achieving proper BP control and consequently decreasing thedeaths associated with CVD, it is essential to know the prevalence of hypertensionin Brazil, clarify how the care and treatment of hypertensive patients are beingconducted in daily clinical practice, and understand the role of multidisciplinaryteams in this scenario.To document the current clinical practice for the treatment ofhypertension in Brazil.Stratify additional cardiovascular risks, considering associatedcomorbidities, target-organ damage, and presence of manifestedcardiovascular disease;Analyze the profile of tests routinely requested for patients withhypertension;Verify the proportion of patients receiving antihypertensivetreatment who are within the goals recommended by the BrazilianSociety of Cardiology;Estimate the adherence to proposed pharmacological andnon-pharmacological therapies using the Morisky scale;Evaluate the presence of a multiprofessional team in the regular careof the patients and, when present, the effectiveness of itsperformance in controlling the BP levels;Assess eventual differences in the approach to hypertensive patientsin private and public centers.This first Brazilian registry of hypertension will be a prospective,observational, multicenter, national study in which the subjects will bescreened and evaluated in internal medicine and specialized outpatient clinicsduring a follow-up of 12 months.The study will include individuals undergoing primary or secondary prevention,diagnosed with hypertension and meeting the inclusion criteria. After thesubjects sign a free and informed consent form (FICF), their medical recordswill be analyzed, and they will be interviewed for completion of the electronicclinical charts  for inclusion in thestudy.A follow-up visit will be scheduled between 6 months and 1 year from theinclusion in the study. In the event of more than one visit during this period,this additional visit may also be documented as an intermediate visit.Patients older than 18 years, with a diagnosis of hypertension for at least 4weeks.VI Diretrizes Brasileiras deHipertensão) or use of antihypertensive medication; andregular registration in the participating center/institution.Signature of the FICF; age above 18 years; diagnosis of hypertension for at least4 weeks, with a systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP)≥ 90 mmHg, measured with the participant seated and according to the VIBrazilian Hypertension Guidelines ;Smoking, considering as smokers those individuals who routinely smokeone or more cigarettes or who routinely smoked up to 1 year beforeinclusion, and as previous smokers those individuals who stoppedsmoking more than 1 year before inclusion;Alcoholism, considering as current alcoholism the consumption of atleast 30 g of ethanol for men  and 15 g of ethanol for women  at least three times a week,and as previous alcoholism the interruption of the habit for atleast 1 year;Physical activity, considering as regularly performed those physicalactivities performed for at least 30 minutes three times a week;Menopause, characterized by the absence of menstrual periods for atleast 1 year;Weight and height, measured with an anthropometric scale;2 and > 18 kg/m2, as overweight thosewith a BMI ≥ 25 kg/m2 and < 30 kg/m2, and as obese those with a BMI≥ 30 kg/m2;Body mass index (BMI), calculated with the formula weight divided bythe square of the height. Will be considered as eutrophic thoseindividuals with a BMI < 25 kg/mWaist circumference (WC), measured with an inelastic measuring tapeat the middle distance between the anterior superior iliac crest andthe lower edge of the last costal arch with the patient standing andat the end of expiration;17BP, measured with any type of regulated sphygmomanometer usedroutinely at the center, with two measures taken with the subjectseated with an interval of at least 1 minute between each.Hypertension will be considered as the routine use ofantihypertensive drugs or measurement of office BP equal to or above140 x 90 mmHg. Individuals will be considered as having resistanthypertension when presenting uncontrolled BP levels despite the useof three classes of synergistic antihypertensive drugs in optimizeddoses, ideally including a diuretic; or if using fourantihypertensive classes or more to achieve BP control;Dyslipidemia, considered present in subjects using any hypolipidemicdrug or with an LDL-c measurement above 160 mg/dL, and/ortriglyceride level above 150 mg/dL, and/or HDL-c level below 40mg/dL in men and 50 mg/dL in women, and/or total cholesterol above200 mg/dL;Metabolic syndrome (MS), which will be diagnosed according to theInternational Diabetes Federation (IDF) criteria, detailed in The primary outcomes will include hospital admission for at least 24 hoursdue to hypertensive crisis; cardiovascular event (acute coronary syndrome[ACS] and/or stroke / transient ischemic attack [TIA]) documented in medicalrecords or summary of hospital discharge; cardiovascular death  confirmed by descriptions in the medicalrecords and/or death certificate.The secondary outcomes will include hospitalization due to decompensatedheart failure documented in medical records or summary of hospitaldischarge, and requirement of dialysis therapy.Comitê de Ética emPesquisa, CEP).The patients will be recruited from outpatient clinics, and their participationin the study will begin after they sign the FICF previously approved by theResearch Ethics Committee  in the last 6 months (if available), analysis of otherrelevant tests in the investigator's opinion and performed in the previous year,lifestyle questionnaire, ambulatory BP in the previous 6 months (if available),and treatment adherence assessed with the Morisky scale.In the follow-up visit, the evaluating data will include BP measurements,medications in use, estimate of adherence to pharmacological andnon-pharmacological treatment using the Morisky scale, hospitalization due toCVD , beginning ofdialysis, and death.A protocol subgroup including 15% of the sample will undergo a noninvasiveassessment of the central BP with a validated Mobil-O-Graph equipment  in the inclusion and follow-upvisits.The central hemodynamic parameters will be obtained using a noninvasive methodthat verifies simultaneously the pulse wave of the arterial blood flow, allowinganalysis of the BP, central systolic pressure (cSP), pulse wave velocity (PWV),and augmentation index (AIx) by the method ARCsolver, Austrian Institute ofTechnology. This method determines the cSP based on brachial pulse wavesrecorded with a cuff connected to the Mobil-O-Graph, the oscillometric devicethat records the BP. The records will be obtained by inflating the cuff for 10seconds at the DBP level, using conventional cuffs for adults (available in thesizes 24-34 cm and 32-42 cm) and a high-fidelity MPX50550 pressor sensor. The method considers the influence of arterialimpedance using a transfer function, as well as the hemodynamics of the aortausing a mathematic method. The Mobil-O-Graph is a device that allowssimultaneous measurement of central and peripheral pressure. Depending on theprotocol adopted, these measurements may be carried out at pre-establishedintervals. The same preparation methodology described for the measurement ofcasual BP will be adopted, with the use of a suitable cuff, according to thecircumference of the chosen arm.Central parameters are usually performed in a single evaluation. With thisequipment, the assessments can be performed by several protocols with multiplemeasurements.For those research centers with patients participating in this subgroup, thefollowing variables will be collected and entered in the registry's eCRF: cSP,central diastolic pressure (cDP), PWV, AIx (corrected for 75% of the heartrate), and peripheral arterial resistance.This analysis aims to offer an understanding of the reality of the Brazilianpopulation regarding the information mentioned above, and to correlate differentclasses of antihypertensive drugs in terms of action on peripheral BP levels andon variables regulating the central BP control.19 Survival curves will be calculated with theproduct-limit Kaplan-Meier method20 and compared with the log-rank test proposed byMantel,21 followed bySidak's multiple comparisons test, when appropriate. Survival probabilities willbe estimated with 95%CI using log-log transformation.22 Cox univariate and multivariate analyses will be conducted to identify factorsassociated with the survival outcomes evaluated. The proportional hazardsassumptions and functional form (for continuous covariables) in Cox regressionmodels will be assessed according to the Kolmogorov-type supremum test based ona sample of 1,000 simulations of residuals.23 If the linear form is rejected for a continuouscovariate, the covariate will be categorized according to the cutoff points ofclinical importance or according to distribution percentiles. Adjusted andunadjusted hazard ratios with corresponding 95%CIs will be estimated by Coxunivariate and multivariate regression analyses, respectively. In addition,statistical analyses will be conducted in previously defined subgroups indifferent Brazilian regions and according to the type of service performed .A sample of 3,000 individuals will be sufficient to estimate prevalences of 5%(or greater) with an absolute sample error (precision) of 2% (or greater) and a95%CI considering a 20% loss to follow-up.24 Beforedetermining the multivariate model, a diagnosis of multicollinearity will beconducted according to the variance inflation factor (VIF). The cases confirmedas loss to follow-up will be censored at the date of the last follow-up /contact. Associations between categorical variables will be evaluated in 2x2 andgreater than 2x2 contingency tables with Fisher's exact test and its extension,the Fisher-Freeman-Halton test, respectively. Unpaired Student'st test and analysis of variance (ANOVA) will be used tocompare averages among groups of two or more than two, respectively. In cases ofconsiderable data asymmetry, nonparametric alternatives will be applied:Wilcoxon's rank sum and Kruskal-Wallis tests, respectively.25 The normality of the data willbe evaluated with a visual inspection of the histograms and/or application ofthe D'Agostino and Pearson's comprehensive normality test, whenappropriate.26Continuous variables will be described as mean ± standard deviation ormedian (interquartile range), when appropriate. Categorical variables will bedescribed as numbers (percentages). In addition, statistical analyses will beconducted in previously defined subgroups. All probabilities of significance  presented will be bilateral and values below 0.05 will be consideredstatistically significant. The data will be statistically analyzed with SAS 9.3.If a violation of the assumption is observed, weighted Cox regression will beused.This registry is conducted in accordance with national and internationalresolutions such as the Declaration of Helsinki, Resolution CNS196/96 and allthe complementary CNS/MS, ICH Good Clinical Practices guide(1996), and theDocument of the Americas (2005).Each clinical research center will submit this protocol, the FICFs, and all otherapplicable documents to the institutional CEP for analysis and approval prior toany procedure included in the registry.Instituto Brasileiro dePesquisa Clínica, BCRI) in São Paulo, Brazil, wasresponsible for the development of the protocol and operational coordinationof the study, development and implementation of the electronic platform fordata collection (electronic case report form), distribution of requiredmaterials to the research centers, preparation of regulatory dossier,newsletter, quality assurance of the collected data and organization ofmeetings for researchers, preparation of a monitoring plan, determination oftraining for the research centers, periodic monitoring visits, and remotestudy closure. The Institute for Teaching and Research of Hospitaldo Coração  will beresponsible for maintaining the database and analyzing the data.The Brazilian Clinical Research Institute (The Steering Committee will be responsible for the design, implementation,analysis of the study data and allocation of appropriate responsibilities toother committees of the study.Andréa Araújo Brandão, Adriana de S. Thiago Papinutto,Álvaro Rabelo Jr., Antonio Felipe Sanjuliani, Antônio CarlosSobral Sousa, Celso Amodeo, Cristiano Pederneiras Jaeger, Dalton BertolimPrécoma, Estêvão Lanna Figueiredo, Epotamenides MariaGood God, Evandro José Cesarino, Fábio Argenta, FernandoAugusto Alves da Costa, Gilberto Campos Guimarães Filho, GustavoFreitas Feitosa, Helder José Antônio Miranda Abrantes, IranCastro, José Lima Reis, Joaquim David Carneiro Neto, JoãoCarlos Ferreira Braga, João Miguel Malta Dantas, João SoaresFelício, João Roberto Gemelli, Jose Albuquerque de FigueiredoNeto, José Carlos Ayub, José Fernando Vilela Martin, LeilaBeltrami Moreira, Lívia Figueira Avezum Oliveira, Luiz Bortolotto,Luciana Reis Katz Weiand, Luciano Marcelo Backes, Luiz Carlos Bodanese, LuizCésar Nazário Scala, Márcio Kalil, Marco Mota Gomes,Margaret Assad Cavalcante, Maria das Dores de Oliveira Jehá, MarioFritsch Neves, Pedro Barros, Renato Delascio Lopes, Roberto DischingerMirand, Rodrigo Pinto Pedrosa, Rodrigo Ricardo Silva da Costa,Rogério Toshiro Passos Okawa, Rui Manoel dos Santos Póvoa,Sergio Kaiser, Thiago de Souza Veiga Jardim, Wladmir Saporito, Weimar SebbaBarroso, Wilson Nadruz Junior.A better understanding of the way that hypertensive patients are treated in Brazilwill allow the implementation of policies aimed at improving the treatment ofhypertension, contributing to changes in the epidemiological profile and decrease incardiovascular morbidity and mortality in the country.


Background. Central systolic blood pressure (CSBP) has prognostic significance and simplified devices for its estimation have been introduced recently. The aim of this study was to assess the achievement of the target CSBP in treated hypertensive patients. Subjects and Methods. One hundred patients with well-controlled hypertension were analysed. For CSBP estimation, we used the Arteriograph (TensioMed Ltd.), which uses one cuff for all measurements, the “single-point measurement” approach. Results. We found that 62% of patients had CSBP ≥ 130 mmHg, the suggested cut-off value for hypertension. When sex-specific classification was employed , only 13% of patients (mainly women) remained in the hypertensive range. We also found that 55% of patients had a CSBP higher than brachial pressure. Multiple analyses showed that CSBP was significantly associated with sex, height, and return time. Conclusions. A high proportion of treated hypertensive patients had CSBP levels that exceeded their brachial BP. CSBP positively correlated with lower height and shorter return time of the reflected pressure wave and was significantly higher in females compared to males. These findings suggest that, for CSBP classification, it is important to take height and sex-specific differences into account. Arterial hypertension is the most important modifiable cardiovascular risk factor. Blood pressure (BP) measurement has been extensively used for more than a century, and brachial cuff BP has been used for the diagnosis and treatment of hypertension. Consequently, guidelines and classifications are based on this approach , 2.Systolic BP is a result of the interaction between ejected stroke volume and the dampening function of large arteries and propagative and reflected pressure waves. Both pulse pressure and systolic pressure increase due to pulse pressure amplification as pressure waves propagate from the heart to the periphery, and from where the pressure waves reflect back to the heart , 4.Early return of reflected pressure waves (in the case of stiffer arteries) may increase central systolic pressure in the aortic root during late systole and may increase the workload of the left ventricle . StandarCentral systolic blood pressure (CSBP) is considered an important haemodynamic parameter, and several large studies indicate that it is an important prognostic risk factor . CardiovThe standard for noninvasive central BP estimation is generally accepted to be applanation tonometry, in which pulse waves on the radial or carotid arteries are detected by a sensitive probe. The pulse wave curve obtained requires calibration, and this is achieved by entering the BP values from brachial BP measurements and is corrected by the transfer factor. The peripheral pressure waveform is then intertwined with the wave in the ascending aorta , 12. SucNewer and simpler methods rely on cuff-based waveform analyses, in which pressure waves and BP measurements are taken by a single BP cuff on the arm. This technique, called single-point measurement, is operator-independent and such devices have shown some promise for routine clinical use . The obtFor the research and clinical implication of vascular stiffness measurement, it is important to standardise the methodology of examination of arterial stiffness. Methodological aspects of stiffness measurements, wave reflections, central pulse pressure, and aortic pressure estimation are discussed in the Recommendation of the American Heart Association (AHA) 2015 . Papers In this study, we aimed to identify the potential benefits of CSBP measurement in the management of patients with hypertension in clinical practice. Thus, we analysed a group of patients who visited our outpatient department that specializes in providing care for patients with high BP. We also assessed how successful we were in achieving the recommended CSBP level according to data in the current literature and to compare CSBP readings to brachial BP in treated hypertensive patients.2)], and/or significantly increased liver function test values .For this analysis, we retrospectively selected data from 100 patients with well-controlled hypertension  from a group of 199 consecutive patients referred to our outpatient department for further investigation or for a follow-up examination from May 2008 to December 2015. The patients were originally involved in a research project studying central haemodynamics and preclinical cardiovascular disease, which was approved by Ethical committee of University Hospital Commenius University Bratislava. The patients signed an informed consent form after we explained to them the nature and aim of this type of noninvasive BP measurement, which was added to our usual set of examinations devoted to the search for preclinical cardiovascular diseases in patients diagnosed with hypertension. The patients selected for this analysis had undergone a basic clinical examination and a recent echocardiographic examination. They had a blood pressure (measured by arteriography) below 140/90 mmHg and their current medication list was known. The exclusion criteria were as follows: atrial fibrillation, systolic or diastolic BP above the target values, left ventricular systolic dysfunction, heart failure, unstable angina or clinically significant valve disease, advanced renal failure  in 31%, history of transient ischaemic attack or stroke (10%), and PAD (4%) , impaired glucose tolerance (21%), type 2 diabetes mellitus , and obesity (31%), were relatively common . FrequenPAD (4%) . All patPAD (4%) .All patients in the study group were well-treated and achieved the recommended goal for brachial BP (<140/90 mmHg), as measured by the Arteriograph in each measurement cycle. Mean systolic brachial BP in the whole group was 123.6 ± 10.1 mmHg; the values for women were higher than those for men, but the differences were not significant. CSBP was significantly higher in females compared to males .The mean value of the estimated CSBP in the aorta was 123.2 ± 12.1 mmHg, but almost two-thirds of patients (62%) had CSBP ≥ 130 mmHg consistent with central hypertension according to the proposed classification for central BP published in JACC 2013 . The mear = −0.299, p = 0.003), shorter RT , and higher PVVao . Multiple analyses  showed that CSBP was significantly dependent on sex and return time. After removing sex from the model, the height became a significant parameter. After dividing patients according to sex, the PWVao was significant in both sexes, the RT was significant in women, and age was significant in males  classification suggested by a “Working Group for Central Systolic Blood Pressure” published in EHJ 2014 , only 13in males .p value = 0.064); brachial augmentation index  and aortic augmentation index  were higher and return time was shorter  in the group with higher central systolic than brachial BP compared to those in the group with lower central systolic than brachial BP, respectively. Of the 55 persons in this subgroup, 44 were female (80%), and they were older, of shorter stature, and with lower BMI; the differences were significant. An overview of arterial stiffness parameters and related variables are provided in When we compared the central and brachial systolic BPs, we discovered that more than half of our patients (55%) had a higher central systolic BP than brachial BP; mean central systolic BP values in these subgroups were 129 ± 10.3 mmHg for the subgroup with higher central systolic than brachial BP versus 116 ± 10.1 mmHg for the subgroup with lower central systolic than brachial BP , part C.Because of the large proportion of women in the group of patients with high CSBP, we statistically evaluated the group based on the sex distribution. The PWVao was nonsignificantly faster in women. However, they had a significantly higher CSBP (126 mmHg versus 118 mmHg), shorter return time (RT), and higher augmentation indexes than men .Antihypertensive therapy was based on a combination of antihypertensive drugs. The mean count of antihypertensive agents per person was 2.6 ± 1.2 . We did Ltd. The Arteriograph was validated based on the finding of a strong correlation between invasively measured and noninvasively estimated CSBP [r = 0.67, p < 0.001) and the Complior  were considerable, but the techniques are not interchangeable and, therefore, for follow-up measurements, it is necessary to use the same device [In this study, we evaluated CSBP in treated hypertensive patients. Unexpectedly high was the proportion of patients who had CSBP levels higher than brachial SBP. These findings are different from most published data, which show the brachial systolic BP higher than CSBP because of peripheral pressure wave amplification , 27. Forted CSBP . Rossen ted CSBP  found a e device –26, 28. e device .In this study, each patient achieved the target brachial BP (<140/90 mmHg). If we accept the suggested cut-off value of greater or equal to 130 mmHg for the definition of central systolic hypertension , we can It is known that central haemodynamics depends on aortic stiffness and reflections of pressure waves from the peripheral arterial tree and is influenced by risk factors and cardiovascular diseases .We analysed the interdependencies between PWVao (as an indicator of aortic stiffness) and CSBP. According to all criteria used for central hypertension, hypertensive patients, in comparison to normotensives, had only nonsignificantly higher PWV; however, the return time of the reflected wave into the aortic root was significantly shorter in hypertensive patients. This discordance between the velocity of the aortic pulse wave (which was similar in both groups) and the shorter return time of the reflected wave may be explained by a shorter distance  of the reflected pulse wave to reach the central aorta , as the The increase of augmentation pressure, pulse pressure, and late systolic pressure due to shorter return time may increase left ventricular load and can predict heart failure . In agreWhen we applied the sex-specific scale for CSBP classification  presented in EHJ in 2014 , which iBecause females were more frequently among the centrally hypertensive, we also evaluated our patients from a sex-specific aspect. Women had significantly higher CSBP (126 mmHg versus 118 mmHg), lower height (163 cm versus 178 cm), and higher age (66 years versus 61 years) than men  . LVH alsIn a large proportion of our patients (55%), CSBP was higher than brachial systolic BP. In the literature, the prevalent opinion is that CSBP is lower compared to brachial BP because of peripheral BP amplification by wave reflections , 27, 33.Some results have been published suggesting the augmentation of CSBP above the brachial BP values. Munir et al.  emphasisThis situation is frequently present in clinical states, which increase the degree of aortic stiffness, such as hypertension, diabetes mellitus, or renal failure or due to natural age-dependent changes . In receAntihypertensive drugs decrease both brachial BP and CSBP but they differ in the magnitude of decreasing the CSBP, as was shown in a meta-analysis by Manisty and Hughes . They anThis study was a retrospective analysis of treated hypertensive patients who had achieved the recommended target arm blood pressure values. One limitation of the study was that patients were treated with different antihypertensive drugs. Most frequently, ACE inhibitors or ARBs were used in combination with calcium channel blockers and/or diuretics; beta-blockers were also frequently used. The average number of antihypertensive agents per person was 2.6 ± 1.2. In this study, central systolic hypertension was more frequently detected in women. The women in our analysis were older and shorter than the men; these factors likely contributed to higher CSBP. Due to the combination therapy and relatively small number of patients in our study, we did not find the influence of specific drugs on CSBP. However, the purpose of this study was more focused on comparing central and brachial systolic BP in well-controlled hypertension.We found important differences between brachial and CSBPs in our group of patients with well-controlled hypertension, defined as an arm BP below 140/90 mmHg. A significantly large proportion of these patients have high CSBP. While the brachial pressures in the whole group were within the target range, 62% of patients had estimated CSBPs above the proposed cut-off value of 130 mmHg for central systolic hypertension. Using the sex-specific European proposal for CSBP classification, only 13% of patients (mainly women) remained in the hypertensive range. When we used another approach and compared the central systolic and brachial systolic BPs for each individual, we found that the estimated CSBP was higher than the brachial systolic BP in 55% of patients.Factors that significantly contributed to higher CSBP included shorter height, older age, and female sex. Generally, women are of shorter stature, which significantly influences the timing of pressure wave propagation and reflection. In CSBP classification, factors such as sex, age, and height should be taken into account. However, this approach requires more complex classification scales. Such a different approach can be seen in recently published papers in the Journal of the American College of Cardiology 2013  and Euro


Health-Related Quality of Life (HRQoL) assessment after kidney transplantation has become an important tool in evaluating outcomes. This study aims to identify the associated factors with HRQoL among a representative sample size of Kidney Transplant Recipients (KTR) at the time of their inclusion in the study.Data of this cross-sectional design is retrieved from a longitudinal study conducted in five French kidney transplant centers in 2011, and included KTR aged 18 years with a functioning graft for at least 1 year. Measures include demographic, psycho-social and clinical characteristics. To evaluate HRQoL, the Short Form-36 Health Survey (SF-36) and a HRQoL instrument for KTR (ReTransQol) were administered. Multivariate linear regression models were performed.A total of 1424 patients were included, with 61.4% males, and a mean age of 55.7 years (±13.1). Demographic and clinical characteristics were associated with low HRQoL scores for both questionnaires. New variables were found in our study: perceived poor social support and being treated by antidepressants were associated with low scores of Quality of Life (QoL), while internet access was associated with high QoL scores.The originality of our study’s findings was that psycho-social variables, particularly KTR treated by antidepressants and having felt unmet needs for any social support, have a negative effect on their QoL. It may be useful to organize a psychological support specifically adapted for patients after kidney transplantation. In public health and medicine, Health-Related Quality of Life (HRQoL) measurements have become an important outcome measure in addition to morbidity and mortality rates, both in population health assessment and in clinical trials , 2. HRQoIn general, chronic diseases are increasingly widespread . The WorWhen compared with dialysis, renal transplantation has become the most cost-effective treatment –13 for EAlthough the HRQoL advantages in Kidney Transplant Recipients (KTR) were established , 16–21, This is a cross-sectional design retrieved from a longitudinal study carried out continuously during the year 2011, in five French kidney transplant centers: Marseille, Montpellier, Nice, Paris and Nantes University Hospitals. All patients aged 18 years and older with a functioning graft for at least one year were eligible for the study. Multi-organ transplant patients before or simultaneously with their kidney transplant were excluded.Patients were included in 2011 during their regular medical visits. Data of inclusion, including demographic, psycho-social characteristics and HRQoL, were directly collected from the patients who agreed to participate, except health data which were obtained from nephrologists.Demographic and psycho-social variables collected were:➢ Age, gender, level of education: primary or less, college, secondary 1st stage and university➢ Living arrangement: alone or not alone➢ Having children or not, employment status: employed, retired, unemployed➢ Disability pension: patients receiving disability pension or not➢ Monthly incomes in the household (€)➢ Internet and social network use➢ Social support: done by a perceived questionnaire, used to estimate the availability and the quality of this support . It is cTo explore kidney disease: we collected the etiology of End-Stage Renal Disease (ESRD), the previous dialysis treatment and duration, the duration since transplantation, the organ donor type , the organ transplantation (one or two simultaneous kidney grafts), the number of transplantations, the graft rejection episodes and the graft chronic dysfunction.To explore health status and comorbidities: we collected the pathologies frequently associated with KTR , smoking status, Body Mass Index (BMI) and the two validated scales: The Karnofsky Performance Scale (KPS) and The Charlson Comorbidity Index (CCI).Medical measures were grouped into four domains related to kidney disease, health status and comorbidities, treatments (i.e. drugs) along with their side effects and biological data.The Karnofsky Performance Scale (KPS) was evaluated to classify patients according to their functional impairment from 0 to 100%. The lower the Karnofsky score, the worse the survival for most serious illnesses was , 24.3.To explore treatments and their side effects, we collected treatment characteristics. We generated with nephrologists a selective list of the most commonly prescribed drugs with their generic names, previously used in a recent publication . This li4.To explore biological data: we collected creatinine and hemoglobin (Hb) levels directly from nephrologists during the medical visit. Creatinine levels were defined by establishing 3 categories with nephrologists . Anemia was defined by using the World Health Organization (WHO) criteria, which meant that the Hb concentration was below 12 g/dl in women and below 13 g/dl in men .The Charlson Comorbidity Index (CCI) was evaluated to classify patient’s comorbidities. According to Charlson et al. , the CCIHRQoL was measured with the SF-36 and the ReTransQol. French version of the SF-36 , 30 is aThe ReTransQol version 2 , 34 is aScores for both instruments range from 0 to 100, with higher scores indicating better HRQoL.The study methodology was approved by the local Institutional Review Board (CCTIRS n°12-726) and the “Comité National Informatique et Liberté” (CNIL n°1639707), thus ensuring the confidentiality of all the collected informations. All patients agreeing to participate signed a written informed consent before their inclusion in the study.p-value < 0.2 were included as candidate variables in the multivariate analysis. Multivariate Linear Regression models (MLR) were used to estimate the relationship between HRQoL scores and the other characteristics. The β coefficients and p-value were performed. The level of significance was set at a p-value ≤0.05. The assumptions of the MLR were verified for linear relationship, normality of distribution, absence of multicollinearity and residuals. Because missing data were minimal (< 10%), we did not replace them and we only analyzed the available ones (i.e. ignoring the missing data).Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software . Quantitative data were expressed as mean ± standard deviation (SD), minimum and maximum or median, 25th and 75th percentiles, whereas categorical data were expressed as frequency and percentage. Group comparisons were performed using analysis of variance  for quantitative variables. All factors with a At the time of the survey, 1469 KTR met eligible criteria for the study during 2011. Among them, 45 patients (3.1%) without QoL questionnaires were excluded from this study and 1424 were included and selected for analysis. Thus, the participation rate is 96.9%.As presented in Table Regarding the clinical characteristics Table , more thFigure p < 0.2).We selected all variables in the final regression model for both questionnaires (SF-36 and ReTransQol) according to their significance in the univariate analysis . To a lesser extent, advanced age, female gender, having children, unemployment, living alone, a high Charlson Comorbidity Index, high creatinine levels > 250 μmol/L), chronic graft dysfunction, being treated with cardiovascular drugs and presence of side effects related to treatments were associated with low QoL scores Tables  and 5.0 μmol/L,Psycho-social variables were also found to be associated with HRQoL scores for both questionnaires. Perceived poor social support and being treated by antidepressants were associated with low scores of QoL, while internet access was associated with high QoL scores Tables  and 5.This study analyzed the factors associated with HRQoL in a representative sample of 1424 Kideny Transplant Recipients (KTR) from five kidney centers of France. This study goes further from a previous work published in a French national study of 1061 KTR from 8 regions of France, which was the first French report about HRQoL in kidney transplantation . We analIn our study, HRQoL scores, socio-demographic and clinical characteristics of KTR are similar to a French national survey . Socio-dThis study points out that KTR receiving a disability pension have an extremely impaired HRQoL, especially for physical dimensions. This association may be influenced by the impact of manual work . PatientKarnofsky Performance Status (KPS) was strongly associated with good HRQoL scores, whatever the instrument used. Whether KTR could carry normal activity and take care of themselves are the important parameters of measurement of QoL. Zhang L et al.  suggesteFurthermore, treatments with diabetic, cardiovascular and calcium drugs had a negative impact on HRQoL, especially for physical dimensions. In contrast, we did not find any association between immunosuppressive drugs and HRQoL, which suggests that nephrologists should use more effective treatments to prevent rejection and preserve the kidney function without adversely affecting HRQoL. A specific health education for KTR, including how treatments must be adhered, its benefits and side effects, is also recommended for KTR to handle difficulties due to specific treatments.We also found a strong association between antidepressants and bad HRQoL scores for both physical and mental components. It is possible that patients treated with antidepressants tended to somatize more and give more emphasis to the negative effects of transplantation than its positive effects , 57. It Aside from these factors, social support was significantly associated with bad HRQoL scores. KTR with a need for an esteem and emotional support have bad QoL scores in almost all dimensions and specifically in mental dimensions Tables  and 5. TSumming up, these new findings reinforce the importance of patients’ psychological health and strengthen the necessity of psychosocial development and support for these patients. Our patients may, after kidney transplantation, need more psychological interventions aiming to provide information about their medical care. This could help them to deal with their disease and reduce several mental problems (such as stress and anxiety). Therefore, for better post-transplant rehabilitation and given the risks of psychopathology, the development of interdisciplinary interventions such as socio-medical and psychotherapeutic programs are essential.Finally, our sample is representative of general French KTR with a large sample size. To our knowledge, there are few studies with a sample over 1000 patients , 62, 63.The originality of our study’s findings was that new variables, particularly KTR treated by antidepressants and having felt unmet needs for any social support, have a negative effect on their QoL. It may be useful to organize a psychological support specifically adapted for these patients. In order to orientate psychological programs and improve patient care and well-being, a better understanding of how patients anticipate, live and face post-kidney-transplantation and a deep investigation of psychological factors are needed in future QoL studies.