Hyperadrenocorticism (HAC) is associated with an increased prevalence of hypertension. This study investigated the left ventricular function using two-dimensional speckle-tracking echocardiography (2D-STE) in small breed dogs affected with spontaneous HAC.n = 9), dogs with pituitary-dependent hyperadrenocorticism , and dogs with adrenal-dependent hyperadrenocorticism  were included in this study. Conventional echocardiography, global longitudinal and circumferential strain, and strain rate were assessed.Age-matched healthy controls . Neither LVFWd nor IVSd was correlated with systemic blood pressure . The values of all variables derived from the global strain and strain rate in longitudinal and circumferential directions followed the same pattern: highest in the controls, followed by PDH and then ADH . On multiple regression analyses, global longitudinal strain, global longitudinal strain rate in systole and early diastole, and global circumferential strain all decreased linearly with increased IVSd .On group-wise comparison, left ventricular free wall (LVFWd) and interventricular septal thickness in diastole (IVSd) were thickest in the ADH group, followed by the PDH and controls (Left ventricular hypertrophy (LVH) was more prevalent in the HAC group compared to the control group. Association between hypertension and development of LVH was not identified. Decreased global longitudinal and circumferential strains were associated with increased IVSd. 2D-STE revealed significant decreases in systolic functions that were undetected using conventional echocardiography in the ADH and PDH groups. Hyperadrenocorticism (HAC) is a condition of chronically elevated circulating glucocorticoid concentration. In response to stimulation of the renin-angiotensin system and mineralocorticoid and glucocorticoid receptors of myocytes, development of systemic hypertension, left ventricular hypertrophy (LVH), and myocardial fibrosis are commonly observed in human patients with HAC -3. The lHuman patients with HAC and concomitant hypertension have a two-fold greater risk of detection of cardiac mass abnormality compared with normotensive patients and hypertensive controls . HyperteClient-owned dogs visiting the National Taiwan University Veterinary Hospital (NTUVH) during 2010 and 2012 for routine wellness checkups were included in this study. Thorough medical histories were obtained, and physical examinations, routine blood analyses , chest radiographic examinations, abdominal ultrasonographic examinations, echocardiographic examinations , M-mode, and Doppler) and 2D-STE were performed to exclude the presence of any forms of systemic, cardiac, renal, and adrenal disease. Nine dogs  were deemed clinically healthy and categorized as age-matched healthy controls (controls).Client-owned dogs affected with HAC during the same period of time were included in this group. Inclusion criteria of HAC included evidence of clinical signs consistent with a diagnosis of HAC , results of routine serum biochemical analyses consistent with a diagnosis of HAC , and results of ACTH stimulation tests consistent with a diagnosis of HAC. Dogs with inconclusive results from ACTH stimulation tests were excluded from the study. All included dogs with HAC were required to have received an ACTH stimulation test with intramuscular injection of 0.25 mg of synthetic ACTH  prior to treatment. Blood samples for the detection of serum cortisol concentrations were collected via cephalic venipuncture immediately before and one hour after synthetic ACTH was injected . Serum cSystolic blood pressure was measured using the indirect method of Doppler flow detection with a 9.5 MHz transducer. A Doppler Ultrasonic Flow Detector  with an inflatable cuff width of 1.9 or 2.5 cm (approximately 40% of the circumference of the antebrachium) was used. During systemic blood pressure measurement, the antebrachium was maintained at the level of the heart. A series of five readings (with 10 to 20 seconds between consecutive measurements) was obtained for each dog. To minimize procedural stress, all dogs were allowed to assume a comfortable position with only gentle restraint by their owners. The dogs remained in the same position throughout systemic blood pressure measurement. The final systemic blood pressure value was calculated as the mean of five readings. The heart rate was manually recorded by pulse Doppler ultrasound detection over a period of 20 seconds after the systemic blood pressure value was measured. Dogs were considered to be hypertensive if the average systemic blood pressure exceeded 160 mm Hg .Conventional echocardiography was performed without sedation in gently restrained recumbent positions. Standard echocardiographic views were obtained in right and left lateral recumbency using the 2D-guided M mode with ultrasound units equipped with 2–5 and 5–7.5 MHz transducers . Measurements of left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular free-wall thickness (LVFWd) and interventricular septal thickness (IVSd) at end-diastole, ejection fraction (EF), and fractional shortening (FS) were obtained from the right parasternal long-axis view. The left atrium to aorta ratio (LA/AO) was measured in the right parasternal short-axis view. Values for the inflow of the maximal early (E) and late (A) diastolic mitral and tricuspid flow velocities, E/A ratio, and isovolumic relaxation time (IVRT) were determined by pulsed-wave Doppler from the left apical four- or five-chamber view.Inclusion of LVH was based on conventional echocardiographic examinations. LVH was defined as regional or generalized concentric hypertrophy with a diastolic wall thickness ≧ 7 mm of the LVFWd or ≧ 6 mm of the IVSd in dogs with a body weight of < 5 kg, and with a diastolic wall thickness of ≧ 8 mm of the LVFWd or ≧ 7 mm of the IVSd in dogs with a body weight of 5–11 kg .S), circumferential strain rate in early diastole (CSRE), circumferential strain rate in late diastole (CSRA) and peak circumferential strain (CS) were measured from the right parasternal short-axis view at the level of the papillary muscles. The software automatically divided the left ventricle into six segments based on standard segmentation model used in human patients [S), longitudinal strain rate in early diastole (LSRE), longitudinal strain rate in late diastole (LSRA), and peak longitudinal strain (LS) were measured from the left apical long-axis four-chamber view. The software automatically divided into three segments in each the left ventricular free wall and interventricular septum based on standard segmentation model used in human patients [2D-STE examinations were performed at the end of conventional echocardiography for all dogs. The standard left apical long-axis four-chamber and the right parasternal short-axis views at the level of papillary muscles were obtained using a frame rate above 60 per second. For each dog, three consecutive cardiac cycles were recorded using one single loop, and digitally stored in a hard disk for offline analysis on a workstation . The 2D-STE variables included strain, and strain rate. Circumferential strain rate in peak systole . Descriptive statistical analyses were performed with a with commercial computer statistics software  Version 12.0.1, SPSS Inc. in Chicago, IL, USA.). Continuous data were tested for normality by use of the D’Agostino-Pearson omnibus test and Shapiro-Wilk test. All tests were two-tailed, and a P value for multiple comparisons. The relationships between STE-derived variables and age, systemic blood pressure, body weight, LVFWd, and IVSd were assessed using Pearson’s correlation coefficient.Overall group-wise in continuous data , as well as conventional echocardiographic and STE-derived variables, among the PDH, ADH, and control groups were investigated using analysis of variance and post hoc tests with a Scheffe-adjusted t tests.Least squares multiple linear regression analyses were performed with the measured STE-derived variables as dependent variables and the independent variables of gender, age, heart rate, systemic blood pressure, IVSd, and LVFWd. A Chi-square test was used to assess differences in categorical variables among the groups. Comparison of the systemic blood pressure, conventional echocardiographic variables, and 2D-STE derived variables between LVH dogs and controls was performed using Student’s unpaired two-tailed The intra-observer coefficients of variations (CV) of the conventional echocardiographic and 2D-STE derived variables were calculated by a variance component analysis. The CV was determined by dividing the SD value by the overall mean. Six clinically healthy dogs were scanned on three nonconsecutive occasions within one day by the same examiner (HYC), who was unaware of values from the initial examination.The breeds represented in the controls included one miniature dachshund and two each of Maltese terriers, miniature Schnauzers, mixed breeds, and Yorkshire terriers. The mean age of the control was 10.5 ± 2.8 years (range: 7 to 15 years) and the mean body weight was 6.2 ± 2.7 kg (range: 2.6 to 10.0 kg). Nineteen dogs with HAC were included: 10 dogs with pituitary-dependent hyperadrenocorticism (PDH) and nine dogs with adrenal-dependent hyperadrenocorticism (ADH). The breed distribution of the 19 dogs with HAC was as follows: eight Maltese terriers, five Shih-Tzus, and one each of Chihuahua, miniature Schnauzer, Pomeranian, toy poodle, short-haired dachshund, and Yorkshire terrier. The mean age of the 10 dogs  with PDH was 12.5 ± 2.0 years (range: 9 to 15 years) and the mean body weight of this groups was 4.5 ± 1.4 kg (range: 3.2 to 6.6 kg). The mean age of the nine dogs  with ADH was 12.3 ± 2.0 years (range: 9 to 15 years), and the mean body weight of this group was 5.9 ± 2.7 kg (range: 2.1 to 10.0 kg).P = 0.615).No statistically significant differences in body weight and heart rate among controls, the PDH, and the ADH groups were found Table . The femP = 0.005 versus PDH group and controls, Table P = 0.009 versus PDH group and controls, Table The mean systemic blood pressure was highest in the ADH group . Five dogs  were characterized with symmetric LVH, four dogs  were characterized with focal and asymmetric LVH.In conventional echocardiographic examinations, most indices among controls, the PDH, and the ADH groups were not different, except LVFWd and IVSd, mitral E wave, and IVRT values Table . Both LVP = 0.008, Table P = 0.036 and P = 0.001, respectively, Table r2 = 0.05, P = 0.238 and r2 = 0.09, P = 0.113, respectively). Neither LVFWd nor IVSd was correlated with body weight . Systemic blood pressure was negatively correlated with E/IVRT .IVRT was highest in ADH, followed by PDH and controls (n = 9) and controls . No significant differences in systemic blood pressure was found between HAC dogs with LVH (n = 9) and without LVH . Significant decreases in mitral E/A ratio and significant increases in IVRT were also found in LVH dogs compared to controls .No significant differences in systemic blood pressure, FS, or EF were found between dogs with LVH . No correlation between age, body weight, and 2D-STE indices were found.Systemic blood pressure was negatively correlated with global CRSS , global LSRE , global LS , global CSRS  and global CS . The LVFWd was negatively correlated with global LSRS , global LS  and global CS . The E/IVRT was positively correlated with global CSRS , global CSRE  and global CS .The IVSd was negatively correlated with global LSRS, LSRE, LS, global CSRS, CSRE, and CS, were significantly decreased in dogs with LVH compared to controls ; however, these differences between dogs with LVH (n = 9) and without LVH (n = 10) in the HAC group did not reach statistical significance.Seven of eight global 2D-STE variables, namely LSRS, and LSRE all decreased linearly with IVSd and were affected by gender , IVSd had the highest r2 in the final model.In the multiple regression analyses, global LS, global LSRr2 = 0.223, P = 0.007). Global CSRS decreased linearly with IVSd and increased linearly with heart rate , IVSd had the highest r2 in the final model. Global CSRE increased linearly with heart rate and decreased linearly with systemic blood pressure , systemic blood pressure had the highest r2 in the final model.Global CS decreased linearly with IVSd (adjusted CV (%) of 2D-STE variables were all less than 20% Table .Table 6Chronic excessive cortisol concentrations might cause hypertension. Subsequent left ventricular remodeling, hypertrophy, and altered diastolic function are the most important risk factors of cardiovascular mortality in human patients with HAC . Sixty-eCardiac hypertrophy secondary to hypertension and chronic exposure to excess circulating cortisol may also contribute directly to left ventricular concentric remodeling in human patients with HAC. Subsequently, functional abnormality, such as diastolic dysfunction (reduced E/A ratio and/or E velocity) has also been reported in human patients with HAC ,26. In tDevelopment of LVH is generally believed to be associated with concomitant hypertension in HAC. However in this study, the wall thickness of the left ventricle was not correlated with systemic blood pressure. Significant differences in systemic blood pressure were not found between dogs with LVH and controls, or between HAC dogs with LVH and HAC dogs without LVH. No association between hypertension and development of LVH was identified in this study. The mechanism of development of LVH in dogs with HAC could not be clarified in this study.In 2D-STE analysis, global peak systolic and early diastolic strain rate, as well as global strain in longitudinal and circumferential dynamics exhibited a consistent pattern: profound decreases in the ADH and the PDH groups compared to controls, i.e. significant decreases in systolic and diastolic functions were observed in the ADH and PDH groups when compared to controls. Left ventricular systolic and diastolic dysfunction was also reported in human patients with HAC ,28. DiasIn this study, 2D-STE revealed alterations in left ventricular mechanics despite a preserved systolic function detected by conventional echocardiography in dogs with HAC. The indices of left ventricular systolic function derived from conventional echocardiography, such as FS, EF, LVEDD and LVESD, were not significantly different between the HAC group and controls. FS and EF did not reach significant difference between dogs with LVH and the control. However decreased systolic function was revealed using 2D-STE. Decreased systolic function was most prominent in dogs with LVH associated with ADH, with decreasing prominence observed in the PDH group and finally in controls. This finding suggests that dogs with HAC may have subclinical systolic dysfunction that may remain undetected using conventional echocardiographic examination. Similar findings are also reported in human patients with HAC-associated hypertrophic cardiomyopathy: subclinical left ventricular systolic dysfunction is indicated using STE, although the assessment of FS and EF is usually normal or supernormal ,29.S, global LSRE, global CS, and CSRS decreased while IVSd increased, suggesting that decreased magnitude and rate of myocardial deformation is followed by increased LVH. Based on these findings, increased IVSd could be used as predictor of subclinical LV dysfunction in small breed dogs with HAC. In addition, global CSRE decreased linearly with increased systemic blood pressure. Based on this finding, increased systemic blood pressure could be used as predictor of subclinical LV diastolic dysfunction in small breed dogs with HAC.Global LS, global LSRE/IVRT is an index to predict for left ventricular filling pressure, and increases when LV filling pressure is increased in dogs with congestive heart failure characterized by volume overload . In thisLongitudinal deformation was affected by gender in this study. Although dogs with HAC are more commonly female, no gender predilection has been reported. In this study, 57% of the dogs with HAC were females, a rate similar to that previously reported ; howeverIn this study, the differences of longitudinal 2D-STE variables among groups were prominent when the analyses were based upon averaged global deformation comparing to the analyses across six myocardial regions. This might be due the definition of segments. The definition of segment and post-processing software was based on human nomenclature or anatomy, and it may not be necessarily applied to the dogs . AverageLimitations of this study include low number of dogs. The dexamethasone suppression test and ACTH concentrations were not applied to make a differential diagnosis of ADH and PDH. HAC of iatrogenic origin was predominant in the area where the authors practice. The differential diagnosis of ADH and PDH was based on the results of the ACTH stimulation test and ultrasonographic images of adrenal glands. Many HAC cases in which bilaterally and irregularly enlarged/round adrenals were presented were excluded from the study. No corresponding aldosterone concentrations were included in this study.


Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/ and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area).Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA.The within-group error was lower for GFRThe study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors. Accurate assessment of kidney function in the critically ill patient plays an important role in diagnosing acute kidney injury (AKI); in the appropriate prescription and dosing of drugs, whose elimination depends on renal function; and in timely application of therapeutic strategies. In clinical medicine, the concentration of creatinine in serum is used daily as a marker for kidney function. However, serum creatinine concentration may not be suitable for this purpose as it is affected by factors other than kidney function. Creatinine is metabolized from creatine, which is released by the muscles, therefore muscle mass and metabolic transformation of creatine have an impact on serum creatinine concentration . In addiIn critically ill patients with AKI, three main factors influence the accuracy of serum creatinine as a marker of kidney function: true kidney function, fluctuations in creatinine production, and fluid balance. In critically ill patients, creatinine production may be decreased because of immobilization and malnutrition, or increased because of catabolic illness. Increases in total body water, common in these patients, increases the distribution volume of creatinine, and attenuates the increase in serum creatinine concentration caused by AKI ,4-6. Fur123I-iothalamate, diethylene triamine pentaacetic acid and chromium-ethylenediaminetetraacetic acid (51Cr-EDTA) as filtration markers, is considered as the gold standard for assessment of renal function [Glomerular filtration rate (GFR), measured using exogenous substances such as inulin, iohexol, function ,10. UnfoThe second best method for assessment of renal function is urinary creatinine clearance (CrCl), which can be computed from a timed urine collection  and blood sampling for serum creatinine . HoweverGFR can also be assessed using estimating equations. These equations include variables such as age, sex, race and body weight, in addition to serum creatinine, as a substitute for muscle mass and they can therefore overcome some of the limitations associated with using serum creatinine alone ,13-15. E51Cr-EDTA, in critically ill patients with early AKI after complicated cardiac surgery.The aim of this study was to evaluate the agreement  of urinaThe study protocol was approved by the Human Ethics Committee of the University of Gothenburg. Informed consent was obtained from the patient or, if the patient was sedated, the patient's next of kin, before enrolment in the study. Thirty patients who developed AKI after complicated heart surgery were included in the study according to the following inclusion criteria: cardiac surgery with cardiopulmonary bypass; normal preoperative renal function (serum creatinine ≤105 μmol/L); and development of early AKI according to the Acute Kidney Injury Network criteria, defined as a 50% to 300% postoperative increase in serum creatinine from baseline . The fol2, whole body oxygen extraction ≤40%, and mean arterial pressure at 70 to 80 mmHg with or without an intra-aortic balloon pump. A continuous infusion of furosemid (5 to 40 mg/h) was used, if needed, to promote diuresis. When the patient was sedated, neurological status was not included in the sequential organ failure assessment score [In the intensive care unit (ICU), patients who were mechanically ventilated were sedated with propofol. Morphine or fentanyl was used for treatment of postoperative pain. The hemodynamic and renal management of patients were at the discretion of the attending intensive care physician. The treatment protocol included inotropic support with milrinone, dopamine and/or norepinephrine to maintain a cardiac index ≥2.1 L/min/mnt score .Arterial blood pressure was measured by a radial or femoral arterial catheter. All the patients had a central venous catheter. Systemic hemodynamics were measured by a pulmonary artery thermodilution catheter  in 21 out of 30 patients. Measurements of thermodilution cardiac output were performed in triplicate. The pulmonary artery wedge pressure was measured intermittently. Systemic vascular resistance was calculated according to standard formula.Blood samples for serum creatinine were taken within a couple of hours before the experimental procedure. All serum and urinary creatinine measurements were performed in the same laboratory. Serum and urinary creatinine concentrations were analyzed by a standardized enzymatic colorimetric method using the Modular P clinical chemistry analyzer 51Cr-EDTA (0.6 MBq/m2 body surface area) was given, followed by an infusion at a constant rate individualized to body weight and serum creatinine. Serum 51Cr-EDTA activities from arterial blood were measured by a well counter . After an equilibration period of at least 60 minutes, urine was collected in two 30-minute periods to measure urine flow and urine creatinine (period A and period B). An indwelling Foley catheter drained the urinary bladder. The levels of 51Cr-EDTA were obtained from arterial blood at the end of each urine collection period. Clearance for 51Cr-EDTA was obtained as a measure of GFR calculated from the formula:After blood and urine blanks were taken, an intravenous priming dose of 51Cr-EDTA clearances (period A and B) was used for subsequent comparison with the urinary CrCl and the estimating equations. Urinary CrCl was calculated for period A and B from the formula:The mean of the two 2. All the equations used for eGFR are summarized in Additional file GFR was estimated in all patients by the use of three frequently used equations: the CG equation , the simP-value) of less than 0.05 was considered to indicate statistical significance. The data are presented as mean ± standard error of the mean (mean ± SEM). Descriptive data analyses on the 51Cr-EDTA clearance method and the urinary CrCl method for measurement and assessment of GFR were performed according to Bland and Altman [Data on hemodynamic and renal variables from periods A and B were compared using a paired t-test. A probability level , were assessed according to Bland and Altman [The agreements between the gold standard d Altman . The mead Altman .Thirty patients were included in the study, 1 to 12 days after cardiac surgery. Baseline characteristics of the patients are presented in Table P = 0.03) there was no statistically significant differences in hemodynamic data, plasma 51Cr-EDTA concentrations, GFR measured by 51Cr-EDTA infusion clearance (GFR51Cr-EDTA ) and eGFR measured by CrCl (eGFRCrCl) between periods A and B.Individual data on GFR and the various eGFR:s  are shown in Table 51Cr-EDTA was 47.0 ±18.0 ml/min/1.73m2 and for eGFRCrCl was 43.8 ±21.9 ml/min/1.73m2. The within-group error was lower for GFR51Cr-EDTA than eGFRCrCl, 7.2% versus 55.0%, respectively. The repeatability coefficient for GFR51Cr-EDTA and eGFRCrCl were 3.3 and 23.9, respectively, and the mean coefficient of variation for GFR51Cr-EDTA was lower than the mean coefficient of variation for eGFRCrCl, 1.73 ±1.38% versus 13.4 ±11.3%.As shown in Figure 51Cr-EDTA) and estimated GFR (eGFR) with the urinary CrCL method and the prediction equations  are described in Figures 51Cr-EDTA, the between-method bias was 2.6 ml/min for eGFRCrCl, 11.6 ml/min for eGFRMDRD and 11.1 ml/min for eGFRCKD-EPI. The between-method bias was 7.39 ml/min for eGFRCG using actual body weight, 7.43 ml/min for eGFRCG using preoperative body weight and 11.1 ml/min for eGFRCG using preoperative ideal body weight when compared to GFR51Cr-EDTA.The agreement between measured GFR  but wide range of renal (dys)function (serum creatinine: 53 to 590 μmol/l) [et al. [Although commonly used in the ICU, comparisons of the urinary CrCl method for assessing GFR with gold standard GFR measurements have not, to our knowledge, previously been reported in critically ill patients with early AKI. Robert function . They fofunction . Erley e μmol/l) . Althoug [et al. .51Cr-EDTA clearance was high, with a within-method error of only 7.2%. However, urinary CrCl had an unacceptably low repeatability, with a within-method error of 55%. It is therefore not surprising that the agreement between the 51Cr-EDTA clearance and urinary CrCl was very low, with an unacceptably high between-method error of 103%.In a study of method comparison, assessment of within-method repeatability is important, because the repeatability of each of two methods limits the amount of agreement, which is possible ,23. Cleaet al. [51Cr-EDTA to that of the infusion clearance of 51Cr-EDTA measured simultaneously in ICU patients [51Cr-EDTA [The main source of error in the case of urinary CrCl, as demonstrated by Erley et al.  and by tpatients . The lat1Cr-EDTA . This il2 [et al. [51Cr-EDTA clearance, was approximately 45 to 50 ml/min, which could explain the low bias (2.6 ml/min) comparing urinary CrCl to 51Cr-EDTA clearance.Urinary CrCl may grossly overestimate GFR due to creatinine secretion at the tubular level. The magnitude of this overestimation increases as GFR declines, and may be as great as 141% for patients with GFR of <40 mL/min/1.73m2 . Robert  [et al.  comparedDisparities between measured GFR and urinary CrCl in critically ill patients may result from several factors. Clearance methods require a steady state situation, a criteria not always met in critically ill patients. Variations in urine output values, due to changes in hormonal regulation of renal perfusion, changes in systemic hemodynamics, and alterations in creatinine production, secretion and metabolism, secondary to rapidly evolving underlying disease states, influence the accuracy of urinary CrCl in critically ill patients . Inaccur51Cr-EDTA in this group of critically ill patients with early AKI. The biases ranged from 7.39 ml/min  to 11.58 ml/min (eGFRMDRD). The between-group errors were unacceptably large, ranging from 66.8% to 68.7%, with wide limits of agreement for all the equations. The poor performance of the estimating equations in critically ill patients with early AKI may be explained in part by the methods and populations used to develop these equations. All equations were developed and validated in populations of non-ICU patients with chronic kidney dysfunction. The CG equation was originally designed to estimate 24-hour CrCl, and not GFR, in hospitalized patients with mild renal dysfunction [125I-iothalamate clearance as a reference in 1,628 patients with chronic kidney disease [All the GFR estimating equations used in this study, the CG, MDRD and CKD-EPI equations, performed poorly when compared to infusion clearance of function . The MDR disease , and the disease .et al. [2. Urinary creatinine excretion was low in patients with low CrCl, suggesting a pronounced muscle loss and depressed production of creatinine. This could explain why the estimating equations, based on serum creatinine, overestimated GFR in the present study.Another explanation for the poor performance of the estimating equations is depressed production of creatinine, caused by rapid muscle loss, in ICU patients. Hoste et al.  studied Estimating equations are also limited by the use of serum creatinine as a filtration marker. Accurate estimation of GFR from the serum level of creatinine requires a steady state. A rise in serum creatinine levels is observed only after significant loss of kidney function. Thus, serum creatinine concentrations lag behind the decline and recovery in glomerular filtration rate and is affected by factors other than kidney function, as discussed above for estimating GFR with the urinary CrCl method in critically ill patients with AKI. Thus, during non-steady state conditions, using creatinine-based equations to estimate GFR results in inaccurate assessment of kidney function ,22,35.et al. [et al. [The estimating equations used in this study, have not been validated in critically ill patients with early AKI. Two studies have compared the CG formula to gold standard reference method in critically ill patients. In the study by Robert et al. , the per [et al.  compared51Cr-EDTA.An issue regarding the use of the CG equation, is which patient weight should be used , because creatinine generation is a function of muscle mass, not body mass. Recalculating the CG equation with the preoperative body weight and the preoperative ideal body weight, instead of using the actual weight of the patient, did not improve the agreement between the CG equation and the GFRThe commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI shows poor precision. Therefore, it should not be used as a reference method when validating new methods for assessing kidney function in this particular patient population. Furthermore, the commonly used estimating equations  perform poorly when estimating GFR, with high biases and unacceptably high errors.In critically ill patients with early AKI:• Urinary clearance of creatinine should not be used as a reference method when validating new methods for assessing kidney function• Estimating equations for assessment of GFR perform poorly.51Cr-EDTA: chromium-ethylenediaminetetraacetic acid; eGFR; estimated GFR; GFR: glomerular filtration rate; GFR51Cr-EDTA: glomerular filtration rate measured with chromium-ethylenediaminetetraacetic acid infusion clearance; GFRCG: glomerular filtration rate estimated with the Cockcroft-Gault equation; GFRCKD-EPI: glomerular filtration rate estimated with Chronic Kidney Disease Epidemiology Collaboration equation; GFRCrCl: glomerular filtration rate estimated with urinary creatinine clearance; GFRMDRD: glomerular filtration rate estimated with the Modification of Diet in Renal Disease equation; ICU: intensive care unit; MDRD, Modification of Diet in Renal Disease equation.AKI: acute kidney injury; CG: Cockcroft-Gault equation; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration equation; CrCl: creatinine clearance; The authors declare that they have no competing interests.All authors participated in the study design. GB collected and prepared the data and performed the statistical analysis. GB and BR performed the experimental procedures. All authors participated in writing the paper and all read and approved the final manuscript.Supplementary Table 1..Click here for file


Transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring can be used continuously to evaluate PaCO2 in a noninvasive fashion. In this study, we compared the accuracy between PetCO2 and PtcCO2 in predicting PaCO2 during prolonged one-lung ventilation with low tidal volume for thoracic surgeries.There may be significant difference between measurement of end-tidal carbon dioxide partial pressure .Ninety sample sets were obtained. The bias and precision when PtcCO2 monitoring was more accurate for predicting PaCO2 levels during prolonged one-lung ventilation with low tidal volume for patients undergoing thoracic surgeries.PtcCO End-tidal carbon dioxide partial pressure (PetCO2) reflects PaCO2 and becomes a standard monitoring during surgery. However, various pathologic processes of the cardio-respiratory system such as ventilation-perfusion mismatch or shunt as well as changes in patient positioning have been shown to influence the correlation between PaCO2 and PetCO2 ). Written informed consent was obtained from each patient.Eighteen adult patients of ASA physical status I or II who were scheduled to undergo mini-invasive thoracic surgery with an expected OLV duration of two hours or more were recruited for this study. Patients with diagnosed cardiovascular disease were excluded.No premedication was administrated. Before the induction of general anesthesia, an epidural puncture was performed between the fifth and eighth thoracic interspace and an epidural catheter was inserted. A test dose of 3 ml 1% lidocaine was administered and no other epidural medication was used during anesthesia.Intraoperative monitoring included a non-invasive blood pressure, pulse oxygen saturation, an electrocardiogram, nasopharyngeal temperature, urine output, peak airway pressure, and direct arterial blood pressure measurement through a radial artery catheter. General anesthesia was induced with propofol (1–2 mg/kg) and remifentanil (effect site target control infusion at a target of 4–6 ng/ml). And rocuronium (0.6mg/kg) was administered to facilitate endotracheal intubation with a double-lumen tube by direct laryngoscopy. Patients were mechanically ventilated in a volume-controlled manner both in the supine and the lateral decubitus position. During two-lung ventilation (TLV), the fresh gas flow, tidal volume, respiratory rate and inspiratory/expiratory ratio were set at 1 L/min oxygen and 1 L/min air, 6–8 ml/kg, 10–12 breath/min, and 1:2, respectively. Anesthesia was maintained with sevoflurane inhalation  and remifentanil infusion until the end of the surgery. Sufentanil was administered as a bolus when deemed necessary during surgery and before the end of surgery.2 of 90% or higher and a peak airway pressure lower than 25 cmH2O. Intravenous ephedrine or phenylephrine or nicardipine was administrated to maintain blood pressure fluctuation within 30% from baseline. Additional doses of rocuronium were administered to maintain muscle relaxation.For all patients, the position of the double-lumen endobronchial tube was confirmed under direct vision with a fiberoptic bronchoscope (FOB). The patients were then turned to the lateral decubitus position. The tube position was then checked again with the FOB just before OLV, and the effectiveness of lung collapse during OLV was confirmed by direct observation in the operative field. During OLV, the fresh gas flow, tidal volume, respiratory rate and inspiratory/expiratory ratio were set at 1 L/min oxygen, 4–6 ml/kg, 10–16 breath/min, and 1:1.5, respectively, to maintain a SpO2 was measured with a TCM3 transcutaneous CO2/oxygen device . The monitoring technique was standardized by applying the probe to the upper part of the patient’s dependent arm in the lateral decubitus position. Before each study, the device was calibrated by using a two-point self-calibration (5% and 10% CO2) and the working temperature of the electrode was maintained at 42°C to “arterialize” the skin capillary blood flow according to the manufacturer’s recommendations. The monitor used an internal adjustment to compensate for the effects of the heated probe on CO2 tension. It took appropriately 20 minutes for initial stabilization after probe attachment. The end-tidal concentrations of the anesthetics and CO2 were measured with a AS/5 monitor  which was calibrated in 5% CO2 and 20.9% oxygen gas before the study. Continuous sampling was obtained from a connector attached to the proximal end of heat moisture exchanger in the respiratory circuit. Arterial blood samples were obtained during TLV, just before the initiation of OLV, and every 30 minutes during OLV until 120 minutes. Arterial blood gas analysis was performed using a GEM premier 3000 analyzer . Data of PtcCO2, PetCO2, and PaCO2 monitoring results were collected simultaneously. The heart rate, mean arterial pressure, pulse oxygen saturation, and nasopharyngeal temperature were also recorded at same time-points.PtcCO2 and PetCO2 or between PaCO2 and PtcCO2. The bias  and the precision (the SD of the bias) were calculated. Student’s unpaired t-tests were also used to compare the differences between PaCO2 and PetCO2 or between PaCO2 and PtcCO2. A p value of less than 0.05 was regarded as statistically significant. Statistical analysis was conducted using SPSS version 14.0 .Quantitative data were presented as means ± standard deviation (SD). Bland-Altman method was used to analyze the agreement between PaCO2, PetCO2 and PaCO2 at five time points were obtained , technical mistakes  and hypoperfusion  [PtcCOl edema) .2 monitoring has received great attention in neonates [2 monitoring has been confirmed by these studies. However, some others reported that PtcCO2 monitoring cannot precisely predict PaCO2 in preterm infants during in their first 24 hours [2 monitoring is OLV during thoracic surgery.Since its introduction into clinical practice, PtcCOneonates –9. Laterneonates –11, in aneonates –4 and laneonates –15 and ineonates –17. The 24 hours  and in s24 hours , possibl2 during a 2-hour period of OLV with hypercapnia for thoracic surgery. The study of Oshibuchi et al. [2 monitoring provides a more accurate estimation of PaCO2 than PetCO2 during an 1-hour period of OLV with normocapnia (PaCO2 in the range of 30–50 mmHg) for thoracic surgery. In another study, Kelly et al. [2 and PaCO2 deteriorated at high PaCO2 levels (>60 mmHg). Our results extrapolate these ranges, i.e., a 2-hour period of OLV with hypercapnia (PaCO2 in the range of 35–70 mmHg) during thoracic surgery. Long time PtcCO2 monitoring (longer than 2 hours) was only observed in nonsurgical patients in previous studies [OLV is essential for the success of mini-invasive thoracic surgery. Advances in this technique have enabled more complex intrathoracic procedures being performed. Protective ventilation strategy –6 is nowi et al.  found thy et al.  reported studies –22.2 and other carbon dioxide measurement was a clinically acceptable discrepancy [2 and PaCO2 was less than 5 mmHg during either TLV or OLV, whereas the bias between PetCO2 and PaCO2 was lower than -11 mmHg during either TLV or OLV. In the scatter diagram of PetCO2 and PaCO2, 3 of 90 points were outside of the limits of agreement during OLV and all 3 points were beyond 22 mmHg. Whereas in the scatter diagram of PtcCO2 and PaCO2, 4 of 90 points were outside of the limits but only 1 point was beyond 22 mmHg. These also indicated the superiority of PtcCO2 in predicting PaCO2.A difference of 5 mmHg or less between PaCOcrepancy ,13. Our 2 monitoring is still the most convenient method in CO2 measurement and has a unique role in judging the position of artificial airway and ventilation status. The difference between PaCO2 and PetCO2 increases with age, pulmonary disorders, pulmonary embolism, reduced cardiac output, hypervolemia, anesthesia, and other conditions that increase the ventilation-perfusion mismatch. In the present study, the mean difference between PetCO2 and PaCO2 during either TLV or OLV was higher than the previously reported ones in similar patients [2 and PetCO2 assuming that the PaCO2 remains constant. The higher difference between PetCO2 and PaCO2 in our study supports the use of PtcCO2 monitoring during prolonged OLV with lung-protective strategy of low tidal volume ventilation.PetCOpatients –4. This patients . Accordi2 is more accurate than PetCO2 in estimating PaCO2 during prolonged OLV with low tidal volume ventilation for thoracic surgery.In conclusion, our study demonstrated that PtcCOS1 Dataset(XLSX)Click here for additional data file.


Diabetes mellitus (DM) is a risk factor for cardiovascular disease (CVD) . Both trLiraglutide, a long-acting glucagon-like receptor peptide (GLP)-1 analogue, is a recent treatment modality that may tolerably improve glycemic control –10 and p1c (HbA1c) >7.0 % even with diet and exercise therapy. We excluded patients with a recent acute illness, inflammatory bowel disease, a history of ileus, severe nephropathy , liver dysfunction, and type 1 DM. The study protocol was approved by the Jichi Medical University Ethical Committee, and written informed consent was obtained from all participants. If patients were being treated with antiglycemic agents, we discontinued use of α-glucosidase inhibitors, pioglitazone, metformin, and dipeptidyl peptidase 4 inhibitors when treatment with liraglutide was initiated because the health insurance system in Japan indicates that these medications should not be administered with liraglutide. Therefore, no hypoglycemic agents except sulfonylureas were used in this study. Treatment with liraglutide was initiated at a dosage of 0.3 mg/day and titrated up to 0.6–0.9 mg/day when necessary. The dosage of liraglutide or a sulfonylurea was decreased if the glycemic target of fasting glucose was less than 95 mg/dL or causing hypoglycemic symptoms. When treatment with liraglutide was initiated, the dosage of the sulfonylurea was decreased by half.Sixty-five adult outpatients with T2DM (37 men and 28 women) were treated with liraglutide for 24 weeks. Eligibility criteria included the absence of pregnancy, an estimated duration of DM of no more than 15 years, no history of treatment with insulin, and a target hemoglobin A1c, glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, urine albumin, BNP, d-ROMs, and MDA. Plasma BNP levels were measured using an immunoenzymometric assay kit  [At baseline and after 24 weeks of treatment, weight, systolic/diastolic blood pressure, and heart rate were measured and blood/urine samples were collected for measurement of the following parameters: HbA, Japan) . The d-R, Japan) . The MDAt tests were used to examine the changes in respective parameters. Correlations between changes in variables were examined using Pearson correlation tests. Statistical significance was set at a P value of <0.05.The data are presented as mean ± standard deviation for parametric variables, medians and interquartile ranges for nonparametric variables, or numbers for categorical variables. In all analyses, the variables with nonparametric distributions were treated after a log transformation. Paired 2, and duration of DM was 7.0 years. Before this study, 24 patients (36.9 %) had not been treated with an antidiabetic agent and 41 patients (63.1 %) had been treated with a sulfonylurea (n = 32), dipeptidyl peptidase 4 inhibitor (n = 18), or metformin (n = 15).No patients dropped out of this study. The patients were 58.7 ± 10.2 years of age, body mass index was 27.9 ± 5.9 kg/m1c and blood glucose levels were significantly reduced , both HbA1c  or positively to that of systolic blood pressure . The change in d-ROMs levels was significantly and positively correlated to that of MDA  or that of HbA1c . The change in MDA levels was not correlated to that of HbA1c. The change in urine albumin levels was significantly and positively correlated to that of HbA1c  but did not significantly correlate to the changes in blood pressure.A correlation analysis revealed that the change in BNP levels was significantly and negatively correlated to that of HbA1c, blood pressure, and urine albumin but also BNP and d-ROMs, which are nontraditional but potential markers that may in part explain the link between DM and CVD in patients with T2DM.The cardioprotective effects of liraglutide, which is now widely accepted as useful for glycemic control, were described in a recent review of the literature ; howeverDiscrepant findings of increased BNP levels resulting in weight loss and adipocyte lipolysis been reported in obese patients with T2DM . The invThe significant correlation between the change in d-ROMs levels and glycemic control in the current study might suggest a pleiotropic effect of liraglutide against CVD by alleviation of the oxidative stress burden in T2DM. The d-ROMs  and MDAIn summary, treatment with liraglutide may exert a cardioprotective action and partly alleviate the burden of oxidative stress as a possible pleiotropic action in outpatients with T2DM. These data are preliminary, and future work is warranted.


Out of office blood pressure measurements, using either home monitors or 24 hour ambulatory monitoring, is widely recommended for management of hypertension. Though validation protocols, meant to be used by manufacturers, exist for blood pressure monitors, there is scant data in the literature about the accuracy of home blood pressure monitors in actual clinical practice. We performed a chart review in the blood pressure assessment clinic at a tertiary care centre.We assessed the accuracy of home blood pressure monitors used by patients seen in the nephrology clinic in Ottawa between the years 2011 to 2014. We recorded patient demographics and clinical data, including the blood pressure measurements, arm circumference and the manufacturer of the home blood pressure monitor. The average of BP measurements performed with the home blood pressure monitor, were compared to those with the mercury sphygmomanometer. We defined accuracy based on a difference of 5 mm Hg in the blood pressure values between the home monitor and mercury sphygmomanometer readings. The two methods were compared using a Bland-Altman plot and a student’s t-test.The study included 210 patients. The mean age of the study population was 67 years and 61% was men. The average mid-arm circumference was 32.2 cms. 30% and 32% of the home BP monitors reported a mean systolic and diastolic BP values, respectively, different from the mercury measurements by 5 mm Hg or more. There was no significant difference between the monitors that were accurate versus those that were not when grouped according to the patient characteristics, cuff size or the brand of the home monitor.An important proportion of home blood pressure monitors used by patients seen in our nephrology clinic were inaccurate. A re-validation of the accuracy and safety of the devices already in use is prudent before relying on these measurements for clinical decisions. Blood pressure (BP) measurement is the cornerstone for diagnosis and management of hypertension (HTN). Oscillometric BP devices, especially when used by patients at home, offer major advantages over the century old BP assessment by the mercury sphygmomanometer. FirstlyHowever, despite the widespread use of HBP monitors, little data exists on the accuracy of the monitors in use. Three standard protocols exist for BP device validation, published by the Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society (BHS) and the European Society of Hypertension respectively–14. The At our centre, we have been conducting a BP assessment clinic for follow up of hypertensive patients from the nephrology program, with the purpose of providing education about BP management, lifestyle modifications, and to guide self-measurement. Given the importance of home measurement of BP, and the concerns of accuracy, we undertook a chart review with a goal of assessing the accuracy of home BP monitors in our population, and to identify factors that are associated with accuracy of these monitors.A chart review of all patients referred to and seen in the BP assessment clinic from July 1 2011 to Apr 30th 2014 was performed. Only patients who did bring in a home BP monitor to their clinic visit were included in this study. For those who had multiple visits, we only included data from the first visit.From an electronic database, the chart review involved data abstraction of patient demographics and clinical data, including details of the BP measurements (mercury and home monitor), arm circumference, and also the manufacturer of the HBP monitor. Institutional review board approval, from the Ottawa Health Sciences Research Ethics Board (20140619-01H) was obtained prior to conducting the chart review. Patient records were de-identified prior to analysis. Informed consent was waived given this was a retrospective chart review using de-identified data.The BP measurements are all taken in a quiet clinic room, after a minimum of 5 minutes of resting. The mercury sphygmomanometer readings are done using a calibrated machine, and by a registered nurse (RN) trained to follow the standardized protocol of the Canadian Coalition for High Blood Pressure Prevention and Control. After mIn our analysis, we first compared the average of the three measurements with the mercury and the three measurements with the home monitor. A difference of 5 mm Hg in the systolic BP  was considered inaccurate. We comp376 patient-visits occurred over the study period. 3 patients had home BP devices with mis-match between the cuff size and arm circumference; the nurse did not assess for accuracy of the home BP device in these cases and provided a recommendation to obtain the correct cuff size. These three patients did return with the correct cuff size at a subsequent appointment, and the measurements from that appointment were used in the analysis. After excluding patients who did not bring a home monitor, patients with repeat visits and encounters with missing data, we had data available on 210 patients and home monitors .About 60% of the study population was men, with a mean age of 67 years (details in 30% (63 of 210) of the home BP monitors reported mean systolic BP values which were 5 mm Hg or more different from the mercury measurements. There was no significant difference between the monitors that were accurate versus those that were not when grouped according to the patient characteristics, cuff size or the brand of the home monitor . The absFor diastolic BP, 67 monitors (32%) reported mean values that were 5 mm Hg or more different than the mercury. Patients with inaccurate devices were more likely to be older men, however there was no significant difference between the other patient characteristics, cuff size or the brand of the home monitor . The absUsing a different threshold for accuracy (difference more than 10 mm Hg), 16 of 210 (8%) HBP monitors were inaccurate for systolic BP and 18 (9%) for diastolic BP. Four of 210 HBP monitors (2%) were inaccurate using the 20 mm Hg threshold, for both systolic and diastolic BP. The inter-arm difference in BP was more than 5 mm Hg in 28% of the patients, in whom the accuracy comparison was measured by sequential rather than simultaneous measurements. Sensitivity analysis grouping them by sequential (34% inaccuracy) versus simultaneous (30% inaccuracy) measurement did not find a significant difference.The Bland-Altman analysis is presented in Additional analyses conducted between the inaccurate home BP devices that underestimated SBP (N = 25) by more than 5 mm Hg and those that overestimated SBP (N = 38) by more than 5 mm Hg are presented in In this cross-sectional study with 210 patients and HBP monitors, we report a relatively high proportion of inaccurate HBP monitors. Though in the majority of the HBP monitors, the difference between readings by auscultation technique using mercury sphygmomanometer and by the automated oscillometric HBP device was small (<5 mmHg), in a disturbingly high proportion, the differences were greater than 5 mm Hg. These large differences between the measurements could have an adverse impact on the diagnosis and management of HTN. We therefore believe that we have identified a significant gap in the HBP monitoring process which needs to be further investigated, and if confirmed, addressed.Similar to our findings, previous studies have also showed a significant proportion of inaccurate home BP devices , 22–28. Our study has several major strengths compared to the previous data. The evaluation process took place in the tertiary care hospital-based HTN clinic attended by a nurse specialized and trained in the management of patients with HTN, thus minimizing human error in BP measurement. Secondly, our evaluation process included repeated simultaneous measurements of BP by mercury sphygmomanometer and HBP monitor. In addition, we identified that there are differences in patient (more men with higher BMI) and device (brand) characteristics which overestimate SBP in comparison to those that underestimate SBP. Lastly, the results did not vary meaningfully with sensitivity analyses, and were consistent using different thresholds.Our study does have also certain limitations. Firstly, we have information on the brand of the HBP, but not series or model numbers to determine their validation status. In addition, we were unable to track the age of the each individual device. Thus we cannot comment on whether and to what extent the age of the device plays a role in the accuracy of measurements. Secondly, our study was designed as retrospective analysis of collected data, and as much as the results are provocative, they should be interpreted with caution. Third, as the measurements were done in routine clinical practice, only one RN measured the BP. However, the agreement between the home BP monitor and the manual measurements may have been exaggerated given that the RN was not blinded to the previous device readings, thus any bias, if present, would be towards the null, thus making our findings of inaccuracy more robust. The differences that we report between devices that overestimate SBP and those that underestimate SBP are subject to multiple comparison fallacy, and hence should be considered hypothesis generating, though worthy of more studies. Lastly, it is possible that there could be selection bias in the overall study, since the study could only include data on patients who did monitor BP at home and were willing to bring it in for the clinic visit.In conclusion, we believe that we have identified a significant gap in the HBP monitoring process which needs to be further investigated, and if confirmed, addressed. In fact our study raises the issues relating to the re-validation of the accuracy and safety of the devices already in use. Currently standard international protocols developed by the Association for the Advancement of Medical Instrumentation (AAMI) , the BriHome BP monitoring can improve the accuracy of HTN diagnosis, and be quite valuable for HTN management. However, the overall benefit from HBP monitoring can be offset by inaccuracy of the device itself. The magnitude of this inaccuracy in specific cases could indeed lead to an adverse impact in management of HTN. Thus, increased awareness and detection of this phenomenon is warranted.


Introduction: Patients undergoing chronic hemodialysis and kidney transplant patients will be afflicted with various mental and physical problems, which may affect their general health. Previous studies have shown that, general health level in these patients is lower than general population. However, definitive studies comparing the general health between the two groups of patients undergoing hemodialysis and kidney transplant recipients have not been done, yet.Objectives: In this study, we aimed to compare the general health between the two groups of chronic hemodialysis patients and kidney transplant recipients.Methods and Patients: This investigation was a cross-sectional descriptive-analytic study that has been conducted on 31 hemodialysis and 33 kidney transplant patients in two university hospitals of Ahvaz, Iran. Data were collected through a general health questionnaire (GHQ-28) and they were analyzed with SPSS software.Results: The mean score of general health was 28.8 and 27.57 in hemodialysis and kidney transplant patients, respectively. There was no statistically significant difference between the two groups, (p =0.7). Also, anxiety, serious depression, physical symptoms and social function were not significantly different between the two groups (p>0.5).Conclusion: In this study, no difference of general health level between hemodialysis and kidney transplantation was observed. In a study on patients undergoing chronic hemodialysis and kidney transplant recipients, we compared the general health between the two groups. We found that, there is no clear difference between kidney transplant recipients and chronic hemodialysis patients at the level of general health and amount of depression, anxiety, physical symptoms and social function.Chronic and severe kidney dysfunction can cause many physical and mental problems. As disease progresses, accumulation of toxins will reach to an extent that patients usually experience a significant influence in their daily activities including feeling of health and nutrition status. This condition may lead to death unless renal replacement therapy  is started .Due to great efforts to reduce mortality and morbidity in these patients, the number of these patients is increasing considerably . HoweverThe fact that patients survival depends on a chronic dialysis, has a large stress. Indeed, this dependency to the dialysis machine at any time may cause a mental dysfunction. In kidney transplanted patients, there are several problems that may lead to a disorder in the quality of life and their general health such as rejecting the graft, side effects of immunosuppressive medications  and the probability of disease recurrence ,4. In soAccording to the above-mentioned problems and the lack of related studies in the country, we conducted a comparative study between general health level, anxiety, depression, physical and social function in these two groups of patients in Imam and Golestan Hospitals in Ahvaz. We specified areas that are less influenced from the above modalities beside the investigation and comparison of kidney alternative therapeutic options on general health. Also, we tried to find a solution for a higher general health for these patients along with decision making for the better kind of alternative modality.This cross-sectional study was a descriptive-analytic investigation.The participants were selected as conveniently available among patients undergoing chronic hemodialysis  and kidney transplant recipients (grafted > 6 months ago and serum creatinine ≤ 2 mg/dl) that referred to Imam and Golestan hospitals of Ahvaz. They were matched in variables such as age, sex and marital status. Age above 18 and below 65 years and having no history of psychiatric illness were other inclusion criteria. Thirty one hemodialysis patients  and 33 kidney transplant recipients  were enrolled in the study. In order to assess the general health, the general health 28-item questionnaire (GHQ-28), the most recognized screen tool in psychiatry, was used and it was designed to screen non-psychotic mental disorders by Goldberg and Hiller in 1979. In Iran, Palahang . In several previous studies in Iran, the cut-off point of the questionnaire was determined at 21-23 . The cut(1) The research followed the tenets of the Declaration of Helsinki (2); informed consent was obtained (3); the research was approved by ethical committee of Ahvaz Jundishapur University of Medical Sciences.t-test. Data were analyzed by SPSS version 14 and p<0.05 was considered statistically significant.Descriptive statistics including mean, standard deviation, minimum and maximum scores and inferential statistics including the comparison of the two groups were done through The mean scores of general health in the kidney transplant recipients and patients under hemodialysis were 27.57 and 28.8, respectively. According to p=0.7, the differences of general health level between the two groups were not significant . Also, bet al. on patients before and after kidney transplant with the GHQ-28 questionnaire reported consistent results  have been completely observed by the authors.This study was funded by Ahvaz Jundishapur University of Medical Sciences. (Grant# A-108)


Catheter-based sympathetic renal denervation (RDN) is a recent therapeutic option for patients with resistant hypertension. However, the impact of RDN in left ventricular (LV) mass and function is not completely established. Our aim was to evaluate the effects of RDN on LV structure and function (systolic and diastolic) in patients with resistant hypertension (HTN).2 (p<0.001), an increase in LV end diastolic volume , an increase in LV ejection fraction  and mitral valve E deceleration time  at 1-year follow up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups.From a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up echocardiogram were included in this analysis. Mean age was 65±7 years, 48% were males, 71% had type 2 diabetes. Most had hypertension lasting for more than 10 years (90%), and were being treated with a median number of 6 anti-hypertensive drugs, including 74% on spironolactone. At 1-year, there was a significant decrease both on office SBP  and DBP , and also in 24h ABPM SBP  and DBP . There was also a significant decrease in LV mass from 152±32 to 136±34g/mIn this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and ABPM blood pressure and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up. Long-standing hypertension (HTN) results in cardiac remodelling including myocardial hypertrophy, diastolic dysfunction and left atrial (LA) enlargement leading to atrial and ventricular arrhythmias, heart failure and ultimately to myocardial infarction and stroke, which are the leading causes of death and morbidity in developed countries .The link between chronic sympathetic hyperactivity and drug-resistant HTN is well known for several years, and is the rationale behind the development of catheter-based sympathetic renal denervation (RDN). This treatment approach for drug resistant HTN had very promising results in early non-blinded studies ,3. RecenFrom a single centre prospective registry including 65 consecutive patients with resistant HTN submitted to RDN between July-2011 and April-2015, 31 patients with baseline and 1-year follow-up 24h ABPM and transthoracic echocardiogram were included in this analysis. As per protocol, all patients underwent a comprehensive transthoracic echocardiogram (TTE) at baseline and at 1-year after RDN. The inclusion, exclusion criteria and clinical feature regarding this registry were previously reported . The resIn summary, the patients selected had to be older than 18 years, with an office systolic blood pressure (SBP) above 160mHg while receiving a stable antihypertensive regimen involving at least three drugs (including a diuretic). Before RDN, during pre-scheduled visits at the outpatient clinic for a period not less than 6 weeks, secondary causes for HTN were excluded, compliance to medical treatment was assured and drug therapy was adjusted until maximal tolerated regimens. Only then, if target BP values were not obtained, patients were considered for RDN. Anatomical criteria were adopted from Symplicity trials.,8 DemogrOffice BP readings were taken in a seated position with an oscillometric semiautomatic sphygmomanometer Omron HEM-907 monitor  after 5 min of rest according to the European Guidelines for the management of arterial hypertension  At baselTwenty-four hours ambulatory blood pressure measurements (ABPM) were taken with an ABM monitor , according to the current European Society of Hypertension guidelines.Blood pressure responders to RDN treatment were defined as those who had a reduction in office SBP of ≥10 mmHg at one year follow-up or a reduction of 2mmHg in ABPM 24 hours SBP according to Symplicity HTN3 trial design.® -St. Jude Medical, USA).We have previously reported the details of the RDN procedure in our center . Briefly® (n = 25), the EnligHTN® (n = 4), OneShot® (n = 2) catheter using the standard technique, as previously reported +0.6g), with 2D guided M-mode measurements obtained at end-diastole from the parasternal approach perpendicular to the LV long axis measured at the level of the mitral valve leaflet tips. LV hypertrophy was considered present when LV mass exceeded 115 g/mWe also calculated the relative wall thickness (RWT) measured as twice the posterior wall thickness divided by left ventricular end-diastolic diameter, and determined the LV anatomical pattern in each participant. Normal LVM and RWT were defined as normal LV anatomy, normal LVM and RWT >0.42 as concentric LV remodeling, increased LVM and RWT >0.42 as concentric LVH and increased LVM in the presence of RWT <0.42 as eccentric LVH . Left atLV diastolic function was assessed by pulsed-wave Doppler examination of mitral inflow and Doppler tissue imaging of the mitral annulus. Peak velocities of early (E) and late (A) trans-mitral flow and deceleration time (DT) were determined, and the ratio E/A was calculated. Doppler tissue imaging with pulsed-wave Doppler at the level of septal and lateral mitral annulus was used to measure e’ velocities. The average of septal and lateral mitral annulus e’ peak velocities, were used to calculate the E/e’ ratio. The Valsalva maneuver was performed to distinguish normal from pseudo-normal patterns. Spectral recordings were obtained at a sweep speed of 100 mm/s at end-expiration, and each measurement was averaged over multiple cardiac cycles to account for inter-beat variability.Grade 1 diastolic dysfunction (impaired relaxation) was defined by the presence of an E/A ratio <0.8, a deceleration time >200 ms and E/e′ ratio <8 in the presence of an enlarged left atrium. Moderate  diastolic dysfunction was defined as a mitral E/A ratio >0.8 and <1.5 that decreases by 50% during the Valsalva maneuver, E/e’ ratio 9 to 12 and e’<8 cm/s. Finally, severe (grade 3) diastolic dysfunction corresponds to restrictive LV filling defined by E/A ratio >2, DT <160 ms, and average E/e’>13. All subjects with impaired LV relaxation, pseudo-normal or restrictive filling patterns were defined as having LVDD [t-Student’s test or the Saterwate test for continuous variables. A two-tailed p value <0.05 is considered as statistically significant. Linear regression analyses were used to calculate the correlation between the change in blood pressure and the change in echocardiographic parameters. SPSS, Statistical Package for the Social Sciences®, V.21.0  software was used for data processing and statistical analysis.Continuous variables are reported as mean ± standard deviation. Normality was tested with the Kolmogorov-Smirnov test and/or Q-Q Plot visual assessment. Normally distributed variables were compared between baseline and one year follow-up using a paired Student t test or a Wilcoxon matched-pairs test if not normally distributed. Discrete variables are expressed as frequencies and percentages (in brackets). Statistical comparisons of baseline characteristics and at follow-up were performed using the chi-square test or Fisher’s exact test, when appropriate, for categorical variables and the paired 2), type 2 diabetes in 71%, dyslipidaemia in 68% and active smoking in one patient (3.2%). Coronary artery disease was present in 10 patients (32%) and any vascular disease in 11 (36%). Estimated mean glomerular filtration rate was 76±25mL/min/1.73m2, with five patients having chronic kidney disease, defined as eGFR <60 ml/min/1.73 m2. Baseline characteristics are shown in From the total number of patients evaluated in a dedicated outpatient hypertension clinic (n = 318), 65 patients were submitted to renal denervation, after the exclusion of 253 due to several reasons (listed in The majority of patients (90%) had hypertension lasting for more than 10 years, treated with a median of 5.8 anti-hypertensive agents from a median of 5.5 different pharmacological classes. Almost all patients were treated with calcium antagonists, 96.8% (n = 30), 87% with diuretics, 74% with spironolactone, 61% with ACE inhibitors, 61% with ARB inhibitors, 84% with beta-blockers and 71% with a sympatholytic drug. At baseline, mean office SBP and diastolic blood pressure (DBP) were 176±24 mmHg and 90±14 mmHg, respectively, and mean heart rate was 73±11 bpm. The 24-hour ABPM showed the following average values: SBP 150±20 mmHg, DBP 83±10 mmHg, pulse pressure 67±18mmHg .Overall, at one-year follow-up, there was a significant reduction in both office SBP  and DBP . On 24-hour ABPM, there was a significant drop on: SBP , on DBP  and on pulse pressure from 67±18 to 58±13 mmHg, p = 0.001, a mean decrease of 5 mmHg .This was found in spite of the significant reduction in the number of both antihypertensive drugs and classes in use at 1-year: 5.8±1.1 to 5.0±1.2 (p = 0.002) and 5.5±0.9 to 4.9±1.1 (p = 0.015) respectively.At 1-year follow-up, 22 of patients (71%) were considered office SBP responders and 26 (84%) ABPM SBP responders based on a drop of more than 10mmHg on office SBP and 2mmHg on 24 hours ABPM SBP.2. Distribution among different geometric patterns is shown in 2, and 48.4% had ≥ 34ml/ m2.Transthoracic echocardiography at baseline revealed LV hypertrophy in 27 patients (87%), with a mean LV mass of 152±32 g/mLVDD was diagnosed in 29 (93.5%) patients, 11 (37.9%) of them had grade 1 diastolic dysfunction, 18 patients a pseudo-normal pattern (62.1%); 2 patients were in atrial fibrillation and there were no patients with a restrictive filling pattern . For the2, p<0.001—After one-year, there was an overall significant reduction in LV mass , LV mass also decreased: 166±23 to 129±15g/m2, p = 0.05, although not reaching statistical significance certainly due to sample size. From the scatter-plot graphic : 148±32 to 133±29g/m graphic  where thThere were 3 mild hematomas and 1 femoral pseudoaneurysm, treated with surgery without any permanent sequelae. There were no complications related to the renal arteries, namely dissection or perforation.The main findings of our study were: 1) Renal denervation in patients with resistant HTN was associated with significant reduction in both office and ABPM blood pressure at 1 year follow-up; 2) There was a significant reduction in left ventricle mass index, a recognized marker of HTN target organ damage.Renal denervation has been associated with significant reductions in both office and ABPM blood pressure in many trials,3,17 andBrandt MC et al in a stuIn a multicenter study including 72 patients and using cardiac magnetic resonance imaging, Mahfoud F et al  also demSome additional particular features of the present study should also be taken in consideration. First, our results come from a registry with a very rigorous selection process of patients for renal denervation, perceived from the high mean number (5.8) of antihypertensive drugs, the baseline office and ABPM blood values and the patient selection flowchart presented in The present study has several limitations that should be acknowledged: 1) It is a single centre prospective registry with a small sample size. 2) The lack of a control group and the fact that there was no blinding either for RDN (sham not performed) or for the physicians performing the follow-up echocardiograms; 3) There were changes on antihypertensive drug therapy during the clinical follow-up which can influence the reductions in blood pressure and LV mass, although in our study the mean number of drugs was reduced. This way, the reduction obtained with renal denervation could have been underestimated in this real world setting; 4) No specific techniques were used to control for patient adherence to medication; 5) Echocardiograms were not reviewed in a core lab, which could potentially be associated with less reproducible measurements; 6) Cardiac MRI was not used and could have provided a more accurate evaluation of LV mass changes.In this single centre registry of patients with resistant hypertension, renal denervation was associated with significant reduction in both office and 24h-ABPM blood pressure, and a significant decrease in left ventricle mass evaluated by transthoracic echocardiogram at 1 year follow-up. There were no significant changes in left atrium volume index or in the distribution of patients among the different left ventricle geometric patterns and diastolic function subgroups.


We aimed to investigate whether visceral adiposity could modify the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes.2) was assessed by a dual-impedance analyzer, whereby patients were divided into those with VFA < 100 (N = 341) and those with VFA ≥ 100 (N = 297). Albuminuria was measured in a single 24-h urine collection  and brachial-ankle pulse wave velocity  was used for the assessment of arterial stiffening. Linear regression analyses were used to investigate the association of systolic blood pressure (SBP) and VFA with UAE and baPWV.This cross-sectional study examines the interaction of visceral adiposity with increased blood pressure on arterial stiffness and albuminuria. 638 patients with type 2 diabetes  were enrolled. Visceral fat area  and VFA ≥ 100  patients in the multivariate regression analysis adjusting for covariates including age, gender, HbA1c, diabetic complications and the use of insulin and anti-hypertensive agents. By contrast, the association of SBP with UAE was stronger in patients with VFA ≥ 100  than that in patients with VFA < 100  in the multivariate regression model. In the whole cohort, the significant interaction between SBP and VFA on UAE  but not on ba-PWV  was observed.The effect of increased blood pressure on arterial stiffness is almost similar in type 2 diabetic patients with both low and high visceral adiposity, while its association with albuminuria is stronger in the latter. Blood pressure is a strong risk factor for cardiovascular disease (CVD) , 2 and cObesity, especially increased visceral adiposity is a major cause of hypertension, accounting for 65–75 % of the risk for human essential hypertension . In addiRegarding the association between blood pressure and CVD, the impact of elevated blood pressure on CVD events has been reported to be stronger among people without obesity than those with –19. Also2 or undergoing renal replacement therapy), pregnant women, and those with infectious or malignant diseases were excluded. Type 2 diabetes was diagnosed according to the criteria of the Japan Diabetes Society (JDS)  <15 mL/min/1.73 mty (JDS) . As show−1.094 × age−0.287 [ × 0.739], where SCr stands for serum creatinine in mg/dl, measured by an enzymatic method. Coefficient of variation of R–R intervals (CV-RR) was used for the assessment of diabetic neuropathy. BMI was calculated as weight divided by the square of height (kg/m2). VFA and SFA were measured at the level of umbilicus by dual bioelectrical impedance analyzer . Patients were divided into those with VFA < 100 cm2 (low-V) and those with VFA ≥ 100 cm2 (high-V). Brachial-ankle pulse wave velocity (ba-PWV) was measured using a volume-plethysmographic apparatus , with subjects in the supine position after at least 5 min of rest [Standardized questionnaires were used to obtain information on smoking, medication and past history. Smoking history was classified as either current smoker or non-smoker. CVD was defined as the presence of a previous stroke, myocardial infarction, coronary revascularization procedure. Blood pressure was measured in the sitting position after at least 5 min rest, using an electronic sphygmomanometer . HbA1c was measured by the latex agglutination method. HbA1c levels were expressed in accordance with the National Glycohemoglobin Standardization Programs recommended by the Japanese Diabetes Society . Urinary of rest . The ba- of rest . We simut test or Mann–Whitney U test for continuous variables and Chi square test for categorical variables. Linear regression analyses were used to investigate the association of SBP and VFA with ba-PWV and UAE. We determined the linear relationship and multicollinearity for regression assumptions. We removed one variable if a strong correlation (coefficient of correlation >0.8) was observed between the two independent variables. In order to check the multicollinearity, we evaluated variance infiltration factors. If multicollinearity was found in the data, one variable was removed from the multivariate regression analysis. The following covariates were incorporated into the analysis with a stepwise procedure; duration of diabetes, smoking status, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, HbA1c, eGFR, log CRP and the usage of insulin, calcium channel blockers (CCB), angiotensin receptor blockers (ARB), statins and anti-platelet agents. Age and gender were forced into the model. The interaction between SBP and VFA was also investigated in the multiple linear regression analyses. Differences were considered to be statistically significant at p value less than 0.05.Statistical analysis was performed using programs available in the SPSS version 21.0 statistical package . Data are presented as mean ± SD, median with interquartile range (IQR), or percent as appropriate according to data distribution. Normality was tested by the Kolmogorov–Smirnov test. Differences between low-V and high-V patients were tested with a Among 638 patients, 341 and 297 were classified as low-V and high-V patients. As shown in Table Table Table Table Both increased arterial stiffness and albuminuria are strong predictors for mortality, CVD and CKD in patients with diabetes –36. TherVisceral adiposity has been reported to be associated with incident hypertension , 38 and By which mechanisms are involved in the greater impact of elevated blood pressure on albuminuria in patients with high visceral adiposity than in those with low visceral adiposity? Sympathetic activity and local  renin-angiotensin-aldosterone system could account for the association. Obesity increases sympathetic activity in the kidneys and skeletal muscle; however, cardiac sympathetic activity may not be elevated –46. FurtThe strength of our study is that we directly measured VFA by a dual-impedance analyzer for the assessment of visceral adiposity. Previous studies assessed the interaction of adiposity with the association between hypertension and CVD using BMI or WC , 8, 48. The effect of increased blood pressure on arterial stiffness is almost similar in type 2 diabetic patients with both low and high visceral adiposity, while its association with albuminuria is stronger in the latter.


Low molecular weight heparins (LMWHs) are small enough to pass large pore dialysis membranes. Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration. The aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration.0), ii) 5 min after the start at the inlet line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa activity, thrombin generation, visual clotting score and reduction ratios of urea and beta2microglobulin were measured.In 13 chronic hemodiafiltration patients, 3 approaches of injection were compared in a randomised cross over trial: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0 compared with IN5 and OUT0, and also more thrombin generation was observed with IN0. No differences were observed in visual clotting scores and no clinically relevant differences were observed in solute reduction ratio. An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation. Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin.Anti-Xa activity was lower with INInjection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended. Additionally, we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy.NCT00756145Clinicaltrials.gov  For renal replacement strategies such as hemodialysis and hemodiafiltration, anticoagulants are required to prevent clotting of the extracorporeal circuit. Over-anticoagulation can be associated with hemorrhage and prolonged bleeding at the needle insertion sites. Insufficient inhibition of the coagulation cascade can lead to premature interruption of the dialysis session. More subtle under-anticoagulation could lead to clotting of some fibers with a decrease in membrane exchange surface area eventually resulting in a reduction in dialysis efficiency.Low molecular weight heparins (LMWH) are often preferred to unfractionated heparin  because The aim of this study was to determine the optimal mode of administration of LMWH as anticoagulant during postdilution hemodiafiltration.0), ii) 5 min after the start of the session at the inlet blood line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa levels, thrombin generation, visual appreciation of clotting of the circuit and dialysis performance measured as RR of a small and middle MW molecule were considered.Three approaches of administration of tinzaparin were compared: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0), ii) administration at inlet blood line 5 minutes after the detection of blood by the blood detector (IN5) and iii) administration at the outlet blood line just prior the start of the blood pump (OUT0). The dose of tinzaparin remained unchanged throughout the study. The sequence of the sessions per patient was assigned randomly. For each patient, the experimental sessions were performed with a 1-week interval at the same dialysis day of the week, either first, second, or third session of the week. Blood was sampled from the vascular access at the start of the session, before heparin injection and from the inlet dialyzer blood line at times 10, 30, 120, 180 and 240 min. Also transmembrane pressure (TMP), prefilter pressure, pressure in inlet and outlet bloodline were registered at 10, 30, 60, 90, 120, 150, 180, 210 and 240 min. Primary end-point was the anti-Xa activity at the end of the session. Secondary end-points were: anti-Xa activity at the start, after 30, 120 and 180 min, ETP at the start and after 30, 120, 180 and 240 min, dialysis efficiency measured as reduction ratio of urea and beta2microglobulin after 10, 180 and 240 min. Other secondary end-points were visual clotting scores at the end of the session and pressure measurements along the circuit.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Fourteen patients treated with chronic hemodiafiltration at the Ghent University Hospital were included in the study from september 2008 until march 2010 . InclusiFour patients received antiplatelet therapy, either aspirin (n = 3) and/or clopidogrel (n = 2). Residual renal function measured as average of creatinine and urea clearance was 3.0 (0–5.2) mL/min.Approval of the local ethics committee  was obtained, as well as written informed consent of all patients. The study was registered in clinicaltrials.gov as NCT00756145.The hemodiafiltration treatments were performed with AK200 ULTRA S  dialysis machines with BL200BD and BL208BD  as inlet and outlet blood lines. As dialyzer, single use Helixone membranes  were used. No heparin was added in the rinsing solution of the circuit.As anticoagulant, prefilled syringes containing tinzaparin were used in the same dose as before the study. The hemodiafiltration sessions lasted 240 minutes with the following characteristics: effective blood flow 300 mL/min, dialysate flow 600 mL/min, volume controlled postdilution hemodiafiltration with an effective convection rate of 75 mL/min.During the sessions no other intravenous medication was administered.At the end of the session, the circuit was rinsed by means of an online restitution program.Blood samples were collected in citrated tubes  for measurement of anti-Xa, antithrombin and thrombin generation; in tubes with gel and clotting activator  for CRP, urea and beta2microglobulin and in K-EDTA tubes  for hematocrit.Hematocrit and CRP were measured immediately; serum and plasma samples for all other determinations were kept at −80°C for further analysis.CRP was measured through a particle enhanced immunoturbidimetric assay .Hematocrit was determined by centrifugation .Beta2microglobulin concentrations were quantified using an ELISA kit  and an EL808 Ultramicroplate Reader .Urea was measured by a standard laboratory method on Roche Cobas 6000 chemistry analyzer (Roche Diagnostics).Anti-Xa activity was measured by a chromogenic method  on a STA-C  with detection limit 0.05 IU/mL.Analysis of antithrombin was carried out using a chromogenic method .Automated measurement of thrombin generation was performed by Calibrated Automated Thrombography , as reported previously . ThrombiTransmembrane pressure (TMP), prefilter pressure, pressure in inlet and outlet bloodline as well as hemoconcentration measured by blood volume sensor (BVS) were registered at 10, 30, 60, 90, 120, 150, 180, 210 and 240 min.At the end of the session, immediately after blood restitution, visual clotting score of membrane, blood lines, expansion chamber and bubble trap were rated by two unblinded investigators (AD and RP). They rated independently, followed by consensus. The clotting score of the membrane was as follows: 0 = no clotting, 1 = a few colored fibers, 2 = less than 50% of the visible fibers colored and 3 = more than 50% of fibers colored. Clotting of blood lines, expansion chamber and bubble trap was scored as: 0 = no clotting, 1 = discoloration, 2 = minimal clot, 3 = major clot.Applied compression time was registered.Sample size was set at 14, based on feasibility. No prior data on anti-Xa activity in this setting were available to calculate sample size.The sequence of the sessions per patient was randomized by Quick Calcs (Graphpad software), an online computer system which generates a random number sequence based on the number of experimental groups. The allocation was not concealed.Reduction ratio (RR), concentration at different time points  versus the start of dialysis (C0) expressed in %, was calculated as:Concentrations of beta2microglobulin were corrected for hemoconcentration as measured by BVS:Delta TMP was calculated as the measured TMP at 240 min minus the TMP measured at 10 min. Data are expressed as median and interquartile ranges. Statistics and figures were generated with SPSS  and GraphPad Prism 4.0 . Continuous paired data were analyzed with repeated measures analysis of variance (Friedman) followed by Wilcoxon in case of significance. Chi square test was performed for categorical variables. Correlations were tested with Spearman correlation test. Receiver Operator Characteristic (ROC) analysis was applied to determine cut off values of anti-Xa. Significance was accepted if p<0.05.Initially we intended to measure clearances for urea and beta2microglobulin as measure of dialysis efficiency. This was however not feasible due to the important interference of the decrease in bloodwaterflow due to ultrafiltration. Hence dialysis efficiency was expressed as reduction ratio of urea and beta2microglobulin.Primary and secondary end-points were initially ill-defined; a shift towards secondary end-points with only one primary end-point left was made.0) 2 days later than planned because of a technical problem.Patient N° 5 received his second experimental session . So we ended up with 13 patients completing the study.The median and interquartile range of the administered dose of tinzaparin was 66.0 (54.5–69.8) IU/kg body weight . No premIn 0). No differences in anti-Xa levels were observed between IN5 and OUT0.The evolution of anti-Xa activity is displayed in 0), a higher ETP was observed compared to the sessions where tinzaparin was administered after 5 min (IN5) or at the outlet line (OUT0).The evolution of ETP is presented in Visual clotting score of blood lines was consistently scored 0 for all sessions. Visual clotting scores of membrane, expansion chamber and bubble trap were not different in the three administration schedules .The relation between ETP and anti-Xa activity can be appreciated from Using ROC analysis, an anti-Xa activity of 0.3 IU/mL was able to discriminate for detectable ETP with a sensitivity and specificity of 0.953 and 0.985, respectively .When evaluating the visual clotting score of the membrane, bubble trap and expansion chamber in function of anti-Xa activity at the end of the session, severe clotting (score 3) was not observed in patients with residual anti-Xa activity above 0.3 IU/mL at the end of the session . When co0, from 52 (47–56) to 79 (70–99) for IN5 (p<0.001) and from 54 (48–57) to 90 (77–103) mmHg for OUT0 (p<0.001). No differences were observed between the three groups, neither at 10 nor at 240 min.TMP increased during the session from 53 (48–57) mmHg at 10 min to 85 (78–104) at 240 min (p<0.001) for IN0, IN5 and OUT0, respectively.The increase in TMP at the end of the session expressed as delta TMP was not different between the three administration schedules being 37 (31–48), 27 (22–42) and 38 (24–49) mmHg for INDelta TMP was inversely correlated with hemoconcentration , whereas no relation was seen with anti-Xa level or ETP at 240 min .No significant differences were observed in inlet or outlet line pressures or in prefilter pressure between the three schedules .0, IN5 and OUT0 respectively, being slightly lower with IN0 compared to IN5 (p = 0.013). For the other time points no differences were noted between the three schedules (RR of urea after 240 min was 77.5 (76.0–81.1), 78.9 (73.8–81.9) and 77.5 (73.6–85.1), with INchedules .0, IN5 and OUT0 respectively. No differences in RR of beta2microglobulin between the schedules were observed (RR of beta2microglobulin after 240 min was 82.1 (74.2–84.9), 80.8 (76.5–84.7) and 81.7 (75.9–85.6) with INobserved .As illustrated in RR of urea and beta2microglobulin were also lower in patients with detectable ETP compared to patients with undetectable ETP at the end of the session: 0.75 (0.69–0.78) vs. 0.83 (0.78–0.86) and 0.76 (0.74–0.79) vs. 0.85 (0.83–0.87), respectively (p<0.001).No relation was observed between visual clotting score and RR of neither urea nor beta2microglobulin.0) resulted in lower anti-Xa activity and higher thrombin generation compared to administration at the outlet line (OUT0) or administration 5 min after start of the session (IN5). Anti-Xa levels below 0.3 IU/mL at the end of postdilution hemodiafiltration sessions were associated with more thrombin generation, worse visual clotting score and lower RR for urea and beta2microglobulin.In the present study we found that administration of tinzaparin at the inlet blood line before the start of the session Click here for additional data file.S2 Fig0, open bars: IN5 and hatched bars: OUT0. *: p<0.05 vs. IN0.Full bars: IN(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 Fig(TIF)Click here for additional data file.S5 Fig0, full squares and datched lines: IN5, open triangles and full lines: OUT0.Open squares and full lines: IN(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S1 Text(DOC)Click here for additional data file.S2 Text(DOC)Click here for additional data file.S3 Text(DOC)Click here for additional data file.