Nightly extended hours hemodialysis may improve left ventricular hypertrophy and function and endothelial function but presents problems of sustainability and increased cost. The effect of alternate nightly home hemodialysis (NHD) on cardiovascular structure and function is not known.Sixty-three patients on standard hemodialysis  converted to NHD (6-10 hours/session overnight for 3-5 sessions weekly). 2Dimensional transthoracic echocardiography and ultrasound measures of brachial artery reactivity (BAR), carotid intima-media thickness (CIMT), total arterial compliance (TAC) and augmentation index (AIX) were performed post dialysis at baseline and 18-24 months following conversion to NHD. In 37 patients, indices of oxidative stress: plasma malonyldialdehyde (MDA) and anti-oxidant enzymes: catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured at baseline, 3 and 6 months.Left ventricular mass index (LVMI) remained stable. Despite significant derangement at baseline, there were no changes in diastolic function measures, CIMT, BAR and TAC. AIX increased. Conversion to NHD improved bone mineral metabolism parameters and blood pressure control. Interdialytic weight gains increased. No definite improvements in measures of oxidative stress were demonstrated.Despite improvement in uremic toxin levels and some cardiovascular risk factors, conversion to an alternate nightly NHD regimen did not improve cardiovascular structure and function. Continuing suboptimal control of uremic toxins and interdialytic weight gains may be a possible explanation. This study adds to the increasing uncertainty about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life. Cardiovascular disease is a leading cause of morbidity and mortality, accounting for approximately 30-40% of deaths in end stage kidney disease (ESKD) patients . Left veVascular disease occurs in two main forms: 1) arteriosclerosis with diffuse arterial wall dilatation, thickening, fibrosis and calcification resulting in stiffening and 2) atherosclerosis with abnormal endothelial function and patchy intimal plaques, causing abnormal regulation of vascular tone, fibrinolysis and smooth muscle proliferation with narrowing or obstruction of the arterial lumen. Increasing arterial stiffness raises pulse wave amplitude and velocity, causing reflected pressure waves from the periphery to be stronger and to arrive in the ascending aorta in systole rather than diastole, thus increasing systolic blood pressure and decreasing diastolic blood pressure. The resulting increased pressure load on the left ventricle (LV) during systole promotes LV hypertrophy and the reduced pressure in diastole reduces coronary artery perfusion, promoting myocardial ischemia ,7Traditional risk factors for CV disease are more prevalent in ESKD patients compared to the general population. When adjusted for age, gender and race, ESKD patients have a higher prevalence of diabetes, hypertension, physical inactivity, hypertriglyceridemia and reduced high density lipoprotein . HoweverDaily nocturnal hemodialysis  has been associated in observational studies -18 and 1Alternate nightly hemodialysis(NHD) may reduce the burden and financial cost of dialysis compared with daily regimens, however, its effects on cardiovascular parameters are undefined. We sought to compare cardiovascular responses and cardiovascular risk factor profiles in standard duration hemodialysis (SHD) and alternate nightly NHD regimens, and to identify the correlates of these changes.The study followed a prospective cohort design performed at a single centre. Between 2003 and 2006, consenting adults ≥ 18 years) with ESKD, established on home hemodialysis for ≥ 3 months were converted from a 3.5-6 hours/session, 3-5 sessions weekly home hemodialysis regimen to home NHD (6-10 hours overnight/session for 3-5 sessions weekly). Within the range of 3-5 sessions weekly and 6-10 hours/session, patients tailored their dialysis regimen to suit their lifestyle and sleeping habits. Interdialytic intervals of greater than 2 days were discouraged. Changes to the dialysis prescription are outlined in Tables 8 years w2®  was only continued in patients in whom it was required to maintain serum calcium in the normal range post previous parathyroidectomy or in those with severe hyperparathyroidism . Vitamin D supplements were reintroduced as necessary to maintain predialysis serum calcium levels in the normal range and parathyroid hormone levels 2-6 times the upper limit of the normal range where possible. All patients were prescribed folic acid 5 mg daily, Multi B Forte ® 1 tablet daily  and pyridoxine 25 mg daily as oral supplements. The protocol for conversion to NHD was approved by the Princess Alexandra Hospital Human Research Ethics Committee.A diet low in saturated fat, salt and sugar with a daily protein intake of 1.2-1.4 g/kg dry weight/day and fluid restriction to maintain interdialytic weight gains < 3 kg was recommended. Dietary phosphate and potassium restrictions were relaxed upon commencement of NHD. Phosphate binders were ceased at the time of conversion to NHD and reintroduced only as required to maintain predialysis serum phosphate < 1.6 mmol/L. At baseline, calcitriolCardiovascular structure and function studies were scheduled to be performed at baseline, 6, 12, 18 and 24 months following conversion to NHD. Cardiac and vascular studies at each time point were performed at the same visit. Images were collected post-dialysis and interpreted by experienced staff, blinded to patients' clinical information.2.7, which is a better predictor of mortality in dialysis patients compared to LVmass indexed to body surface area (BSA) [Left ventricular volumes, mass, systolic function, diastolic function and filling pressures were assessed using 2 Dimensional echocardiography. Left ventricular (LV) end diastolic (EDV) and end systolic volumes (ESV) were calculated using the Modified Simpson's Rule. LV mass was calculated using the Devereux method . Left veea (BSA) . LVMI coea (BSA) ) is alsol)[l ratio and left atrial volume (LAVol), calculated using the Modified Simpson's Rule. LAvol index (LAVolI) was calculated by indexing LaVol to BSA (Dubois and Dubois Method). The categorical definition of diastolic dysfunction was that outlined by Omen and Nishimura [Diastolic function was assessed using peak early mitral inflow filling velocity (E), peak mitral filling velocity at atrial contraction (A), E/A, deceleration time of the mitral E wave (DT) and tissue doppler velocity of the mitral annulus (El). LV fillishimura .Brachial Artery Reactivity (BAR), a measure of endothelial function, was calculated as percentage change in brachial artery diameter, measured using high resolution B mode ultrasonography, with the induction of reactive hyperemia induced by arterial occlusion for 4.5 minutes, using a sphygmomanometer cuff ,28. BAR Carotid intima-media thickness (CIMT), a measure of arterial wall thickness, was determined by averaging 3 measurements taken on each carotid artery  measuring the distance between the leading edge of the lumen-intima interface and the leading edge of the collagenous upper layer of the adventitia using high resolution B mode ultrasonography. Measures were taken in areas free of obvious atherosclerotic plaque around the level of the carotid bifurcation. CIMT is a marker for the presence and severity of arteriosclerosis and has been associated with risk factors for cardiovascular disease, all cause and cardiovascular mortality -33 A sysTotal arterial compliance (TAC), a measure of arterial stiffness, was calculated using the pulse-pressure method ,37. ApplAugmentation Index (AIX), which reflects cardiac stroke volume and the effects of vascular stiffness, was calculated using the formula: AIX = augmentation pressure/pulse pressure)*100, where augmentation pressure = systolic blood pressure -pressure at the first inflection point on the central pressure wave form which was generated using a validated generalized transfer function from recordings of the radial artery pulse using applanation tonometry  and pulse pressure = systolic-diastolic blood pressure ,44. PrevInterdialytic weight gains were calculated from pre and post dialysis total body weights measured by patients on bathroom scales. BP was recorded pre- and post-dialysis by patients using digital sphygmomanometers. Serum or plasma levels of lipids, hemoglobin, C reactive protein (CRP), albumin, parathyroid hormone (PTH), calcium, phosphate and homocysteine were measured using standard laboratory techniques on blood samples taken predialysis in the fasting state. Measures of oxidative stress including, plasma malonyldialdehyde (MDA) and red blood cell (RBC) anti-oxidant enzymes catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity, and plasma GPX activity and total antioxidant status (TAS) were measured pre and post dialysis at baseline and 3 and 6 months after conversion to NHD, in the last 37 patients recruited to the study. MDA was measured using high performance liquid chromatography. Activities of CAT, GPX and SOD and TAS were measured using standard spectrophotometric methods. Prescribed medications were determined by review of the medical record and patient interview.Statistical analyses were performed using STATA SE version 10.0. Sample size calculations indicated that 21 patients were required to have 80% power of detecting a 30% decrease in LVMass, allowing for 33% drop-out rate. Fifteen patients were required to have 80% power to detect a 4% change in BAR; 29 patients to detect a 0.05 mm change in CIMT and 13 patients to detect a 0.4 unit change in TAC with conversion to NHD.Variables are expressed as percentages for categorical data and, for continuous data, as mean ± standard deviation if normally distributed and median (interquartile range) if skewed. Longitudinal analysis was performed using paired t-test if normally distributed and Wilcoxon signed rank test if skewed. Univariable and multivariable linear regression analyses were performed to assess correlations between changes in cardiovascular parameters and risk factors. The covariates considered for inclusion in the model included age, gender, duration of renal replacement therapy, diabetes and changes in lipids, systolic and diastolic blood pressure, interdialytic weight gains, parathyroid hormone, phosphate and calcium, hemoglobin, ferritin and transferrin saturation, C reactive protein and albumin. Those with a p < 0.25 on univariable analysis were introduced into a multivariable model. Then a stepwise, backward elimination process was performed, removing variables which contributed least significantly to the model provided they did not change the incident rate ratio by more than approximately 10%.a priori.For correlation analyses, results are reported as the point estimate, β and 95% confidence intervals (CI), the correlation coefficient (r) and p value. P value < 0.05 was considered significant Eighty-seven percent of the eligible home hemodialysis population agreed to participate in the study. Demographic and dialysis prescription data are presented in Tables Four patients died ), 10 received renal transplants (Followed on NHD for 7.5 -17 monthFollow-up cardiac and vascular studies were performed at 18 (12-24) months. The timing of follow up investigations was determined by patient attendance at echocardiograms that were scheduled to occur 6 monthly between baseline and 24 months following conversion to NHD. The majority of patients only attended for 2 echocardiograms. The study performed at the latest time point during the 24 month follow up was utilized for analysis. Paired data was available for echocardiographic parameters in 38 patients, CIMT and BAR in 42 patients and TAC and AIX in 28 patients.2.7).Measures of LV structure and systolic function did not change between baseline and follow up. Table  At baselMeasures of diastolic function and filling pressure remained stable Table . DiastolBAR did not change between baseline and follow-up. Figure : 2.82 1: 0.66 ± Changes in cardiovascular risk factors are presented in Table There was significant improvement in predialysis serum phosphate, calcium-phosphate product and parathyroid hormone levels (PTH). Serum predialysis corrected calcium levels rose. By 12 months following conversion to NHD, seventy-three percent of patients had predialysis serum phosphate levels ≤ 1.6 mmol/L. This was achieved despite a substantial decrease in requirement for phosphate binding medications . Only 6% of patients were not taking any phosphate binders at baseline and this increased to 79% on NHD. Calcium carbonate was prescribed to 90% of patients at baseline at an average dose of 2460 mg per day. On NHD, only 15% of patients were prescribed calcium carbonate at an average dose of 1670 mg/day. Addition of phosphate to the acid component of the dialysate on NHD was required in 29% of patients at an average dose of 20 ml of Fleet/10 L (Fleet contains sodium phosphate monobasic 19 g and sodium phosphate dibasic 7 g per 118 mL and sodium content = 4.4 g/118 mL). Parathyroid hormone levels fell significantly from an average baseline of 290 (140-471) to 160 (62-290) ng/L; p = 0.03. Fifty-eight percent of patients were prescribed calcitriol at baseline in an average dose of 1.4 mcg/week. After 12 months on NHD, 53% were prescribed calcitriol at an average dose of 1.8 mcg/week.There was no significant change in predialysis plasma MDA. The increase in MDA observed during dialysis was attenuated after conversion to NHD. Predialysis RBC-CAT activity significantly increased between baseline and 6 months and change during dialysis remained stable. Predialysis RBC-GPX activity decreased and there was no change during dialysis. Plasma GPX activity increased marginally pre dialysis and had a greater increase during dialysis at 3 months. This was not sustained at 6 months. RBC-SOD and plasma TAS levels predialysis and change in these levels with dialysis remained stable , p = 0.02, R2 = 0.36, E/EI and CRP: 0.003 (0.0005-0.005), p = 0.02, R2 = 0.35 and E/EI and Albumin: 0.006 (0.001-0.011), p = 0.02, R20.35, early transmitral flow velocity and transferrin saturation: -0.008 (-0.13 to -0.003), p = 0.005, R2 = 0.48, E/A ratio and transferrin saturation: -0.012 (-0.022 to -0.003) p = 0.01, R20.36, deceleration time and ferritin: 0.08 (0.02-0.13), p = 0.01 R2 = 0.49, early transmitral flow velocity and PTH: -0.0003 (-0.0006 to-4.01e-6), p = 0.05, R2 = 0.48 and deceleration time and PTH: 0.05 (0.004-0.10), p = 0.02, R2 = 0.49). LaVol Index was associated with interdialytic weight gain (9.47 (3.29-15.64), p = 0.004, R20.45) on multivariable analysis.There were no strong associations between change in cardiovascular outcome measures and cardiovascular risk factors measured in this study. There were no significant associations on univariable or multivariable analysis with change in LVMI. Changes in diastolic parameters were associated on multivariable analysis with changes in markers of inflammation and nutrition, iron stores and PTH: early transmitral flow velocity and CRP: 0.008 (0.00001- 0.18), p = 0.05, R2 = 0.32). Change in CIMT was associated on multivariable analysis with change in predialysis serum phosphate (0.34 (0.043-0.065), p = 0.03 and CRP (-0.002 (-0.004 to -0.003), p = 0.03, R2 = 0.24). Change in AIX was associated on multivariable analysis with change in triglycerides , p = 0.003, R2 = 0.52).Change in BAR was associated on multivariable analysis with age (-0.14 (-0.27 to -0.006), p = 0.04, RIn this study, conversion from conventional home HD to alternate nightly home NHD had no significant effects on cardiovascular structure and function indices, after a mean follow-up of 18 months, despite favorable changes in recognized cardiovascular risk factors.Previous studies examining the effects of using increased intensity dialysis or renal transplantation (RTx) to improve the uremic milieu, on cardiovascular structure and function have come to inconsistent conclusions. Some studies, including 1 randomized controlled trial  have shown improvement in LV geometry with conversion to daily hemodialysis regimens . The Frequent Hemodialysis Trial Group recently published important data from 2 randomized controlled trials. The first compared LVmass, measured by cardiac magnetic resonance imaging (MRI), in 125 patients managed with short daily hemodialysis with 120 patients managed on conventional thrice weekly hemodialysis . Short dThis study is the first to explore the effect of an extended hours hemodialysis regimen on cardiac diastolic function and no improvement was shown. Studies in renal transplantation, the gold standard for management of ESKD, have also consistently reported no improvement in diastolic dysfunction ,50. ThisChan et al reported significant improvement in BAR from -2.7 ± 1.8% to 8.0 ± 1.0% in 18 patients and TAC from 0.98 ± 0.13 to 1.43 ± 0.2 mL/mmHg in only 10 patients, 2 months following conversion to daily NHD. They have explored possible pathologic mechanisms driving this improvement and found increased baroreflex sensitivity for heart rate and proliferation and migration of endothelial and vascular smooth muscle cells with normalization of markers of vascular smooth muscle cell biology including caspase-3 and RunX-2 -22,51. S2, appreciably lower than the baseline measurements reported by Ayus et al (154 ± 33 g/m2), Chan et al (180 ± 54 g/m2 and 147 ± 42 g/m2) and Culleton et al (177.4 ± 51.1 g/m2) [One possible explanation for our findings is that patients in our study had lower baseline LVMI and less derangement of baseline BAR and TAC compared to patients in other quotidian hemodialysis studies where improvements were shown. Baseline LVMI indexed to BSA in our study was 106 ± 24 g/m.1 g/m2) . Some ofWe note that in our study cardiac diastolic dysfunction and vascular structure and function parameters were significantly deranged at baseline in our population and did not improve with conversion to NHD. Conversion to alternate nightly NHD, which increased session duration but not frequency, did not improve LVH even in the subset of patients with high baseline LVMI. Therefore, an alternate explanation for the lack of improvement in cardiovascular parameters in our study may be inferior control of interdialytic weight gains (IDWG) and uremic toxins compared with the daily hemodialysis regimens or RTx. IDWG increased with conversion to alternate nightly NHD and may have negated any improvement associated with better control of other uremia toxins.There is increasing literature supporting the hypothesis that all increased intensity hemodialysis regimens may not be associated with equal benefits to measures of cardiovascular structure and function. Both the FHN Trial group studies  and 1 puPrevious studies in ESKD have found complex and inconsistent associations between proposed risk factors and cardiovascular disease ,66. RandThis study is the first to examine the effects of extended hours hemodialysis on oxidative stress. The procedure of hemodialysis has been postulated to increase oxidative stress through contact with bio-incompatible dialysis equipment and contaminated dialysis water, microhemolysis, alterations in lipid metabolism during heparin exposure and removal of antioxidants during dialysis . TherefoVitamins C and E have been identified as important plasma antioxidants which may be lost in increased amounts during extended hours HD. We did not measure serum vitamin C or E levels, although vitamin C was routinely replaced in all patients. Vitamin C deficiency has been documented in extended hours dialysis patients where supplementation has not been routine . This maThis is the largest trial examining the effects of increasing dialysis duration on multiple measures of endothelial function and arterial wall thickness and stiffness and it is the only study examining cardiac diastolic function and oxidative stress markers. Echocardiograms and vascular ultrasound studies were all performed and interpreted in one experienced laboratory. Patients were all managed in one unit with uniform policies and procedures. We performed multivariable analyses to adjust for known confounders. We were powered to detect clinically significant changes in LVMI, BAR, TAC and CIMT.However, our conclusions are limited by the non randomized study design. The baseline dialysis regimen was not a thrice weekly regimen as is standard in most facilities and may have been responsible for the more normal baseline LVMI in our study. It could be postulated that the observation periods used in our, and other studies have been too short to allow cardiovascular remodeling. 2Dimensional echocardiography is less precise and is more reliant on derived rather than directly measured values compared to cardiac magnetic resonance imaging for assessing LVMI . FurtherConversion to an alternate nightly home hemodialysis regimen, which only increased dialysis duration and not frequency, did not result in a significant improvement in cardiovascular structure and function. Continuing suboptimal control of uremic toxin levels, BP and fluid balance with alternate daily hemodialysis compared to daily hemodialysis or RTx may be a possible explanation. The relatively normal LVMI at baseline in our population also likely contributed to our failure to show improvement in this parameter. A wide range of traditional and novel cardiovascular risk factors did not strongly correlate with cardiovascular structure and function parameters.This study adds to the increasing uncertainty in the published literature about the nature of improvement in cardiovascular parameters with conversion to intensive hemodialysis regimens. More work is needed to better understand the exact mechanisms driving cardiovascular dysfunction in ESKD and how we might prevent progression or reverse existing disease. Future randomized controlled trials will be important to determine whether increases in dialysis session duration, frequency or both are most beneficial for improving and slowing the progression of cardiovascular disease whilst minimizing costs and the impact of dialysis on quality of life.Authors on this paper have received travel and research grants and fees for lectures from Fresenius Medical Care, Baxter and Gambro. Carmel Hawley and David Johnson have been members of the advisory boards for Fresenius Medical care, Baxter and Gambro.CvE: Design, coordination, data collection cardiovascular risk profiles, recruitment, statistical analysis, drafting and revising the manuscript. LJ: Performed and analyzed ECHO and vascular USS studies. BH: Performed and analyzed vascular USS studies particularly TAC and AIX. CH: Conceived the study, participated in statistical analysis and drafting and revising the manuscript JC: Conceived and supervised the oxidative stress component of the study and participated in manuscript revision AM: Carried out the oxidative stress assays, DJ: acquired funding, manuscript revision, SC: Manuscript revision, NI: Acquired funding, manuscript revision, DM: Manuscript revision, TM: Conceived the study, acquired funding, provided overarching supervision, manuscript revision. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/12/51/prepub


The microcirculation plays a pivotal role in oxygen delivery to the tissue. Microcirculatory alterations have been observed to occur independently of the major inflow variable for microcirculation: mean arterial pressure. According to physiological theory, the microcirculation is considered to be a low-pressure compartment. Maximum optimal central venous pressure (CVP) according to Surviving Sepsis Campaign (SSC) guidelines is 12 to 15 mmHg in mechanically ventilated patients. We hypothesized that a CVP >12 mmHg would hamper microcirculatory perfusion but not diffusion, by acting as outflow obstruction.We retrospectively analyzed combined measurements of CVP and sidestream dark-field derived sublingual microcirculatory variables in patients with severe sepsis or septic shock. Measurements were made 0, 0.5, 2, 12 and 24 hours after resuscitation in accordance with SSC guidelines. Differences in small vessel microvascular flow index (MFI) and total vessel density (TVD) between two groups (CVP ≤12 mmHg and CVP >12 mmHg) were analyzed with a Mann-Whitney U test.P = 0.032), whereas TVD in both groups did not differ significantly (14 (12.84 to 15.75) vs. 14.3 (13 to 15.8) mm/mm2, P = 0.38). See also Figure A total of 345 measurements in 70 patients (APACHE II 21 (6.5) (mean (SD))) were included. MFI in patients with CVP >12 mmHg was significantly lower than in CVP ≤12 mmHg (1.83 (0.92 to 2.75) vs. 2.25 (1.35 to 2.90) (median (IQR)), In septic patients with CVP >12 mmHg after resuscitation, microcirculatory flow was significantly lower as compared to patients with CVP ≤12 mmHg, whereas capillary density did not differ between groups.


Patients aged 60 years and older represent the fastest-growing population with end-stage renal disease worldwide, and the need for a kidney transplant among this population is increasing. Due to the severe shortage of deceased donors in Japan, ABO-incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved, and the rates of graft survival in these patients are currently similar to those in recipients of ABO-compatible grafts. However, the outcomes of ABO-incompatible kidney transplantation in elderly patients over 60 years of age have not been well studied yet.2). The patients with high anti-A/B antibody titers (≥1:512) underwent splenectomy and received 2 doses of rituximab. The pretransplant immunosuppressive protocol included B-lymphocyte suppression with 4 weeks of mycophenolate mofetil (0.5 g/day for low-titer protocol and 1 g/day for high-titer protocol).We studied 4 elderly kidney transplant patients who received their grafts from ABO-incompatible living donors at our institution between December 2006 and December 2011, focusing on the immunosuppressive protocols, complications and graft survivals. The mean observation period was 21.5 months . Our immunosuppressive protocols were as follows: to remove the anti-A/B antibodies, the patients underwent 4–8 sessions of double-filtration plasmapheresis and/or plasma exchange prior to kidney transplantation until the anti-A/B titers were less than 1:16. For the patients with low anti-A/B titers (<1:512), the immunosuppressive protocol consisted of a single dose of rituximab (150 mg/mAll 4 patients underwent successful transplantation. At the end of follow-up, their mean serum creatinine was 1.18 mg/dl. No patient experienced antibody-mediated rejection or acute cellular rejection. Late-onset neutropenia occurred in two cases. Two cases experienced cytomegalovirus reactivation by cytomegalovirus antigenemia. In one patient, diffuse hemorrhage required surgical intervention. However, there were no severe complications.Although a careful evaluation of patients is needed, ABO-incompatible kidney transplantation may become a viable treatment option for elderly patients with end-stage renal disease. Patients aged 60 years and older represent the fastest-growing population with end-stage renal disease worldwide , and then = 3) and a child (daughter) (n = 1). The patient characteristics are shown in Table n = 1), renal sclerosis (n = 1) and unknown (n = 2). The cytomegalovirus serostatus pattern was donor positive/recipient positive in all cases.Four patients aged 60 years and older who received their grafts from ABO-incompatible living donors at our institution between December 2006 and December 2011 were enrolled in this study. The patients had anti-A/B titers ranging from 1:16–1:2,048. The donors were spouses  1.0 g/day and methylprednisolone (MP) 8 mg/day [2 at 2 weeks prior to the transplantation, and pretransplant immunosuppression included B-lymphocyte suppression for 4 weeks of MMF 0.5 g/day and MP 8 mg/day to avoid over-immunosuppression  underwent standard antibody removal consisting of 3 sessions of double-filtration plasmapheresis (DFPP) and 1 session of plasma exchange (PE). When the anti-A/B antibody titers did not decrease to less than 1:16, additional antibody removal was performed. The one recipient with high titers (≥1:512) underwent 5 sessions of DFPP and 3 sessions of PE prior to kidney transplantation until the anti-A/B titers were ≤1:16.For postoperative immunosuppression, the same regimen as that for ABO-compatible cases was followed, in which calcineurin inhibitors were initiated 3 days before transplantation combined with two doses of basiliximab. Cyclosporin was given so as to maintain a blood trough level of 250–300 ng/ml during the first month after operation, 200–250 ng/ml during the second month, 150–200 ng/ml during the third month and 100–150 ng/ml thereafter. Tacrolimus was given so as to maintain a blood trough level of 10–13 ng/ml during the first month after operation, 8–10 ng/ml during the second month, 6–8 ng/ml during the third month and 3–6 ng/ml thereafter. Basiliximab was infused on day 0 and 4 at a dose of 20 mg. The MMF dosage after transplantation was maintained at pretransplant doses in both protocols. These protocols were approved by our Human Ethics Committee. All subjects gave informed consent for participation in the study. All procedures were in accordance with the Helsinki Declaration of 2000.Anti-A/B antibody titers were measured pre- and post-transplantation. The anti-IgM titer was measured using the saline agglutination technique, and anti-IgG titer was measured using the indirect Coombs’ test.Surveillance biopsies were performed once within a month after surgery and before discharged from hospital in all patients. When clinically indicated by rising serum creatinine or decreasing urine output, episode biopsies were performed.All 4 patients had immediate graft function and underwent successful kidney transplantations. In all cases, no apparent cellular or humoral rejection was observed during the observation periods after kidney transplantation. None of the cases received episode biopsies. Subclinical rejection was not diagnosed on surveillance biopsies in any of the recipients. All recipients had good graft function Table .Table 2OA 64-year-old man with end-stage chronic renal failure due to chronic glomerulonephritis visited our hospital to receive ABO-incompatible (type B to A) living-unrelated donor kidney transplant from his 62-year-old wife. The anti-B antibody titer was 1:2,048 using the Coombs’ method. Because of a high (more than 1:512) anti-A antibody titer, the patient underwent both administration of rituximab and splenectomy as desensitization. Immunosuppressive therapy consisted of tacrolimus, MMF, basiliximab and methylprednisolone. The kidney transplantation was performed uneventfully. He became positive for cytomegalovirus antigenemia 48 days after transplantation. However, no obvious invasive tissue disease occurred. As preemptive therapy, a 10-day administration of ganciclovir induced the elimination of cytomegalovirus antigenemia.A 74-year-old man with end-stage chronic renal failure due to renal sclerosis visited our hospital to receive ABO-incompatible (type AB to B) living-related donor kidney transplant from his 50-year-old daughter. The patient received only a single dose of rituximab without splenectomy as desensitization. The kidney transplantation was performed uneventfully. However, on postoperative day 1 urine output decreased suddenly, and he was suffered from abdominal fullness. Computer tomography showed postoperative diffuse hemorrhage in pelvis, leading to surgical intervention. Thereafter, he was uneventful. Immunosuppressive therapy consisted of cyclosporin, MMF, basiliximab and methylprednisolone. However, he became positive for cytomegalovirus antigenemia 24 days after transplantation. Although ganciclovir was administered for 12 days, the patient did not become negative for cytomegalovirus antigenemia and experienced ganciclovir-induced leukocytopenia. After the discontinuation of ganciclovir, this patient was successfully treated with foscarnet. He experienced late-onset neutropenia 116 days after transplantation due to the administration of rituximab and MMF. Other drugs that could induce myelosuppression were not given to these patients at neutropenia onset, and the primary causes of neutropenia such as viral and bacterial infections did not occur. He recovered from neutropenia by granulocyte colony-stimulating factor administration.A 70-year-old man with end-stage chronic renal failure visited our hospital to receive ABO-incompatible (type A to O) living-unrelated donor kidney transplant from his 65-year-old wife. The patient received only a single dose of rituximab without splenectomy as desensitization. Immunosuppressive therapy consisted of cyclosporin, MMF, basiliximab and methylprednisolone. The kidney transplantation was performed uneventfully. Since the first two patients developed cytomegalovirus viremia, a prophylaxis protocol for cytomegalovirus was applied to this patient. He had an elevation of C-reactive protein and β-D-glucan 80 days after kidney transplantation. Because computer tomography of the chest showed interstitial pneumonitis, pneumocystis pneumonia was suspected. Interstitial pneumonitis was treated by administration of sulfamethoxazole trimethoprim. He experienced neutropenia 95 days after transplantation. He recovered from neutropenia by granulocyte colony-stimulating factor administration.A 69-year-old man with end-stage chronic renal failure due to chronic glomerulonephritis visited our hospital to receive ABO-incompatible (type B to A) living-unrelated donor kidney transplant from his 66-year-old wife. The patient received only a single dose of rituximab without splenectomy as desensitization. Immunosuppressive therapy consisted of cyclosporin, MMF, basiliximab and methylprednisolone. The kidney transplantation was performed uneventfully. A prophylaxis protocol for cytomegalovirus was also applied to this patient.Although patient 1 with high anti-A/B titers experienced antibody rebound slightly after plasmapheresis, the rebound was eliminated after the third or fourth plasmapheresis. The other cases with low titers did not experience any rebound of ABO antibody titers Table .Table 3AThe outcomes of ABO-incompatible kidney transplantation in elderly patients older than 60 years of age have not been well studied yet. The present study demonstrated our modifications in immunosuppressive protocols for these recipients. All of our patients underwent successful transplantations with no severe complication or rejection. To our knowledge, this is the first demonstration of ABO-incompatible kidney transplantation in elderly patients over 60 years. Our results suggested that this method is a radical but effective treatment for elderly patients with ESRD.Transplantation improves the cumulative survival of ESRD patients compared with dialysis as shown by Wolfe et al. : Individ2). A previous report demonstrated excellent graft and patient survival in elderly recipients from older living donors, showing that older living donors may be an important option for elderly transplantation candidates and should be considered for older patients with a willing and suitable older donor [In 3 out of the 4 recipients, the donors were spouses aged 60 years and over, and their graft function was satisfactory  of kidney transplants have improved quality of life including physical functioning and mental health on nationally standardized SF-36 questionnaires. These results were found to be equivalent to national age and sex appropriate norms. It should be appreciated that these results were reported despite a significantly reported incidence of surgical and post-transplant medical complications . All eld2 at 2 weeks prior to transplantation, and pretransplant immunosuppression included B-lymphocyte suppression with 4 weeks of MMF 1.0 g/day and MP 8 mg/day [2 at 2 weeks prior to transplantation, and pretransplant immunosuppression included B-lymphocyte suppression with 4 weeks of MMF 0.5 g/day and MP 8 mg/day to avoid over-immunosuppression. In our case series, there were no cytomegalovirus serology–naïve kidney transplant patients of cytomegalovirus serology–positive organs. However, intractable cytomegalovirus reactivation occurred in one case, and thereafter, measures were taken for prophylaxis of cytomegalovirus. One patient experienced an elevation of β-d-glucan, for which Pneumocystis jiroveci infection was suspected. Two patients experienced late-onset neutropenia. Although spousal kidney transplantation, which could have presented poor tissue antigen compatibility, was performed in 3 of the 4 cases, there were no episodes of acute cellular or humoral rejection during the follow-up period. Furthermore, none of the patients experienced any rebound of ABO antibody titers during the pre- and postoperative period. Although our modified protocol for elderly recipients had enough immunosuppressive effectiveness to control the elevation of antibody titers and acute rejection, it may induce over-immunosuppression. An effort to develop a tailored desensitization protocol for elderly recipients of ABO-incompatible kidney transplants may be necessary.Although ABO-incompatible kidney transplantation is an immunologically high-risk procedure, the development of powerful immunosuppressant drug combinations has resulted in excellent graft and patient survivals . Increas8 mg/day , 7. The Recipients with high antibody titers at baseline have been reported to be at high risk of antibody-mediated rejection and graft loss . ABO-incIn conclusion, this small preliminary study showed that ABO-incompatible kidney transplantation could be accomplished in elderly recipients without any severe complications. Although complications including cytomegalovirus reactivation, diffuse hemorrhage and pneumocystis pneumonia occurred, all patients recovered successfully. Elderly patients receiving ABO-incompatible kidney transplantation are more susceptible to developing adverse effects related to immunosuppressant therapy. An effort to develop a tailored protocol for elderly recipients of ABO-incompatible kidney transplants may be necessary. Although a careful evaluation of the comorbidities of patients is needed, ABO-incompatible kidney transplantation may become a viable treatment option for elderly patients with ESRD. Larger and longer trials are further needed to assess the safety and effectiveness of this procedure.


Objectives: The aim of the present study is to compare cardiovascular safety profiles of two dental anesthetics: articaine versus two standard mepivacaine solutions used during etiological periodontal treatment in cardiovascular patients. Study Design: Using a cross-over study design, ten cardiovascular patients were randomly assigned to dental treatment with 1.8mL of a local anesthetic injected on each quadrant of the mouth: Articaine (40mg with Epinephrine 0.5mg % and 40mg with Epinephrine 1mg %) or Mepivacaine (30mg and 20mg with Epinephrine 1mg %). A computer programme enabled continuous longitudinal data collection: O2 saturation, blood pressure (BP) and heart rate (HR).Results: No severe clinical side effects were observed. During the treatment period, we observed statistically significant differences as regards HR between injections with and without adrenalin (p< 0.039) and as regards systolic (p< 0.046) and diastolic (p < 0.046) blood pressure during the stabilization period. In both cases, the parameters under study increase. Age, gender, jaw treated, treatment duration and the rest of cardiovascular variables did not affect the results. None of the patients underwent ischemic alterations or any other complication derived from the treatment or the anesthesia.Conclusions: According to the results of our study, dental anesthetics with standard concentrations of Epinephrine seem to alter HR and BP. Although no cardiac ischemic alterations or any other cardiovascular complications have been observed, we must be cautious with the administration of anesthetics containing vasoconstrictors in patients with cardiovascular diseases. Key words:Dental anesthesia, cardiovascular diseases, chronic periodontitis, drug toxicity. An essential factor which determines a successful causal periodontal treatment is the administration of good-quality local anesthesia (LA). Though mepivacaine has been traditionally used as the dental anesthetic of choice, clinically potent local anesthetic substances, such as mepivacaine and articaine, are used in combination with vasoconstrictors. Vasoconstrictors, mainly adrenaline or epinephrine, contribute to successful LA as they increase the depth and duration of analgesia. Such effect of epinephrine on mepivacaine or articaine-based LA solutions has already been demonstrated.  VasoconsPhysiological responses associated with local anesthetics containing a vasoconstrictor include changes in heart rate and blood pressure -7, dysrrWhen these vasoconstrictor-induced physiological responses exceed the normal range, the risk of morbidity or even mortality increases. This is of special relevance in the case of cardiovascular patients. Although most current literature accepts that adrenaline has a safety range ,18, its Although the information available as regards the cardiovascular response to dental LA with articaine and epinephrine and with mepivacaine with epinephrine is limited to healthy patients ,22, it mThe purpose of the present study is to examine the hemodynamic response to four LA solutions in cardiovascular patients: Articaine 40mg with epinephrine 0.5mg %, articaine 40mg with epinephrine 1mg %, mepivacaine 30mg without epinephrine and mepivacaine 20mg with epinephrine 1mg %. The hypothesis is that the synergy of a short half-life time LA agent with a proper concentration of epinephrine would be safer for cardiovascular patients.Study design and patients selectionA prospective, randomized, single-blinded, crossover, controlled comparative study was performed at the Department of Special Care in Dentistry, Seville University, Faculty of Odontology during 2009. The study was conducted with the approval of the University of Seville Ethics Committee and in accordance with the Declaration of Helsinki.All patients gave their informed consent to take part in the study prior to the initiation of the dental treatment. Randomization was achieved by using a computer-generated random number list. Ten patients with cardiovascular disease who met the inclusion criteria were enrolled in the study.The inclusion criteria were the following: (a) controlled hypertension (HTN) with blood pressure values ≤ 160/100 mm Hg; (b) ischemic heart disease (IHD) including stable angina pectoris, post-myocardial infarction (≥ 6 months); (c) chronic periodontitis affecting the four quadrants of the oral cavity.Exclusion criteria comprised: (a) cardiovascular instability including unstable angina pectoris, recent myocardial infarction (≤ 6 months), refractory dysrrhythmias, untreated or uncontrolled hypertension, untreated or uncontrolled CHF, uncontrolled hyperthyroidism; (b) uncontrolled diabetes mellitus; (c) sulphite sensitivity; (d) steroid-dependent asthma; (e) pheochromacytoma; (f) tricyclic antidepressant treatment; (g) previous history of psychiatric disorder, chronic use of central nervous system depressants or antidepressants or mental instability.All patients underwent clinical and radiographic examination . Patients who presented with chronic periodontitis affecting the four quadrants of the oral cavity treatable with etiological periodontal therapy (root planning) were randomly allocated in order to determine the order in which each of the anesthetics would be applied to the different quadrants. Root planning was programmed following a weekly schedule for each of the quadrants. In each of the treatment arms, a different LA solution was used: (a) mepivacaine 30 mg without epinephrine  total dose: 108 mg of mepivacaine chlorhydrate; (b) articaine 40 mg with epinephrine 0.5mg%  total dose: 144 mg articaine hydrochloride with 0.018 mg of epinephrine; (c) articaine 40 mg with epinephrine 1 mg%  total dose: 144mg articaine hydrochloride with 0.036mg of epinephrine, and (d) mepivacaine 20mg with epinephrine 1mg%  total dose: 72mg mepivacaine chlorhydrate with 0.036 mg of epinephrine. We used a cross-over study design with a washing period of one week.Treatment protocolThe study time frame for each subject comprised a baseline period of 5 minutes followed by LA injection. Anesthesia was carefully induced with aspiration and slow injection of anesthetic. All patients were administered a standard dose of 3.6 mL. A minimum of 5 minutes was necessary to achieve LA effectiveness. Treatment lasted until completion of dental procedure (one session of root planning and polishing per quadrant). Patients were asked to remain seated for several minutes after the completion of the treatment. The same two investigators attended every treatment session, one of them in charge of the treatment and the other one in charge of monitoring and data recording.Monitoring A non-invasive monitor  was used to record systolic, diastolic and mean blood pressure  at 5-minute intervals. Oxygen blood saturation (SO2) and heart rate (HR) were continuously recorded. Online transmission of data from the pulsioximeter to a personal computer was mediated with software nVISION v. 5.1e . Monitoring began at the onset of the baseline period and continued every 5 minutes after completion of the periodontal treatment.StatisticsStandard time points and time intervals were defined: (a) Baseline: beginning of monitoring; (b) Baseline + 5 minutes: end of stabilization period; (c) LA: injection timing; (d) LA + 5 minutes: 5 minutes after injection; (e) Treatment: onset of dental treatment; (f) End: completion of treatment.The hemodynamic indices measured at the above mentioned points were used to carry out the descriptive statistic analysis . Demographic parameters and hemodynamic indices of the 4 treatment arms were compared using t-test and analysis of variance . Kolmogorov-Smirnov test was used to confirm the normal distribution of data.Baseline characteristics of patients were compared in the two groups as regards mean age (63±12.5 yrs), jaw under treatment and duration of treatment (26.38±9.9 minutes).Programmed dental procedure was completed in all 10 patients. No severe adverse effects were observed in any of the patients. Clinical data of patients are shown in .Hemodynamic indices of HR, sysBP and SO2 at various time points and time intervals showed no statistical differences when comparing both groups. The group receiving Mepivacaine 2% with epinephrine 1:100,000 showed statistical differences with the rest of the groups as we observed increased diaBP levels at the stabilization period (p< 0.038) and meaBP (p< 0.01) at the stabilization period and in the treatment period (p< 0.039) .To analyse the effect of epinephrine on the anesthetics, clinical data were divided into two study groups: with (n= 30) and without (n=10) adrenaline. Hemodynamic indices of HR (p< 0.039), sysBP (p< 0.046), diaBP (p< 0.046), at various time points and time intervals (treatment and stabilization periods) were statistically different in both groups .The use of local anesthetics associated to vasoconstrictors is somewhat controversial among the professionals of odontology because, together with the beneficial effects of such combinations, other side effects have been detected, mainly of cardiovascular nature -7.Such side effects may be adverse, although the use of these substances is not contraindicated in healthy subjects whenever the adequate doses and correct administration procedure is followed. In fact, most studies on the alterations of vascular parameters associated with the use of dental anesthetics containing vasoconstrictors have been carried out in healthy subjects, which would explain the possible bias observed in the results -27.In Western civilization, the number of cardiovascular patients who visit a dental clinic is increasing. Very few studies have so far analysed the effect of dental anesthetics containing vasoconstrictors on cardiovascular patients ,29. TherThe criterion used to group patients with cardiovascular diseases is not homogeneous in the different studies published so far. The present study analyses a 100% of patients with arterial hypertension. Conrado et al.  study a In the present study, alterations in heart rate were not significant when we compared the four study groups. Nevertheless, when we compared the use of anesthetics without and with vasoconstrictors, in the first group we observed a significant decrease in heart rate in comparison to the second group. This effect is similar to the one reported by Matthews et al. , who detAs regards arterial pressure, we have observed few significant alterations, mainly referring to an increase of diastolic arterial pressure and mean blood pressure during the stabilization period in comparison with baseline levels. Diastolic arterial pressure and mean blood pressure increased significantly in group 4  in comparison to the rest of groups. If we focus on the first three study groups , the alterations detected are similar to those reported by Conrado et al. , Neves eWhen we classify the results obtained according to the use or not of vasoconstrictors, we observed alterations in diastolic and systolic blood pressure between the baseline period and the stabilization period. This would confirm the critical nature of this period, already observed in previous reports ,31.As regards oxygen partial pressure, our results do not show remarkable alterations when comparing the different study groups, similarly to what Matthews et al.  had alreFinally, we must add some points about the different treatment regimes analysed. All of them have been well tolerated by patients. Even in the case of cardiovascular patients, some of them suffering from more than one disease, no adverse side effects have been detected. As a result, and considering the results obtained, we can confirm that these treatments are very safe in all cases.Yet, as has been clearly demonstrated, the combination of anesthetics and vasoconstrictors provokes cardiovascular alterations which could have serious clinical consequences in patients with more severe pathologies than the ones here studied.It would be advisable to increase the level of complexity of the techniques used to obtain data  in order to identify ischemic events of short duration. However, we should also justify the necessity of these complex techniques.In our opinion, more complex studies would be justified in the case of severe cardiovascular patients as alterations which are unimportant in the case of healthy subjects could have clinical relevance in these patients. Nevertheless, such studies should be accompanied by greater safety measures in the case of patients more severely compromised.


Patients with chronic kidney disease are at significantly increased risk for cardiovascular disease and sudden cardiac death. One mechanism underlying increased cardiovascular risk in patients with renal failure includes overactivation of the sympathetic nervous system (SNS). Multiple human and animal studies have shown that central sympathetic outflow is chronically elevated in patients with both end-stage renal disease (ESRD) and chronic kidney disease (CKD). SNS overactivation, in turn, increases the risk of cardiovascular disease and sudden death by increasing arterial blood pressure, arrythmogenicity, left ventricular hypertrophy, and coronary vasoconstriction and contributes to the progression renal disease. This paper will examine the evidence for SNS overactivation in renal failure from both human and experimental studies and discuss mechanisms of SNS overactivity in CKD and therapeutic implications. Patients with chronic renal failure are at profoundly higher risk for cardiovascular (CV) morbidity and mortality. Multiple epidemiologic studies have demonstrated that both reduced renal function and proteinuria are significantly and independently associated with an increased risk of CV death –5. In muThe nature of CV disease in patients with renal failure differs from that of the general population. Whereas the most common manifestations of CV disease in the general population include coronary atherosclerotic disease, patients with renal failure are far more likely to suffer from chronic heart failure and sudden cardiac death , 6. SuddThe mechanisms underlying CV risk in CKD are multifactorial and begin early in the course of renal disease. Not only are traditional CV risk factors such as hypertension and diabetes highly prevalent in the CKD population, but nontraditional risk factors specific to CKD and ESRD patients are also highly prevalent and contribute to risk . These i Epidemiologic studies have demonstrated that SNS overactivity is independently associated with an increased risk of cardiovascular mortality in patients with renal failure and other disease states , 18, 19. Chronic SNS activation likely also plays a role in the progression of chronic kidney disease. Sympathetic innervation of the kidney increases renovascular tone, and leads to activation of the renin-angiotensin aldosterone system, and increased sodium reabsorption, that contributes to extracellular fluid volume expansion and increased BP. SNS activation also contributes to progression of glomerulosclerosis and proteinuria , 31, 32.Studies in humans and animals have provided convincing evidence that chronic renal failure is characterized by SNS overactivity. Plasma norepinephrine levels have been shown to be significantly elevated in patients with ESRD, roughly two-fold higher than in controls , 34, andThe kidney functions as a sensory organ that is richly innervated with chemoreceptors and baroreceptors . These r Human studies using direct recordings of MSNA via microneurography corroborate the findings from experimental studies. In hemodialysis patients with intact kidneys, MSNA was significantly elevated when compared to controls . HoweverThe specific factors that bind and activate the renal nerves are unknown and largely unstudied. Purported ligands include urea, and adenosine, a product of renal ischemia. Chemoreceptor activation via ischemic metabolites may cause reflex increases in SNS outflow in order to attempt to redirect blood flow away from other areas of the body, to the ischemic tissues. In a study of uninephrectomized dogs, changes in blood pressure and renal sympathetic nerve activity were measured during intrarenal infusion of adenosine, before and after renal denervation . There wDecreased NO bioavailability likely contributes to chronic SNS overactivation in CKD. NO has a tonic inhibitory effect on central SNS outflow. In rats that were chronically treated with N Nitro L arginine methyl ester (L-NAME), an inhibitor of NO synthase (NOS), blood pressure increased due to decreased NO bioavailability . When mi ESRD and CKD patients have reduced NO bioavailability due to multiple causes that include oxidative stress, inflammation, uremic toxins, and accumulation of endogenous inhibitors of NOS, including asymmetric dimethylarginine (ADMA). ADMA is an endogenous inhibitor of NOS that accumulates in CKD and ESRD patients and is not removed during dialysis –56. The Patients with CRF have elevated baseline oxidative stress which contributes to increased CV risk –64. OxidHigh circulating Ang II levels also likely contribute to sympathetic activation in CKD. Circulating Ang II can easily reach the area postrema of the medulla which lacks a blood brain barrier and has a multitude of AngII receptors . The areClearly, patients with ESRD and CKD have SNS overactivity that contributes to increased risk of CV disease and sudden death, as well as progression of renal dysfunction. However, whether treatment with sympatholytic agents reduces CV risk or modifies the rate of end-organ damage in CKD is yet unknown. Inhibitors of the renin-angiotensin system, including ACE-inhibitors, ARBs, and direct renin inhibitors, have been shown to significantly reduce MSNA in patients with CKD , 38, 73.In ESRD patients, short daily dialysis has been shown to reduce ambulatory blood pressure, nocturnal blood pressure dip, and MSNA when compared to conventional hemodialysis . The mecFinally, newer nonpharmacologic approaches to the treatment of hypertension, particularly resistant or difficult to control hypertension, target reduction of central SNS outflow and may become applicable in the treatment of hypertension in patients with renal disease. These include renal denervation and baroreceptor stimulation. Renal denervation is performed via transcatheter ablation of both afferent and efferent renal nerves and has been shown to substantially reduce blood pressure and MSNA in patients with resistant hypertension –86. The Patients with CKD and ESRD have chronic sympathetic overactivity that contributes to the substantially increased risk of CV disease and mortality , 16, 17.


Recent experimental data suggest that continuous external negative-pressure ventilation (CENPV) results in better oxygenation and less lung injury than continuous positive-pressure ventilation (CPPV). The effects of CENPV on patients with acute respiratory distress syndrome (ARDS) remain unknown.n = 1), aspiration (n = 3), sepsis (n = 1) or both (n = 1). We used a tidal volume of 6 ml/kg predicted body weight and matched lung volumes at end expiration. Haemodynamics were assessed using the pulse contour cardiac output (PiCCO) system, and pressure measurements were referenced to atmospheric pressure.We compared 2 h CENPV in a tankrespirator ("iron lung") with 2 h CPPV. The six intubated patients developed ARDS after pulmonary thrombectomy (P < 0.05). Tank pressures were -32.5 cmH2O (minimum-maximum -30 to -43) at end inspiration and -15 cmH2O (minimum-maximum -15 to -19 cmH2O) at end expiration. NO Inspiratory transpulmonary pressures decreased (P = 0.04) and airway pressures were considerably lower at inspiration (-1.5 cmH2O (minimum-maximum -3 to 0 cmH2O) vs 34.5 cmH2O (minimum-maximum 30 to 47 cmH2O), P = 0.03) and expiration (4.5 cmH2O (minimum-maximum 2 to 5) vs 16 cmH2O (minimum-maximum 16 to 23), P =0.03). During CENPV, intraabdominal pressures decreased from 20.5 mmHg (12 to 30 mmHg) to 1 mmHg (minimum-maximum -7 to 5 mmHg) (P = 0.03). Arterial pressures decreased by approximately 10 mmHg and central venous pressures by 18 mmHg. Intrathoracic blood volume indices and cardiac indices increased at the initiation of CENPV by 15% and 20% (P < 0.05), respectively. Heart rate and extravascular lung water indices remained unchanged.CENPV resulted in better oxygenation compared to CPPV  vs 256 mmHg (minimum-maximum 123 to 419 mmHg) (CENPV with a tank respirator improved gas exchange in patients with ARDS at lower transpulmonary, airway and intraabdominal pressures and, at least initially improving haemodynamics. Our observations encourage the consideration of further studies on the physiological effects and the clinical effectiveness of CENPV in patients with ARDS. Acute respiratory distress syndrome (ARDS) is usually treated with invasive continuous positive-pressure ventilation (CPPV) , which cExternal negative-pressure ventilation with tank respirators is very successful in treating patients with chronic obstructive pulmonary disease , but theWe speculated that, similarly to recent experimental data, CENPV with a tank respirator would also result in better oxygenation in intubated patients with ARDS, even when low tidal volumes were used. Therefore, we performed a physiologic study to compare CENPV with CPPV using matched lung volumes at end expiration and matched low tidal volumes. Favourable physiologic effects may help to promote CENPV as an applicable and even noninvasive ventilatory mode for patients with ARDS.2O in patients 1 through 5 (and to 23 cmH2O in patient 6). The patients were ventilated with a lung-protective strategy using a tidal volume of 6 ml/kg predicted body weight .n = 3 patients) or 2 hours of CPPV first and then 2 hours of CENPV (n = 3 patients) in an unchanged supine position. Between both ventilatory modes, we returned the ventilation, ventilation is the correct word to baseline, and the whole experiment lasted 6 to 7 hours.We compared 2-hour CENPV using a tank respirator with 2-hour CPPV using biphasic positive airway pressure/airway pressure release ventilation with an Evita 1 ventilator . We randomised the sequence of the ventilatory mode to balance the effects of the previous ventilation period. The six patients were randomized to receive 2 hours of CENPV first and then 2 hours of CPPV . This step was repeated two more times, and the average value of the three measurements was calculated. Next, lung volumes at end expiration of the second ventilation mode were matched to those measured with the first one. To find out the corresponding pressure at end expiration, we first measured the lung volume at a similar positive or negative pressure. We then increased or decreased pressure according to the achieved volumes and repeated the measurement manoeuvre until the difference between lung volumes at end expiration was smaller than 50 ml. We then performed three measurements again as described above.We matched tidal volume, respiratory frequency and the lung volume at end expiration that represented the difference between functional residual capacity (FRC) with and without end-expiratory pressure. The ratio of inspiration to expiration was 1:1. After a recruitment manoeuvre of six deep breaths with an inspiratory pressure of 60 cmH2O. We performed this manoeuvre to standardise the history of lung volume [To achieve comparable conditions, we recruited the lungs again immediately before CPPV or CENPV with 25 deep breaths applied during 1 minute using inspiratory peak pressures of 60 cmHg volume  to improThanks to an initiative of Prof Ina Pichlmayr the tank respirator and the pump aggregate to generate negative pressures had been manufactured at our institution during the early 1980s . The tra2O in the pressure support mode of the Evita 1 ventilator. The conventional ventilator was set to 0 cmH2O at end expiration. The ventilatory circuits, arterial and central venous lines, gastric tube, urine catheter, electrocardiographic leads, pulse oximeters and other connections to the patient were led out of the tank via apertures from its bottom.During CENPV, the inspiratory changes of airway flow caused by the tank respirator triggered the conventional mechanical ventilator that delivered flow at a peak inspiratory pressure of 5 cmHAirway pressures were measured via the side hole of a modified Swan-Ganz catheter that was introduced via the endotracheal tube and placed into the trachea 1 cm distal to the tip of the tube. Oesophageal pressures were measured with a conventional balloon catheter system . The oesophageal balloon catheter was passed to a depth of 60 cm, and placement of the balloon in the stomach was confirmed by a transient increase in pressure during gentle compression of the abdomen. We then withdrew the catheter until oesophageal placement was confirmed by the presence of cardiac artefacts and pressure changes during tidal ventilation . IntraabP-values less than 0.05 were considered significant.Cardiac index, intrathoracic blood volume index, extravascular lung water index and stroke volume variation were assessed by thermal dilution using the PiCCO system with an arterial catheter inserted into a femoral artery. The Wilcoxon signed-rank test was used to compare values between CENPV and CPPV, and 2/FiO2 ratio) increased by 92 mmHg (40%) after 1 hour and by 76 mmHg (30%) after 2 hours. However, the individual responses varied considerably between patients during both CPPV and CENPV  decreased and pH increased during CENPV, but statistical significance was reached only at 1 hour  (airway pressure minus tank pressure) were about 3 cmH2O in three patients, which may also reflect very similar degrees of lung injury.The TRP differences between CENPV and CPPV, which varied considerably at inspiration and expiration, might be cause by different distributions of positive and negative pressures, depending on individual differences in pulmonary mechanics. Despite our study design, in which we used matched tidal volumes and randomization of ventilatory modes, we found the same TRP value of 31 cmHThe high intraabdominal pressures  decreaseIn comparison to arterial pressures, the quite elevated central venous pressures decreased more extensively during CENPV, indicating the relatively greater impact on the venous circulation than on the arterial circulation, where the vessel tone is stronger. When central venous pressures decreased during CENPV, the high intrathoracic blood volume indices further increased by 15%, reflecting improved venous return, and the cardiac index improved considerably by 20%. Compared to CPPV, this improved venous return may result in less alteration of mixed venous oxygen content and therefore may contribute to maintaining higher levels of arterial oxygen content during CENPV.et al. observed very similar increases in cardiac output at lower intrathoracic blood volumes when a poncho was used to apply continuous negative pressure during IPPV [et al. did not observe changes in cardiac output when a whole-body device was used, but they did when negative pressure was applied to the chest only [In the present study, the heart rate also remained unchanged, indicating that the greater transpulmonary blood flow during CENPV apparently resulted from higher stroke volumes. Borrelli ing IPPV . The greest only .CENPV has been suspected to increase extravascular lung water compared to CPPV as a result of more negative pleural and interstitial pressures and because of higher left ventricular filling after enhanced venous return ,25. In o2/FiO2 responses to CENPV was apparently independent of the underlying disease, the efficiency of the prior lung recruitment manoeuvre or the severity of lung injury. Interestingly, increased oxygenation in response to placement in the prone position also was not related to lung recruitability in response to positive pressures [The very small number of patients in this study represents its main limitation and primary source of errors. In four of the six patients, pulmonary aspiration of gastric content was either the main or one contributory predisposing factor in the development of ARDS. Extrapolating this observation to patients with other predisposing factors must be done with caution. In any case, the considerable variation in PaOressures . FinallyAs a possibly less injurious and more effective mode of ventilation, CENPV appears especially attractive when the potential to eliminate endotracheal intubation is taken into consideration. Tank respirators were used decades ago to apply continuous external negative pressure in three patients with severe pneumonia who were not intubated -10. ThisOur results demonstrate for the first time that CENPV is applicable and effective, even in severely critically ill patients in a modern intensive care setting. The present study confirms recent experimental data and encourages consideration of further studies of the physiological effects and clinical effectiveness of CENPV in patients with ARDS.• CENPV differs substantially from CPPV and improves oxygenation under more physiologic conditions in patients with ARDS.2: fraction of inspired oxygen; FRC: functional residual capacity; ECG: electrocardiogram; IPPV: intermittent positive-pressure ventilation; paO2: arterial oxygen tension; paCO2: carbon dioxide tension; PEEP: positive end-expiratory pressure; PiCCO: Pulse Contour Cardiac Output; SAPS: Simplified Acute Physiology Score; TRP: trans-respiratory system pressure.ARDS: acute respiratory distress syndrome; CENPV: continuous external negative-pressure ventilation; CPPV: continuous positive-pressure ventilation; FiOThe authors declare that they have no competing interests.KR, UM, MC, WK and AC participated in the design of the study; KR, UM and MC participated in the collection and the assembly of the data; KR and TD performed the statistical analysis; BS, JA, CW and AC gave technical or logistical support; KR, UM, TD, JA, CW and AC helped to draft the manuscript and, all authors read and approved the final manuscript.


Recent studies have highlighted the deleterious role of cardiovascular risk factors, including hypertension, on the incidence of dementia. Although midlife hypertension is associated with later development of dementia, the role of late-life hypertension remains unclear. We explored the association of hypertension and its treatment with incident dementia in 13978 older (median = 74 years) adults followed from 1981 to 2010 (median = 13 years) and calculated risk estimates using Cox regression analysis in two age groups (<75 and 75+ years) in men and women separately. Dementia status was determined from in-person evaluations, followup questionnaires, hospital data, and death certificates. In the older women, current users of blood pressure medication at baseline had a 26% increased risk of dementia (95% CI 1.06–1.51). In the younger men, those with untreated hypertension and those with past use of blood pressure medication use had about a 30% nonsignificant increased risk of dementia. High blood pressure and its treatment appear to have different effects in men and women and in the old and older. As a result of an aging population, the prevalence of dementia, which in 2005 affected 24.3 million people worldwide, is expected to afflict more than 81 million by 2040 [The focus of the present study was to examine the possible role of hypertension and its treatment as predictors of dementia in elderly men and women. We report here the results in a large cohort (nearly 14000) of elderly (median age 74 years) men and women followed for up to 29 years (median 13 years).The Leisure World Cohort Study was established in the early 1980s when 13978 residents of a California retirement community (Leisure World Laguna Hills) completed a postal health survey. Residents were recruited in four waves: those who owned homes in Leisure World on June 1, 1981; new residents who had moved into the community and were living there on June 1, 1982; on June 1, 1983; on October 1, 1985. The baseline survey asked demographic information, brief medical history, medication use, and personal habits including cigarette smoking, exercise, alcohol consumption, and beverage intake. The subjects were asked if a doctor ever told them they had high blood pressure and if they had ever taken or were currently taking specific medications including “Reserpine ” and “other blood pressure medication, water pills.” The population and the cohort are mostly Caucasian, well educated, upper-middle class, and elderly. Followup of the cohort is maintained by periodic resurvey , review of local hospital discharge data (1981–2001), and determination of vital status by search of governmental and commercial death indexes and ascertainment of death certificates. The 1983 followup questionnaire asked new diagnoses of high blood pressure since the baseline survey. The 1998 questionnaire again asked if the subject had ever been told by a doctor that they had high blood pressure and the frequency of use of high blood pressure medication.Dementia cases were identified from in-person evaluations as part of a dementia study , hospitat-tests for testing differences in means of continuous variables. Age-adjusted hazard ratios (HRs) of dementia associated with hypertension were estimated using Cox proportional hazard regression analysis with age at study entry being the age when the baseline survey was completed and the event of interest being age at dementia. Separate analyses were done for two age groups: <75 years and 75+ years of age at baseline, with additional adjustment for age (continuous). Because women differ from men on many variables, women live longer on average than men, and for comparison with other studies limited to one sex, we performed separate analyses for men and women. Statistical analyses were performed using SAS version 9.2 . No adjustment in the P values was made for multiple comparisons.Chi-square tests were used for comparison of categorical variables and Previous reports present details of the methods and the reliability of recall of the self-reported information –9. The In = 690), hospitalization record (n = 199), followup questionnaire (n = 264), and death certification (n = 1768); these categories are not mutually exclusive.At study entry, the participants' mean and median age was 74 years (standard  deviation = 7). By December 31, 2010, 2429 participants had been diagnosed with dementia and 13134 had died. Age at dementia ranged from 66 to 106 years . Dementia cases were identified by The 90+ Study .Characteristics of the study participants are shown in Tables Followup questionnaires identified few additional individuals with hypertension. Of the 9731 who returned the 1983 followup survey, 188 (2%) reported a new diagnosis of high blood pressure. In 1998, 219 (11%) of 1963 who returned the questionnaire reported having high blood pressure in 1998 but not at baseline. In recent years the strict division between Alzheimer's disease and vascular dementia has faded with advancing research in neuropathology, neuroradiology, and epidemiology. Most dementia patients, irrespective of their clinical diagnosis, have mixed pathology (Alzheimer's changes and cerebrovascular lesions) at autopsy , 11. HigAssociations in longitudinal studies of late-life hypertension and dementia have been less consistent. Some found blood pressure levels were higher in individuals who developed dementia , AlzheimOur study extends the available literature on the role of hypertension and dementia in the very elderly but has several limitations. Information on hypertension and blood pressure medication was self-reported; we performed no blood pressure determinations. However, previous studies in our population and others support the reliability of self-reported health practices, drug usage, and medical history of major chronic disease , 9. AlthClinical trials of antihypertensive medication in older subjects have also yielded inconsistent results (reviewed by –4). RandOthers have detailed the possible mechanisms by which hypertension may increase risk of dementia . HypAlthough not establishing a cause and effect relationship between incident dementia and high blood pressure and its treatment, this large elderly cohort suggests an increased risk of dementia in the younger (<75 years) men with untreated hypertension and with past use of hypertensive medication. This agrees with the findings of earlier studies showing an increased risk of dementia with higher measured blood pressure levels. In women the risk among current (at baseline) users of blood pressure medication, which was the strongest in the older age group (75+ years), highlights the need for careful monitoring of blood pressure in the elderly. Decline in blood pressure is common at ages above 75 years, and the Kungsholmen Project found low blood pressure to be associated with dementia risk  . PeriodsAlthough treating hypertension has a clear effect on stroke, cardiovascular disease, and mortality, the effect of hypertension and its treatment on dementia is more complex. While previous studies have found midlife hypertension to be related to dementia, results for late-life hypertension and its treatment are inconsistent. Our study in older adults suggests that the effect varies not only with age (with a difference between those less than 75 years old and those 75+ years old) but also with sex. Future studies examining the role of hypertension in older adults should perform sex-specific analyses.


The effect of ethnicity on the prevalence and management of hypertension and associated chronic kidney (CKD) disease in the UK is unknown.We performed a cross sectional study of 49,203 adults with hypertension to establish the prevalence and management of hypertension and associated CKD by ethnicity. Routinely collected data from general practice hypertension registers in 148 practices in London between 1/1/07 and 31/3/08 were analysed.The crude prevalence of hypertension was 9.5%, and by ethnicity was 8.2% for White, 11.3% for South Asian and 11.1% for Black groups. The prevalence of CKD stages 3-5 among those with hypertension was 22%. Stage 3 CKD was less prevalent in South Asian groups  compared to Whites (reference population) with Black groups having similar rates to Whites. The prevalence of severe CKD (stages 4-5) was higher in the South Asian group  compared to Whites, but did not differ between Black and White groups. In the whole hypertension cohort, achievement of target blood pressure (< 140/90 mmHg) was better in South Asian  and worse in Black groups  compared to White patients. Hypertensive medication was prescribed unequally among ethnic groups for any degree of blood pressure control.Significant variations exist in the prevalence of hypertension and associated CKD and its management between the major ethnic groups. Among those with CKD less than 50% were treated to a target BP of ≤ 130/80 mmHg. Rates of ACE-I/ARB prescribing for those with CKD were less than optimal, with the lowest rates (58.5%) among Black groups. Hypertension is a major risk factor for cardiovascular disease (CVD) and for progression of chronic kidney disease (CKD) towards end stage kidney disease (ESKD) ,2. The pThe introduction of performance related pay for general practice, the quality and outcomes framework (QOF) in 2004  has contIn the UK, the effect of ethnicity on blood pressure control and associated CKD in a hypertensive population is not known. Previous studies of primary care hypertension management in the UK have excluded or had very low numbers of patients with CKD ,11 or haThis study uses data from a large, multi-ethnic population with hypertension and high recorded levels of self reported ethnicity. We have excluded patients with a diagnosis of diabetes mellitus, as this group has previously been the subject of a related study . Our aimThe study was set in the three geographically contiguous east London Primary Care Trusts (PCTs) of Newham, Tower Hamlets and City & Hackney, with a combined GP registered population of 829,710 in mid 2008. In the 2001 UK census 51.3% of the population in these three PCTs was recorded as of non-White ethnic origin  (see AddPractice computer databases were interrogated using Morbidity Information Query and Export Syntax (MIQUEST) software which has been validated as an accurate and appropriate method for data extraction of patients with CKD in general practice . All adu2), stage 3b CKD (eGFR 30-44 ml/min/1.73 m2), stage 4 CKD (eGFR 15-29 ml/min/1.73 m2) and stage 5 CKD (eGFR < 15 ml/min/1.73 m2). All eGFR measures have been corrected for Black ethnicity (multiply eGFR by 1.21). Different methods for measuring the serum creatinine  are used in the study area, however, as we report elsewhere [Isolated systolic hypertension (ISH) is defined as stage 1 ≥ 140 and ≤ 90 mmHg and stage 2 as ≥ 160/≤ 90 mmHg. Renal function is expressed as stage of chronic kidney disease defined by current UK guidelines  based on2 p < 0.001). A blood pressure reading was recorded for 92%, total cholesterol for 73%, and smoking status for 80.7%. Due to low levels of recorded proteinuria (5%) and body mass index (BMI) (15%) during the study we excluded these variables from the analysis.During the study period, of the 75,103 adults coded with hypertension, 92.4% had ethnicity recorded. We excluded the 28% with a diagnosis of diabetes  mid-year 2006 age banded population estimates by ethnic group [All statistical analyses used Stata version 10 . DiffereIn this cohort 45.3% were males, the average age for males was 59.7, and for females was 62.4 years. The crude prevalence of hypertension among adults in east London was 9.5% and by ethnic group was 8.2% for White, 11.3% for South Asian and 11.1% for Black groups. East London has a very young population, the crude population prevalence rises to 14.8% when age standardized to the European standard population. The prevalence of hypertension by age and ethnicity was examined (removing those with diagnosed diabetes mellitus), using practice data as numerator, and the midyear population estimates from the Greater London Authority as denominator. Figure 2) among the hypertensive population was 22%. The prevalence of CKD risk factors by ethnicity and gender was examined. The White group had a higher mean age and smoking rates than other groups (p < 0.001). Black groups had the lowest rates of recorded ischaemic heart disease (p < 0.001). The distribution of risk factors for CKD by ethnicity, and the prevalence of CKD among all those with an eGFR value are shown in tables The crude prevalence of CKD (eGFR < 60 ml/min/1.73 m2) by ethnicity among all hypertensives, adjusted for age and sex and clustered by practice. Compared to the White population the South Asian population had a significantly lower overall prevalence of CKD stage 3  and this difference remains with further adjustment for systolic blood pressure, total cholesterol, smoking status and diagnosis of ischaemic heart disease , by conducting a further analysis restricted to cases with an eGFR < 60 ml/min/1.73 m2 to determine if ethnicity is marker for disease severity in established cases of CKD. This showed that South Asian groups had a significantly greater risk of severe CKD  compared to the White population   regardless of CKD status, adjusted by age and sex and clustered by practice. Achievement of target blood pressure control was better in South Asian  and worse in Black groups  compared to the White population.Table The mean number of prescribed medications for hypertension for those without CKD was 1.83, and for those with CKD was 2.17. Among those with CKD less than 50% were treated to a target BP of ≤ 130/80 mmHg. A higher proportion of South Asian patients (42.7%) achieved this target than other ethnic groups. Among this hypertensive population only 3.2% had stage 2 ISH (SBP > 160 and DBP < 90 mmHg).Table Table This study is the first of its kind to examine the association of ethnicity, hypertension and CKD in a UK population. Using routine clinical data from a socially deprived multiethnic population with uniquely high levels of self reported ethnicity, we examine variation in prevalence and management of hypertension and associated CKD. The exclusion of patients with diabetes mellitus, which has much higher rates among the South Asian population, allows us to evaluate the effect of hypertension on CKD in isolation (see Additional File Blood pressure control in the UK has shown steady improvement over time . Pay for2, a recommended blood pressure of < 130/80 mmHg [In patients with an eGFR < 60 ml/min/1.73 m/80 mmHg . The ren/80 mmHg -30 and c/80 mmHg . However/80 mmHg .2 compared to those with a eGFR > 60 ml/min/1.73 m2 . Previous studies have demonstrated improved blood pressure control in the presence of two or more comorbidities compared to hypertension alone [We found that achievement of target blood pressure to < 140/90 mmHg was superior in patients with an eGFR < 60 ml/min/1.73 mon alone . This suOur finding that South Asian patients have higher rates of more severe CKD, in spite of better blood pressure control than other groups requires further consideration, particularly given that the lower mean blood pressure in this group would be expected to result in a lower prevalence of severe renal disease. There are several potential explanations for this finding, one being that hypertension affects South Asians at a younger age than other ethnicities, and the longer duration of disease may lead to more severe complications such as advanced CKD.Recently the MYH 9 gene has been identified as a marker for more rapid progression to ESKD in Black patients ,32 due tGeographic variations in cardiovascular mortality at a similar blood pressure level are well documented . The uniThe strengths of this study include the size of the study population which includes over 50% of patients from ethnic minorities. Our population is likely to be representative of other multiethnic, low income, urban areas in the UK, hence our findings should be generalisable, and of interest to clinicians and health service commissioners. The exclusion of patients with diabetes highlights the higher than expected prevalence of CKD in this patient group with hypertension alone.The limitations of this study are linked to the pragmatic nature of this primary care database. The entry criteria for a diagnosis of hypertension depends on decisions made in a routine clinical setting, and we use only the latest BP data point for each case for analysis. Similarly the accuracy of comorbid diagnoses, and the completeness of clinical measurements will be subject to routine clinical variation. eGFR values were available for 57% of cases and there was significant variation by ethnic group. We recognise that this may introduce bias. Within the UK health system there are no structural barriers to healthcare, hence differential access to care is unlikely. We are aware that combining sub groups within the South Asian and Black populations may mask important differences in behavior and health beliefs between population groups which in turn may contribute to health outcomes.We did not have access to individual drug dosing regimes, and so cannot comment on the intensity of hypertension treatment  or on whQuestions also remain about the validation and use of adjustments of the MDRD generated eGFR by ethnicity. Despite these concerns, it is currently in universal use to classify CKD and monitor progression of renal disease. Until more refined equations enter the mainstream, it remains the best tool available to us.The data from this large cross sectional study identifies differences by ethnicity in the prevalence of hypertension and associated CKD, and in the achievement of blood pressure control and drug prescribing. These disparities in hypertension management have persisted in spite of steady improvements in primary care hypertension management in the UK.Potential strategies to reduce the observed disparities include improved awareness by clinicians, and the public, of the excess risk associated with certain ethnic groups, and a greater use of ACE-I/ARB and diuretics to improve blood pressure control and reduce progression of kidney disease. The inclusion of annual measures of eGFR, BMI and proteinuria, potentially modifiable risk factors for cardiovascular and progressive renal disease ,35,36, iAdditional studies need to identify whether target blood pressure for the prevention of CKD progression should to be tailored by reference to ethnicity. Whereas this strategy may have merit at a biological level, any benefit must be measured against the risk of increasing the complexity of blood pressure guidelines. Improving current practice to reach national standards should be the focus of attention while prospective studies are conducted to address some of the unanswered questions.ACE-I: angiotensin converting enzyme inhibito; ARB: angiotensin receptor blocker; BMI: body mass index; BP: blood pressure; CCB: calcium channel blocker; CKD: chronic kidney disease; CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; ESKD: end stage kidney disease; GLA: greater London authority; ISH: isolated systolic hypertension; JNC: Joint National Committee; MIQUEST: Morbidity Information Query and Export Syntax; NKF KDOQI: National Kidney Foundation Kidney Disease Outcomes Quality Initiative; ONS: office of national statistics; OR: odds ratio; PCT: Primary care trust; QOF: quality and outcomes framework.All authors declare that there is no conflict of interest, financial or otherwise, with respect to this study and the above manuscript.MMY, SH and AC and GD designed the study, EB undertook the analysis. GD and SH led on writing the manuscript with all authors contributing to and reviewing the submitted version. All authors are guarantors for the study. GD and SH contributed equally. All authors read and reviewed the final manuscriptThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/12/41/prepubThe relationship of ethnicity to the prevalence and management of hypertension and associated chronic kidney diseaseSupplementary demographic information for manuscript - . Table 1 contains the demographic comparison between East London and the UK using 2001 census data. Table 2 contains data on the prevalence of hypertension by age and aggregated ethnic groups using low east London GLA population estimates for 2006 as denominator. Tables 3 and 4 show the effect of ethnicity on CKD and hypertension including patients with diabetes mellitus.Click here for file