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Abstract Subjects with amputation of the lower limbs are at increased risk of cardiovascular mortality and morbidity. We hypothesize that amputation-induced alterations in the arterial tree negatively impact arterial biomechanics, blood pressure and flow behavior. These changes may interact with other biological factors, potentially increasing cardiovascular risk. To evaluate this hypothesis regarding the purely mechanical impact of amputation on the arterial tree, we used a simulation computer model including a detailed one-dimensional (1D) arterial network model (143 arterial segments) coupled with a zero-dimensional (0D) model of the left ventricle. Our simulations included five settings of the arterial network: (1) 4-limbs control, (2) unilateral amputee (right lower limb), (3) bilateral amputee (both lower limbs), (4) trilateral amputee (lower-limbs and right upper-limb), and (5) quadrilateral amputee (lower and upper limbs). Analysis of regional stiffness, as calculated by pulse wave velocity (PWV) for large-, medium- and small-sized arteries, showed that, while aortic stiffness did not change with increasing degree of amputation, stiffness of medium and smaller-sized arteries increased with greater amputation severity. Despite a staged decrease in cardiac output, the systolic and diastolic blood pressure values increased, resulting in an increase in both central and peripheral pulse pressures but with an attenuation of pulse pressure amplification. The most significant increase in peak systolic pressure and decrease in peak systolic blood flow was observed at the site of the abdominal aorta. Wave separation analysis indicated no changes in the shape of the forward and backward wave components. However, the results from wave intensity analysis showed that with extended amputation, there was an increase in peak forward wave intensity and a rise in the inverse peak of the backward wave intensity, suggesting potential alterations in cardiac hemodynamic load. In conclusion, this simulation study showed that biomechanical and hemodynamic changes in the arterial network geometry could interact with additional risk factors to increase the cardiovascular risk in patients with amputations.

BackgroundArterial stiffness and medial vascular calcification, leading to isolated systolic blood pressure (BP), are major cardiovascular risk factors in patients with chronic kidney disease (CKD) and mineral bone disorders (MBD). The impact of BP on MBD-induced medial vascular calcification in CKD remains uncertain. We investigated whether BP reduction improves arterial stiffness and medial vascular calcification in a rat model of CKD-MBD.MethodsCKD was induced in Wistar rats by subtotal nephrectomy. Then, MBD was generated by a Ca/P-rich diet with calcitriol supplementation to induce medial vascular calcification. Two antihypertensive treatments were evaluated: (1) the angiotensin AT1 receptor antagonist losartan, and (2) the combination of the thiazide diuretic hydrochlorothiazide and the direct vasodilator hydralazine (HCTZ/HY). After 5 weeks, mean BP (MBP), pulse pressure (PP), and pulse wave velocity (PWV) were determined. Vascular calcification was assessed in the thoracic aorta.ResultsWhile MBP was similar in CKD-MBD and control CKD rats, PP and PWV were increased in CKD-MBD rats. The heightened arterial stiffness in CKD-MBD rats was associated with diffused medial calcification along the thoracic aorta. Although both losartan and HCTZ/HY reduced MBP in CKD-MBD rats, losartan did not affect PP and PWV nor medial vascular calcification, whereas HCTZ/HY, unexpectedly, further increased arterial stiffness and medial vascular calcification.ConclusionIn the rat model of CKD-MBD, antihypertensive treatment with losartan did not affect arterial stiffness or medial vascular calcification. However, HCTZ/HY treatment aggravated arterial stiffness and vascular calcification despite a similar reduction of MBP, suggesting a blood pressure-independent mechanism for vascular calcification.

Immune checkpoint inhibitors are known to have a wide range of autoimmune toxicities, such as acute interstitial nephritis. Immunotherapy induced glomerulonephritis has been described, but anti-glomerular basement membrane disease (anti-GBM) is rarely reported. We present a case report of a 60-year-old woman with squamous cell carcinoma of the cervix who was treated with pembrolizumab, an anti-programmed cell death protein 1, and who developed severe acute kidney injury 4 months after therapy initiation. The immune workup showed a positive serum anti-GBM antibody (24 U/mL). The kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G2 glomerular basement membrane staining, compatible with anti-GBM glomerulonephritis. The patient was treated with plasmapheresis, IV steroids, and cyclophosphamide, but she developed kidney failure, necessitating dialysis. Few case reports, such as the present case, provide a possible link between anti-GBM glomerulonephritis and immune checkpoint inhibitors, warranting early clinical suspicion and investigation in patients who are treated with these agents and subsequently develop acute kidney injury.

Background: Emerging data favor central blood pressure (BP) over brachial cuff BP to predict cardiovascular and kidney events, as central BP more closely relates to the true aortic BP. Considering that patients with advanced chronic kidney disease (CKD) are at high cardiovascular risk and can have unreliable brachial cuff BP measurements (due to high arterial stiffness), this population could benefit the most from hypertension management using central BP measurements. Objective: To assess the feasibility and efficacy of targeting central BP as opposed to brachial BP in patients with CKD G4-5. Design: Pragmatic multicentre double-blinded randomized controlled pilot trial. Setting: Seven large academic advanced kidney care clinics across Canada. Patients: A total of 116 adults with CKD G4-5 (estimated glomerular filtration rate [eGFR] < 30 mL/min) and brachial cuff systolic BP between 120 and 160 mm Hg. The key exclusion criteria are 1) ≥ 5 BP drugs, 2) recent acute kidney injury, myocardial infarction, stroke, heart failure or injurious fall, 3) previous kidney replacement therapy. Methods: Double-blind randomization to a central or a brachial cuff systolic BP target (both < 130 mm Hg) as measured by a validated central BP device. The study duration is 12 months with follow-up visits every 2 to 4 months, based on local practice. All other aspects of CKD management are at the discretion of the attending nephrologist. Outcomes: Primary Feasibility : Feasibility of a large-scale trial based on predefined components. Primary Efficacy : Carotid-femoral pulse wave velocity at 12 months. Others : Efficacy (eGFR decline, albuminuria, BP drugs, and quality of life); Events (major adverse cardiovascular events, CKD progression, hospitalization, mortality); Safety (low BP events and acute kidney injury). Limitations: May be challenging to distinguish whether central BP is truly different from brachial BP to the point of significantly influencing treatment decisions. Therapeutic inertia may be a barrier to successfully completing a randomized trial in a population of CKD G4-5. These 2 aspects will be evaluated in the feasibility assessment of the trial. Conclusion: This is the first trial to evaluate the feasibility and efficacy of using central BP to manage hypertension in advanced CKD, paving the way to a future large-scale trial. Trial registration: clinicaltrials.gov (NCT05163158)

Abstract End‐stage kidney disease (ESKD) is associated with increased arterial stiffness and cognitive impairment. Cognitive decline is accelerated in ESKD patients on hemodialysis and may result from repeatedly inappropriate cerebral blood flow (CBF). The aim of this study was to examine the acute effect of hemodialysis on pulsatile components of CBF and their relation to acute changes in arterial stiffness. In eight participants (age: 63 ± 18 years, men: 5), CBF was estimated using middle cerebral artery blood velocity (MCAv) assessed with transcranial Doppler ultrasound before, during, and after a single hemodialysis session. Brachial and central blood pressure, along with estimated aortic stiffness (eAoPWV) were measured using an oscillometric device. Arterial stiffness from heart to MCA was measured as the pulse arrival time (PAT) between electrocardiogram (ECG) and transcranial Doppler ultrasound waveforms (cerebral PAT). During hemodialysis, there was a significant reduction in mean MCAv (−3.2 cm/s, p

BackgroundNon-invasive estimation of central blood pressure (BP) may have better prognostic value than brachial BP. The accuracy of central BP is limited in certain populations, such as in females and the elderly. This study aims to examine whether statistical modeling of central BP for clinical and hemodynamic parameters results in enhanced accuracy.MethodsThis study is a cross-sectional analysis of 500 patients who underwent cardiac catheterization. Non-invasive brachial cuff and central BP were measured simultaneously to invasive aortic systolic BP (AoSBP). Central BP was calibrated for brachial systolic (SBP) and diastolic BP (Type I calibration; C1SBP) or brachial mean and diastolic BP (Type II calibration; C2SBP). Differences between central SBP and the corresponding AoSBP were assessed with linear regression models using clinical and hemodynamic parameters. These parameters were then added to C1SBP and C2SBP in adjusted models to predict AoSBP. Accuracy and precision were computed in the overall population and per age or sex strata.ResultsC1SBP underestimated AoSBP by 11.2 mmHg (±13.5) and C2SBP overestimated it by 6.2 mmHg (±14.8). Estimated SBP amplification and heart rate were the greatest predictors of C1- and C2-AoSBP accuracies, respectively. Statistical modeling improved both accuracy (0.0 mmHg) and precision (±11.4) but more importantly, eliminated the differences of accuracy seen in different sex and age groups.ConclusionStatistical modeling greatly enhances the accuracy of central BP measurements and abolishes sex- and age-based differences. Such factors could easily be implemented in central BP devices to improve their accuracy.

Abstract Background Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. It is especially important in nephrology due to the complexity of chronic kidney disease (CKD). The present study sought to define health literacy levels in patients followed in predialysis clinic, in-center dialysis (ICHD), peritoneal dialysis (PD) and home hemodialysis (HHD). Methods This transversal monocentric observational study analysed 363 patients between October 2016 and April 2017. The Brief Health Literacy Screen (BHLS) and the Health Literacy Questionnaire (HLQ) were used to measure health literacy. Multivariate linear regressions were used to compare the mean scores on the BHLS and HLQ, across the four groups. Results Patients on PD had a significantly higher BHLS’score than patients on ICHD (p = 0.04). HLQ’s scores differed across the groups: patients on HHD (p = 0.01) and PD (p = 0.002) were more likely to feel understood by their healthcare providers. Compared to ICHD, patients on HHD were more likely to have sufficient information to manage their health (p = 0.02), and patients in the predialysis clinic were more likely to report high abilities for health information appraisal (p

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population‐based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10‐year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c‐index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow‐up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population‐based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Arterial stiffness (AS), as assessed via pulse wave velocity (PWV), is a major biomarker for cardiovascular risk assessment in patients with chronic kidney disease (CKD). However, the mechanisms responsible for the changes in PWV in the presence of kidney disease are not yet fully elucidated. In the present study, we aimed to investigate the direct effects attributable to biomechanical changes in the arterial tree caused by staged renal removal, independent of any biochemical or compensatory effects. Particularly, we simulated arterial pressure and flow using a previously validated one-dimensional (1-D) model of the cardiovascular system with different kidney configurations: two kidneys (2KDN), one single kidney (1KDN), no kidneys (0KDN), and a transplanted kidney (TX) attached to the external iliac artery. We evaluated the respective variations in blood pressure (BP), as well as AS of large-, medium-, and small-sized arteries via carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and radial-digital PWV (rdPWV), respectively. Our results showed that BP was increased in 1KDN and 0KDN, and that systolic BP values were restored in the TX configuration. Furthermore, a rise was reported in all PWVs for all tested configurations. The relative difference in stiffness from 2KDN to 0KDN was higher in the case of crPWV (15%) in comparison with the increase observed for cfPWV (11%). In TX, we observed a restoration of the PWVs to values close to 1KDN. Globally, it was demonstrated that alterations of the outflow boundaries to the renal arteries with staged kidney removal led to changes in BP and central and peripheral PWV in line with previously reported clinical data. Our findings suggest that the PWV variations observed in clinical practice with different stages of kidney disease may be partially attributed to biomechanical alterations of the arterial tree and their effect on BP.

Background: Physiologically, the aorta is less stiff than peripheral conductive arteries, creating an arterial stiffness gradient, protecting microcirculation from high pulsatile pressure. However, the pharmacological manipulation of arterial stiffness gradient has not been thoroughly investigated. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio).Methods: In 93 subjects (age: 61 years, men: 67%, chronic kidney disease [CKD]: 41%), aortic, brachial, and femoral stiffnesses were determined by cf-PWV, carotid-radial (cr-PWV), and femoral-dorsalis pedis artery (fp-PWV) PWVs, respectively. The measurements were repeated 5 min after the sublingual administration of NTG (0.4 mg). The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fp-PWV, respectively. The central pulse wave profile was determined by radial artery tonometry through the generalized transfer function.Results: At baseline, cf-PWV, cr-PWV, and fp-PWV were 12.12 ± 3.36, 9.51 ± 1.81, and 9.71 ± 1.89 m/s, respectively. After the administration of NTG, there was a significant reduction in cr-PWV of 0.86 ± 1.27 m/s (p < 0.001) and fp-PWV of 1.12 ± 1.74 m/s (p < 0.001), without any significant changes in cf-PWV (p = 0.928), leading to a significant increase in the AB-PWV ratio (1.30 ± 0.39 vs. 1.42 ± 0.46; p = 0.001) and AF-PWV ratio (1.38 ± 0.47 vs. 1.56 ± 0.53; p = 0.001). There was a significant correlation between changes in the AF-PWV ratio and changes in the timing of wave reflection (r = 0.289; p = 0.042) and the amplitude of the heart rate-adjusted augmented pressure (r = − 0.467; p < 0.001).Conclusion: This study shows that acute administration of NTG reduces PWV of muscular arteries (brachial and femoral) without modifying aortic PWV. This results in an unfavorable profile of AB-PWV and AF-PWV ratios, which could lead to higher pulse pressure transmission into the microcirculation.

Introduction Patients with end-stage renal disease are at higher risk of cardiovascular morbidity and mortality, a risk mediated in part by increased aortic stiffness. Arterial stiffness is assessed at different anatomical locations (central elastic or peripheral muscular arteries) using a variety of mechanical biomarkers. However, little is known on the robustness of each of these mechanical biomarkers following a haemodynamic stress caused by a single haemodialysis (HD) session.Methods and analysis A systematic review has been designed and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A targeted search strategy applicable in key databases (PubMed, Embase, the Cochrane Library, Web of Science and grey literature) is constructed to search articles and reviews from inception to 16 October 2020. Only articles of studies conducted with adults under chronic HD for kidney failure, with repeated measures of arterial stiffness metrics (pulse wave velocity, Augmentation Index, arterial distensibility or stiffness) following a before-and-after design surrounding a HD session will be selected. The screening process, data extraction and assessment of risk bias will be done by two independent pairs of reviewers. Meta-analysis will enable adjustments for potential confounders and subgroup analyses will be performed to discriminate changes in arterial stiffness metrics from elastic, muscular or global arterial territories.Ethics and dissemination This study does not require ethical approval. Findings will be submitted for publication to relevant peer-reviewed journals and will be presented at profession-specific conferences.PROSPERO registration number CRD42020213946.

Introduction: Increased carotid-femoral pulse wave velocity (cf-PWV) in end-stage renal disease (ESRD) indicates enhanced aortic stiffness and mortality risk. We conducted a systematic review and meta-analysis of nonpharmacologic interventions in adults with ESRD to determine their effects on cf-PWV, systolic blood pressure (SBP), and intervention-associated adverse events. Methods: MEDLINE, EMBASE, and EBM databases were searched. Study screening, selection, data collection, and methodological quality assessments were performed by 2 independent reviewers. Pooled-effect estimates from mean differences and 95% confidence intervals (CIs) were calculated using random effect models. Results: A total of 2166 subjects with ESRD from 33 studies (17 randomized; 16 nonrandomized) were included. Four intervention-comparator pairs were meta-analyzed. Quality of evidence ranged from very low to moderate. Kidney transplantation decreased cf-PWV (−0.70 m/s; CI: –1.3 to −0.11; P = 0.02) and SBP (−8.3 mm Hg; CI: −13.2 to −3.3; P < 0.001) over pretransplantation. In randomized trials, control of fluid overload by bio-impedance reduced cf-PWV (−1.90 m/s; CI: −3.3 to −0.5); P = 0.02) and SBP (−4.3 mm Hg; CI: −7.7 to −0.93); P = 0.01) compared with clinical assessment alone. Cross-sectional studies also demonstrated significantly lower cf-PWV and SBP in normovolemia compared with hypervolemia (P ≤ 0.01). Low calcium dialysate decreased cf-PWV (−1.70 m/s; CI: −2.4 to −1.0; P < 0.00001) without affecting SBP (−1.6 mm Hg; CI: −8.9 to 5.8; P = 0.61). Intradialytic exercise compared with no exercise reduced cf-PWV (−1.13 m/s; CI: −2.2 to −0.03; P = 0.04), but not SBP (+0.5 mm Hg; CI: −9.5 to 10.4); P = 0.93). Conclusions: Several nonpharmacologic interventions effectively decrease aortic stiffness in ESRD. The impact of these interventions on cardiovascular outcomes and mortality risk reduction in ESRD requires further study. Keywords: aortic stiffness, end-stage renal disease, pulse wave velocity, renal dialysis, renal transplantation, vascular stiffness

Introduction Kidney donors have been reported to have accelerated progression of aortic stiffness and decreased glomerular filtration compared with healthy non-donors. This is a concern because increased aortic stiffness is an independent predictor of overall cardiovascular disease and all-cause mortality in the general population. To confirm if arterial stiffness increases after donation, we will systematically review all studies that evaluated indices of arterial stiffness in healthy individuals who underwent unilateral nephrectomy for kidney donation compared with age-matched healthy non-nephrectomised controls.Methods/analysis We will comprehensively search for studies published between 1 January 1960 and 15 March 2021 in MEDLINE, EMBASE, Cochrane Central, OVID and EBM reviews. All prospective (cohort, case–control, case series and before-and-after studies) and retrospective non-randomised studies reporting indices of arterial stiffness in nephrectomised and non-nephrectomised healthy participants will be included. Primary outcome will be the difference in the functional metrics of arterial stiffness between donors and non-donors. Secondary outcomes will be the differences in systolic/diastolic blood pressures, serum creatinine, glomerular filtration, carotid artery intima–media thickness and vascular calcification. Study screening, selection and data extraction will be performed by two independent reviewers. Risk of bias will be independently assessed with the ROBINS-I tool and confidence in evidence by the Grading of Recommendations Assessment, Development and Evaluation recommendations. Qualitative and quantitative data syntheses as well as clinical and statistical heterogeneity (Forest plots, I2 and Cochran’s Q statistics) will be evaluated. If clinical and statistical heterogeneity are acceptable, inverse variance-weighted effects will be analysed by random effect models.Ethics and dissemination No ethical approval is necessary. Our results will be disseminated through peer-review publication and presentations to guide stakeholders on the evaluation and follow-up care of kidney donors.PROSPERO registration number CRD42020185551.

Purpose/Background/Objective: We have previously shown that restoration of kidney function through kidney transplantation (KTx) is associated with improved aortic stiffness. In this study, we aim to examine whether this change in aortic stiffness translates into improvement of radial artery systolic-diastolic pulse transit time. Methods: Before and three months after KTx, we obtained radial pressure waveforms using applanation tonometry, in a group of 61 patients with restored renal function (eGFR > 45 ml/min/1,73 m2). Radial waveforms were recorded over a 10 seconds period and ensemble-averaged (using in house-MATLAB program) to obtain a single waveform and then modelled using two Gaussian functions, was then determined as the transit time between the first systolic peak T1 and the early diastolic peak T2. Results: 61 patients (66% male, mean age: 48 ± 14 years, mean eGFR 3 months after Ktx: 66.0 ± 17.1) were assessed. After KTx, there was a significant reduction in central systolic (125,266 ± 21,848 to 108,994 ± 14,407, p < 0.001) and diastolic BP (84,718 11,679 to 74,092 9,774, p < 0.001), carotid-femoral PWV (11,444 2,626 to 10,235 1,890, p < 0.001) and carotid-radial PWV (9,350 1,485 to 8,831 1,291, p = 0,003). While T1 declined (0.184 [0.173–0.198] to 0.180 [0.168–0.194], p = 0.018), there were no significant changes in T2 (0.322 [0.295–0.360] to 0.318 [0.283–0.355], p = 0.169) and in dT1-2 (0.135 [0.119–0.161] to 0.134 [0.117–0.167], p = 0.457). Conclusions: Contrary to our expectation, three months after KTx, we did not observe a significant change in radial systolic-diastolic pulse transit time after kidney transplantation, despite an improvement of BP, aortic and brachial stiffness.

Purpose/Background/Objective: Cognitive decline is highly prevalent amongst end-stage renal disease (ESRD) patients and is accelerated upon initiation of hemodialysis (HD) [1]. ESRD increases aortic stiffness and blood flow pulsatility, which may damage small vessels of target organs like the brain [2]. In this pilot study, we aimed to evaluate the acute effect of HD on cerebral blood flow and its relation to arterial stiffness. Methods: Before, every hour during and after HD (T0–T4), we measured cerebral flow velocity (FV) using transcranial Doppler, blood pressure (BP) via digital finger cuff (Nexfin), cardiac activity using ECG and aortic pulse wave velocity (PWV) with Mobile-O-Graph. FV pulsatility index (PI) and transit times between ECG peak and the foot of both FV and BP waveforms (cerebral dT; digital dT) were computed using in house MATLAB-based analysis. Changes during HD were evaluated with Generalized Estimating Equation models adjusting for multiple comparisons in SPSS 26.0. Results: In eight participants aged 63 ± 17 y. old (4 diabetics, 3 women), peak FV decreased from baseline at T1 and T2 (−11.2 cm/s, p = 0.007; −12.2 cm/s, p < 0.001), PI decreased at T1 (0.81 to 0.77, p = 0.005), whilst minimum FV, mean BP and partial pressure of CO2 remained unchanged. Digital dT increased at T3 (0.19 to 0.22, p < 0.001) and cerebral dT increased throughout HD (T1–T4, p < 0.005), whereas aortic PWV did not change. Conclusions: During hemodialysis, cerebral and digital transit times increased, suggesting decreased stiffness of small peripheral vessels, without significant changes in aortic stiffness. Reduced stiffness of cerebral arteries may partially explain decreased cerebral flow pulsatility.

Purpose/Background/Objective: According to reservoir-wave approach (RWA) arterial pressure is the sum of a reservoir pressure (RP) accounting for dynamic storage and release of blood from arteries, and an excess pressure (XSP) analogous to flow. RP is the minimal left ventricular work required to generate aortic flow, while XSP corresponds to surplus cardiac workload. We have previously shown that kidney transplantation (KTx) improves aortic stiffness [1], however, by adding renal vessels to existing vascular network, KTx may increase cardiac output. Thus, we aimed to examine whether XSP increases after KTx. Methods: Before and 3 months after KTx, carotid pressure waves were recorded using arterial tonometry, calibrated using brachial diastolic and mean blood pressure. Using pressure only approach, reservoir-wave analysis was used to derive RP, XSP and their integrals (RPI, XSPI). RWA parameters were compared with Wilcoxon non-parametric test using SPSS 26.0. Results: 75 patients (69% male, mean age 51 ± 13 years) were assessed. Three months after KTx, both carotid RP (121.2 ± 20.7 vs 103.5 ± 15.7, p < 0.001) and RPI (11192.52 ± 2763.11 vs 9531 ± 1978, p < 0.001) decreased significantly, but carotid XSP and XSPI remained unchanged. Carotid systolic (131.0 ± 23.2 vs 114.1 ± 15.5, p < 0.001) and diastolic (83.4 ± 11.9 vs 72.8 ± 9.93, p < 0.001) blood pressures were also reduced. Conclusion: KTx decreased reservoir pressure, suggesting a decrease in minimal cardiac workload. However, we did not see an increase in excess pressure or its integral, suggesting that addition of a donor renal artery does not significantly alter cardiac outflow and excess workload 3 months after KTx.

Pulse wave velocity (PWV) has been used to evaluate arterial stiffness of large arteries. Here, we examine the feasibility of radial-digital PWV (RD-PWV) as a measure of stiffness of smaller arteries, and its response to changes in local mean arterial pressure. In 29 healthy subjects, we used Complior probes to record arterial pulse wave at radial artery and tip of the index. To determine transit time, we used both second derivative and intersecting tangents of the entire recordings using the device-embedded algorithms, in house Matlab analyses of only reliable waves, and by numerical simulation using arterial tree model. In 15 subjects, we examine the response of RD-PWV to changes in local MAP by vertical displacement of the hand above and below the mid-axillary line. Using second derivative, RD-PWV were 4.68 ± 1.18, 4.69 ± 1.21, 4.32 ± 1.19 m/s respectively for device-embedded, Matlab-based and numerical simulation analyses, respectively. Using intersecting tangents RD-PWV were 4.73 ± 1.20, 4.45 ± 1.08, 4.50 ± 0.84 m/s, respectively for device-embedded, Matlab-based and numerical simulation analyses, respectively. The strongest correlation (r = 0.92) was seen between device-embedded and Matlab-based second derivatives. The intersession coefficients of variation were 7.0 ± 4.9% and 3.2 ± 1.9% (p = 0.04) for device-embedded and Matlab-based second derivative algorithms. We estimated that each increase of 10 mm Hg in local MAP by vertical displacement of the hand resulted in an increase in RD-PWV of 0.28 m/s. This study shows that RD-PWV can be used for the non-invasive assessment of stiffness of small-sized arteries.

Abstract Background/Objectives We previously demonstrated a different regional stiffness response of elastic and muscular arteries after the administration of nitroglycerin, leading to an alteration of aortic-brachial stiffness gradient. Regional stiffness of smaller arteries may respond differently to vasodilation drugs. The objectives of this study were 1- to assess the feasibility of measuring arterial stiffness of the hand, i.e. radial-finger pulse wave velocity (RF-PWV) using piezoelectric sensors, and 2- to measure RF-PWV and its response to nitroglycerin. Methods This exploratory study was conducted in 11 healthy participants (55% were men, mean age was 33.6 ± 10.6 yrs). Piezoelectric sensors (Complior) were placed simultaneously on carotid and radial arteries, and tip of the third finger, to obtain carotid-radial PWV (CR-PWV) and RF-PWV (in triplicates), before and after 4 minutes of 0.4 mg NTG sublingual spray. Results Visually, pressure curves at the finger and detection of the foot of the wave were obtained with a similar quality than radial and carotid pressure curves. The RF-PWV intra-session coefficient of variation was 7.3%. At baseline, mean CR-PWV and RF-PWV were respectively of 9.07 ± 1.24 m/s and 4.80 ± 1.42 m/s. After NTG, CR-PWV decreased (7.75 ± 1.32 m/s) and RF-PWV increased (6.75 ± 2.58 m/s), both significantly (p < 0.01). Conclusion This first attempt to measure small arteries stiffness shows that it is possible to measure hand PWV. Again, we observed opposite changes in regional stiffness of different vascular territories with a vasodilator drug. These results may open up the path to a better understanding of microcirculation consequences of an altered stiffness gradient.

Background: The range of central blood pressure (BP) found in individuals with high-normal brachial BP overlaps the one found in hypertension (HTN) and normotension. As central BP is possibly a better predictor of cardiovascular (CV) disease, the aim of this study was to determine the risk associated with different central/brachial BP patterns. Methods: 13,759 participants from a populational cohort with central BP and prospective data from governmental databases who were not treated for HTN were selected. Major adverse CV events (MACE) comprised myocardial infarction, stroke, heart failure and CV death. Thresholds for brachial and central HTN were identified as 135 and 125 mmHg respectively. Individuals were separated into 4 BP patterns: normal BP; isolated brachial HTN; isolated central HTN; concordant brachial and central HTN. CV risk for each pattern was compared to normal BP with a Cox proportional hazard model adjusted for multiple covariables. Results: 688 MACE occurred over a median follow-up of 70.0 months. Characteristics of individuals in each BP phenotype are presented in Table 1. Only the concordant brachial and central HTN pattern had higher risk of MACE [HR 1.37 95% CI (1.15–1.64), p = 0.001] compared to normal BP. Sensitivity analyses with different definitions of central HTN and after stratification for sex yielded similar results. Demographic characteristics Normal BP (n = 10,611) Isolated brachial HTN (n = 394) Isolated central HTN (n = 496) Concordant HTN (n = 2,258) n 10,611 394 496 2,258 Age 51 (46–57) 53 (47–60) 54 (49–62) 56 (51–63) Male sex 43% 88% 38% 58% Caucasian race 89% 88% 91% 89% Cardiovascular disease 2% 2% 4% 2% Diabetes 4% 8% 3% 6% Active smoking 19% 22% 16% 21% BMI (kg/m2) 26 ± 5 28 ± 3 28 ± 5 28 ± 5 eGFR (ml/min/1.73 m2) 90 ± 14 87 ± 15 89 ± 14 88 ± 14 10-year Framingham risk score (%) 8 ± 7 17 ± 10 11 ± 7 18 ± 12 LDL-c (mmol/L) 3.1 ± 0.8 3.1 ± 0.9 3.3 ± 0.9 3.3 ± 0.9 Heart rate (bpm) 70 ± 10 77 ± 11 65 ± 9 71 ± 11 Aspirin 6% 8% 11% 9% Statin 10% 16% 16% 13% Conclusions: In untreated individuals, both central and brachial BP need to be elevated to increase CV risk. These findings provide support for the utility of routine central BP measurements in clinical practice.

Background: Increased carotid-femoral pulse wave velocity (cf-PWV), a surrogate of increased aortic stiffness, is a risk factor for cardiovascular events and all-cause mortality in end-stage renal disease (ESRD). To minimize the deleterious effects of an increased aortic stiffness in ESRD patients, several interventions have been developed and cf-PWV has been used to monitor responses. Objective: The aim of this study was to determine the effects of pharmacologic interventions that target aortic stiffness on cf-PWV and systolic blood pressure (SBP) in adults with ESRD. Study design: This study implements a systematic review and meta-analysis. Data sources: MEDLINE, EMBASE, Cochrane Central, Health Technology Assessment, and EBM databases were searched. Study eligibility, participants, and interventions: Randomized and non-randomized studies involving adults (>18 years) with ESRD of any duration, receiving or not renal replacement therapy (hemodialysis, peritoneal dialysis) and exposed to a pharmacologic intervention whose effects were assessed by cf-PWV. Methods: Study screening, selection, data extraction, and quality assessments were performed by 2 independent reviewers. Narrative synthesis and quantitative data analysis summarized the review. Results: We included 1027 ESRD participants from 13 randomized and 5 non-randomized studies. Most pharmacologic interventions targeted bone mineral metabolism disorder or hypertension. Treatment with vitamin D analogues or cinacalcet did not decrease cf-PWV or SBP over placebo or matched controls ( P > .05). Calcium-channel blockers (CCB) decreased cf-PWV and SBP compared with placebo or standard care ( P < .05). Renin-angiotensin system inhibitors did not show any advantage over placebo in decreasing cf-PWV ( P > .05). Limitations: Quality of evidence ranged from very low to moderate. Overall evidence was limited by the low number of studies, small sample sizes, and methodological inconsistencies. Conclusions: Pharmacologic interventions targeting aortic stiffness in ESRD have mixed effects on reducing cf-PWV, with some strategies suggesting potential benefit. The quality of evidence, however, is insufficient to draw definitive conclusions on their use to slow progression of aortic stiffness in ESRD. Further well-designed studies are needed to confirm these associations and their impact on cardiovascular outcomes in ESRD. Registered in PROSPERO (CRD42016033463)

Purpose/Background/Objectives: According to reservoir-wave theory, excess pressure (XSP) is analogous to flow and related to excess cardiac workload. In end-stage renal disease (ESRD) patients, we have shown that XSPI is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). Recently AVF has been proposed treatment for treatment of resistant hypertension. However, this benefit may be mitigated through an increase in cardiac output. Therefore, we examine whether XSPI increases after creation of an AVF in ESRD patients. Methods: Hemodynamic assessments were performed within 1 month before and 6 months after creation of AVF in ESRD patients. Carotid pressure waves were recorded using arterial tonometry, calibrated using brachial diastolic and mean arterial pressure. Using pressure only approach, reservoir-wave analysis was used to derive reservoir pressure (RP), XSP and their integrals (RPI, XSPI). Results: 38 patients (63% male, mean age 59 ± 15 years) were assessed 3.9 ± 1.2 months Post-AVF. Carotid RP decreased slightly (115 ± 18 vs 109 ± 24, p = 0.060), due to the reduction of diastolic BP (79 ± 10 vs 73 ± 12 mm Hg, p = 0.003). While, carotid systolic BP (123 ± 20 vs 119 ± 27 mm Hg, p = 0.380) remained unchanged, XSP and XSPI increased (XSP: 14 [12–19] to 17 [12–22] mmHg, p = 0.031; XSPI: 275 [212–335] to 334 [241–349] kPa.s, p = 0.015). Conclusion: While AVF creation reduced diastolic BP, it resulted in higher XSPI, which has been associated with increased mortality. Therefore, the long-term efficacy of AVF in reducing clinical outcomes should be specifically addressed.

Background Reservoir‐wave approach is an alternative model of arterial hemodynamics based on the assumption that measured arterial pressure is composed of volume‐related (reservoir pressure) and wave‐related components (excess pressure). However, the clinical utility of reservoir‐wave approach remains debatable. Methods and Results In a single‐center cohort of 260 dialysis patients, we examined whether carotid and radial reservoir‐wave parameters were associated with all‐cause and cardiovascular mortality. Central pulse pressure and augmentation index at 75 beats per minute were determined by radial arterial tonometry through generalized transfer function. Carotid and radial reservoir‐wave analysis were performed to determine reservoir pressure and excess pressure integral. After a median follow‐up of 32 months, 171 (66%) deaths and 88 (34%) cardiovascular deaths occurred. In Cox regression analysis, carotid excess pressure integral was associated with a hazard ratio of 1.33 (95% CI, 1.14–1.54; P

Background: In chronic kidney disease (CKD), anomalies of mineral bone disorder (MBD) play a central role in vascular calcification and increased aortic stiffness. The impact of antihypertensive drugs on MBD-induced vascular calcification remains uncertain. The aim of this study was to examine whether endothelin A receptor antagonist (ETAA), angiotensin type-1 receptor antagonist (AT1A) and the combination of hydralazine/hydrochlorothiazide (HDZ/HCT) can reduce vascular stiffness in a rat model of CKD-MBD. Method: Using a remnant kidney model of CKD in rats, vascular calcification was induced by creating MBD through high a calcium-phosphate diet and vitamin D supplementation. Three antihypertensive treatments were investigated: atrasentan (ETA blocker), losartan (AT1 blocker) and HDZ/HCT. Blood pressures (BPs) were measured invasively after (6 weeks) and aortic stiffness was determined by the assessment of pulse wave velocity (PWV). Results: PWV and mean BP increased in rats with CKD-MBD as compared to CKD (640 ± 130 vs. 390 ± 34 cm/s and 100 ± 17 vs. 92 ± 21 mmHg; p p < 0.05). Treatment of CKD-MBD rats with ETAA and AT1A, but not HDZ/HCT, reduced PWV (517 ± 94, 596 ± 134 and 761 ± 116 cm/s respectively) despite similar reduction of mean BP by the different treatments (73 ± 16, 75 ± 19 and 70 ± 20 mmHg, respectively). Creatinine clearance and mineral metabolism parameters were relatively similar among groups. Conclusion: MBD-induced aortic stiffness in CKD rats was improved by atrasentan and losartan, but not the combination of HDZ/HCT, indicating blood pressure-independent protective effects of ETAA and AT1A.

Background: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. Objective: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. Design: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. Setting: Ten sites in Canada. Patients: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. Measurements: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. Methods: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. Results: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. Limitations: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin

Background: A new model has been proposed to explain hemodynamic consequences of arterial stiffness, which integrates both wave propagation and aortic reservoir function. The aim of this study was to assess the association between parameters of reservoir-wave analysis and all-cause mortality in a population with accelerated vascular ageing. Methods: Among 311 patients with chronic kidney disease on dialysis, central arterial pressures were derived from applanation tonometry (Sphygmocor) of radial artery. Reservoir wave analysis was applied on radial pressure waveforms (without generalized transfer function) to obtain reservoir pressure (Peak RP), its integral (RP integral), excess pressure parameters (Peak XS, XS integral), and systolic (SC) and diastolic time constant (DC). Results: During a median follow-up of 33 months, 204 (66%) deaths occurred. In Kaplan–Meier survival curves, only increasing tertiles of DC was associated with a significant decrease in survival time (p < 0.001). Amongst all parameters, only DC and XS integral were predictors of all-cause mortality in univariate Cox analysis as shown by hazard ratios for changes in 1-standardized deviation (HR 1-SD, Table 1). However, DC and XS integral were no longer significant when age was introduced in the model (p-value > 0.179). Continuous variables HR 1-SD 95% CI p-value Peak RP(mmHg) 1.121 0.987–1.273 0.079 RP integral(mmHg·sec) 1.050 0.920–1.197 0.470 Peak XS(mmHg) 1.112 0.966–1.281 0.138 XS integral(mmHg·sec) 1.217 1.062–1.395 0.005 SC(×10−2) 1.099 0.970–1.244 0.138 DC(×10−2) 1.186 1.60–1.328 0.003 Conclusions: Amongst all parameters of the reservoir-wave analysis, DC was the most important parameter associated with survival time and mortality. Despite its hypothetically more integrated approach to arterial tree function, none of the derived parameters showed a robust and independent association with mortality in this population. The study shows that despite its simplicity, arterial stiffness gradient remains the best predictor of mortality in this population.

Purpose/ Background/ Objectives: We have shown that aortic stiffness improves as early as 3 months post-kidney transplantation (KTx). Aortic stiffness index β0, a blood pressure independent parameter, has been proposed to be a better indicator of vascular wall property. This study was designed to examine 1) the early versus late changes in aortic stiffness index β0 and 2) to define the characteristics of patients with favourable and unfavourable trajectories of aortic stiffness index β0 after KTx. Methods: In 79 patients who underwent KTx, aortic stiffness was assessed before, 3, 6 and 24 months after KTx. Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV), while aortic stiffness index β0 was obtained using a formulae proposed by Spronck and colleagues. Cytokines profile was measured in plasma by ELISA. Results: There was a reduction of β0 3 months after KTx (29.0±2.0 to 25.8±1.2, P = 0.033). Then, aortic stiffness index β0 gradually increased at 6 (28.0±1.4, P = 0.005 vs 3 months) and 24 months (28.3±1.3, P = 0.003 vs 3 months). Unfavourable progression of β0 was not related to renal function, age, comorbidities or kidney donor characteristics. However, the unfavourable progression of β0 was associated with higher levels of interleukin-6 (P = 0.029). Conclusions: The improvement of aortic stiffness index β0 3 months after KTx suggests that KTx leads to an early improvement of the intrinsic mechanical properties of aorta. However, this improvement is followed by a late progression of β0, which is associated with increased pro-inflammatory cytokine, suggesting that activation of immune system may be involved in arterial wall remodeling in kidney transplant recipients.

Background: Central blood pressure (CBP) is a better predictor of cardiovascular burden than peripheral blood pressure (BP). While studies have suggested a reduction in peripheral BP with statins, it remains uncertain to what extent statins reduce CBP and whether this reduction is mediated through a decrease in LDL-cholesterol (LDL). Methods: Of the 20,004 CARTaGENE participants, 17,011 had CBP and LDL measurements (n = 13,439 without, n = 3,133 with statins). Linear and logistic regression analyses were used to evaluate the association between CBP, LDL and statin use (after stratification for treatment indication for the latter). The impact of LDL on the association between statin use and CBP was determined by mediation analyses. All analyses were adjusted for age, sex, diabetes, cardiovascular disease, smoking, eGFR, BMI, uric acid, heart rate, anti-hypertensive agents and aspirin. Results: Lower levels of LDL were associated with lower systolic and diastolic CBP in participants treated with (b = 0.098 and 0.125; p < 0.001) and without statins (b = 0.089 and 0.105; p < 0.001). Statin use as primary prevention (per ACC/AHA guidelines; n = 8,865) was also associated with lower systolic CBP, diastolic CBP and central pulse pressure (b = −0.091, −0.073 and −0.055; p < 0,001). Mediation analyses demonstrated that 15%, 46% and -22% of these effects were achieved through the concomitant changes in LDL (Table 1). In secondary prevention (n = 995), statins use was not associated with lower CBP, although the small sample size may lack power. Conclusion: In this populational cohort, statin use as primary prevention is associated with lower CBP. These changes are mediated directly by statins but also indirectly through effects on LDL.

BackgroundEnd‐stage kidney disease is associated with increased arterial stiffness. Although correction of uremia by kidney transplantation (KTx) could improve arterial stiffness, results from clinical studies are unclear partly due to small sample sizes. Method and ResultsWe conducted a systematic review and meta‐analysis of before‐after design studies performed in adult KTx patients with available measures of arterial stiffness parameters (pulse wave velocity [PWV], central pulse pressure [PP], and augmentation index) before and at any time post‐KTx. Mean difference of post‐ and pre‐KTx values of different outcomes were estimated using a random effect model with 95% confidence interval. To deal with repetition of measurement within a study, only 1 period of measurement was considered per study by analysis. Twelve studies were included in meta‐analysis, where a significant decrease of overall PWV by 1.20 m/s (95% CI 0.67‐1.73, I2=72%), central PWV by 1.20 m/s (95% CI 0.16‐2.25, I2=83%), peripheral PWV by 1.17 m/s (95% CI 0.17‐2.17, I2=79%), and brachial‐ankle PWV by 1.21 m/s (95% CI 0.66‐1.75, I2=0%) was observed. Central PP (reported in 4 studies) decreased by 4.75 mm Hg (95% CI 0.78–10.28, I2=50%). Augmentation index (reported in 7 studies) decreased by 10.5% (95% CI 6.9‐14.1, I2=64%). A meta‐regression analysis showed that the timing of assessment post‐KTx was the major source of the residual variance. ConclusionsThis meta‐analysis suggests a reduction of the overall arterial stiffness in patients with end‐stage kidney disease after KTx.

Background: Chronic kidney disease is associated with increased arterial stiffness. Correction of the uremic milieu by kidney transplantation (KTx) may be improve arterial stiffness. However, results from clinical studies are not uniformly convincing. This could be related to small sample size of studies, heterogeneity in methods and timing of assessment of arterial stiffness after KTx. We aim to measure the reversibility of arterial stiffness after KTx. Design and Method: Observational studies and randomized controlled trials with measurements of pulse wave velocity (PWV), pulse pressure (PP) and/or augmentation index (AIx) were extracted from MEDLINE, EMBASE, COCHRANE LIBRARY, and Web of Science from their inception to January 2016. Two reviewers independently identified eligible studies comparing PW, PP and/or AIx pre to post KTx and extracted data including population characteristics, interventions and outcomes. Results: 13 studies of 981 met our inclusion criteria. 11 Studies (408 renal transplant) have been included in meta-analysis. There was a standard mean change of PWV by −0.45 (95% CI: − 0.68 −0.20, I2=58%) post-KTx. Both studies using aortic PWV (5 studies, 160 patients) and those using brachial-ankle PWV, showed a significant decrease of PWV by −1.58 m/s (95% CI: −2.97 − 0.19, I2= 87%) and by −1.21 m/s (95% CI: − 1.89 – 0.54, I2=0 %) post-KTx, respectively. Analysis of central PP and AIx showed significant reduction post-KTx by −4.77 (95% CI: −9.19 −0.35, I2=55%) and by −11.59 (95% CI:-15.64 −7.53, I2=43%), respectively. Only two studies have reported adjusted parameters for mean arterial pressure. Conclusions: There is a significant reduction in PWV, central PP and AIx after KTx. Heterogeneity among studies are globally moderate. Further analysis is required to examine the importance of changes in different vascular beds taking into account changes in blood pressure.

Introduction: Cardiovascular diseases are the primary cause of morbidity and mortality in patients with chronic kidney disease (CKD). Aortic stiffness is a non-traditional risk factor in these patients. Using an animal model of CKD with vascular calcification, we reported that inflammation is involved in the development of aortic calcification and stiffness. Hence, increased vascular production of IL-1β, IL-6 and TNFα was associated with aortic calcification. Therefore, we investigated the impact of the latter cytokines on aortic stiffness and determined the profile of inflammatory cytokines in a cohort of CKD patients. Methods: This is a transversal study involving 196 CKD patients on dialysis, in which aortic stiffness was determined non-invasively by the assessment of carotid-femoral pulse wave velocity (cf-PWV) using Complior SP (Artech Medical, Pantin, France). The profile of inflammatory cytokines (IFNv, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 and TNF α) was determined in plasma by ELISA using a Multiplex (Aushon, Maine, USA). Results: Mean cf-PWV of the cohort was 12.8±3.9 m/s. Median plasma levels of IL-1β, IL-6 and TNFα were 1.01 pg/ml, 4.26 pg/ml and 3.33 pg/ml, respectively. IL-6 levels positively correlated with cf-PWV (β = 0.218, P = 0.006, R = 0.129), suggesting a role in aortic stiffness. In contrast, no correlation between PWV and plasma levels of IL-1β or TNFα was established. Conclusion: This study reveals a relationship between an inflammatory cytokine, Il-6, and aortic stiffness in patients with CKD. Our results, together with our previous findings in an experimental animal model, indicate that IL-6 may represent a novel therapeutic target of cardiovascular diseases in CKD.

Background: Aortic reservoir function is associated with increased cardiovascular events. Patients with chronic kidney disease in need of dialysis have increased aortic stiffness and reversal of the aortic-to-brachial stiffness gradient, which could impair aortic reservoir function. The aim of this study was to determine the relationship between the aortic-to-brachial stiffness gradient and aortic reservoir function. Methods: Among 310 patients with chronic kidney disease on dialysis, aortic and brachial stiffness were measured by pulse wave velocity (PWV), with the aortic-to-brachial stiffness gradient calculated by the ratio of aortic and brachial PWV (PWV ratio). Aortic reservoir function was measured by radial tonometry-derived reservoir pressure (RP) and excess pressure (XSP) integrals. Results: RP was significantly and positively associated with PWV ratio (Standardized β=0.168 p

Background: Arterial stiffness has been considered as an index of vascular ageing. However, the relationship between age and stiffness of various segments of the arterial tree is heterogeneous. Moreover, the hemodynamic impact of vascular stiffness is thought to be related to the attenuation or even reversal of the physiological arterial stiffness gradient. The objectives of the present study were to evaluate the impact of age on aortic (central elastic artery) and brachial (muscular conduit artery) stiffness and to assess hemodynamic correlates of the arterial stiffness gradient. Method/results: In 310 dialysis patients (67 years [25th-75thpercentiles: 56–76], 185(60%) men, 134(43%) diabetes and 162(52%) cardiovascular disease), we measured aortic and brachial stiffness by pulse wave velocity of carotid-femoral (cf-PWV) and carotid-radial (cr-PWV) using direct distances (Complior). Arterial stiffness gradient was determined by cf-PWV/cr-PWV (PWV ratio). Central pulse wave parameters were obtained through generalized transfer function applied to the radial artery pulse profile (Sphygmocor). Mean cf-PWV, cr-PWV and PWV ratio were respectively of 13.52 ±4.07m/s, 8.76 ±1.68m/s and 1.59 ±0.52m/s. Cr-PWV decreased with age (β=−0.031, R=−0.274, P0.001), while cf-PWV (β=0.144, R=0.529, P0.001) and PWV ratio (β=0.021, R=0.613, P0.001) increased. In contrast to cf-PWV and cr-PWV, PWV ratio was not associated with MBP (P=0.997). Conclusion: The use of PWV ratio may be a more logical choice for risk determination than aortic stiffness as it provides a better estimation of the loss of arterial stiffness gradient and is not influenced by MBP in this population.

In cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF).In a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration.There were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181).Therefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.

Arterial stiffness is the major determinant of isolated systolic hypertension and increased pulse pressure. Aortic stiffness is also associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease, hypertension, and general population. Hemodynamically, arterial stiffness results in earlier aortic pulse wave reflection leading to increased cardiac workload and decreased myocardial perfusion. Although the clinical consequence of aortic stiffness has been clearly established, its pathophysiology in various clinical conditions still remains poorly understood. The aim of the present paper is to review the studies that have looked at the impact of dialysis calcium concentration on arterial stiffness. Overall, the results of small short-term studies suggest that higher dialysis calcium is associated with a transient but significant increase in arterial stiffness. This calcium dependant increase in arterial stiffness is potentially explained by increased vascular smooth muscle tone of the conduit arteries and is not solely explained by changes in mean blood pressure. However, the optimal DCa remains to be determined, and long term studies are required to evaluate its impact on the progression of arterial stiffness.