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Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Supplemental Digital Content is available in the text., The SPARTE study (Strategy for Preventing cardiovascular and renal events based on ARTErial stiffness; URL: https://www.clinicaltrials.gov; Unique identifier: NCT02617238) is a multicenter open-label randomized controlled trial with blinded end point evaluation, undertaken at 25 French research centers in university hospitals. Patients with primary hypertension were randomly assigned (1:1) to a therapeutic strategy targeting the normalization of carotid-femoral pulse wave velocity (PWV) measured every 6 months (PWV group, n=264) versus a classical therapeutic strategy only implementing the European Guidelines for Hypertension Treatment (conventional group, n=272). In the PWV group, the therapeutic strategy used preferably a combination of ACE (angiotensin-converting enzyme) inhibitor or angiotensin receptor blocker and calcium channel blockers, as well as maximal recommended doses of ACE inhibitors and angiotensin receptor blockers. The primary outcome was a combined end point including particularly stroke and coronary events. Secondary outcomes included the time-course changes in brachial office blood pressure (BP), ambulatory BP, PWV, and treatments. After a median follow-up of 48.3 months, there was no significant between-group difference in primary outcome (hazard ratio, 0.74 [95% CI, 0.40–1.38], P=0.35). In the PWV group, combinations of renin-angiotensin-system blockers and calcium channel blockers were prescribed at higher dosage (P=0.028), office and ambulatory systolic blood pressure and diastolic blood pressure decreased more (P

International audience; Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.

OBJECTIVES Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. Volume overload is the main mechanism of increased blood pressure (BP) in these individuals. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound (US)-guided strategy on ambulatory BP in hypertensive hemodialysis patients. METHODS This is the report of the 12-month follow-up of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized to dry-weight reduction guided by prehemodialysis lung ultrasound and to standard care. A 48-h ambulatory BP monitoring (ABPM) was performed in all study participants at baseline and after 12 months. RESULTS During follow-up, a greater proportion of patients in the active group underwent dry-weight reduction compared with the control group (71.4% vs. 22.2%; P

Background Few studies show that ambulatory blood pressure (BP) monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. Methods Major medical databases were searched for studies enrolling adult KTRs undergoing 24-h ABPM compared with office or home BP measurements. The main outcomes were associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. Results Twenty-two studies (2078 participants) were reviewed. Among 12 studies collecting data on renal endpoints, 10 studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine and/or creatinine clearance or estimated glomerular filtration rate, than traditional office measurements. Twelve studies analysed the relation between different BP recordings and CV target organ damage and reported robust correlations between echocardiographic abnormalities (i.e. left ventricular mass index) and 24-h ABPM, but not with office BPs. Furthermore, 24-h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness, diffuse thickening and endothelial dysfunction. Additionally, an abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. Conclusions In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, an altered circadian BP profile associated with renal and CV target organ damage.

Arterial stiffness is a strong predictor of death and cardiovascular (CV) events in hemodialysis patients. Only few studies tested interventions aiming to improve arterial stiffness in this population. This study examines the effect of dry-weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory aortic blood pressure (BP) and arterial stiffness parameters in hemodialysis. Seventy-one clinically euvolemic hemodialysis patients with hypertension, were included in this single-blind randomized clinical-trial. Patients were randomized in the active group (n = 35), following dry-weight reduction guided by the total number of US-B lines before a mid-week dialysis session and the control group (n = 36), following standard treatment. Patients underwent office evaluation of arterial stiffness and 48-h ABPM to capture ambulatory central systolic (cSBP) and diastolic BP (cDBP) and arterial stiffness indexes at baseline and after 8-weeks. US-B lines decreased in the active and slightly increased in the control group (p

Introduction Since infammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifer of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. Objective and methods We investigated the efect modifcation by systemic infammation (serum CRP) on the relationship between a surrogate of the flling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantifed by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. Results At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r=0.23, P

Highlights •CKD is associated with very high risk of CAD. CAD management is complicated in CKD patients, due to comorbid conditions and potential side effects during interventions. •There are few trials related to CAD with focus on CKD patients, particularly in those with advanced CKD. •Additional prospective studies focusing on diagnosis, prevention, and treatment of CAD are needed in CKD.

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.

CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.

Background Hypertension (HTN) is common following renal transplantation and it is associated with adverse effects on cardiovascular (CV) and graft health. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure (BP) status, since HTN misclassification by office BP (OBP) is quite common in this population. We performed a systematic review and meta-analysis aimed at determining the clinical utility of 24-h ABPM and its potential implications for the management of HTN in this population. Methods Ovid-MEDLINE and PubMed databases were searched for interventional or observational studies enrolling adult kidney transplant recipients (KTRs) undergoing 24-h ABP readings compared with OBP or home BP. The main outcome was the proportion of KTRs diagnosed with HTN by ABPM, home or OBP recordings. Additionally, day–night BP variability and dipper/non-dipper status were assessed. Results Forty-two eligible studies (4115 participants) were reviewed. A cumulative analysis including 27 studies (3481 participants) revealed a prevalence of uncontrolled HTN detected by ABPM of 56% [95% confidence interval (CI) 46–65%]. The pooled prevalence of uncontrolled HTN according to OBP was 47% (95% CI 36–58%) in 25 studies (3261 participants). Very few studies reported on home BP recordings. The average concordance rate between OBP and ABPM measurements in classifying patients as controlled or uncontrolled hypertensive was 66% (95% CI 59–73%). ABPM revealed HTN phenotypes among KTRs. Two pooled analyses of 11 and 10 studies, respectively, revealed an average prevalence of 26% (95% CI 19–33%) for masked HTN (MHT) and 10% (95% CI 6–17%) for white-coat HTN (WCH). The proportion of non-dippers was variable across the 28 studies that analysed dipping status, with an average prevalence of 54% (95% CI 45–63%). Conclusions In our systematic review, comparison of OBP versus ABP measurements disclosed a high proportion of MHT, uncontrolled HTN and, to a lesser extent, WCH in KTRs. These results suggest that HTN is not adequately diagnosed and controlled by OBP recordings in this population. Furthermore, the high prevalence of non-dippers confirmed that circadian rhythm is commonly disturbed in KTRs.

Endothelial dysfunction, one of many causes of arterial changes in end-stage kidney disease (kidney failure), is a likely link between early vascular aging and the risk of thrombosis or bleeding in this condition. To evaluate this, we compared links between arterial stiffness and endothelial/coagulation factors in 55 patients receiving hemodialysis therapy and 57 age-/sex-matched control individuals. Arterial stiffness was assessed from carotid-femoral pulse wave velocity, and coagulation status from the endogenous thrombin generating potential. Markers of endothelial dysfunction (von Willebrand factor, tissue factor pathway inhibitor), neutrophil extracellular traps and tissue factor-positive extracellular vesicles were higher in patients with kidney failure. Prothrombin fragments 1 and 2, and D-dimer markers of in vivo coagulation activation were also higher. However, in vitro in the presence of platelets, endogenous thrombin generating potential was lower and its downregulation by activated protein C impaired. Antiplatelet drugs did not affect these parameters. In multiple regression analysis, prothrombin fragments 1 and 2, D-dimer, factor VIII and monocyte-derived tissue factor-positive extracellular vesicles correlated with higher carotid-femoral pulse wave velocity. In patients with kidney failure, in vivo hypercoagulability occurred with reduced thrombin generation in platelet-rich plasma, likely explaining the opposing thrombotic and bleeding tendencies in patients with kidney failure. Importantly, arteriosclerosis is more closely related to a prothrombotic state. Thus, coagulation changes plus arterial stiffness highlight a major therapeutic challenge for anticoagulant and antiplatelet drug use.

Background and Aims Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. The main mechanism leading to BP elevation in these individuals is their inability to maintain water homeostasis. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory BP in hypertensive hemodialysis patients. Method This is the report of the 12-month trial phase of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized (1:1 ratio) in the active group (23 male and 12 female), following dry-weight reduction guided by the total number of US-B lines prior to a mid-week dialysis session and the control group (24 male and 12 female), following standard-of-care treatment. A 48-hour ABPM was performed in all study participants at baseline and after 12 months. Results During follow-up more patients in the active compared to control group had dry weight reduction (71.4% vs 22.2%; p Conclusion A lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely decrease ambulatory BP levels during a 12-month follow-up period This method is a simple treatment approach to improve hypertension management in hemodialysis patients.

Background and Aims Bone fragility fractures (bone fractures) are extremely frequent in haemodialysis (HD) patients. Serum phosphate (P) has been suggested as a risk factor for bone fracture, nonetheless, evidence is poor. The aim of this study was to assess the association between incidence of bone fractures and serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) in patients from the COSMOS study. Method COSMOS is an observational, prospective, open cohort study with 3 years of follow-up including 6797 haemodialysis patients from 227 centres randomly selected from 20 European countries. At baseline, demographics, comorbidities, treatments, serum biochemical parameters of the previous six months and bone fractures of the previous 12 months were collected. Every 6 months, all these variables, outcomes, and incident bone fractures, were collected. Patients who had at least one bone fracture during follow-up were compared with those who had not. Multivariate binary logistic regression and Poisson regression were used to assess the association between incidence of bone fractures and serum P, Ca and PTH. Time to fracture (and possible re-fracture) was also evaluated using Cox regression and Cox regression for recurrent events. All the results were adjusted by 23 variables including Ca, P, PTH, albumin and haemoglobin (full adjusted model). Results Analysis included 6274 patients who had follow-up data and non-missing information regarding bone fractures at baseline and during follow-up; 252 patients (4.0%), suffered at least one incident bone fracture. The fractured patients were older (68.1±12.9 vs. 63.8±14.5 years, p Multivariate binary logistic regression showed that “well known risk factors for bone fracture”, such as a previous bone fracture (OR: 7.78[95%CI:4.83-12.55], p 800 pg/mL (OR: 1.60[95%CI: 1.01-2.55], p=0.047), were associated with a higher incidence of follow-up bone fractures. In addition to the “well known bone risk factors for fracture”, serum P > 6.1 mg/dL (OR: 1.50[95% CI: 1.07-2.11], p=0.02) and serum Ca > 9.7 mg/dL (OR: 1.42[95%CI: 1.01-2.03], p=0.043), were also associated with a higher incidence of bone fractures in the full-adjusted model. These findings were partly consistent with Poisson regression for serum P >6.1 mg/dL (IRR: 1.46[95% CI: 1.00-2.13], p=0.0085) and serum Ca > 9.7 mg/dL (IRR: 1.49[95%CI: 1.06-2.08], p=0.0047), but not for PTH. In addition, Cox regression analysis showed association between bone fractures and serum P >6.1 mg/dl (HR: 1.61 [95%CI: 1.16-2.24], p=0.0049) and 1.60 [95%CI: 1.14-2.24] (p=0.0066) for simple and recurrent events respectively, but no association was found with serum Ca and PTH in the 2 full-adjusted models for the Cox regression analyses. Conclusion In COSMOS, a large haemodialysis patient’s cohort with 3 years follow up, serum P was the only biochemical parameter that remained as a significant risk factor for bone fractures after 4 statistic approaches. Thus, for the first time, in a large scale well controlled study, high serum P has been identified as a new independent potential risk factor for incident bone fractures in haemodialysis patients.

Background Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients. Method We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH. Results The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload. Conclusion TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.

Background and Aims Diabetes is the most common cause of chronic kidney disease (CKD) stage 5 and a relevant risk factor for mortality. The available CKD-MBD guidelines do not make differences between diabetics and non-diabetics regarding the optimal targets of the serum bone and mineral biochemical parameters. Thus, the objective of this analysis of COSMOS was to compare the association between the main serum bone and mineral biochemical parameters (calcium-Ca, phosphorus-P and parathyroid hormone-PTH) and mortality in diabetic and non-diabetic patients in haemodialysis. Method COSMOS is a 3-year, observational, prospective, open-cohort study that includes 6797 patients from 227 dialysis centres that were randomly selected from 20 European countries. Cox proportional hazard regression models with penalized splines smoothing were used to analyse the association between relative risk of mortality vs. Ca, P or PTH. Hazard ratios were adjusted by demographics, comorbidities, treatments and biochemical parameters. Interaction analysis was used to analyse if diabetes can influence the association between relative risk of mortality and Ca, P and PTH. Results The present analysis includes 6306 patients with follow-up data and accurate information on diabetes status. The mortality rate in COSMOS was 13.3 deaths per 100 patient-years (17.8 in diabetics and 11.4 in non-diabetics). At baseline, diabetic patients were older (66.7 ± 11.7 vs. 62.8 ± 15.3 years, p Conclusion These results suggest for the first time a differential effect of diabetes on the association between relative risk of mortality and serum PTH. High serum PTH predicts death only in diabetics. These findings could have relevant implications for the diagnosis and treatment of CKD-MBD in diabetic and non-diabetic patients in haemodialysis.

Blood pressure (BP) is routinely measured as a vital sign before, during and/or after dialysis (peridialysis BP). Even if peridialytic measurements are widely used, the agreement with the interdialytic BP is poor and is often biased by many technical errors [1]. Since accurate BP measurements are critical for making decisions and evaluating a patient’s cardiovascular risk, Working Groups from the ERA-EDTA and the European Society of Hypertension (ESH) issued recommendations on standardized BP measurement in dialysis patients [2]. Previous studies have underlined substantial differences between recommendations for BP measurement in general and effective BP measurements performed by medical staff [3], but whether these recommendations are followed in dialysis centres has not been investigated so far. The objectives of this multi-centric, cross-sectional survey were (i) to assess the adherence to current recommendations [4] on BP measurements in dialysis centres both according to physicians’ and patients’ perspectives and (ii) to evaluate the use of out-of-office BP measurements in dialysis patients. [...]

The American Society of Nephrology, the European Renal Association–European Dialysis and Transplant Association and the International Society of Nephrology Joint Working Group on Ethical Issues in Nephrology have identified ten broad areas of ethical concern as priority challenges that require collaborative action. Here, we describe these challenges — equity in access to kidney failure care, avoiding futile dialysis, reducing dialysis costs, shared decision-making in kidney failure care, living donor risk evaluation and decision-making, priority setting in kidney disease prevention and care, the ethical implications of genetic kidney diseases, responsible advocacy for kidney health and management of conflicts of interest — with the aim of highlighting the need for ethical analysis of specific issues, as well as for the development of tools and training to support clinicians who treat patients with kidney disease in practising ethically and contributing to ethical policy-making. Here, the ASN-ERA-EDTA-ISN Joint Working Group on Ethical Issues in Nephrology highlights ten areas of ethical concern as priority challenges that require collaborative action and discusses the need for development of ethical training and guidance tools to manage these issues.

High pulse wave velocity (PWV) is a hallmark of end-stage kidney disease (ESKD) where it is considered useful for risk stratification. We investigated whether PWV adds meaningful prognostic information to 2 simple, well-validated, clinical risk scores specific to ESKD (the Annualized Rate of Occurrence scores) for predicting all-cause and cardiovascular mortality by applying state-of-the-art prognostic tests including discrimination (Harrell C-index), risk reclassification (integrated discrimination improvement), and calibration. We performed these analyses in the 2 largest ESKD cohorts with available PWV data, the Manhes-Hospital cohort in Paris (n=287 patients) and the Quebec Research Center cohort in Canada (n=246 patients). The Harrell C-index of the 2 clinical risk scores was consistently higher than that by PWV both for all-cause (Manhes cohort, 77.5% versus 73.7%; Quebec cohort, 61.5% versus 58.9%) and cardiovascular mortality (Manhes cohort, 77.9% versus 77.2%; Quebec cohort, 63.8% versus 60.3%). Furthermore, PWV provided a very modest increase in discriminatory power over and above clinical risk scores by Harrell C-index (from 0.5% to 1.8%) and in risk reclassification by Integrated Discrimination Improvement (from 0.9% to 5.1%) and actually worsened models calibration. In patients with ESKD, PWV has a prognostic power for all-cause and cardiovascular mortality inferior to that by simple clinical risk scores and only modestly improves the risk discrimination and reclassification by the same risk scores and worsens models calibration. Clinicians may better rely on available clinical risk scores rather than on PWV for risk stratification in the ESKD population.

Background. The aim of the third French Phosphorus and Calcium Observatory (Photo-Graphe (R) 3) was to assess the achievement of international Kidney Disease: Improving Global Outcomes (KDIGO) recommendations on optimal serum phosphate, calcium and parathyroid hormone (PTH) levels and possible associations with mortality in patients with chronic kidney disease (CKD). Methods. This was a prospective, observational study conducted with nephrologists in France who were selected using a clustering approach. Adult patients with non-dialysis Stage 4 or 5 CKD and no kidney graft history were eligible. Data about clinical events, serum biochemistry and treatment were collected every 6 months for 2.5 years and 12 months thereafter. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model for identification of factors associated with survival. Results. Overall, 566 CKD Stage 4 patients (men, 56%) and 153 CKD Stage 5 patients (men, 62%) were included. In Stage 4, only 14-15% patients achieved the three main 2009 KDIGO targets during the first 2 years and 22% at 2.5 years. In Stage 5 patients, the proportion remained \textless6% throughout. The percentages of patients achieving the three main 2017 KDIGO targets were slightly higher at each time point. Overall, 14% of Stage 4 and 10% of Stage 5 patients died in the observation period. Only age and haemoglobin level were significantly associated with risk of all-cause mortality. Conclusions. Few CKD patients achieved KDIGO mineral targets. Increased mortality risk was linked to older age and lower haemoglobin level, but not to serum calcium, phosphate or PTH targets.

Background Progression of coronary artery calcification is an important marker for cardiovascular morbidity in end-stage renal disease patients. Therefore, we reviewed the evidence on coronary artery calcification progression in different renal replacement therapies. Methods MEDLINE (PubMed), Embase and TRIP databases were searched from 1999 – 2016. Additionally, bibliographies were searched by hand and citation tracking of key publications was performed. Prospective studies were included that examined coronary artery calcification with two or more multislice computed tomography scans ≥6 months apart in patients 18–75 years old receiving any renal replacement therapy, including kidney transplantation. Reporting of separate scores for different modalities was required. Two researchers extracted data independently with pilot-tested forms and assessed the risk of bias using a validated tool. Results We identified 29 eligible studies that assessed coronary artery calcification progression in end-stage renal disease patients, of which 19 studies evaluated haemodialysis and 8 kidney transplantation. Evidence on progression in peritoneal dialysis (three studies) and nocturnal haemodialysis (one study) was limited. Meta-analysis was not possible due to diverse reporting methods of coronary artery calcification scores and definitions of progression. Median coronary artery calcification scores were considerably higher in haemodialysis cohorts at baseline, presumably due to a generally higher age and dialysis vintage. Median coronary artery calcification progressed universally. Visual inspection suggested the least progression in kidney transplant recipients. Conclusions There is insufficient evidence to compare the influence of renal replacement therapies on coronary artery calcification progression. We advocate the adoption of a standardized reporting method of coronary artery calcification progression.

Aims To assess real-world effectiveness and safety of intravenous (IV) HX575, a biosimilar epoetin-α, in hemodialysis (HD) patients. Materials and methods This prospective, observational, pharmacoepidemiological study of adult HD patients treated with IV HX575 for renal anemia for up to 24 months was conducted in 114 centers in 10 European countries. Of 2,086 enrolled subjects (safety sample), 2,023 had ≥ 1 follow-up visit (effectiveness sample). Results Most (59.3%) patients were male, median age was 68 years. At enrollment, most (82.5%) had been treated with an erythropoiesis-stimulating agent, and 73.0% had adequate iron stores. At baseline, mean (± standard deviation) baseline hemoglobin (Hb) was 11.09 (± 1.14) g/dL and HX575 dose 106.5 (± 78.7) international units (IU)/kg/week; at month 24, Hb was 11.25 (± 1.19) g/dL and HX575 dose 113.0 (± 102.5) IU/kg/week. Variations in mean HX575 dose and Hb over the study were not statistically significant. As to safety, 140 patients (6.7%) experienced ≥ 1 adverse event; of these, 19 events (16 patients; 0.8%) were related to HX575 treatment, 148 (108 patients; 5.2%) were reported as serious, including 12 events in 11 patients (0.5%) stated to be related. No cases of anti-epoetin antibodies or pure red cell aplasia were reported. Conclusions MONITOR-CKD5 confirmed the real-world effectiveness and safety profile of IV biosimilar HX575. HD patients treated for up to 24 months showed stable dosing patterns and Hb outcomes. The safety profile of HX575 is likewise comparable to reference epoetin-α. .

Resume Il y a peu de donnees sur la prise en charge des troubles du metabolisme mineral et osseux (TMO) de la maladie renale chronique avant le stade de la dialyse en France. Une meilleure connaissance de la prise en charge actuelle pourrait conduire a une amelioration de l’implementation des recommandations internationales (KDIGO). L’Observatoire national du metabolisme mineral et osseux Photo-Graphe (Sanofi), dans sa 3 e version, a inclus une cohorte de patients aux stades 4 et 5 de la maladie renale chronique (MRC) dans le but d’examiner les TMO de la MRC ainsi que la qualite de leur prise en charge chez des patients suivis par 62 nephrologues repartis dans 20 regions francaises. Les TMO et leurs traitements ont ete etudies en octobre 2011, soit 1 an apres l’inclusion des patients. Nous avons examine en particulier le pourcentage de patients ayant une anomalie des parametres biologiques refletant les TMO, mais ne recevant pas de traitement adequat selon les recommandations des KDIGO. Au total, 456 patients au stade 4 et 154 au stade 5 ont ete etudies, avec un âge moyen de 72,9 ± 14,2 ans et de sexe masculin dans 58 % des cas. Les cibles des KDIGO (stades 4 et 5) n’etaient pas atteintes dans respectivement 80 et 84 % des cas pour la PTH serique, dans 8 et 22 % des cas pour la calcemie et dans 12 et 46 % des cas pour la phosphatemie. Une explication potentielle peut etre une prise en charge medicamenteuse insuffisante estimee respectivement a 45 et 60 % pour l’hyperparathyroidie secondaire (HPTS) et a 36 % pour l’hyperphosphatemie au stade 5. A noter que 55,5 et 57,5 % respectivement des patients aux stades 4 et 5 recevaient de la vitamine D native. Dans cet observatoire national, la prise en charge des TMO de la MRC aux stades 4 et 5 apparait suboptimale, surtout pour ce qui concerne l’HPTS qui n’est pas traitee dans pres de 50 % des cas. L’hyperphosphatemie est egalement frequente et insuffisamment controlee au stade 5. Une amelioration de la prise en charge des TMO de la MRC passe par une sensibilisation des nephrologues a l’importance de viser les cibles biologiques et aux moyens d’y arriver.

Background The Acute Dialysis Quality Initiative (ADQI) XI Workgroup has suggested defining heart failure (HF) in patients with end-stage renal disease by the presence of at least one out of eight predefined echocardiographic criteria. Given the high prevalence of echocardiographic alterations in chronic kidney disease (CKD) patients, we hypothesized that application of echocardiographic ADQI criteria will result in overdiagnosis of HF, without providing substantial prognostic information. Methods Among 472 CKD stage G2-G4 patients recruited in the CARE FOR HOMe study, we assessed the presence of left-ventricular (LV) hypertrophy, valvular dysfunction, high left-atrial volume index (LAVI), systolic and diastolic LV dysfunction, enlarged LV diameter, and altered regional LV wall contractility. According to the ADQI proposal, presence of one or more of these alterations defined HF. We followed all patients for the occurrence of cardiac decompensation, defined as hospital admission for decompensated HF. Results A total of 313 (66%) out of 472 patients fulfilled at least one ADQI echocardiographic criterion for HF. Echocardiographic alterations were more common in advanced (G3b/G4: 80%) than in milder (G2/G3a: 56%) CKD. Within subcategories of echocardiographic criteria, an increased LAVI (50%) and diastolic dysfunction (30%) were the most frequent findings. During follow-up of 4.3 ± 2.0 years, the majority (87%) of all 313 patients who fulfilled ADQI echocardiographic criteria were not hospitalized for cardiac decompensation. Conclusions Echocardiographic criteria proposed by ADQI as a precondition for the clinical staging of HF are virtually omnipresent among CKD patients. By labelling a majority of CKD patients as having HF, application of ADQI criteria fails to specifically identify patients at high risk for future cardiac events.

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease. Sin financiación 22.673 JCR (2019) Q1, 2/138 Cardiac & Cardiovascular Systems 5.883 SJR (2019) Q1, 4/362 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

In patients with end-stage renal disease treated with hemodialysis or peritoneal dialysis, hypertension is very common and often poorly controlled. Blood pressure (BP) recordings obtained before or after hemodialysis display a J-shaped or U-shaped association with cardiovascular events and survival, but this most likely reflects the low accuracy of these measurements and the peculiar hemodynamic setting related with dialysis treatment. Elevated BP by home or ambulatory BP monitoring is clearly associated with shorter survival. Sodium and volume excess is the prominent mechanism of hypertension in dialysis patients, but other pathways, such as arterial stiffness, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, endothelial dysfunction, sleep apnea and the use of erythropoietin-stimulating agents may also be involved. Nonpharmacologic interventions targeting sodium and volume excess are fundamental for hypertension control in this population. If BP remains elevated after appropriate treatment of sodium-volume excess, the use of antihypertensive agents is necessary. Drug treatment in the dialysis population should take into consideration the patient's comorbidities and specific characteristics of each agent, such as dialysability. This document is an overview of the diagnosis, epidemiology, pathogenesis and treatment of hypertension in patients on dialysis, aiming to offer the renal physician practical recommendations based on current knowledge and expert opinion and to highlight areas for future research., Spanish government funds ISCIII RETIC REDNREN; FEDER

Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension ( P P P P =0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.

Objectives Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies in such patients showed that when BP decrease is accompanied by PWV decrease the survival is improved. This study examines the prognostic role of the mean BP (MBP)-PWV association for cardiovascular outcomes and all-cause mortality in hemodialysis. Methods A total of 242 hemodialysis patients underwent 48-h ambulatory BP monitoring with Mobil-O-Graph-NG and were followed for 33.17 ± 19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the β-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, nonfatal myocardial infarction or nonfatal stroke. Secondary end-points were all-cause mortality, cardiovascular mortality and a combination of cardiovascular events. Results Higher quartiles of β-coefficients (indicating strong within-individual association of MBP with PWV) were related to greater cumulative freedom from the primary end-point (50.8, 60.0, 70.0 and 80.3% for quartiles 1-4, respectively; log-rank P = 0.001), better overall survival (60.7, 61.7, 73.3, 86.9%; log-rank P = 0.002) and better cardiovascular survival (78.7, 75.0, 81.7, 91.8% for quartiles 1-4; log-rank P = 0.044). The future risks of the primary end-point, all-cause and cardiovascular mortality and the combined outcome were progressively increasing with lower quartiles of β-coefficients, indicating patients with weak MBP-PWV association (hazard ratios for all-cause mortality 3.395; 95% confidence interval: 1.524-7.563, P = 0.003 for quartile 1 vs. quartile 4). Conclusion Weaker within-individual MBP-PWV association, based on ABPM recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that arterial stiffness insensitive to BP changes is the underlying factor for adverse outcomes in these individuals.

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research.

Introduction and purpose Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies showed that when BP decrease is accompanied by PWV decrease the survival is improved. The aim of this study is to examine the prognostic significance of BP sensitivity of PWV for major cardiovascular outcomes and all-cause mortality in hemodialysis patients. Methods This is a prospective cohort study including 242 hemodialysis patients [age, 62.6±14.2 years; female, 91 (37.6%); hemodialysis vintage, 41.53±43.46]. All subjects underwent 48-hour-ABPM with Mobil-O-Graph-NG and followed-up for 33.17±19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the beta-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular events. Results Patients who experienced the primary end-point during follow-up had significantly lower beta-coefficient levels (primary end-point: 19.877±3.975 vs 18.483±3.550, p=0.008). Higher quartiles of beta-coefficients (indicating dependency of PWV on MBP) were associated with higher cumulative freedom from the primary end-point (50.8%, 60.0%, 70.0% and 80.3% for quartiles 1 to 4 respectively; logrank-p=0.001), higher overall survival (60.7%, 61.7%, 73.3%, 86.9%; logrank-p=0.002) and higher cardiovascular survival (78.7%, 75.0%, 81.7%, 91.8% for quartiles 1 to 4; logrank-p=0.044). The future risk for the primary end-point, all-cause and cardiovascular mortality and the combined outcome was progressively increasing for lower quartiles of beta-coefficients (HR for all-cause mortality 3.395; 95% CI: 1.524–7.563, p=0.003 for quartile 1 vs quartile 4). Age (OR: 1.046, 95% CI: 1.016–1.077 per year increase, p=0.003) and 48h heart rate (OR: 0.949, 95% CI: 0.916–0.982 per bpm increase, p=0.003) were independently associated with weaker relationship between 48h-MBP and 48h-PWV. Conclusions Lower within-individual MBP-PWV association, based on AMBP recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that BP-independent arterial stiffness may be the underlying factor for adverse outcomes in these individuals.

Background Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. Methods A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. Results The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P Conclusions The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

Background DOPPS reported that thousands of life-years could be gained in the US and Europe over 5 years by correcting six modifiable haemodialysis practices. We estimated potential life-years gained across 10 European countries using MONITOR-CKD5 study data. Methods The DOPPS-based target ranges were used, except for haemoglobin due to label changes, as well as DOPPS-derived relative mortality risks. Percentages of MONITOR-CKD5 patients outside targets were calculated. Consistent with the DOPPS-based analyses, we extrapolated life-years gained for the MONITOR-CKD5 population over 5 years if all patients were within targets. Results Bringing the 10 MONITOR-CKD5 countries’ dialysis populations into compliance on the six practices results in a 5-year gain of 97,428 patient-years. In descending order, survival impact was the highest for albumin levels, followed by phosphate levels, vascular access, haemoglobin, dialysis adequacy, and interdialytic weight gain. Conclusions Optimal management of the six modifiable haemodialysis practices may achieve 6.2% increase in 5-year survival. Trial Registration NCT01121237. Clinicaltrials.gov registration May 12, 2010 (retrospectively registered). Electronic supplementary material The online version of this article (10.1186/s12882-019-1251-z) contains supplementary material, which is available to authorized users.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

Resume Rationnel La maladie renale chronique induit progressivement des troubles du metabolisme phosphocalcique, associes a des anomalies osseuses et cardiovasculaires. Des etudes precedentes ont montre que les concentrations seriques de calcium, de phosphore et d’hormone parathyroidienne (PTH) n’etaient controlees que chez peu de patients hemodialyses selon les cibles K/DOQI (Kidney-Disease Outcomes Quality Initiative). Nous avons voulu etudier l’impact des differentes strategies therapeutiques, et en particulier de la mise en place des recommandations KDIGO (Kidney-Disease: Improving Global Outcomes) en 2009 sur le controle de ces trois parametres. Patients et methodes En France, l’observatoire du metabolisme phosphocalcique Photo-Graphe tm a permis d’analyser a l’echelon local, regional et national, le statut phosphocalcique des patients dialyses et son evolution dans le temps. Nous avons compare les resultats recueillis en juin 2008 ( n = 1914 patients) a ceux obtenus en octobre 2012 ( n = 2481) chez des patients adultes traites par hemodialyse periodique. Resultats En 2012, une plus faible proportion de patients etaient hyperphosphoremiques (55,1 % vs 64,7 %), hypocalcemiques (35,5 % vs 40,3 %) et hyperparathyroidiens (9,8 % vs 10,1 %) selon les recommandations KDIGO, et un plus grand nombre de patients etaient hypophosphoremiques (9,6 % vs 6,5 %), hypercalcemiques (3,9 % vs 2,2 %) et hypoparathyroidiens (31,5 % vs 25,8 %) ( p p p = 0,002 respectivement pour les concentrations seriques de phosphore, de calcium et de PTH entre 2008 et 2012). La concentration moyenne (± deviation standard [DS]) de 25 OH vitamine D serique a augmente de 1,6 fois, passant de 48,3 ± 42,6 en 2008 a 76,6 ± 45,8 nmol/L en 2012. Alors que l’utilisation du sevelamer (HCl ou carbonate) et de la vitamine D native a augmente, la prescription des chelateurs du calcium, du cinacalcet, du carbonate de lanthane et des derives actifs de la vitamine D a diminue entre ces deux periodes. Conclusion Malgre les ameliorations observees dans cette periode, seule une minorite de patients ont atteint les cibles des recommandations KDIGO pour les trois principaux parametres biologiques du metabolisme phosphocalcique (11,5 % en 2012 vs 11,1 % en 2008).

Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.

BACKGROUND: The prognostic impact of nutrition and chronic kidney disease (CKD) complications has already been described in elderly haemodialysis patients but their relative weights on risk of death remain uncertain. Using structural equation models (SEMs), we aimed to model a single variable for nutrition, each CKD complication and cardiovascular comorbidities to compare their relative impact on elderly haemodialysis patients' survival. METHODS: This prospective study recruited 3165 incident haemodialysis patients \textgreater/=75 years of age from 178 French dialysis units. Using SEMs, the following variables were computed: nutritional status, anaemia, mineral and bone disorder and cardiovascular comorbidities. Systolic blood pressure was also used in the analysis. Survival analyses used Poisson models. RESULTS: The population average age was 81.9 years (median follow-up 1.51 years, 35.5% deaths). All variables were significantly associated with mortality by univariate analysis. Nutritional status was the variable most strongly associated with mortality in the multivariate analysis, with a negative prognostic impact of low nutritional markers \incidence rate ratio [IRR] 1.42 per 1 standard deviation [SD] decrement [95% confidence interval (CI) 1.32-1.53]\. The 'cardiovascular comorbidities' variable was the second variable associated with mortality [IRR 1.19 per 1 SD increment (95% CI 1.11-1.27)]. A trend towards low intact parathyroid hormone and high serum calcium and low values of systolic blood pressure were also associated with poor survival. The variable 'anaemia' was not associated with survival. CONCLUSIONS: These findings should help physicians prioritize care in elderly haemodialysis patients with CKD complications, with special focus on nutritional status.

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium–glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.

Background End-stage renal disease (ESRD) patients even without known cardiovascular (CV) disease have high mortality rates. Whether neurohormonal blockade treatments improve outcomes in this population remains unknown. The aim of this study was to assess the effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), β-blockers or both in all-cause mortality rates in incident ESRD patients without known CV disease starting renal replacement therapy (RRT) between 2009 and 2015 in the nationwide Réseau Epidémiologie et Information en Néphrologie registry. Methods Patients with known CV disease and those who started emergency RRT, stopped RRT or died within 6 months were excluded. Propensity score matching models were used. The main outcome was all-cause mortality. Results A total of 13 741 patients were included in this analysis. The median follow-up time was 24 months. When compared with matched controls without antihypertensive treatment, treatment with ACEi/ARBs, β-blockers and ACEi/ARBs + β-blockers was associated with an event-rate reduction per 100 person-years: ACEi/ARBs 7.6 [95% confidence interval (CI) 7.1–8.2] versus matched controls 9.5 (8.8–10.1) [HR 0.76 (95% CI 0.69–0.84)], β-blocker 7.1 (6.6–7.7) versus matched controls 9.5 (8.5–10.2) [HR 0.72 (0.65–0.80)] and ACEi/ARBs + β-blockers 5.8 (5.4–6.4) versus matched controls 7.8 (7.2–8.4) [HR 0.68 (0.61–0.77)]. Conclusions Neurohormonal blocking therapies were associated with death rate reduction in incident ESRD without CV disease. Whether these relationships are causal will require randomized controlled trials.

Accelerated ageing is observed in patients with chronic kidney disease (CKD)/end-stage renal disease. Premature vascular aging and arterial stiffening are the most characteristic features of this “progeria” that is already observed in those with the early stages of CKD. Aortic stiffening is associated with high characteristic impedance, left ventricular hypertrophy, decreased coronary perfusion, and is a strong prognostic marker of mortality and cardiovascular morbidity. With aging, the arterial stiffening is more pronounced in the aorta and central arteries than in peripheral conduit arteries. This leads to progressive decrease and inversion of the arterial stiffness gradient and systemic reflection coefficient, leading to less protection of the microcirculation in the event of high-pressure transmission towards it Arterial stiffening is multifactorial with systemic microinflammation being one of the most important associated factors primarily associated with vascular calcifications.

Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.

Background Carotid stiffening is considered a key element in the pathogenesis of stroke. However, results of studies evaluating the association between carotid stiffness and incident stroke have been inconsistent. Objectives This study investigated whether carotid stiffness (as determined by ultrasonography) is associated with incident stroke and whether this association is independent of aortic stiffness as estimated by carotid-femoral pulse wave velocity (cfPWV). Additionally, we evaluated the incremental value of carotid stiffness for stroke risk prediction beyond Framingham risk factors and cfPWV. Methods This study included a systematic review and meta-analyses of aggregate and individual participant data (IPD), the latter of which was obtained by requesting individual-level data of all cohort studies with available data on carotid stiffness and cfPWV. Results Ten studies (n = 22,472) were included in the aggregate data meta-analysis and 4 (n = 4,540) in the IPD meta-analysis. After adjusting for cardiovascular (CV) factors, the aggregate data meta-analysis showed that greater carotid stiffness (per SD) was associated with stroke (hazard ratio: 1.18; 95% confidence interval: 1.05 to 1.33). In addition, carotid stiffness was associated with total CV events and CV and all-cause mortality, but not with coronary heart disease events. In the IPD meta-analysis, additional adjustment for cfPWV did not materially change these associations. Carotid stiffness did improve stroke risk prediction beyond Framingham and cfPWV (integrative discrimination improvement: 0.4 percentage point [95% confidence interval: 0.1 to 0.6 percentage point] and continuous net reclassification improvement: 18.6% [95% confidence interval: 5.8% to 31.3%]). Conclusions Carotid stiffness is associated with incident stroke independently of CV factors and aortic stiffness. In addition, carotid stiffness improves stroke risk prediction beyond Framingham and aortic stiffness.

International audience; Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3-5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m(2) and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action.

Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%–29%.

HYPERTENSION––AT A CRITICAL CROSSROADS? Hypertension (HTN), through its high incidence, prevalence, and dire consequences, remains a major contributor to the global burden of disease. The noncommunicable disease burden now exceeds that of infectious disease even in the developing world, with precious few resources anywhere to manage this burgeoning challenge. Nevertheless, HTN control rates remain unacceptably low. Currently, approximately 73 million Americans have HTN, and blood pressure (BP) is controlled in only around 50% of the cases. Between 1988–1994 and 2007–2010, the prevalence of uncontrolled high BP declined for all age groups. However, in 2007–2010, nearly one half of adults with HTN continued to have uncontrolled high BP. Good, clear guidance about how to screen for, detect, and treat HTN is needed for patients, health-care providers, insurance companies, public health bodies, agencies, and governments. The question we posed in 2014 was whether we have this guidance or whether the multiple overlapping and sometimes even contradictory statements recently issued do not in fact provide a perfect storm of confusion.