Search

The aim of this prospective cohort study was: to identify the association between different biomarkers [proprotein convertase subtilisin/kexin 9-PCSK9, lipoprotein(a)-Lp(a) and high-sensitivity C-reactive protein-hsCRP] and the cardiovascular events; to evaluate the relationship between the 3 biomarkers mentioned above and the renal outcomes that contributed to end-stage renal disease (ESRD).We studied 110 patients with chronic kidney disease (CKD) stages 2 to 4. The identification of the new cardiovascular events and the renal outcomes were performed by clinical and paraclinical explorations.350 patients were examined and 110 (31.4%) were included in this study. The mean age was 55.6 ± 10.9 years, with a higher number of men compared to women. The CKD patients with de novo cardiovascular events and new renal outcome during the study, had significantly increased values of total cholesterol (TC), low density cholesterol lipoprotein (LDL-C) at 6 and 12 months and higher levels of Lp(a), PCSK9, hsCRP and low ankle-brachial index (ABI) and ejection fraction (EF) values compared to patients without cardiovascular and renal events. In CKD patients, PCSK9 220 ng/mL was a predictor of cardiovascular events, while the EF 50% was a predictor for renal outcomes. For CKD patients with PCSK9 220 ng/mL and hsCRP 3 mg/L levels, the time-interval for the new cardiovascular and renal events occurrence were significantly decreased compared to patients displaying low values of these biomarkers.The results of this study show that PCSK9 220 ng/mL was predictor for cardiovascular events, while EF 50% was predictor for CKD progression to ESRD. PCSK9 220 ng/mL and hsCRP 3 mg/L were associated with the occurrence of renal and cardiovascular events earlier.

The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994–2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.

Background: A bidirectional kidney–gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. Materials and methods: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. Results: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. Conclusions: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking.In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management.Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE.Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

Chronic kidney disease (CKD) is a global public health burden, needing comprehensive management for preventing and delaying the progression to advanced CKD. The role of nutritional therapy as a strategy to slow CKD progression and uremia has been recommended for more than a century. Although a consistent body of evidence suggest a benefit of protein restriction therapy, patients’ adherence and compliance have to be considered when prescribing nutritional therapy in advanced CKD patients. Therefore, these prescriptions need to be individualized since some patients may prefer to enjoy their food without restriction, despite knowing the potential importance of dietary therapy in reducing uremic manifestations, maintaining protein-energy status.

First described in 1998, apelin is one of the endogenous ligands of the apelinergic receptor. Since its discovery, its possible role in human physiology and disease has been intensively studied. Apelin is a native cardioprotective agent that the body synthesizes to create atheroprotective, antihypertensive, and regenerative effects in the body. By antagonizing the RAA system, apelin could play an important role in heart failure and hypertension. It is also involved in myocardial protection against ischemia/reperfusion injury, post-ischemic remodeling, and myocardial fibrosis. A small number of studies even suggest that serum apelin levels may be involved the development of life-threatening arrhythmias. All this information generated excitement about potential therapeutic effects in patients with heart failure and myocardial infarction. The therapeutic index of apelin is unknown but is anticipated to be favorable based on the small number of studies. In this review, we summarize the mechanisms by which apelin exerts its cardioprotective effects and its connection with the cardiorenal axis. Also, we report the potential therapeutic applications of synthetic and native regulated apelin. If larger studies can be performed, it is possible that apelin-mediated drug treatment may play a major role for a large number of patients worldwide in the future.

Background Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. Methods In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre–post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. Results According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between −1.1 and 1.1 L, fluid depletion with an AFO below −1.1 L, moderate FO with an AFO compartment >1.1 but 2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22–1.93], HR 2.04 (95% CI 1.59–2.60) and HR 1.88 (95% CI 1.07–3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57–0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11–1.75); severe FO: HR 2.29 (95% CI 2.01–3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05–1.70); severe FO: HR 2.34 (95% CI 1.67–3.28)] as compared with normohydrated patients. Using pre–post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO 1.1 L pre-dialysis and 1.1 L pre-dialysis and between −1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29–5.84)]. Conclusion We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

Adequate assessment of fluid status is an imperative objective in the management of all types of patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension, heart failure, left ventricular hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has received growing attention in clinical research. This article summarizes available studies that compare LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, it also presents the association of LUS with different outcomes (physical functioning, mortality, and cardiovascular events) in the same population. It appears that this simple bedside noninvasive technique has significant clinical potential in nephrology.

Overhydration is a frequent complication in dialysis patients. It has been linked with hypertension, left ventricular hypertrophy, arterial stiffness, atherosclerosis uremic cardiomyopathy, and all-cause mortality or cardiovascular morbidity. In addition, predialysis underhydration is also associated with increased risk of death in ESRD patients. In this context, the optimal evaluation of hydration status is a must. However, this mission is not easy or accurate. In the last 10 years, several new methods have been tested in dialysis patients, particularly bioimpedance and lung ultrasonography. The precise clinical value of these techniques in the daily care of hemodialysis patients is not obvious yet. Sodium is also an important piece of this puzzle. Salt intake and/or removal of sodium during dialysis are essential determinants of optimal hydration status. Recent studies have revealed that salt and water homeostasis is also dependent of tissue sodium storage-increased in hemodialysis patients. However, the significance of increased sodium tissue storage as a cardiovascular risk factor and the relationship between tissue sodium content and hard CV endpoint have not yet been elucidated yet.

There is evidence that serum iron levels, regardless of the presence of anemia, directly impact outcomes in congestive heart failure (CHF) including quality of life, hospitalization rate and overall survival. Despite modern medical treatments, the prognosis of CHF remains grim. Ironically, simple iron replenishment may serve as a powerful tool in the armamentarium. This review will start from fundamental concepts of iron in oxygen delivery and analyze evidence-based outcomes in CHF iron-directed therapeutic trials. Imaging rationale that dovetails with this pathophysiology will also be detailed in a clinician-directed fashion.

Introduction : Fluid overload is one of the most important, yet modifiable, risk factors associated with worse outcomes in hemodialysis (HD) patients. However, its precise assessment in clinical practice is still under investigation. Material and methods : This is an observational prospective study which included 285 stable patients with end-stage renal disease on standard thrice-weekly HD therapy. Overhydration was assessed by the combination of relative fluid overload (RFO), using bioimpedance spectroscopy, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The outcome of interest was all-cause mortality. Results : The median values for NT-proBNP and RFO were 4595 pg/ml and 6.9%, respectively. We divided the study population into four groups according to these median levels: group 1 – low NT-proBNP and low RFO; group 2 – high NT-proBNP and low RFO; group 3 – low NT-proBNP and high RFO; group 4 – high NT-proBNP and high RFO). During the follow-up (mean: 41.1, median: 48.7 months), 89 (31.2%) patients died. In the univariable Cox survival analysis only patients in group 4, and not those from group 2 or 3, had significantly higher HRs as compared to those in group 1 (HR = 1.5, 95% CI: 0.8–2.8, HR = 1.6, 95% CI: 0.8–2.9 and HR = 2.4, 95% CI: 1.3–4.2, for group 2, 3 and 4, respectively). Furthermore, these results were maintained in the multivariable Cox analysis. Conclusions : Including both bioimpedance and NT-proBNP monitoring in a more comprehensive fluid status assessment could improve the diagnosis of fluid overload with a final improvement in patients’ outcome.

See related article, pp 863–869 Children with chronic kidney disease (CKD) have an increased mortality risk during childhood and as a young adult. Precisely, the lifespan of a pediatric patient on dialysis is shortened by 50 years compared with that of control individuals, matched for age and ethnicity.1 Children with end-stage renal disease have a 10-year survival rate of ≈80% and an age-specific mortality rate of ≈30× that seen in children without end-stage renal disease.2 In spite of a lower exposure to classical risk factors (diabetes mellitus, smoking, and hyperlipidemia), the most common cause of death in these children is cardiovascular disease. Hypertension, alterations in mineral metabolism, anemia, or chronic inflammation may explain part of this increased cardiovascular risk. In adults with CKD, increased aortic stiffness may lead to left ventricular hypertrophy and left ventricular dysfunction and is an important independent predictor of future cardiovascular events and mortality. In children with moderate to severe CKD, there are fewer reports showing that arterial stiffness may contribute to cardiovascular morbidity or mortality. In addition, carotid-femoral pulse wave velocity (cfPWV) assessed by applanation tonometry—the most commonly used measure of arterial stiffness—may be challenging to measure, especially in younger children, because it is time-consuming and require patient collaboration.3 Finally, even if the patient is cooperative, it can be more difficult to maintain a sufficiently strong signal from the smaller arteries of younger children. It also requires a trained operator and access to the femoral artery in the inguinal area—a potentially disturbing maneuver, particularly in adolescents. Oscillometric assessment of pulse wave velocity (PWV) using a pressure cuff has the advantages of being quick, convenient, and operator independent.3 In the last 10 years, …

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)—including death, stroke, and myocardial infarction. During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64–1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio—0.81, 95% CI 0.68–0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio—1.26, 95% CI 1.16–1.37). This study shows that a LUS–bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

Atrial fibrillation (AF), one of the most common dysrhythmia in clinical practice, remains frequently in people with chronic kidney disease (CKD). AF is associated with a fivefold risk of stroke, a threefold incidence of heart failure, and an increased risk of death. Co-existence of AF and CKD raises substantially morbidity and mortality. Moreover, the optimal treatment approach (rate versus rhythm control) remains debated due to lack of hard evidence. Oral anticoagulation is challenging, since these patients have both a prothrombotic state and an increased risk of stroke and an inherent platelet and vascular dysfunction and an amplified rate of bleeding. Although promising, the newer anticoagulation agents were not tested in severe CKD. Furthermore, fatal bleeding has been reported.

The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis.This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria 0.3 g per 24 h (urinary protein-creatinine rate 300 mg/g [ 30 mg/mmol]]; partial remission (proteinuria 0.3 but 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events.At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance.Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Management of elderly people with end-stage renal disease is difficult. This type of patients’ needs to know all the proper information about prognosis, about the natural history of their disease without dialysis. Also they need to know all the implications, outcomes and subsequent complications of the diverse dialysis modalities. Elderly patients on dialysis classically receive in center hemodialysis, and only a small proportion is on peritoneal dialysis. However, hemodialysis can be complicated by vascular access- related problems, decreased tolerance to ultrafiltration and an amplified risk of hypotension, brain injury, dementia, and an increased risk of accidental falls. Peritoneal dialysis, an alternative choice, can be problematic because of functional impairment and cognitive dysfunction. Incremental dialysis, changes in hemodialysis frequency, or assisted peritoneal dialysis could be used as a substitute and can ameliorate quality of life in elderly patients.

Vascular calcification (VC) is a common feature of patients with advanced CKD and it could be, at least in part, the cause of increased cardiovascular mortality in these patients. From a morphologic point of view, there are at least two types of pathologic calcium phosphate deposition in the arterial wall—namely, intima calcification (mostly associated with atherosclerotic plaques) and media calcification (associated with stiffening of the vasculature, resulting in significantly adverse cardiovascular outcomes). Although VC was viewed initially as a passive phenomenon, it appears to be a cell-mediated, dynamic, and actively regulated process that closely resembles the formation of normal bone tissue, as discovered recently. VC seems to be the result of the dysregulation of the equilibrium between promoters and inhibitors. The determinants are mostly represented by altered calcium and phosphorus metabolism, secondary hyperparathyroidism, vitamin D excess, high fibroblast growth factor 23, and high levels of indoxyl sulphate or leptin; meanwhile, the inhibitors are vitamin K, fetuin A, matrix G1a protein, osteoprotegerin, and pyrophosphate. A number of non-invasive imaging techniques are available to investigate cardiac and vascular calcification: plain X-rays, to identify macroscopic calcifications of the aorta and peripheral arteries; two-dimensional ultrasound for investigating the calcification of carotid arteries, femoral arteries, and aorta; echocardiography, for assessment of valvular calcification; and, of course, computed tomography technologies, which constitute the gold standard for quantification of coronary artery and aorta calcification. All these methods have a series of advantages and limitations. The treatment/ prevention of VC is currently mostly around calcium-mineral bone disease interventions, and unproven. There are interesting hypotheses around vitamin K, Magnesium, sodium thiosulphate and other potential agents.

Patients with end-stage renal disease (ESRD) have an increased risk of all-cause mortality. The prognostic value of the new cardiac biomarkers, cardiotrophin 1 (CT-1) and galectin 3 (GAL-3), has not yet been defined in hemodialysis (HD) patients. The aim of this study was to determine the use of these novel biomarkers for predicting mortality in HD patients. Plasma GAL-3 and CT-1 concentrations were determined (at baseline) in 88 HD patients followed for 22.2 ± 4.7 months. During the follow-up period, 21 (23.9%) deaths were recorded. According to Cox analysis, the cutoff point for GAL-3 as a predictor of mortality was 23.73 ng/mL, while the cutoff point for CT-1 as a predictor of mortality was 36 pg/mL. In univariate analysis, only GAL-3 >23.73 ng/mL was an independent predictor of mortality (hazard ratio 2.60; 95% confidence interval, 1.09-6.18). In a multivariable Cox proportional hazards model, GAL-3 levels above the cutoff value remained an independent predictor of all-cause mortality. Our data suggest that similar to the general population, GAL-3 is an independent predictor of mortality in HD patients.

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. Two bedside methods are increasingly utilized to evaluate objectively fluid status-bioimpedance and lung ultrasonography, but there is no available direct, head-to-head comparison of their prognostic significance. Importantly, their predictive abilities have never been tested in a HD population, alongside those of a classic model that also incorporates established echocardiographic parameters of increased mortality risk. Between 26 May 2011 and 26 October 2012, we included in the study 173 patients undergoing chronic HD treatment for at least 3 months in a single dialysis unit. Relative fluid overload (RFO) and B-lines score (BLS) were used as candidate predictors. From Cox survival analysis we evaluated the increase in the predictive abilities for all-cause mortality of adding continuous RFO or BLS to a model including conventional predictors . 31 patients (17.9 %) died during a median follow-up of 21.3 (interquartile range 19.9-30.3) months. All Cox models showed good calibration. The C statistic for the all-cause mortality prediction increased significantly when the RFO was included into the baseline model (ΔC statistics 0.058 95 %CI = 0.003-0.114), but not when the BLS was included into the baseline model. Only the model that incorporated RFO showed significantly better risk reclassification abilities than the baseline model (IDI = 3.6 % and continuous NRI = 24.8 %). Fluid overload, as assessed by bioimpedance, and not by lung ultrasonography, improves risk prediction for death, beyond classical and echocardiographic-based risk prediction scores/parameters.

The aim of the study was to evaluate the correlation between electrocardiographic parameters and heart rate variability with cardiovascular events and mortality among chronic hemodialysis patients. In this prospective study, we enrolled 116 asymptomatic patients in whom we performed ambulatory 24-h electrocardiographic Holter monitoring and before and after hemodialysis electrocardiographs. We measured the interval (PR, QRS, QTc, QTc dispersion) differences on the surface electrocardiographs and obtained frequency-domain measures from Holter monitoring (VLF, LF, HF and the LF/HF ratio). During the follow-up period, 13 participants died (11.2 %) and 16 (13.8 %) patients experienced a cardiovascular event. The pre–post-dialysis difference in QTc interval was the best predictor for cardiovascular events (95 % CI 0.453–0.786), while pre-dialysis QRS interval was the predictor for all-cause mortality (95 % CI 1.134–3.136). Also, both outcomes were predicted by pre–post-dialysis difference in PR interval and VLF. Interval changes during hemodialysis are predictive for cardiovascular events and mortality. Autonomic dysfunction and changes in PR should be monitored routinely, particularly in patients with suspected coronary artery disease.

Patients with chronic kidney disease (CKD) have an increased cardiovascular (CV) risk and a higher mortality rate. This case report aims to reveal the prognostic value of cardiac biomarkers in patients with CKD stage 5 on dialysis. Several biomarkers have proven their utility for early detection of CV risk in dialysis patients. Most promising biomarkers are: N-terminal pro–B-type (NT-proBNP), high sensitivity cardiac troponin T (Hs–cTnT), Cardiotrophin-1 (CT-1) and Galectin-3 (GAL-3). We report the case of a 44 year-old woman with end stage renal disease on dialysis without any cardiac pathology, but who had, at screening evaluation, high values of cardiac biomarkers, with increasing levels of NT-proBNP at serial determination; Hs-cTnT was constant. Recently, our patient was admitted in cardiology unit with unstable ischemic cardiopathy. In this context, we review the prognostic value of cardiac biomarkers in CV morbidity and mortality. The particularity of this case was the preemptive assessment of cardiac biomarkers. High serum levels of these biomarkers, in a patient without any cardiac concerns at evaluation moment, should promote for early invasive investigations.

The most important studies – from randomized controlled trials to perspective studies and meta-analyses, and guidelines in the topics of blood pressure and kidney research published in 2016 (and at the beginning of 2017) were reviewed. In the blood pressure area, the most important were the Systolic Blood Pressure Intervention Trial (SPRINT), which might have a great impact on the clinical practice as well as on the forthcoming guidelines, including the US recommendations recently published. Similarly important was the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, which clearly confirmed that only combination therapy with antihypertensive drugs and statins might be effective in prevention of cardiovascular outcomes in patients at high risk of cardiovascular disease events. The research on kidney diseases was very interesting and extensive in 2016, and we have tried to present the most important data from the following areas: glomerulopathies, diabetic nephropathy, lupus nephritis, acute kidney injury, chronic kidney disease – risk factors, management and complications, and hemodialysis.

Cardiovascular (CV) disease is a major cause of death in hemodialysis patients. Biomarkers used to identify high-risk asymptomatic patients would allow early evaluation of cardiac dysfunction and appropriate therapeutic intervention. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 (Gal-3) may serve this purpose. Plasma levels of NT-proBNP and Gal-3 were measured in 173 patients. Patients were prospectively followed for occurrences of major CV events or death. The association of NT-proBNP and Gal-3 with outcome was analyzed. The prognostic abilities for the combined outcome of Gal-3 and/or NT-proBNP were evaluated. During a median follow-up of 36 months, there were 47 incident outcomes (death and CV events). In the univariable Cox analysis, age, hypertension, albumin, phosphorus levels, and combined elevation of NT-proBNP with Gal-3 above the median (hazard ratio [HR] = 3.65, 95% confidence interval [CI] = 1.45-9.21) were associated with outcomes. In multivariable Cox analysis, both NT-proBNP and Gal-3 values above the median remained associated with outcomes (HR = 3.34, 95% CI = 1.30-8.56). In clinically asymptomatic dialysis patients, combined use of NT-proBNP and Gal-3 may improve risk stratification for death and CV events.

Background: Although chronic kidney disease (CKD) is an independent risk factor for stroke, official recommendations for the primary prevention of stroke in CKD are generally lacking. Summary: We searched PubMed and ISI Web of Science for randomised controlled trials, observational studies, reviews, meta-analyses and guidelines referring to measures of stroke prevention or to the treatment of stroke-associated risk factors (cardiovascular disease in general and atrial fibrillation (AF), arterial hypertension or carotid artery disease in particular) among the CKD population. The use of oral anticoagulation in AF appears safe in non-end stage CKD, but it should be individualized and preferably based on thromboembolic and bleeding stratification algorithms. Non-vitamin K antagonist oral anticoagulants with definite dose adjustment are generally preferred over vitamin K antagonists in mild and moderate CKD and their indications have started being extended to severe CKD and dialysis also. Aspirin, but not clopidogrel, has limited indications for reducing the risk for atherothrombotic events in CKD due to its increased bleeding risk. Carotid endarterectomy has shown promising results for stroke risk reduction in CKD patients with high-grade symptomatic carotid stenosis. The medical treatment of arterial hypertension in CKD often fails to efficiently lower blood pressure values, but recent data regarding the use of interventional procedures such as renal denervation, baroreflex activation therapy or renal artery stenting are encouraging. Key Messages: In the absence of clear guidelines and protocols, primary prevention of stroke in CKD patients remains a subtle art in the hands of the clinicians. Nevertheless, refraining CKD patients from standard therapies often worsens their prognosis.

In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD. Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study. One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3–1.2, p = 0.15; HR 0.56, 95% CI 0.26–1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p

Background Chronic subclinical volume overload happens very frequently in hemodialysis patients and is associated directly with hypertension, increased arterial stiffness, left ventricular hypertrophy, and ultimately higher mortality. Study Design Randomized controlled parallel-group trial. Setting & Participants 131 patients from one hemodialysis center, randomly assigned into 2 groups. Intervention Dry weight prescription using results derived from repeated 3-month bioimpedance measurements to guide ultrafiltration for strict volume control (bioimpedance group; n=62) compared with clinical judgment without bioimpedance measures (clinical-methods group; n=69) for 2.5 years. Outcomes The primary outcome was all-cause mortality over 2.5 years (the duration of the intervention). Secondary outcomes were change in relative arterial stiffness, fluid overload, and blood pressure (BP) over 2.5 years. Measurements Bioimpedance measurements were performed using a Body Composition Monitor device. Pulse wave velocity analysis was performed at baseline, 2.5 years (end of intervention), and 3.5 years (end of study). Relative fluid overload and BP were assessed at 3-month intervals. Results The unadjusted HR for all-cause death in the bioimpedance group (vs the clinical-methods group) was 0.100 (95% CI, 0.013-0.805; P =0.03). After 2.5 years, we found a greater decline in arterial stiffness, relative fluid overload, and systolic BP in the bioimpedance group than the clinical-methods group. Between-group differences in change from baseline to the end of intervention were −2.78 (95% CI, −3.75 to 1.80)m/s for pulse wave velocity ( P P =0.05), and −2.43 (95% CI, −7.70 to 2.84)mmHg for systolic BP ( P =0.4). Limitations Echocardiography was not performed as cardiovascular assessment and the caregivers were not masked to the intervention. Conclusions Our study showed improvement in both surrogate and hard end points after strict volume control using bioimpedance to guide dry weight adjustment. These findings need to be confirmed in a larger trial.

Hypertension is one of the most common worldwide diseases. Is linked with increased morbidity and mortality and amplified costs to society; in this context, preventing and treating hypertension is an imperative public health challenge. Unidentified, clinically unapparent volume expansion is an important cause for hypertension. Optimization of fluid status was associated with an improvement in BP control, a substantial regression of the left ventricular mass index, arterial stiffness and better survival rate in several cohorts. Clinical assessment of hydration status is an inaccurate clinical science. Bioimpedance provides a noninvasive and reliable, simple, reproducible technology for diagnosing subclinical fluid accumulation. Several small studies and a recent meta-analysis performed in patients with resistant hypertension reported an improved BP control in the impedance treated group compared with the group of patients treated as per clinical judgment alone. A combined approach (using both sphygmomanometers and bioimpedance) and individualized antihypertensive treatment in hypertensive's patients it seems probable to improve BP control and possibly end organ damage. i 2014 S. Karger AG, Basel

The use of lung ultrasonography to evaluate extravascular lung water and its consequences has received growing attention in different clinical areas, including, in recent years, end-stage renal disease patients treated by haemodialysis (HD). Lung congestion is a direct consequence of either overall overhydration and/or cardiac dysfunction, but the exact contribution of each of these tests to mortality is unknown.In this prospective observational study, we enrolled 96 patients from a single HD unit undergoing thrice weekly HD. We used three different methods of evaluation: lung ultrasonography (pre- and post-dialysis), bioimpedance spectroscopy (pre- and post-dialysis) and echocardiography (pre-dialysis). The objective of the study was to test for the first time the prognostic value of ultrasound lung comets (ULC) combined with bioimpedance-derived data [total body water (TBW), extravascular water, hydration status-ΔHS] and several echocardiographic parameters. Mortality was analysed after a median of 405.5-day follow-up.Pre-dialysis lung congestion was classified as moderate (ULC = 16-30) in 19.8% of the patients and severe in 12.5% of patients (ULC30), while only 19.8% appear to be hyperhydrated (ΔHS15%). The pre-dialysis ultrasound lung congestion score correlated significantly with all of the bioimpedance-derived parameters. In a multivariate Cox model that included ULC score, demographic, ecocardiographic and bioimpedance parameters, the factors that remained significantly associated with survival time were the pre-dialysis ULC score and left ventricular mass index. The pre-HD ULC score has a significant discriminating power for survival, while the bioimpedance-derived hydration status has no discriminatory abilities in terms of survival.To our knowledge, this study is the first one that compares three different strategies to predict mortality in haemodialysed patients. The lung comet score emerged as the best predictor for the relationship hydration status-mortality, independently of bioimpedance-derived parameters in this population.

Worldwide, it is estimated that more than 1 billion adults have hypertension; its prevalence is projected to climb to 1.5 billion by the year 2025 (World Health Organization. A global brief on hypertension. WHO/DCO/WHD/2013.2. April 3, 2013 (http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf)); it is associated with premature death, stroke, and heart disease. The pathogenesis of hypertension is complex, involving increased systemic vascular resistance, arterial stiffening, cardiac output, excess salt intake, fluid retention, or a combination of all of these factors. The kidney plays an essential role in blood pressure (BP) pathogenesis, by appropriate renal adjustments of sodium balance and blood volume.

Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population. J Atheroscler Thromb, 2013; 20:000-000.

Periodontal disease is a chronic infectious disease. Individuals with end-stage kidney disease (ESKD) experience impaired quality of life (QoL) and low oral health. This is the first comprehensive study which aimed to explore the link between periodontal disease and quality of life, assessed with the Short Form 36-Item Health Survey in hemodialysis patients. In total, 101 patients (57 females) with ESKD were recruited from two Romanian dialysis centers. Periodontal disease assessment included the measurement of periodontal disease index, with its three components: the gingival and periodontal index (GP), the bacterial plaque index (PI) and the calculus index (CI). For assessing QoL, we used the Short Form 36-Item Health Survey (SF-36), with its two components: physical component (PCS) and mental component (MCS). The mean age was 52.5 ± 14.3 years. The dialysis vintage was 6.7 ± 5.6 years. According to periodontal status, the mean value of GP was 4.0 ± 1.3, mean PI was 1.8 ± 0.9, and mean CI was 1.3 ± 0.7. Regarding the QoL, the means for PCS and MCS were 38.0 ± 17.3 and 45.0 ± 16.3, respectively. In univariate analysis, the physical and mental components of QoL were significantly associated with the gingival and periodontal index, the bacterial plaque index and the calculus index. In the multivariable linear regression, only the gingival and periodontal index remained significantly associated with physical component (β = −3.26, p = 0.04, 95% CI −6.39 to −0.13) and mental component (β = −5.57, p = 0.001, 95% CI −8.74 to −2.41) of QoL. Our study shows a high prevalence and severity of periodontal disease. The gingival and periodontal index was associated with low QoL, both on physical and on mental components.

Introduction In ST-elevation myocardial infarction (STEMI) patients, multisite artery disease represents a serious issue influencing evolution, outcomes and prognosis. We evaluated for the first time the power of the Myocardial Infarction SYNTAX Score (MI SS) and Clinical SYNTAX Score (MI CSS) as predictors for renal artery stenosis (RAS) in STEMI. We also stratified the study population according to the two scores, and identified the variables correlated with the higher score. Material and methods We used data from the REN-ACS study, which included 181 consecutive patients prospectively investigated for presence of RAS (through renal angiography), arterial stiffness (carotid-femoral pulse wave velocity, cf-PWV) and hydration status (bioimpedance). MI SS and CSS were computed. Results Multivariate regressions indicated that the independent variables correlated with MI SS were left ventricular ejection fraction < 40%, significant RAS (> 50%, defined as RAS+), history of heart failure, and multivascular coronary disease (CAD, p < 0.03 for each), while those correlated with MI CSS were RAS+, cf-PWV, history of CAD, multivascular CAD, cholesterol, and total body water (p < 0.02 for each). In order to evaluate the ability to predict RAS+ we generated receiver operating characteristics and areas under curves, and the Youden index for MI SS and CSS. Conclusions Both scores correlated with extensive atherosclerotic disease and presence of RAS+. A lower CSS proved to be a good predictor for exclusion of RAS+, with high specificity (85%) and negative predictive value (92%), and fair sensitivity (60%). We aim to further pursue this line of research and design a better predictor for RAS, with the inclusion of a novel biomarker in order to increase sensitivity.

In this pro-con debate, we will analyse the relevance of data supporting the prime role of uraemic toxins versus salt and volume overload as the main driver for the impressive mortality and morbidity characteristic of any end-stage re- nal disease patient. Firstly, we are going to review the circumstantial evidence and associated studies/clinical observational data which only weakly suggest that uraemic solutes are indeed linked to damage to the body and its constituents, especially the car- diovascular (CV) system. At the same time, we will equally thoroughly discuss the 'fact' that decreasing salt and fluid load is essential for any dialysed patient. Evidence in favour of a prominent role for uraemic toxins is appealing from a pathophysiological point of view, but unfortunately is mis- leading in real life practice. Evidence in favour of salt and water reduction is overwhelmingly stronger. This difference in apparent evidence strength notwith- standing the weaker support for uraemic toxins does not take away from clinical importance of minimizing uraemic tox- icity load in the large majority of the dialysis population. filtration (HDF) or more frequent/longer dialysis, was only partially associated with better results. Moreover, in the ma- jority of the positive studies, alternative interpretations of the results is possible, including a contribution of better volume control achievable with these particular dialysis techniques. Some 'observational' studies (2-7) showed a beneficial effect of high-flux versus low-flux synthetic dialysis mem- branes on survival, whereas prospective random controlled trials (RCTs) were inconclusive. In the Haemodialysis (HEMO) study, the largest random- ized clinical trial conducted in haemodialysis (HD) so far, patients were randomized to either a high-dialysis dose (achieved eKt/V ¼ 1.53 � 0.09, sp Kt/V ¼ 1.71 � 0.11) or a standard-dose goal (achieved eKt/V ¼ 1.16 � 0.08, sp Kt/V ¼ 1.32 � 0.09) and to dialysis with either high-flux dialysers (b2-microglobulin clearance of > 20 mL/min) or to low-flux dialysers—(b2-microglobulin clearance < 10 mL/ min). The results showed that a higher HD dose was not associated with a lower mortality risk compared with con- ventional HD dose (8). Thus, while a minimumKt/V ,a ccord- ing to the guidelines, is mandatory, the HEMO study clearly demonstrated that there are no advantages in further increas- ing the urea Kt/V, even in the high-flux membrane group. At the same time, each 10 mg/L increase in b2-M level was associated with an 11% increase in mortality, even after ad- justment for years on dialysis and residual kidney function. These results deserve further specifically designed studies in order to clarify if it is a matter of larger molecule removal or better fluid removal. In the other large trial in the field, the Membrane Perme- ability Outcome study, there was no significant difference in survival between high- and low-flux groups when all patients were included in the analysis (9). However, patients with serum albumin � 40 g/L on enrolment and with diabetes had a significantly better survival in the high-flux arm. High-flux dialysis was associated with a significantly lower accumulation of b2-microglobulin. Again, it is important to clarify if the better outcome was related to larger molecule removal or better fluid removal. Compared with conventional HD, HDF could theoretically offer some advantages: better clearance of middle- and

The most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2015 were reviewed. In lipid research, the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial revalidated the concept “lower is better” for low density lipoprotein (LDL)-cholesterol as a target for therapy, increasing the necessity of treatment the high-risk patients to achieve LDL-C goals. After these results, ezetimibe might become the preferred additional drug in the combination therapy of lipid disorders because of oral dosage form and lower acquisition cost. However, for the statin-intolerant patients and those patients requiring essential reductions in LDL-C to achieve their goals, new therapies, including PCSK9 inhibitors remain promising drugs. In blood pressure research, American Heart Association (AHA)/American College of Cardiology (ACC) 2015 guidelines recommended a target for blood pressure below 140/90 mmHg in stable or unstable coronary artery disease patients and below 150/90 mmHg in patients older than 80 years of age, however the recent results of the Systolic Blood Pressure Intervention Trial (SPRINT) trial have suggested that there might be significant benefits, taking into account cardiovascular risk, for hypertensive patients over 50 without diabetes and blood pressure levels

Dialysis patients exhibit higher rates of death compared withthe general population [1], with an almost similar increase inthe proportion of cardiovascular (CV) and non-CV deaths[1]; however, the CV mortality risk in patients starting dialy-sis is much higher compared with the general population(unstandardized CV risk—15-fold higher/age-standardizedCV risk—8.8 higher than in matched individuals from thegeneral population) [1] and is not determined by the samerisk factors. Indeed, classical atherosclerotic disease is not themost important and common cause of death in a moderndialysis population. Sudden cardiac death (SCD) [2] andheart failure are the most frequent forms of death in dialysispatients; the overall incidence of these events is much greaterthan the incidence of coronary events [3]. Moreover, the riskpersists after coronary vascularization [4]. Important factorsfor this significant CV morbidity include left ventricular (LV)hypertrophy, electrolyte shifts during haemodialysis (HD),poor volume control [5] and abnormalities in myocardialultra-structure and function, including endothelial dysfunc-tion, interstitial fibrosis, impaired coronary flow reserve anddiminished ischaemia tolerance.One potential important player in the mechanisms behindthis excess mortality is the HD procedure. It is obvious thatthe HD procedure is stressful for the CV system; almost 30%of HD sessions are associated with significant intra-dialytic hy-potension [6]. Intermittent HD treatments may induce globaland segmental myocardial ischaemia [7, 8]. This was suggestedby Selby’s studies using echocardiography [9, 10] and cardiactroponin levels [11] and by Singh et al.[12] using 99Tc-sesta-mibi single-photon emission computed tomography. Confir-mation that an HD session is undeniably capable of inducingregional myocardial ischaemia was provided recently by McIn-tyre et al. [7]. Using intra-dialytic H215O positron emissiontomography and echocardiography, they showed that HDtreatment elicited reversible (LV) regional wall motion ab-normalities (RWMAs) with matched reductions in myocardialblood flow (MBF). Dasselaar et al.[8] reconfirmed 1 year laterthese results in non-diabetic non-cardiac-compromisedpatients. They observed a significant reduction in MBF, earlyduring dialyses that were not accompanied by significant fluidremoval.In the general population, repeated episodes of transientmyocardial ischaemia lead to a spectrum of disease encom-passing myocardial stunning, myocardial hibernation andending in myocardial remodelling and scarring, with irrevers-ible loss of contractile function. Myocardial stunning isdefined as a prolonged LV dysfunction without histologicalsigns of irreversible injury to cardiomyocytes. It occurs eachtime when ischaemia and reperfusion are present: in patientswith coronary artery disease, after percutaneous transluminalcoronary angioplasty, after coronary bypass or cardiac trans-plantation or following resuscitation. Myocardial stunninghas been well described in the general population as a causa-tive mechanism for heart failure [9]. Myocardial hibernationis described also as depressed myocardial contractility, butthe ischaemic myocardium remains viable and the LV dys-function can be partially or completely restored to normality,by improving/restoring blood flow. In pathophysiologicalterms, a severe reduction in coronary flow reserve is commonfor both conditions, and recovery of function is paralleled byrestoration of an adequate coronary flow reserve.The reduction in MBF during HD is associated with myo-cardial remodelling and eventually non-viable myocardiumwith irreversible reduction in LV function. This processbecomes increasingly appreciated as a principal pathophysio-logic contributor to the excess CV mortality in HD patients