Search

BackgroundResidual renal function (RRF) affects sodium and fluid balance. The aim of this analysis was to examine the impact of RRF on the effect of a sodium-reduced peritoneal dialysis fluid (PDF) on blood pressure (BP).MethodsThis is a post-hoc analysis of a prospective, randomized, controlled double-blind clinical trial with 82 patients on continuous ambulatory PD (CAPD) treated with a low-sodium (125 mmol/L Na) or a standard-sodium (134 mmol/L Na) PDF. Subgroups according to glomerular filtration rate (GFR) at baseline (≤ / > 6 mL/min/1.73 m2) were analyzed for BP and antihypertensive medication.ResultsIn the low-GFR group on low-sodium PDF ( N = 26), systolic BP was reduced from 152 ± 24 mmHg at baseline to 137 ± 21 mmHg at week 12, diastolic BP from 90 ± 16 mmHg to 83 ± 11 mmHg. In the low-GFR group on standard-sodium PDF and in the high-GFR group on both PDF types, only minor changes were observed. For the low-GFR subgroup, the confounder-adjusted mean study group difference in systolic BP at week 12 between low-sodium and standard-sodium PDF was -16.9 (95% confidence interval [CI] -27.2 to -6.6) mmHg, for diastolic BP, it was -7.0 (95% CI -12.6 to -1.4) mmHg. In both GFR subgroups, more patients had a reduced daily dose of antihypertensive medication and fewer patients an increased daily dose in the low-sodium compared with the standard-sodium group at week 12.ConclusionsThe reduction of BP with a sodium-reduced PDF seems to be more effective in patients with no or low RRF than in patients with residual capacity of renal sodium and fluid control.

Background: Calcium (Ca) is an essential element that plays a critical role in many biological processes. In dialysis patients, the regulation of Ca balance is highly complex, given the absence of kidney function, endocrine disturbances and the use of drugs such as phosphate binders, vitamin D analogues, and calcimimetics. Also, the use of different dialysate Ca (DCa) baths has profound effect on Ca balance, which depends both on the difference between the Ca concentration in the bath and the serum of the patients, as on the ultrafiltration volume. Summary: The choice of DCa may have important short- and long-term consequences. While lower DCa (especially < 2.5 mEq/L) concentrations have been associated with an increased risk of sudden cardiac death in observational studies, DCa in the higher ranges (3.0 mEq/L and above) may contribute to vascular pathology. Intra-dialytic hemodynamics may also be affected by the choice of DCa. In general, lower DCa concentrations are associated with an increase, and higher DCa concentrations with a decrease in parathyroid hormone (PTH) levels. Preliminary data has suggested that a DCa of 2.75 mEq/L may help in obtaining a net zero intradialytic Ca balance in individual patients, but clinical experience is still limited. Key Message: The optimal Ca balance depends on multiple parameters including blood Ca levels, PTH and the use of phosphate binders and vitamin D analogues, as well as on the risk of hemodynamic stability and cardiac arrhythmias. Therefore, DCa prescription should be individualised. A DCa of 2.75 mEq/L may be useful adjunct for dialysis providers.

Contains fulltext : 190533.pdf (Publisher’s version ) (Open Access) BACKGROUND: Red cell distribution width (RDW) is a standard component of the automated blood count, and is of prognostic value in heart failure and coronary heart disease. We investigated the association between RDW and cardiovascular events in patients with adult congenital heart disease (ACHD). METHODS AND RESULTS: In this prospective cohort study, 602 consecutive patients with ACHD who routinely visited the outpatient clinic were enrolled between 2011 and 2013. RDW was measured in fresh venous blood samples at inclusion in 592 patients (median age 33 [IQR 25-41] years, 58% male, 90% NYHA I) and at four annual follow-up visits. During 4.3 [IQR 3.8-4.7] years of follow-up, the primary endpoint (death, heart failure, hospitalization, arrhythmia, thromboembolic events, cardiac intervention) occurred in 196 patients (33%). Median RDW was 13.4 (12.8-14.1)% versus 12.9 (12.5-13.4)% in patients with and without the primary endpoint (P

Die multifaktorielle Genese kardiovaskularer Erkrankungen hat in der Primar- und Sekundarprophylaxe zur Polypharmazie mit evidenzbasierten Therapeutika wie Statinen, Antihypertensiva und Thrombozytenhemmern gefuhrt. Die Anzahl verschriebener Phamaka korreliert umgekehrt mit der Adharenz, was die Effektivitat der Therapie beeintrachtigen kann. Fixe Kombinationspraparate („Polypill“) konnten die Adharenz der Patienten steigern und damit kardiovaskularen Ereignissen vorbeugen. Literaturrecherche in Medline (via PubMed) und The Cochrane Library sowie der Studiendatenbank ClinicalTrials.gov. In den bisher durchgefuhrten Studien zur kardiovaskularen Primarpravention zeigt die Polypill eine uberlegene Kontrolle der Risikofaktoren (Hypertonie, „Low-density-lipoprotein“-Cholesterin [LDL-C]) gegenuber Placebo und gegenuber einer Standardtherapie aus Einzelpraparaten mindestens eine Nichtunterlegenheit. In der Sekundarpravention zeigen Kombinationspraparate vorwiegend Vorteile bei nichtadharenten Patienten bezuglich Blutdruckkontrolle und Reduktion der LDL-C-Konzentration. Der Nachweis, dass die Polypill die kardiovaskulare Morbiditat und Mortalitat gegenuber einer Standardtherapie absenkt, steht aus. Kombinationspraparate sind nach Risiko-Nutzen-Einschatzung als Alternative zur Polypharmazie, insbesondere bei nichtadharenten Patienten in Erwagung zu ziehen. Inwieweit durch die erwiesene Senkung der Risikofaktoren kardiovaskulare Ereignisse verhindert werden konnen, ist Gegenstand laufender Untersuchungen. Limitiert sind die gegenwartigen Polypills durch eine zu geringe Auswahl an Dosierungen der Einzelwirkstoffe, um eine Uber- und Untertherapie in der individuellen Behandlung zu vermeiden.

Purpose Lymphedema is a chronic and disabling sequel of breast cancer treatment that can be treated by lymphatico-venous anastomosis (LVA). Artificial connections between the venous and lymphatic system are performed supermicrosurgically. This prospective study analyses the effect of LVA on quality of life. Methods A prospective study was performed between November 2015 and July 2016 on consecutive patients in the Maastricht University Medical Centre. Quality of life was considered as the primary outcome, and the Lymphedema International Classification of Functioning (Lymph-ICF) questionnaire was used. Discontinuation of compressive stockings and arm volume, using the Upper Extremity Lymphedema index (UEL-index), were the secondary outcomes. Results Twenty women with early-stage breast cancer-related lymphedema (BCRL) were included. The mean age was 55.9 ± 4 years and the median BMI was 25.1 [21–30] kg/m2. The mean follow-up was 7.8 ± 1.5 months. Statistically significant improvement in quality of life was achieved in the total score and for all the quality of life domains after one year of follow-up (p

The title of the recent editorial by Prof. Kjeldsen et al. [1] suggests that the latest guidelines of the International Society of Hypertension (ISH) [2] have introduced a drug treatment recommenda...

Brown adipose tissue (BAT) is known to secrete regulatory factors in response to thermogenic stimuli. Components of the BAT secretome may exert local effects that contribute to BAT recruitment and activation. Here, we found that a thermogenic stimulus leads to enhanced secretion of kininogen (Kng) by BAT, owing to induction of kininogen 2 (Kng2) gene expression. Noradrenergic, cAMP-mediated signals induce KNG2 expression and release in brown adipocytes. Conversely, the expression of kinin receptors, that are activated by the Kng products bradykinin and [Des-Arg9]-bradykinin, are repressed by thermogenic activation of BAT in vivo and of brown adipocytes in vitro. Loss-of-function models for Kng (the circulating-Kng-deficient BN/Ka rat) and bradykinin (pharmacological inhibition of kinin receptors, kinin receptor-null mice) signaling were coincident in showing abnormal overactivation of BAT. Studies in vitro indicated that Kng and bradykinin exert repressive effects on brown adipocyte thermogenic activity by interfering the PKA/p38 MAPK pathway of control of Ucp1 gene transcription, whereas impaired kinin receptor expression enhances it. Our findings identify the kallikrein–kinin system as a relevant component of BAT thermogenic regulation that provides auto-regulatory inhibitory signaling to BAT., Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

Raised blood pressure is the biggest single risk factor responsible for mortality worldwide. Despite this, the majority of people with hypertension are unaware of having it, are untreated, or are on treatment but uncontrolled. May Measurement Month is a global campaign initiated by the International Society of Hypertension with the aim of raising awareness of high blood pressure. In the first year of the campaign in 2017, over 1.2 million people were screened in 80 countries across the world, finding over 100 000 people with hypertension who were not on treatment and over 150 000 people on anti-hypertensive treatment who were not controlled. The individual national results from 39 countries are presented in this supplement. In this article, we discuss the background to the campaign, along with some of the logistical and methodological challenges that were faced in setting up the campaign, and in collecting and analysing the data from such a large cross-sectional study. With the lessons learned from the 2017 campaign, the campaign was repeated in 2018 and is to be repeated again in 2019.

BackgroundCardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited.MethodsWe examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N-is an element of-(carboxymethyl) lysine (CML), N-is an element of-(carboxyethyl) lysine (CEL), N-delta-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-alpha.ResultsAfter adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI.ConclusionsIn individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.

INTRODUCTION: The concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate. The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum.METHODS: Chronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles.RESULTS: Eighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90-152]min) compared to A1.25 (83 [43-108]min, pCONCLUSION: Calcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.

Background Health-related quality of life (HrQoL) varies among dialysis patients. However, little is known about the association of dialysis modality with HrQoL over time. We describe longitudinal patterns of HrQoL among chronic dialysis patients by treatment modality. Methods National retrospective cohort study of adult patients who initiated in-center dialysis or a home modality (peritoneal or home hemodialysis) between 1/2013 and 6/2015. Patients remained on the same modality for the first 120 days of the first two years. HrQoL was assessed by the Kidney Disease and Quality of Life-36 (KDQOL) survey in the first 120 days of the first two years after dialysis initiation. Home modality patients were matched to in-center patients in a 1:5 fashion. Results In-center (n=4234) and home modality (n=880) patients had similar demographic and clinical characteristics. In-center dialysis patients had lower mean KDQOL scores across several domains compared to home modality patients. For patients who remained on the same modality, there was no change in HrQoL. However, there were trends towards clinically meaningful changes in several aspects of HrQoL for patients who switched modalities. Specifically, physical functioning decreased for patients who switched from home to in-center dialysis (p< 0.05). Conclusions Among a national cohort of chronic dialysis patients, there was a trend towards different patterns of HrQoL life that were only observed among patients who changed modality. Patients who switched from home to in-center modalities had significant lower physical functioning over time. Providers and patients should be mindful of HrQoL changes that may occur with dialysis modality change. Electronic supplementary material The online version of this article (10.1186/s12882-018-1198-5) contains supplementary material, which is available to authorized users.

Background: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality. Methods: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2. Results: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 > 11% was associated with a significantly increased HR for all-cause mortality. Conclusion: High ScvO2 variability during dialysis is associated with increased all-cause mortality.

Contains fulltext : 196098.pdf (Publisher’s version ) (Open Access) BACKGROUND: Peripheral arterial disease (PAD) is a global health problem that is frequently underdiagnosed and undertreated. Noninvasive tools to predict the presence and severity of PAD have limitations including inaccuracy, cost, or need for intravenous contrast and ionizing radiation. HYPOTHESIS: A clinical/biomarker score may offer an attractive alternative diagnostic method for PAD. METHODS: In a prospective cohort of 354 patients referred for diagnostic peripheral and/or coronary angiography, predictors of >/=50% stenosis in >/=1 peripheral vessel (carotid/subclavian, renal, or lower extremity arteries) were identified from >50 clinical variables and 109 biomarkers. Machine learning identified variables predictive of obstructive PAD; a score derived from the final model was developed. RESULTS: The score consisted of 1 clinical variable (history of hypertension) and 6 biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1, and eotaxin-1). The model had an in-sample area under the receiver operating characteristic curve of 0.85 for obstructive PAD and a cross-validated area under the curve of 0.84; higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 65% sensitivity, 88% specificity, 76% positive predictive value (PPV), and 81% negative predictive value (NPV) for obstructive PAD and performed consistently across vascular territories. Partitioning the score into 5 levels resulted in a PPV of 86% and NPV of 98% in the highest and lowest levels, respectively. Elevated score was associated with shorter time to revascularization during 4.3 years of follow-up. CONCLUSIONS: A clinical/biomarker score demonstrates high accuracy for predicting the presence of PAD.

Background: The local recurrence rate in oral squamous cell cancer (OSCC) hardly decreases. This is partly due to the presence of (pre) malignant cells in the remaining tissue after resection, that may lead to the development of a new tumor in time. Detection of histologically (pre) malignant cells in the tumor resection margins should predict these patients at risk for recurrence, however this appears to be difficult in routine practice. Purpose of this study was to apply easy-to-use molecular tests for more accurate detection of (pre) malignant cells in histopathologically tumor-free margins, to improve diagnosis of patients at risk.Methods: 42 patients with firstly diagnosed, radically resected primary OSCC with histopathologically confirmed tumor-free resection margins (treated between 1994 and 2003) were included. Inclusion criteria comprised of follow-up >= 5 years, and radical surgery without postoperative treatment. Formalinf-ixed paraffine-embedded tissue sections of 42 tumors, 290 resection margins, and 11 recurrences were subjected to fluorescence in situ hybridization (FISH) to examine chromosome 1 and 7 copy number variations (CNV), and to p53 immunohistochemistry (IHC).Results: 11 out of the 42 patients developed a local recurrence within 5 years. FISH analysis showed that nine of eleven recurrences exhibited CI in at least one of the resection margins (p = 0.008). P53 overexpression and routine histopathologic classification were not correlated with recurrent disease. The presence of CI in the resection margins revealed a significantly worse progression-free survival (log-rank p = 0.012).Conclusions: CI in the resection margins of OSCC can reliably identify patients at risk for developing a local recurrence. (C) 2016 Elsevier Ltd. All rights reserved.