Age-related and prognostic risk factors in dialysis patients

The replacement of renal function by dialysis is one of the major achievements of modern medicine. However, given the fact that renal failure shares common causes with cardiovascular diseases, dialysis patients are a population with a risk profile of almost unique severity. In fact, it was remarked that the risk of cardiovascular death of a young man (<30 years) on dialysis equals that of a healthy man over 85 years in the general population, suggesting that the pathogenetic processes linked to aging may be accelerated in dialysis patients

Telecommuting, Off-Time Work, and Intrusive Leadership in Workers' Well-Being

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the COVID-19 pandemic. There is still limited evidence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telecommuting to fill out a questionnaire to evaluate intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (Bergen Work Addiction Scale (BWAS)), effort/reward imbalance (ERI), happiness, and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occupational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety, and depression. These results indicate the need to guarantee the right to disconnect to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism

Effects of Vitamin E-Coated versus Conventional Membranes in Chronic Hemodialysis Patients: A Systematic Review and Meta-Analysis

Introduction: Accruing evidence suggests that vitamin E-coated membranes (ViE-m) might improve the clinical management of chronic hemodialysis (HD) patients. Methods: We conducted a systematic review and meta-analysis of RCTs comparing ViE-m to conventional HD. Endpoints of interest were a series of biomarkers pertaining to anemia status, inflammation, oxidative stress and dialysis efficacy/status. Results: Sixty studies were included. ViE-m significantly improved the Erythropoietin Resistance Index but had no impact on other anemia parameters. As for oxidative stress and inflammation, ViE-m produced a significant decrease in interleukin-6 levels, thiobarbituric acid reactive substances, plasma and red blood cell (RBC) malonylaldehyde and a significant increase in blood and RBC vitamin E. Conversely, ViE-m use had no impact on lipid profile, dialysis adequacy, blood pressure, albumin and uric acid. Conclusions: ViE-m might ameliorate anemia management by reducing oxidative stress and inflammation. Benefits of these bio-membranes on harder clinical outcomes are uncertain and need to be investigated by future, targeted trials

Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD

Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD.BackgroundCardiovascular risk stratification is important in the clinical management of patients with end-stage renal diseases (ESRD) and biomarkers are increasingly used in these patients.MethodsIn a cohort of 246 dialysis patients without heart failure at baseline we tested the combined prognostic power of three well-established biomarkers: brain natriuretic peptide (BNP), C-reactive protein (CRP), and asymmetric dimethyl arginine (ADMA). The independent prognostic value of individual and combined biomarkers was estimated in separate Cox models, including standard risk factors in dialysis patients and comorbidities.ResultsWhen the prediction power of the three biomarkers was evaluated individually, BNP, ADMA, and CRP added significant predictive value (P≤ 0.01) to all-cause and cardiovascular mortality models and the explanatory gain attributable to these biomarkers were of similar degree (ranging from 3.3% to 5.7%). When the biomarkers were evaluated jointly, a score based on the BNP-CRP combination, increased by 9.9% (all-cause) and by 10.5% (cardiovascular) the explained mortality variance of standard Cox models and such gain in power was similar to that achieved by the CRP-ADMA combination (all-cause death 9.0% and cardiovascular death 8.4%). Of note, the explanatory gain derived by the simultaneous use of the three biomarkers was very similar (all-cause death 11.6% and cardiovascular death 10.5%) to that achieved by the use of two biomarkers.ConclusionThese findings indicate a potential role for CRP, BNP, and ADMA to be incorporated into diagnostic and therapeutic strategies aimed at detection and treatment of atherosclerotic complications and at preventing heart failure in the dialysis population

Sleep‐Disordered Breathing and 24‐Hour Ambulatory Blood Pressure Monitoring in Renal Transplant Patients: Longitudinal Study

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Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients

Plasma adrenomedullin during acute changes in intravascular volume in hemodialysis patients.BackgroundAdrenomedullin, is a potent vasorelaxant that is highly expressed in the adrenal medulla, kidney, heart and lung. Since there is indirect evidence that hypervolemia enhances the release of this peptide, we measured plasma adrenomedullin in 9 uremic patients on chronic dialysis treatment and in 10 healthy subjects matched for age and gender.MethodsMeasurements were performed in baseline conditions, after isotonic fluid subtraction (by isolated ultrafiltration) and during a 70° tilt. Tilt was performed in volume-depleted state, that is, after isolated ultrafiltration (UF). In the control experiment patients underwent sham UF (UF = 0) followed by a period of supine resting identical to the one they had spent in tilted position in the active experiment. Adrenomedullin was measured on pre-extracted plasma samples (Sep-Pak C-18 cartridges) by a specific RIA for human adrenomedullin 1-52.ResultsThe average plasma adrenomedullin was 2.6 times higher (P < 0.01) in uremic patients (103 ± 8pg/ml) than in healthy subjects (39 ± 7pg/ml). After fluid subtraction (-2.6 ± 0.2 liter) adrenomedullin fell to 79. ± 8pg/ml (P = 0.02) but remained well above the upper limit of the 95% CI in normal subjects (52pg/ml). There was no relationship between adrenomedullin and ANF changes. In the control experiment sham UF did not modify plasma adrenomedullin. Tilt did not significantly change plasma adrenomedullin either in dialysis patients or healthy subjects.ConclusionsPlasma adrenomedullin is markedly raised in uremic patients on dialysis, which confirms that the kidney has a major role in the clearance of this peptide. However, the fall in plasma adrenomedullin after isolated UF indicates that the plasma concentration of this peptide is influenced by the body fluid volume status. Whether or not adrenomedullin participates in the counter-regulatory response to fluid subtraction in uremic patients remains to be explored by specific antagonists of this substance

ASSOCIATION OF CALCIFEDIOL LEVELS WITH VERTEBRAL FRACTURES, VASCULAR CALCIFICATIONS AND MORTALITY.

The best biomarker of Vitamin D status is calcifediol [25(OH)D]. We investigated the relationship between serum calcifediol levels and vertebral fractures (VF), vascular calcifications (VC) and mortality in hemodialysis patients. Within a multicenter, cross-sectional study in 18 hospital based dialysis centers in Italy, we included 387 hemodialysis patients (143 F, 37% ; 244 M, 63%), mean age 64±14 (SD) years, median dialytic age 49 months, BMI 25± 4 Kg/m2. We determined total 25(OH)D using the LIASON® 25 OH Vitamin D kit (DiaSorin Inc., Stillwater MN, USA). We evaluated VF with a computerized analysis of scanned L-L vertebral X-rays (T4 to L5). Reduction of > 20% of vertebral body height was considered a VF, while reductions between 15% and 20% were considered borderline fractures (BF). Fracture severity was estimated as mild, moderate or severe (reduction: 20–25%, 25–40% or >40%, respectively). VC assessments were also centralized. Witteman's method (Lancet, 1994) was used for blinded assessments in duplicate. VC were quantified by measuring the length of calcific deposits along the anterior and posterior wall of the aorta (mild 0.1-5 cm, moderate 5.1-10 cm and severe >10 cm). We also evaluated the presence or absence of calcifications of the iliac arteries in the same radiograph (mild 0.1-3 cm, moderate 3.1-5 cm and severe >5cm). Any differences in VC were resolved by consensus. Follow up was 2.7±0.5 years. Bone markers were: Ca 9.15±0.68 mg/dl, P 4.8± 1.28 mg/dl, median ALP 83 U/L and median PTH 244 pg/ml. We found a median 25(OH)D level of 28.9 ng/ml. Nine ( 2.3%) patients had vitamin D deficiency (30 ng/ml). We found that 55% of patients had VF and 30.9% of patients had BF. Prevalence of VC was 80.6% (mild 20.1%, moderate 30.8%, severe 29.7%) in the aorta and 55,1% in the iliac arteries. Males had more VF than Females (60% versus 48%, P=0.019). No associations were found between VF and biochemical parameters including calcifediol levels (p=0.662), while we found an association between low calcifediol levels and a higher prevalence of severe aortic calcifications (36.8 vs 28.2, p=0.0044). Furthermore, we found a OR 1.85 (1.04-3.29 CI, p=0.0367) for Aortic Calcification in patients with calcifediol levels lower than the median value of 29 ng/ml. During follow-up (2.7±0.5 years) mortality was of 19.9%. No association was found between mortality and calcifediol levels (p=0.5394). In conclusion, despite good control of bone and mineral metabolism parameters, hemodialysis patients showed high prevalence of VF and VC. Our study suggests that high calcifediol levels could be protective against progression of severe aortic calcificatio

Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198

Inflammation and outcome in end-stage renal failure: Does female gender constitute a survival advantage?

Inflammation and outcome in end-stage renal failure: Does female gender constitute a survival advantage?BackgroundElevated C-reactive protein (CRP) is a strong predictor of cardiovascular events and all-cause mortality in end-stage renal disease (ESRD) patients. However, although sex hormones may influence serum levels of inflammatory proteins, gender has not been taken into consideration in previous studies of inflammation and outcome in ESRD patients.MethodsWe included 663 (374 males) ESRD patients (59 ± 1 year) from three European renal centers (Sweden, Germany and Italy) in which CRP levels and outcome data (follow-up 33 ± 1 months) were available. The relation between outcome and serum levels of the soluble intercellular adhesion molecule (sICAM-1) was evaluated in 312 of the patients.ResultsThe present study shows that elevated CRP is a strong predictor of outcome, but whereas no difference in all-cause mortality was observed between non-inflamed (CRP ≤3.4 mg/L) males and females, inflamed males had a significantly (log rank 6.1; P = 0.01) higher mortality rate than inflamed females. A strong positive correlation between CRP and sICAM-1 was found in the combined patient material (ρ = 0.37; P < 0.0001) as well as in the male (ρ = 0.25; P < 0.01) and female (ρ = 0.52; P < 0.0001) subgroups. The Cox proportional hazard model showed that whereas both elevated sICAM-1 and log CRP predicted outcome in males, neither predicted outcome significantly in females.ConclusionsAs inflamed female patients have a better outcome that inflamed males the present observation suggests that sex hormones may have important cardioprotective effects that limit the effect of inflammation on vascular injury in female ESRD patients

Spatiotemporal patterns of distribution of large predatory sharks in Calabria (central Mediterranean, southern Italy)

During the 2000-2009, a survey study on the spatiotemporal patterns of distribution of large predatory sharks was carried out in the Calabria region. A total of 12 species were recorded and among them the blue shark Prionace glauca and the bluntnose sixgill shark Hexanchus griseus were the most common ones. Also of interest was the frequency of species such as Carcharodon carcharias, Sphyrna zygaena and Cetorhinus maximus. 57% of all reported records derived from the Tyrrhenian side of the region and 43% on the Ionian side. A significant relationship between season of the year versus number of records was found, but this could be related to the small number of observers that were active during the winter months. The presence of Sphyrna lewini is reported for the study area; this species was previously recorded only in the western part of the Mediterranean Sea. This paper also provides evidence of the second and first documented accounts of white shark predation upon Tursiops truncatus and Stenella coeruleoalba, respectively, in the Mediterranean Sea. The recover ing of Ionian Sphyrna zygaena populations and the declining of Lamna nasus populations were also noted