High-Target Hemodiafiltration Convective Dose Achieved in Most Patients in a 6-Month Intermediary Analysis of the CONVINCE Randomized Controlled Trial.

Introduction: High convection volumes in hemodiafiltration (HDF) result in improved survival; however, it remains unclear whether it is achievable in all patients. Methods: CONVINCE, a randomized controlled trial, randomized patients with end-stage kidney disease 1:1 to high-dose HDF versus high-flux hemodialysis (HD) continuation. We evaluated the proportion of patients achieving high-dose HDF target: convection volume per visit of ≥23 l (range ±1 l) at baseline, month 3, and month 6. We compared baseline characteristics in the following 2 ways: (i) patients on target for all 3 visits versus patients who missed target on ≥1 visits and (ii) patients on target for all 3 visits or missing it once versus patients who missed target on ≥2 visits. Results: A total of 653 patients were randomized to HDF. Their mean age was 62.2 (SD 13.5) years, 36% were female, 81% had fistula vascular access, and 33% had diabetes. Across the 3 visits, 75 patients (11%), 27 patients (4%), and 11 patients (2%) missed the convection volume target once, twice, and thrice, respectively. Apart from diabetes, there were no apparent differences in patient characteristics between patients who always achieved the high-dose target (83%) and those who missed the target either once or more (17%) or twice or more (6%). Conclusion: Achieving high-dose HDF is feasible for nearly all patients in CONVINCE and could be maintained during the 6-month follow-up period. Apart from diabetes, there were no other indications for confounding by indication on multivariable analyses that may explain the potential survival advantage for patients receiving high-dose HDF.

Partition of Omega-like facility into two configurations of 24 and 36 laser beams to improve implosion performance.

An Omega-like beam configuration is considered where the 60-beam layout can be separated into two independent sub-configurations with 24 and 36 laser beams, each minimizing direct drive illumination non-uniformity. Two different laser focal spot profiles, one associated with each configuration, are proposed to apply the zooming technique in order to increase the laser-target coupling efficiency. This approach is used by 1D hydrodynamics simulations of the implosion of a direct-drive capsule characterized by a relatively large aspect ratio A = 7 and an optimized laser pulse shape delivering a maximum of 30 TW and 30 kJ, with different temporal pulse shapes in each of the two sets of beams. It is shown that zooming allows for an optimistic 1D thermonuclear energy gain greater than one while without zooming the thermonuclear gain remains largely below one. While this is incompatible with the as-built Omega laser, it provides a promising option for a future intermediate-energy direct drive laser system.

Effect of collisions with a second fluid on the temporal development of nonlinear, single-mode, Rayleigh-Taylor instability.

Goncharov's [Phys. Rev. Lett. 88, 134502 (2002)0031-900710.1103/PhysRevLett.88.134502] nonlinear model of a single-mode Rayleigh-Taylor instability (RTI) is investigated for a partially ionized plasma in a predominantly neutral background. Terminal bubble and spike velocities are derived from the nonlinear equations in the case where the RTI dynamics is dominated by collisions between neutrals and ions. Direct numerical simulations are used to justify the use of Goncharov's model in this regime and observe its limitations.

Clinical outcomes of hemodialysis patients in a public-private partnership care framework in Italy: a retrospective cohort study.

BACKGROUND: Innovative care models such as public-private partnerships (PPPs) may help meet the challenge of providing cost-effective high-quality care for the steadily growing and complex chronic kidney disease population since they combine the expertise and efficiency of a specialized dialysis provider with the population care approach of a public entity. We report the five-years main clinical outcomes of a population of patients treated on hemodialysis within a PPP-care model in Italy. METHODS: This descriptive retrospective cohort study consisted of all consecutive hemodialysis patients treated in the NephroCare-operated Nephrology and Dialysis unit of the Seriate Hospital in 2012-2016, which exercises a PPP-care model. Clinical and treatment information was obtained from the European Clinical Database. Hospitalization outcomes and cumulative all-cause mortality incidences that accounted for competing risks were calculated. RESULTS: We included 401 hemodialysis patients (197 prevalent and 204 incident patients) in our study. The mean cohort age and age-adjusted Charlson Comorbidity Index were 67.0 years and 6.7, respectively. Patients were treated with online high-volume hemodiafiltration or high-flux hemodialysis. Parameters of treatment efficiency were above the recommended targets throughout the study period. Patients in the PPP experienced benefits in terms of hospitalization (average number of hospital admissions/patient-year: 0.79 and 1.13 for prevalent and incident patients, respectively; average length of hospitalization: 8.9 days for both groups) and had low cumulative all-cause mortality rates (12 months: 10.6 and 7.8%, 5 years: 42.0 and 35.9%, for prevalent and incident patients, respectively). CONCLUSIONS: Results of our descriptive study suggest that hemodialysis patients treated within a PPP-care model framework received care complying with recommended treatment targets and may benefit in terms of hospitalization and mortality outcomes.

CVD diamond detector with interdigitated electrode pattern for time-of-flight energy-loss measurements of low-energy ion bunches.

Ion stopping experiments in plasma for beam energies of few hundred keV per nucleon are of great interest to benchmark the stopping-power models in the context of inertial confinement fusion and high-energy-density physics research. For this purpose, a specific ion detector on chemical-vapor-deposition diamond basis has been developed for precise time-of-flight measurements of the ion energy loss. The electrode structure is interdigitated for maximizing its sensitivity to low-energy ions, and it has a finger width of 100 µm and a spacing of 500 µm. A short single α-particle response is obtained, with signals as narrow as 700 ps at full width at half maximum. The detector has been tested with α-particle bunches at a 500 keV per nucleon energy, showing an excellent time-of-flight resolution down to 20 ps. In this way, beam energy resolutions from 0.4 keV to a few keV have been obtained in an experimental configuration using a 100 µg/cm2 thick carbon foil as an energy-loss target and a 2 m time-of-flight distance. This allows a highly precise beam energy measurement of δE/E ≈ 0.04%-0.2% and a resolution on the energy loss of 0.6%-2.5% for a fine testing of stopping-power models.

Unraveling the relationship between mortality, hyponatremia, inflammation and malnutrition in hemodialysis patients: results from the international MONDO initiative.

BACKGROUND/OBJECTIVES: Hyponatremia is a risk factor for mortality in hemodialysis (HD) patients. It is not well known to which extent the comorbidities, malnutrition, fluid status imbalance and inflammation are related to hyponatremia and affect outcomes. SUBJECTS/METHODS: We studied 8883 patients from the European subset of the international MONitoring Dialysis Outcomes initiative. Nutritional and fluid statuses were assessed by bioimpedance spectroscopy. Fluid depletion was defined as overhydration⩽-1.1 l and fluid overload as overhydration>+1.1 l, respectively. Malnutrition was defined as a lean tissue index below the 10th percentile of age- and gender-matched healthy controls. Hyponatremia and inflammation were defined as serum sodium levels <135 mEq/l and C-reactive protein levels>6.0 mg/l, respectively. We used logistic regression to test for predictors of hyponatremia and Cox proportional hazards analysis to assess the association with all-cause mortality. RESULTS: Hyponatremia was predicted by the presence of malnutrition (odds ratio (OR)=1.49 (95% confidence interval (CI)=1.30-1.70), inflammation (OR=1.44 (95% CI=1.26-1.64)) and fluid overload ((>+1.1 l to +2.5 l) OR=0.73 (95% CI=0.62-0.85)) but not by fluid depletion (OR=1.34 (95% CI=0.92-1.96)). Malnutrition, inflammation, fluid overload, fluid depletion and hyponatremia (hazard ratio=1.70 (95% CI=1.46-1.99)) were independent predictors for all-cause mortality. CONCLUSIONS: In HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.

Association between pre hemodialysis serum sodium concentration and blood pressure: results from a retrospective analysis from the international monitoring dialysis outcomes (MONDO) initiative.

A recent study from the United Kingdom indicates an association between pre hemodialysis (HD) serum sodium (SNa(+)) and systolic and diastolic blood pressure (SBP and DBP) in chronic HD patients. We extend this analysis to an international cohort of incident HD patients. The Monitoring Dialysis Outcomes initiative encompasses patients from 41 countries. Over 2 years monthly pre-HD SNa(+) levels were used as predictors of pre-HD SBP and DBP in a linear mixed model (LMM) adjusted for age, gender, interdialytic weight gain, diabetes, serum albumin and calcium. Similar models were constructed with DBP as outcome. Analyses were carried out stratified by continent (North and South America; Europe and Asia). LMMs were also constructed for the entire observation period of 2 years, and separately the first and the second year after HD initiation. We studied 17 050 incident patients and found SNa(+) to have a significant slope estimate in the LMM predicting pre-HD SBP and DBP (ranging from 0.22 to 0.29 and 0.10 to 0.21 mm Hg per mEq l(-1), respectively, between the continents). The findings were similar in subsets of SBP and SNa(+) tertiles, and separately analyzed for the first and second year. Our analysis shows an independent association between SNa, SBP and DBP in a large intercontinental database, indicating that this relation is a profound biological phenomenon in incident and prevalent HD patients, generalizable to an international level and independent of SBP and DBP magnitude.

Cumulative iron dose and resistance to erythropoietin.

INTRODUCTION: Optimizing anemia treatment in hemodialysis (HD) patients remains a priority worldwide as it has significant health and financial implications. Our aim was to evaluate in a large cohort of chronic HD patients in Fresenius Medical Care centers in Spain the value of cumulative iron (Fe) dose monitoring for the management of iron therapy in erythropoiesis-stimulating agent (ESA)-treated patients, and the relationship between cumulative iron dose and risk of hospitalization. METHODS: Demographic, clinical and laboratory parameters from EuCliD(®) (European Clinical Dialysis Database) on 3,591 patients were recorded including ESA dose (UI/kg/week), erythropoietin resistance index (ERI) [U.I weekly/kg/gr hemoglobin (Hb)] and hospitalizations. Moreover the cumulative Fe dose (mg/kg of bodyweight) administered over the last 2 years was calculated. Univariate and multivariate analyses were performed to identify the main predictors of ESA resistance and risk of hospitalization. Patients belonging to the 4th quartile of ERI were defined as hypo-responders. RESULTS: The 2-year iron cumulative dose was significantly higher in the 4th quartile of ERI. In hypo-responders, 2-year cumulative iron dose was the only iron marker associated with ESA resistance. At case-mix adjusted multivariate analysis, 2-year iron cumulative dose was an independent predictor of hospitalization risk. DISCUSSION: In ESA-treated patients cumulative Fe dose could be a useful tool to monitor the appropriateness of Fe therapy and to prevent iron overload. To establish whether the associations between cumulative iron dose, ERI and hospitalization risk are causal or attributable to selection bias by indication, clinical trials are necessary.

Change in inertial confinement fusion implosions upon using an ab initio multiphase DT equation of state.

Improving the description of the equation of state (EOS) of deuterium-tritium (DT) has recently been shown to change significantly the gain of an inertial confinement fusion target [S. X. Hu et al., Phys. Rev. Lett. 104, 235003 (2010)]. Here we use an advanced multiphase EOS, based on ab initio calculations, to perform a full optimization of the laser pulse shape with hydrodynamic simulations starting from 19 K in DT ice. The thermonuclear gain is shown to be a robust estimate over possible uncertainties of the EOS. Two different target designs are discussed, for shock ignition and self-ignition. In the first case, the areal density and thermonuclear energy can be recovered by slightly increasing the laser energy. In the second case, a lower in-flight adiabat is needed, leading to a significant delay (3 ns) in the shock timing of the implosion.

Fewer dose changes with once-monthly C.E.R.A. in patients with chronic kidney disease.

BACKGROUND: Frequent dosing and requirements for dose adjustments of erythropoiesis-stimulating agents (ESAs) create significant burdens for healthcare providers and have been associated with hemoglobin (Hb) cycling, hampering maintenance of target Hb levels. We compared the frequency of dose changes in dialysis patients who received methoxy polyethylene glycolepoetin beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter-acting ESA. METHODS: Data were analyzed from three Phase III maintenance trials, using almost identical protocols, in dialysis patients treated with C.E.R.A. every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or darbepoetin alpha; at their previous dose/administration interval). Dosage was adjusted to maintain Hb ± 1 g/dl of baseline and 10 - 13.5 g/dl during titration (28 weeks) and evaluation (8 weeks), and 11 - 13 g/dl during follow-up (16 weeks). RESULTS: Data were analyzed from 564 patients treated with C.E.R.A. q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing interval. Significantly fewer dose changes were needed in patients receiving C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with comparator ESAs. CONCLUSION: This retrospective analysis suggests that C.E.R.A. q4w maintains Hb levels in dialysis patients and requires fewer dose changes compared with other ESAs.

[Physical principles of renal replacement therapy applied to end stage renal disease patients]. / Principes et modalités d'application de l'hémodialyse au traitement de l'insuffisance rénale chronique.

"Hemodialysis" is the generic term that refers to all forms of renal replacement therapy (RRT) able to restore periodically the "internal milieu" composition in end stage renal disease patients (ESRD). RRT includes several modalities (hemodialysis, hemofiltration, hemodiafiltration) that induce basic physical principles (diffusion, convection, adsorption) via an exchange module (dialyser) and an electrolytic exchange solution (dialysis fluid). The cleansing property of the RRT depends on different factors: the treatment modality itself, the uremic toxin considered, patient's characteristic and the operational conditions (duration of treatment, session frequency, blood and dialysate flow rates). Solute instantaneous clearances reflect the dialyser's performances used in optimal conditions but not necessarily the body clearance. The effective solute body clearance is more difficult to assess in clinical practice since it includes some variables such as the treatment duration, the biological complexity of internal milieu and the variability of the patient/dialysis system interaction. The "dialysis adequacy" concept that governs the treatment efficacy in ESRD patients could not be reduced to the urea Kt/V ratio. It must integrate a selection of pertinent clinical and biological markers covering the complete spectrum of uremic abnormalities. Adequate knowledge of those basic physical principles that control the solute exchange in hemodialysis patient is highly recommended to any nephrologist who looks forward to improve treatment efficacy and reduce mortality in ESRD patients.

[Carbonyl stress and oxidatively modified proteins in chronic renal failure]. / Stress carbonylé et modifications oxydatives des protéines au cours de l'insuffisance rénale chronique.

Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis.

Formaldehyde-fixed arterial allograft as a novel vascular access alternative in end-stage renal disease patients.

Liu and co-workers report on a preliminary study with formaldehyde-fixed arterial allografts. In this way they provide a novel alternative for solving the problem of failing to achieve vascular access in hemodialysis patients. Formaldehyde fixation offers an effective way of reducing the antigenicity of heterologous arterial allograft. Preliminary clinical experience shows that technical survival of such preserved arterial allograft appears quite promising. Further studies will help to define the place of this allograft material in vascular access management of ESRD patients.

[Sodium determination in biological fluids]. / Méthodes de dosage du sodium dans les liquides biologiques.

Electrolyte disorders are frequently observed in nephrology and intensive care unit department and Na determination is routinely performed in biochemistry laboratories. Three methods are currently available. Flame photometry remains the reference method. With this method the serum sample is diluted before the actual measurement is obtained. Results are expressed as molarity (per Liter of plasma). Potentiometric methods have an increasing importance due to the advances in ion sensitive (selective) electrodes (ISE). Whereas the instruments for routine chemical analysis typically use indirect potentiometry (involving te dilution of samples) to measure sodium levels, the equipment for measuring arterial blood gases use direct potentiometry without any dilution. Thus, results obtained with indirect potentiometry are expressed in molarity (per liter of plasma) while results obtained with direct potentiometry are initially given in morality (per kg of plasma water) then converted in molarity. Analytical performances are in all cases satisfactory and therefore all the methods could be used in both normal and pathological ranges. Methods involving sample dilution such as flame photometry or indirect potentiometry, the serum sodium value would be expected to be low in case of decrease plasma water (pseudohyponatremia). By contrast, with direct potentiometry where no sample dilution takes place, no interference would be expected since the activity of sodium in the water phase only is being measured. Thus, the classical pseudohyponatremia observed with hyperlipemia or paraproteinemia are not further observed with direct potentiometry. These differences in methodology should be taken into account to explain discrepancies between results obtained with classical biochemistry analyser and with blood gas apparatus.

[Residual renal function in dialysis patients]. / Rôle de la fonction rénale résiduelle dans la balance sodée du dialysé: est-ce un bénéfice ou un risque?

Residual renal function (RRF) contributes to the achievement of treatment adequacy in CKD-5 patients. It may facilitate patients' acceptance of renal replacement therapy (RRT) in minimizing dietary and fluid restriction. It has been confirmed to improve dialysis patient outcomes. Attempts to preserve RKF in incident CKD-5 patients are still subject to controversies. In this review we analyze the role of RRT in dialysis patient. What are the positive and the beneficial effects of maintaining RRF? What are the negative and the risks of maintaining a RRF? At what expense the maintenance of RRF is achieved? Preservation of RRF is undoubtedly an interesting means to enhance the efficacy of renal replacement therapy and reduce dietary fluid restriction. However, maintainance of RRF should not be considered as a goal of dialysis adequacy in dialysis patients but rather a means of optimizing RRT. Further, preservation of RRF should be considered as a permanent trade-off between patient comfort and chronic fluid volume overload with its deleterious effects.