The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

Length of Dialysis Session Is More Important Than Large Kt/V in Hemodialysis

Long, slow hemodialysis (3 × 8 hours/week) has been used without significant modification in Tassin, France, for 30 years with excellent morbidity and mortality rates. A long dialysis session easily provides high Kt/V_urea and allows for good control of nutrition and correction of anemia with a limited need for erythropoietin (EPO). Control of serum phosphate and potassium is usually achieved with low-dose medication. The good survival achieved by long hemodialysis sessions is essentially due to lower cardiovascular morbidity and mortality than in short dialysis sessions. This, in turn, is mainly explained by good blood pressure (BP) control without the need for antihypertensive medication. Normotension in this setting is due to the gentle but powerful ultrafiltration provided by the long sessions, associated with a low salt diet and moderate interdialytic weight gains. These allow for adequate control of extracellular volume (dry weight) in most patients without important intradialytic morbidity. Therefore, increasing the length of the dialysis session seems to be the best way of achieving satisfactory long-term clinical results.     

Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension

Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end-stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow-mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid-femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow-mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow-mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross-sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology.     

Inherent Errors in the Quantitation of Dialysis Delivery: Implications For CAPD and Daily Hemodialysis

When compared to intermittent dialysis, the theoretical advantages of continuous dialysis may be less important than its practical disadvantage: the inability to accurately quantify dialysis. With intermittent dialysis the change in blood urea nitrogen over the course of the treatment allows the ratio of K (urea clearance) to V (volume of distribution of urea or total body water) to be determined, hence an accurate Kt/V. In continuous dialysis this approach cannot be used due to the steady-state nature of blood urea levels. Instead, V is estimated, generally from the Watson equations. This estimate has sufficient inaccuracy to result in substantial unrecognized underdialysis in many patients.     

Pre to post‐dialysis plasma sodium change better predicts clinical outcomes than dialysate to plasma sodium gradient in quotidian hemodialysis

Sodium balance across a hemodialysis treatment influences interdialytic weight gain (IDWG), pre‐dialysis blood pressure, and the occurrence of intradialytic hypotension, which associate with patient morbidity and mortality. In thrice weekly conventional hemodialysis patients, the dialysate sodium minus pre‐dialysis plasma sodium concentration (δDPNa+) and the post‐dialysis minus pre‐dialysis plasma sodium (δPNa+) are surrogates of sodium balance, and are associated with both cardiovascular and all‐cause mortality. However, whether δDPNa+ or δPNa+ better predicts clinical outcomes in quotidian dialysis is unknown. We performed a retrospective analysis of clinical and demographic data from the Southwestern Ontario Regional Home Hemodialysis program, of all patients since 1985. In frequent nocturnal hemodialysis, δPNa+ was superior to δDPNa+ in predicting IDWG (R² = 0.223 vs. 0.020, P = 0.002 vs. 0.76), intradialytic change in systolic (R² = 0.100 vs. 0.002, P = 0.02 vs. 0.16) and diastolic (R² = 0.066 vs. 0.019, P = 0.02 vs. 0.06) blood pressure, and ultrafiltration rate (R² = 0.296 vs. 0.036, P = 0.001 vs. 0.52). In short hours daily hemodialysis, δDPNa+ was better than δPNa+ in predicting intradialytic change in diastolic blood pressure (R² = 0.101 vs. 0.003, P = 0.02 vs. 0.13). However, δPNa+ was better than δDPNa+ in predicting IDWG (R² = 0.105 vs. 0.019, P = 0.04 vs. 0.68) and pre‐dialysis systolic blood pressure (R² = 0.103 vs. 0.007, P = 0.02 vs. 0.82). We also found that the intradialytic blood pressure fall was greater in frequent nocturnal hemodialysis patients than in short hours daily patients, when exposed to a dialysate to plasma sodium gradient. These results provide a basis for design of prospective trials in quotidian dialysis modalities, to determine the effect of sodium balance on cardiovascular outcome.     

A meta‐analysis of sodium profiling techniques and the impact on intradialytic hypotension

Introduction Hemodialysis has improved in recent years, however, despite such improvements, intra‐dialytic hypotensive episodes still persist which can lead to a reduction in the overall effectiveness of the treatment. Profiling sodium levels during dialysis can improve vascular refilling and therefore may prevent hypotensive events. A number of profiling methods exist and this meta‐analysis set out to examine the effectiveness of these methods. Methods To assess the effectiveness of hemodialysis sodium profiling techniques. A review and meta‐analysis analytical framework was used. A search was conducted using Medline, Embase and CINAHL, Scopus and Web of Knowledge between 1946 and 2014 of published English‐language peer reviewed randomized control studies. In total 10 articles were retrieved and included in the review. All data was abstracted with a standardized data collection form. Stata 11.2 (Stata Corp) was used to analyse the data. Actual numbers of hypotensive events were pooled between studies. Analysis of subgroups was performed on sodium profile type. The data were further investigated using meta‐regression. Publication bias was also tested. Findings Stepwise profiling was shown to be statistically significantly effective in reducing intradialytic episodes. Results demonstrated that linear sodium profiling was not effective in reducing hypotensive events during dialysis. Discussion This review has shown that using stepwise profiling is more effective at reducing intra‐dialytic symptoms than other profiling methods. There was no evidence that linear profiling method was any more effective than conventional dialysis and in fact the results showed the reverse.     

Volume Effects of Daily Hemodialysis

Daily hemodialysis appears to be well tolerated, with hypotension rarely complicating such therapy, a finding that is the subject of this review. When daily hemodialysis utilizes a shorter treatment time, this may limit the intradialytic reduction in plasma volume. This reduction is a function of treatment time, ultrafiltration rate (UFR), and plasma refilling rate (PRR). However, daily therapy may be associated with a higher UFR and lower PRR, both of which may accentuate the fall in plasma volume. The reduced frequency of intradialytic hypotension may, in part, be related to other aspects of such therapy, such as the smaller oscillations and decreased dialytic flux of hemodynamically active solutes.     

Measurement of Hemodialysis Adequacy in a Changing World

Defining adequacy of dialysis remains an elusive goal. The application of the Kt/V_urea concept to clinical dialysis was a major improvement in trying to define a dialysis dose. Intuitively, the Kt/V concept makes a great deal of sense: the urea clearance of the dialyzer during dialysis (K), multiplied by the time (t) of dialysis, divided by the patient's urea distribution volume (V) ought to give the best number to compare the efficiency of dialyses that patients receive. There are, however, many pitfalls associated with the whole Kt/V_urea concept.     

Kinetic analysis of daily hemofiltration

Background: Daily hemofiltration (D‐HF) is a new treatment modality that shows unique solute removal characteristics and possibly provides a high quality of life for patients with end‐stage renal disease. We evaluated solute removal characteristics of D‐HF for five patients by kinetic modeling analysis. Methods: Five patients treated with normal 3 × 4 hr/week hemodialysis (HD) were switched to D‐HF (6 × 2 hr/week). Ultrafiltration rates (Q_F) or small‐solute clearances ranged from 63 to 106 mL/min. All the necessary kinetic parameters were determined from patients' physical data and HD portion of the clinical measurements. The two‐compartment kinetic model predicted the concentration changes after switching from normal HD to D‐HF. Results: Concentrations of small solutes such as urea nitrogen (UN) increased, whereas that of β₂‐microglobulin (β₂‐MG) decreased after switching from normal HD to D‐HF in all five patients. Predicted solute concentrations and clinical measurements for UN and β₂‐MG were in good agreement with mean error less than 10%. The model predicted that Q_F = 155 mL/min may be necessary for time‐averaged concentration (TAC) of UN to be unchanged. The model also predicted that the 7 times/week D‐HF should not increase the pretreatment concentration of UN, expecting even much lower β₂‐MG concentration after switching from normal HD to D‐HF. Conclusion: D‐HF is superior to normal HD for removing larger solutes but may increase the TAC of small solutes. Seven‐day (7 times/week) D‐HF may improve the solute removal capacity of small solutes.     

Assessment of subjective and hemodynamic tolerance of different high‐ and low‐flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: A randomized controlled trial

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open‐label, randomized, cross‐over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high‐flux, Gambro, Stockholm, Sweden), B (Helixone high‐flux, Fresenius), C (Xevonta high‐flux, BBraun, Melsungen, Germany), and D (Helixone low‐flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1–10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low‐ compared with the high‐flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low‐flux membrane correlated to higher blood pressure levels compared with the high‐flux ones. The Helixone high‐flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.     

Use of Systemic Blood Urea Nitrogen Levels Obtained 30 Minutes before the End of Hemodialysis to Portray Equilibrated,Postdialysis Blood Urea Nitrogen Values

Blood urea nitrogen (BUN) levels obtained at 30 minutes before the end of dialysis were found to be closely similar to equilibrated, postdialysis BUN values obtained 30 minutes after the end of dialysis. Because of this similarity, the former BUN values can be used to derive equilibrated urea reduction ratio, or equilibrated Kt/V instead.     

Effect of the decrease in dialysate sodium in pediatric patients on chronic hemodialysis

Optimal dialysate sodium (dNa) is unknown, with both higher and lower values suggested in adult studies to improve outcomes. Similar studies in pediatric hemodialysis (HD) population are missing. This is the first report of the effect of two constant dNa concentrations in pediatric patients on chronic HD. 480 standard HD sessions and interdialytic periods were studied in 5 patients (age 4–17 years, weight 20.8–66 kg) during a period of 6–11 months per patient. dNa was 140 mEq/L during the first half, and 138 mEq/L during the second half of the study period for each patient. Lowering dNa was associated with improved preHD hypertension, decreased interdialytic weight gain, decreased need for ultrafiltration, lower sodium gradient and was well tolerated despite lack of concordance with predialysis sNa, that was variable. Further studies are needed to verify our findings and to investigate if an even lower dNa may be more beneficial in the pediatric HD population.     

Facile synthesis and electrochemical sodium storage of CoS<Subscript>2</Subscript> micro/nano-structures

We report the synthesis and electrochemical sodium storage of cobalt disulfide (CoS₂) with various micro/nano-structures. CoS₂ with microscale sizes are either assembled by nanoparticles (P-CoS₂) via a facile solvothermal route or nanooctahedrons constructed solid (O-CoS₂) and hollow microstructures (H-CoS₂) fabricated by hydrothermal methods. Among three morphologies, H-CoS₂ exhibits the largest discharge capacities and best rate performance as anode of sodium-ion batteries (SIBs). Furthermore, H-CoS₂ delivers a capacity of 690 mA·h·g^?1 at 1 A·g^?1 after 100 cycles in a potential range of 0.1–3.0 V, and ～240 mA·h·g^?1 over 800 cycles in the potential window of 1.0–3.0 V. This cycling difference mainly lies in the two discharge plateaus observed in 0.1–3.0 V and one discharge plateau in 1.0–3.0 V. To interpret the reactions, X-ray diffraction (XRD) and transmission electron microscopy (TEM) are applied. The results show that at the first plateau around 1.4 V, the insertion reaction (CoS₂ + xNa⁺ + xe^? → Na _x CoS₂) occurs; while at the second plateau around 0.6 V, the conversion reaction (Na _x CoS₂ + (4 ? x) Na⁺ + (4 ? x)e^? → Co + 2Na₂S) takes place. This provides insights for electrochemical sodium storage of CoS₂ as the anode of SIBs.

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Rapid and Low‐Temperature Salt‐Templated Production of 2D Metal Oxide/Oxychloride/Hydroxide

2D materials have played an important role in electronics, sensors, optics, electrocatalysis, and energy storage. Many methods for the preparation of 2D materials have been explored. It is crucial to develop a high‐yield, rapid, and low‐temperature method to synthesize 2D materials. A general, fast (5 min), and low‐temperature (≈100 °C) salt (CoCl₂·6H₂O)‐templated method is proposed to prepare series of 2D metal oxides/oxychlorides/hydroxides in large scale, such as MoO₃, SnO₂, SiO₂, BiOCl, Sb₄O₅Cl₂, Zn₂Co₃(OH)₁₀ 2H₂O, and ZnCo₂O₄. The as‐synthesized 2D materials possess an ultrathin feature (2–7 nm) and large aspect ratios. Additionally, these 2D metal oxides/oxychlorides/hydroxides exhibit good electrochemical properties in energy storage (lithium/sodium‐ion batteries) and electrocatalysis (hydrogen/oxygen evolution reaction).     

Stable Na Plating and Stripping Electrochemistry Promoted by In Situ Construction of an Alloy‐Based Sodiophilic Interphase

Sodium metal anodes are poor due to the reversibility of Na plating/stripping, which hinders their practical applications. A strategy to form a sodiophilic Au–Na alloy interphase on a Cu current collector, involving a sputtered Au thin layer, is shown to enable efficient Na plating/stripping for a certain period of time. Herein, electrochemical behaviors of Na plating on different substrates are explored, and it is revealed that the sodiophilic interphase can be achieved universally by in situ formation of M–Na (M = Au, Sn, and Sb) alloys during Na plating prior to Na bulk deposition in the initial cycle. Moreover, it is found that repetitive alloying–dealloying leads to falling‐off of thin film sodiophilic materials and thus limits the lifespan of efficient Na cycling. Therefore, an approach is further developed by employing particles of sodiophilic materials combined with the control over the cutoff potential, which significantly improves the stability of Na plating/stripping process. Especially, the low‐cost Cu@Sn‐NPs and Cu@Sb‐MPs composite current collectors allow Na plating and stripping to cycle for 2000 and 1700 times with the average efficiency of 99.9% at 2 mA cm^?2.     

Generic Synthesis of Carbon Nanotube Branches on Metal Oxide Arrays Exhibiting Stable High‐Rate and Long‐Cycle Sodium‐Ion Storage

A new and generic strategy to construct interwoven carbon nanotube (CNT) branches on various metal oxide nanostructure arrays (exemplified by V₂O₃ nanoflakes, Co₃O₄ nanowires, Co₃O₄–CoTiO₃ composite nanotubes, and ZnO microrods), in order to enhance their electrochemical performance, is demonstrated for the first time. In the second part, the V₂O₃/CNTs core/branch composite arrays as the host for Na⁺ storage are investigated in detail. This V₂O₃/CNTs hybrid electrode achieves a reversible charge storage capacity of 612 mAh g^?1 at 0.1 A g^?1 and outstanding high‐rate cycling stability (a capacity retention of 100% after 6000 cycles at 2 A g^?1, and 70% after 10 000 cycles at 10 A g^?1). Kinetics analysis reveals that the Na⁺ storage is a pseudocapacitive dominating process and the CNTs improve the levels of pseudocapacitive energy by providing a conductive network.     

Boosting the Reversibility of Sodium Metal Anode via Heteroatom‐Doped Hollow Carbon Fibers

Sodium (Na) metal anodes stand out with their remarkable capacity and natural abundance. However, the dendritic Na growth, infinite dimensional changes, and low Coulombic efficiency (CE) present key bottlenecks plaguing practical applications. Here, heteroatom‐doped (nitrogen, sulfur) hollow carbon fibers (D‐HCF) are rationally synthesized as a nucleation‐assisting host to enable a highly reversible Na metal. The “sodiophilic” functional groups introduced by the heteroatom‐doping and large surface area (≈1052 m² g^?1) synchronously contribute to a homogenous plating morphology with dissipated local current density. High “sodiophilicity” of the D‐HCF is confirmed by first‐principle calculations and experimental results, where strong adsorption energy of ?3.52 eV with low Na⁺ nucleation overpotential of 3.2 mV at 0.2 mA cm^?2 is realized. As such, highly reversible plating/stripping is achieved at 1.0 mA cm^?2 with average CE approximating 99.52% over 600 cycles. The as‐assembled Na@D‐HCF symmetric cells exhibit a prolonged lifetime for 1000 h. A full‐cell paired with Na₃V₂(PO₄)₃ cathode further demonstrates stable electrochemical behavior for 200 cycles at 1 C along with excellent rate performance (102 mAh g^?1 at 5 C). The results clearly show the effectiveness of the D‐HCF in manipulating Na⁺ deposition and thus the significance of nucleation control in realizing dendrite‐free metal anodes.     

Controllable Design of MoS2 Nanosheets Grown on Nitrogen‐Doped Branched TiO2/C Nanofibers: Toward Enhanced Sodium Storage Performance Induced by Pseudocapacitance Behavior

In this work, expanded MoS₂ nanosheets grown on nitrogen‐doped branched TiO₂/C nanofibers (NBT/C@MoS₂ NFs) are prepared through electrospinning and hydrothermal treatment method as anode materials for sodium‐ion batteries (SIBs). The continuous 1D branched TiO₂/C nanofibers provide a large surface area to grow expanded MoS₂ nanosheets and enhance the electronic conductivity and cycling stability of the electrode. The large surface area and doping of nitrogen can facilitate the transfer of both Na⁺ ions and electrons. With the merits of these unique design and extrinsic pseudocapacitance behavior, the NBT/C@MoS₂ NFs can deliver ultralong cycle stability of 448.2 mA h g^?1 at 200 mA g^?1 after 600 cycles. Even at a high rate of 2000 mA g^?1, a reversible capacity of 258.3 mA h g^?1 can still be achieved. The kinetic analysis demonstrates that pseudocapacitive contribution is the major factor to achieve excellent rate performance. The rational design and excellent electrochemical performance endow the NBT/C@MoS₂ NFs with potentials as promising anode materials for SIBs.