Convective Volume Research Articles

The Boreal Summer Madden–Julian Oscillation and Moist Convective Morphology over the Maritime Continent

Abstract While the boreal summer Madden–Julian oscillation (MJO) is commonly defined as a planetary-scale disturbance, the convective elements that constitute its cloud dipole exhibit pronounced variability in their morphology. We therefore investigate the relationship between the intraseasonal cloud anomaly of the MJO and the convective elements that populate its interior by simulating a boreal summer MJO event over the Maritime Continent using a cloud-resolving model. A progressive relationship between convective cell morphology and the MJO within the convectively enhanced region of the MJO was identified and characterized as follows: anomalously long-lasting cells in the initial phases, followed by an increased number of cells in the intermediate phases, progressing into more expansive cells in the terminal phases. A progressive relationship does not seem to exist within the convectively suppressed region of the MJO within the simulated domain, however. Within the convectively enhanced region of the MJO, the progressive relationship is partially explained by the evolution of bulk atmospheric characteristics, such as instability and wind shear. Positive midlevel moisture anomalies coincide with anomalously long-lasting convective cells, which is hypothesized to further cascade into an increase in convective cell volume, although variability in the number of convective cells seems to be related to an unidentified variable. This intraseasonal relationship between convective cell morphology and the boreal summer MJO within the Maritime Continent may have broader implications for the large-scale structure and evolution of the MJO, related to both convective moistening and cloud-radiative feedbacks.

Long-Term Peridialytic Blood Pressure Patterns in Patients Treated by Hemodialysis and Hemodiafiltration

IntroductionOnline postdilution hemodiafiltration (HDF) is associated with a lower all-cause and cardiovascular mortality than hemodialysis (HD). This may depend on a superior peridialytic (pre- and postdialysis, and the difference between these 2 parameters) hemodynamic profile.MethodsIn this retrospective cohort analysis of individual participant data (IPD) from 3 randomized controlled trials (RCTs) (n = 2011), the effect of HDF and HD on 2-year peridialytic blood pressure (BP) patterns was assessed. Long-term peridialytic systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), as well as the deltas (post- minus predialytic) were assessed in the total group of patients. Thereafter, these variables were compared between patients on HD and HDF, and in the latter group between quartiles of convection volume.ResultsMean pre- and postdialysis SBP, DBP, and MAP declined significantly during follow-up (predialytic: SBP −2.16 mm Hg, DBP −2.88 mm Hg, MAP −2.64 mm Hg), PP increased (predialytic 0.96 mm Hg). Peridialytic deltas remained unaltered. Differences between the 2 modalities, or between quartiles of convection volume were not observed. BP changes were independent of various baseline characteristics, including the decline in body weight over time.ConclusionWe speculate that the combination of a decreasing SBP and an increasing PP may be the clinical sequelae of a worsening cardiovascular system. Because especially HDF with a high convection volume has been associated with a beneficial effect on survival, our study does not support the view that superior peridialytic BP control contributes to this effect.

Уровень N-терминального фрагмента прогормона мозгового натрийуретического пептида у пациентов с разным объемом замещения при on-line гемодиафильтрации

Уровень N-терминального фрагмента прогормона мозгового натрийуретического пептида у пациентов с разным объемом замещения при on-line гемодиафильтрации

Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: an observational prospective study

BackgroundOnline haemodiafiltration (OL-HDF) may improve middle molecular clearance in contrast to conventional haemodialysis (HD). However, OL-HDF requires higher convective flows and cannot sufficiently remove large middle molecules. This study evaluated the efficacy of a medium cut-off (MCO) dialyser in removing large middle molecular uraemic toxins and compared it with that of conventional high-flux (HF) dialysers in HD and predilution OL-HDF.MethodsSix clinically stable HD patients without residual renal function were investigated. Dialyser and treatment efficacies were examined during a single midweek treatment in three consecutive periods: 1) conventional HD using an HF dialyser, 2) OL-HDF using the same HF dialyser, and 3) conventional HD using an MCO dialyser. Treatment efficacy was assessed by calculating the reduction ratio (RR) for β2-microglobulin (β2M), myoglobin, κ and λ free light chains (FLCs), and fibroblast growth factor (FGF)-23 and measuring clearance for FLCs.ResultsAll three treatments showed comparable RRs for urea, phosphate, creatinine, and uric acid. MCO HD showed greater RRs for myoglobin and λFLC than did HF HD and predilution OL-HDF (myoglobin: 63.1 ± 5.3% vs. 43.5 ± 8.9% and 49.8 ± 7.3%; λFLC: 43.2 ± 5.6% vs. 26.8 ± 4.4% and 33.0 ± 9.2%, respectively; P < 0.001). Conversely, predilution OL-HDF showed the greatest RR for β2M, whereas MCO HD and HF HD showed comparable RRs for β2M (predilution OL-HDF vs. MCO HD: 80.1 ± 4.9% vs. 72.6 ± 3.8%, P = 0.01). There was no significant difference among MCO HD, HF HD, and predilution OL-HDF in the RRs for κFLC (63.2 ± 6.0%, 53.6 ± 15.5%, and 61.5 ± 7.0%, respectively; P = 0.37), and FGF-23 (55.5 ± 20.3%, 34.6 ± 13.1%, and 35.8 ± 23.2%, respectively; P = 0.13). Notably, MCO HD showed improved clearances for FLCs when compared to HF HD or OL-HDF.ConclusionsMCO HD showed significantly greater RR of large middle molecules and achieved improved clearance for FLCs than conventional HD and OL-HDF, without the need for large convection volumes or high blood flow rates. This would pose as an advantage for elderly HD patients with poor vascular access and HD patients without access to OL-HDF.Trial registrationClinical Research Information Service (CRIS): KCT 0003009. The trial was prospectively registered on the 21 Jul 2018.

The effect of natriuretic C-type peptide and its change over time on mortality in patients on haemodialysis or haemodiafiltration.

BackgroundC-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality.MethodsIn a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used.ResultsIn total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume.ConclusionsIn our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients.

Albumin losses during hemodiafiltration: all dialyzers are not created equal - a case report

BackgroundOnline hemodiafiltration (OL-HDF) is associated with better removal of both small and middle molecules and might improve survival compared to conventional hemodialysis (HD). Nevertheless, hemodiafiltration (HDF) can lead to an increase in albumin loss across the dialyzer, especially with high permeability membrane and high convective volume (CV). We present the case of a patient treated by OL-HDF who developed severe hypoalbuminemia resulting from massive albumin loss into dialysate.Case presentationA 71-year-old woman with ESRD started renal replacement therapy in December 2016. She was treated by high volume post-dilution OL-HDF, 4 h, 3 times per week. The dialyzer was the Phylther HF20SD (a 2.0m2 heat sterilized high flux (HF) polyphenylene membrane from Bellco). At the initiation of dialysis, the serum albumin was 4.0 g/dl. During the following months, the patient developed severe hypoalbuminemia. The lowest value observed was 2.26 g/dl in July 2017. Diagnostic workup excluded nephrotic syndrome, hepatic failure and malabsorption. The patient was shifted from OL-HDF to standard HF HD, keeping the same dialyzer and dialysis schedule. During the following months, we observed a progressive correction of the hypoalbuminemia (3.82 g/dl at last follow-up). To precise the impact of the epuration technique on the albumin losses in this patient, we measured the amount of albumin in dialysate during one session with the Phylther HF20SD on OL-HDF and one session with the same filter but on standard HD. The CV was 29.0 l for the HDF session. The total albumin losses were 23.6 g on OL-HDF and 4.6 g on HD.ConclusionOL-HDF can lead to significant albumin loss into the dialysate, especially with high permeability membrane and high CV. When prescribing post-dilutional OL-HDF, the choice of the dialyzer membrane should be made with caution. Users of the steam sterilized polyphenylene membrane, the Phylther SD, should be informed of the risk of large albumin loss with this membrane during post-dilution OL-HDF.

Study on the influence law of ventilation conditions on heat loss in a roadway of high altitude mine

It is necessary to study the heat loss law along the roadway of high altitude mines for the design of anti-freezing ventilation system. With a mine adit as the research object, this article used FLUENT software to carry out numerical simulations to study the influence of altitude and ventilation conditions on the heat loss along the roadway. Using the uniform design and regression analysis method, the prediction formulas of heat loss with different influential factors were fitted out. The results showed that the heat loss along the roadways has a negative exponential correlation with altitudes while is positively correlated with inlet airflow volume and convective temperature difference. The main factors impacting the heat loss along the roadway in a descending sequence was as follows, convective temperature difference, airflow volume, roadway length, and altitude. When given a confidence interval of 95%, the regression model of the heat loss parameter along the roadway is highly significant. With the fitting error controlled within 15% which can meet the needs of engineering prediction.

Heat and Mass Transfer Characteristics of Nanofluids in a Rotating System: A Convective Boundary Layer Flow

Introduction: Convective heat and mass transfer in nanofluids is a topic of major contemporary interest in both science and technology. In view of this, an unsteady MHD free convective flow of nanofluids through a porous medium bound by a moving vertical semi-infinite permeable flat plate with a constant heat source and convective boundary condition in a rotating frame of reference is studied theoretically. Experimental: The novelty is the consideration of constant heat source and convective boundary condition in a rotating frame. The velocity along the plate i.e., slip velocity is assumed to oscillate in time with constant frequency so that the solutions of the boundary layer are of the same oscillatory type. The dimensionless governing equations for this investigation are solved analytically using small perturbation approximation. Two types of nanofluids, namely Cu-water and Al2O3-water are used. Results: The effects of various parameters on the flow, heat and mass transfer characteristics are discussed through graphs and tables. Conclusion: An increase in the convective parameter and nanoparticle volume fraction leads to increase the thermal boundary layer thickness but opposite effect occurs for heat generation.

SAT-040 HAEMODIAFILTRATION IMPROVES THE CARDIOVASCULAR RISK PROFILE AND PATIENT RELATED OUTCOME MEASURES COMPARED TO CONVENTIONAL HAEMODIALYSIS IN CHILDREN – THE HDF, HEART AND HEIGHT (3H) STUDY

Fluid overload, hypertension and cardiovascular disease are common in children on dialysis. In adults, haemodiafiltration (HDF) is shown to reduce cardiovascular mortality compared to conventional haemodialysis (HD), but causes for this are not clear and data in children are scarce. We performed a non-randomized parallel-arm clinical trial within the International Paediatric Haemodialysis Network registry to compare outcomes on HD versus post-dilution on-line HDF: the HDF, Heart and Height (3H) study. Co-primary outcome measures were annualised changes in carotid intima-media thickness standard deviation score (cIMT-SDS) and height-SDS. ClinicalTrials.gov: NCT02063776 190 children (from 28 centres in 10 countries across Europe and North America) were recruited, and 177 fulfilled inclusion criteria. 133 children (78 on HD and 55 on HDF) completed one-year follow-up. There was no difference between HD and HDF groups in age, gender, underlying renal disease, comorbidities, dialysis vintage, access type, blood flow or presence of residual renal function. There were 44 dropouts, mainly (79%) due to transplantation; there were no deaths. The median convective volume achieved in the HDF group was 13.33 (inter-quartile range 12.4 to 14.5) ml/m2/session. Annualised change in cIMT SDS was 10-fold lower in HDF compared to HD (0.013 vs 0.48; p=0.002; Figure 1). On propensity score analysis, after adjusting for potential confounders, children on HD had a +0.47 greater increase in annualised cIMT-SDS (95%CI 0.07-0.87; p=0.02) compared to those on HDF. The 24-hour mean arterial pressure (MAP)-SDS increased on HD but reduced on HDF. Serum β2-microglobulin, PTH and high-sensitivity CRP were lower and haemoglobin was higher in HDF patients at 1-year. Predictors of higher cIMT-SDS and MAP-SDS at 12-months (data adjusted for country and baseline values) were HD group, higher inter-dialytic weight gain and ultrafiltration rate and higher β2-microglobulin. Height-SDS increased in HDF but remained static in HD. Importantly, the type of vascular access, blood flow rate and residual renal function did not correlate with cIMT SDS, suggesting that convective clearance is a significant determinant of outcome. Patient related outcome measures that are primarily associated with fluid status, such as the post-dialysis recovery time, headaches, dizziness and cramps, were less frequent and less severe in HDF compared to HD patients. Lower inter-dialytic weight gain on HDF, implying lower ultrafiltration rates per session and greater hemodynamic stability, was strongly associated with fewer symptoms. HDF patients had improved school attendance and greater physical activity scores, but there was no difference in hospitalisation rates. A significant limitation of the study is that randomization was not possible due to small patient numbers. In conclusion, 3H, the largest paediatric dialysis study to date, has shown that HDF improves blood pressure and hemodynamic stability and increases the removal of middle-molecular weight uremic toxins that may, in turn, may halt the progression of vascular disease, improve growth rates and patient related outcome measures compared to conventional HD. Randomised trials to study to confirm these outcomes are required.

Online hemodiafiltration and mortality risk in end-stage renal disease patients: A critical appraisal of current evidence.

The life expectancy of end-stage renal disease patients undergoing regular hemodialysis (HD) remains significantly lower than in the general population. Reducing excess mortality by improving renal replacement options is an unmet medical need. Online post-dilution hemodiafiltration (HDF) has been promoted as the gold standard, offering improved clinical outcomes, based on numerous observational studies that suggest a reduced mortality risk and lower morbidity with HDF compared with standard HD. However, most randomized controlled trials (RCTs) have failed to demonstrate a significant beneficial effect of HDF on all-cause mortality. The effects on secondary outcomes were often negligible or absent. Unfortunately, these RCTs were characterized by a moderate to high risk of bias. In post-hoc analyses of the largest RCTs and meta-analysis of individual participant data from four RCTs, HDF patients receiving the highest convection volume consistently and dose-dependently saw superior outcomes. However, as these studies were not designed a priori to clarify this issue, and there are no indisputable mechanisms underlying reduced mortality risks, we cannot exclude the possibility that the health status of patients (with vascular access as a proxy) may affect outcomes more than the convective technique itself. There is currently insufficient evidence to support the contention that high-volume HDF confers relevant benefits to patients over standard HD. The conflicting data of published RCTs reduce confidence in the superiority of high-volume convective therapy. Hopefully, ongoing large RCTs (for example, CONVINCE) may supply an indisputable answer to the crucial question of high-volume HDF.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BackgroundYKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. MethodsWe performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24–66) months, CV events were recorded.ResultsThe mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/Vurea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, β2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009–1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009–1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224–0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554–3.172); P: 0.008]. Kaplan–Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). ConclusionsYKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Measuring intradialyser transmembrane and hydrostatic pressures: pitfalls and relevance in haemodialysis and haemodiafiltration.

BackgroundPost-dilutional haemodiafiltration (HDF) with high convection volumes (HCVs) could improve survival. HCV-HDF requires a significant pressure to be applied to the dialyser membrane. The aim of this study was to assess the pressure applied to the dialysers in HCV-HDF, evaluate the influence of transmembrane pressure (TMP) calculation methods on TMP values and check how they relate to the safety limits proposed by guidelines.Methods Nine stable dialysis patients were treated with post-dilutional HCV-HDF with three different convection volumes [including haemodialysis (HD)]. The pressures at blood inlet (Bi), blood outlet (Bo) and dialysate outlet (Do) were continuously recorded. TMP was calculated using two pressures (TMP2: Bo, Do) or three pressures (TMP3: Bo, Do, Bi). Dialysis parameters were analysed at the start of the session and at the end of treatment or at the first occurrence of a manual intervention to decrease convection due to TMP alarms.ResultsDuring HD sessions, TMP2 and TMP3 remained stable. During HCV-HDF, TMP2 remained stable while TMP3 clearly increased. For the same condition, TMP3 could be 3-fold greater than TMP2. This shows that the TMP limit of 300 mmHg as recommended by guidelines could have different effects according to the TMP calculation method. In HCV-HDF, the pressure at the Bi increased over time and exceeded the safety limits of 600 mmHg provided by the manufacturer, even when respecting TMP safety limits.ConclusionsThis study draws our attention to the dangers of using a two-pressure points TMP calculation, particularly when performing HCV-HDF.

High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration

Background and objectiveOnline haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyze the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. Material and methodsProspective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated hemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analyzed. ResultsAge at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m2, with 48 (35.5–76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=−0.531, p=0.005), 2 years (r=−0.463, p=0.046), and at the end of follow-up (r=−0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1–2.22]mg/dL vs. 1.01 [0.15–6.96]mg/dL, p=0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=−0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=−0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (−0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. ConclusionThere is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.

Numerical analysis of the heat transfer and fluid flow characteristics of a nanofluid-cooled micropin-fin heat sink using the Eulerian-Lagrangian approach

In the present study, the thermofluid characteristics of a water and nanofluid-cooled micropin-fin heat sink have been evaluated by implementing a two-phase Eulerian-Lagrangian model. The nanofluid consisted of an aqueous suspension of the spherical-shaped alumina nanoparticles with the particle volume fraction (φ) ranging from 0.25% to 1%. The analysis has been performed by considering a heat sink comprising the staggered arrangement of 72 micropin-fins of the circular cross-section without tip clearance. A constant heat flux of 300 kW/m2 was subjected at the base of the heat sink, whilst the utilised pressure drop (∆P) across the heat sink was limited to ∆P<3000Pa. Heat transfer and fluid flow parameters were evaluated in terms of the local heat transfer coefficient, the enhancement ratio of the average convective heat transfer coefficient, thermal resistance and volume flow rate through the heat sink. Additionally, the temperature contours and flow streamlines across the heat sink elaborated the temperature distribution and flow attributes. Results indicated that under identical ∆P conditions, replacing water coolants with nanofluids optimised the thermal performance of the heat sink with a perceptible margin at the higher particle loadings. At the optimal pressure drop and particle concentration, nanoparticle dispersion into the hosting fluid demonstrated a maximum of 16% enhancement in the average heat transfer coefficient.

Middle molecule elimination in expanded haemodialysis: only convective transport?

BackgroundNew high-retention onset dialysers have shown improved efficacy in the elimination of uraemic toxins, and their depurative capacity has been compared with high convective volumes of online haemodiafiltration. Haemodialysis (HD) using high-flux membranes leads to convective transport by internal filtration [direct filtration (DF)/backfiltration (BF)] and allows the removal of middle molecules (MMs). The aim of this study was to assess solute transport mechanisms in expanded HD (HDx).MethodsIn 14 4-h HDx sessions with Theranova-500 dialysers under similar dialysis conditions (blood flow 400 mL/min, dialysate flow 700 mL/min, dialysate temperature 35.5°C), pressures at the inlet and outlet of both dialyser compartments (Pbi, Pbo, Pdi and Pdo) were collected hourly to estimate DF/BF volumes by semi-empirical methods. Uraemic toxins with various molecular weights were measured pre-dialysis, at 1 h (pre-filter and post-filter) and post-dialysis to calculate molecules’ reduction over time and dialyser in vivo clearances.ResultsUltrafiltration was 1.47 ± 0.9 L and Kt/V 1.74 ± 0.3. Hydrodynamic data (Pbi: 259 ± 39, Pbo: 155 ± 27, Pdi: 271 ± 30, Pdo: 145 ± 29 mmHg and oncotic pressure 22.0 ± 3.5 mmHg) allowed the estimation of DF/BF rates. DF flow ranged from 29.5 ± 4.2 to 31.3 ± 3.9 mL/min and BF flow ranged from 25.1 ± 2.3 to 23.4 ± 2.6 mL/min. The highest calculated DF volume was 7506.8 ± 935.3 mL/session. Diffusive clearances (Kd) of all solutes were higher than their convective transport (all P < 0.001) except for prolactin (23 kDa) clearances, which showed no differences. Total clearances of all solutes were correlated with their Kd (ρ = 0.899–0.987, all P < 0.001) and Kt/V correlated with all reduction rates (ρ = 0.661–0.941, P = 0.010 to <0.001). DF flow was only associated with urea (ρ = −0.793, P = 0.001), creatinine (ρ = −0.675, P = 0.008) and myoglobin clearance (ρ = 0.653, P = 0.011).ConclusionResults suggest that diffusive transport is a main mechanism of MM elimination in HDx. HDx offers an efficient depuration of MM without the need for high convective volumes.

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online

Background and objectiveOnline haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. Material and methodsProspective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. ResultsAge at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=–0.531, p=0.005), 2 years (r=–0.463, p=0.046), and at the end of follow-up (r=–0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p=0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=–0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=–0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (–0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. ConclusionThere is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.

Differences in Amino Acid Loss Between High-Efficiency Hemodialysis and Postdilution and Predilution Hemodiafiltration Using High Convection Volume Exchange—A New Metabolic Scenario? A Pilot Study

The objective of the study was to quantify the loss of total amino acids (TAAs), nonessential amino acids, essential amino acids, and branched chain amino acids (BCAAs) produced by high-efficiency hemodialysis (HEHD), postdilution hemodiafiltration (HDFpost), and predilution hemodiafiltration (HDFpre) using high ultrafiltration volumes; and to define the specific AA losses registered in HEHD, HDFpost, and HDFpre; to identify a potential metabolic and nutritional decline into protein energy wasting; to compare AA analysis of arterial blood samples taken from healthy controls and patients with end-stage renal disease undergoing hemodialysis. Identical dialysis monitors, membranes, and dialysate/infusate were used to homogenize extracorporeal body influence. Ten patients were recruited and randomized to receive treatment with HEHD, HDFpost, and HDFpre it was used on-line dialytic water methodologies (OL); patients' AA arterial concentrations were measured at the start and on completion of dialysis; TAA from the dialyzer filter was calculated, and baseline levels were subsequently compared with findings obtained 1year later. Finally, the results obtained were compared with the data from a study of 8 healthy volunteers conducted using bioimpedance analysis and laboratory blood tests to assess nutritional status. A higher convective dose results in a higher weekly loss of TAA, nonessential AAs, essential AAs, and BCAAs (HEHD: 15.7g; HDFpost-OL: 16.1g; HDFpre-OL: 16.3g, P<.01). After 12months, the same hemodialys patients showed a reduced body and water intracellular mass and reduced phase angle. Arterial concentrations of TAAs and BCAAs were lower than those detected in healthy subjects (P<.01). The study shows that the AA losses in dialytic liquid are greater after high exchange volume HDF techniques, especially HDFpre. The AA losses are not metabolically compensated, so these increase the derangements of predialytic arterial plasma AA levels. Both AA losses and arterial AA perturbations further worsened body composition already after 12months of additional dialysis.

Effect of Increased Convection Volume by Mid-Dilution Hemodiafiltration on the Subclinical Chronic Inflammation in Maintenance Hemodialysis Patients

Mid-dilution hemodiafiltration (MID) is a dialytic technique that might improve systemic inflammation of patients in chronic hemodialysis (HD) by increasing substitution volumes. To verify this hypothesis, we performed a prospective cross-over study comparing the effect on inflammatory biomarkers of higher convection by MID versus standard convection by post-dilution hemodiafiltration (HDF). Patients under chronic HD were therefore treated by MID and HDF by crossover design. Each treatment period lasted 4 months, with 1 month of wash-out where patients were treated by HD, for a total of 9 months. Primary outcome was the change of serum pre-dialytic C-Reactive Protein (CRP), interleukin 6 (IL-6), IL-1, IL-10, transforming growth factor-β (TGF-β), tumor necrosis factor-α, albumin and pre-albumin. Samples were obtained monthly. Ten HD patients were enrolled (age: 64.9 ± 12.6 years; 70% males; dialytic vintage: 10.6 [2.7–16.2] years). Mean convection volume was 40.1 ± 2.5 L/session in MID and 20.1 ± 2.6 L/session in HDF. A significant reduction of β2-Microglobulin was detected as a result of either treatment. In MID, CRP decreased from 11.3 (3.2–31.0) to 3.1 (1.4–14.4) mg/L (p = 0.007), IL-6 from 12.7 (5.0–29.7) to 8.3 (4.4–14.0) pg/mL (p = 0.003), and TGF-β from 10.6 (7.4–15.6) to 7.4 (5.9–9.3) ng/mL (p = 0.001). A significant reduction of CRP from 8.5 (3.2–31.0) to 4.6 (3.2–31.0) mg/L was also detected in HDF (p = 0.037), whereas no significant reduction of IL-6 (p = 0.147) and TGF-β (p = 0.094) was found. Percentage reduction of IL-6 correlated with mean convective volume in HDF (R = 0.666; p = 0.036) and in MID (R = 0.760; p = 0.020). Therefore, MID and HDF are associated with an attenuation of inflammatory pattern that is correlated with a high convective volume.

Current approaches to middle molecule removal: room for innovation.

Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and MCOs, respectively) membranes, convective therapy and protein adsorptive membranes are available. When we use HCO or MCO membranes for convective therapy, we have to take care to avoid massive albumin leakage during a dialysis session. Convection volume is an important element to increase middle molecule removal; however, a larger convection volume has a risk of larger leakage of albumin. Predilution hemodiafiltration is a useful measurement to increase larger LMWPs without massive albumin leakage. β2-microglobulin (B2M), α1-microglobulin (A1M) and albumin leakage during a dialysis session are useful parameters for assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35% are favorable to improve severe dialysis-related symptoms. The efficacy of middle molecule removal should be evaluated in comparison with clinical outcomes, mortality, morbidity and the improvement of dialysis-related symptoms. Recently some dialysis-related symptoms such as sleep disturbance, skin itchiness and dialysis hypotension have been recognized as good surrogate makers for mortality. Further studies to evaluate the relationship between middle molecule or PBUTs removal and the improvement of patient symptoms should be performed in well-designed randomized controlled trials.

Moving beyond small solute clearance: What evidence is there for more permeable dialyzers and haemodiafiltration?

Dialyzers were initially developed for diffusive clearance of uraemic toxins. Diffusion most effectively clears small uncharged solutes from plasma water, such as urea. Sessional urea clearance targets have been shown to be important for short-term patient survival, but over the longer term, although low-flux dialysis can prolong patient survival, accumulation of middle-sized uraemic toxins, such as β2 microglobulin can lead to disabling arthropathy. Although the introduction of high-flux dialyzers, designed to increase β2 microglobulin clearance, has reduced the prevalence of arthropathy; this has not been translated into a demonstrable significant improvement in patient survival. However, analysis of individual patients recruited into trials of haemo-diafiltration reported that greater convective clearance was associated with better survival, although the individual trials reported mixed outcomes. Most haemodiafiltration trials were not designed to study the effect of convective dose, so although reported patient survival was greater for those receiving greater convective volume exchange, these results could potentially be confounded by patient or center effects. An alternative approach to increasing middle-sized solute clearances would be to use more permeable dialyzers, but as yet there are no trials reporting survival with larger cutoff dialyzers. As such, although there is increasing evidence that increasing middle-sized molecular uraemic solute clearance is associated with improved patient survival, further prospective trials are required to determine whether as with Kt/Vurea there is a threshold effect of how much convective or middle-sized solute clearance is required to improve patient survival.