OPTIMIZED CONVECTIVE VOLUME IN ONLINE HEMODIAFILTRATION

Hemodiafiltration (HDF) adds convective elimination of middle molecules (MM), proportional to filtered volume (Vconv) on the top of diffusion-based elimination of small molecules (SM) by conventional hemodialysis (HD). Studies, both observational and randomized controlled ones, performed so far generally indicated positive impact of higher Vconv on all-cause mortality in HDF patients, although the magnitude of Vconv at which HDF becomes apparently superior to HD differed widely among the studies. Also the issue of a suitable anthropometric parameter by which the Vconv should be normalized has not yet been solved. Data from the ESHOL study seems to indicate that patient´s body surface area (BSA) could well be used for this—mortality was decreasing with increasing Vconv/BSA with a bottom plateau starting at about 15 L/m2. We have therefore devised a formula and a graph for determination of Vconv which fulfils the requirement Vconv/BSA= 15. Assuming maximum feasible and safe filtration fraction QF/QB= 0.3, the Vconv actually defines the necessary blood flow (QB) to reach Vconv/BSA= 15 as QB=15·BSA/(0.3·t) (t – session time). It is also possible to check what QB is needed in terms of sufficient diffusion-based transport (target Kt/V) and compare both QB values to see if adequate combined elimination of both SM and MM can be achieved at the same time and under what conditions, respectively.

Beta-2 microglobulin removal with postdilution online hemodiafiltration - comparison of three different dialysis membranes

Introduction/Objective. Accumulation of middle molecular weight uremic toxins causes various complications in chronic hemodialysis (HD) patients. Postdilution online hemodiafiltration (OL-HDF) efficiently removes these molecules. This study aimed to assess the effectiveness of three different dialysis membranes in removing ?2- microglobulin (b2m) within a single session of postdilution OL- HDF. Method. A prospective single-center study was carried out in 30 patients (23 males and 7 females, average age 54.87 ? 11.66 years, time on dialysis 4.95 ? 5.40 years) on maintenance HD. Each patient was followed for 3 consecutive weeks on OL-HDF with three different dialyzers: DiacapPro 19H, FX CorDiax 800, and Elisio 21H, randomly switched weekly. The reduction ratios (RR) of ?2m and albumin were compared individually. Results were analyzed with the Kolmogorov-Smirnov test, ANOVA, and the Kruskal-Wallis test. Results. The average convective volume for all patients was 21.38 ? 2.97 L/session. ?2-m RR was 70.86 ? 6.87%, 74.69 ? 6.51% and 70.04 ? 9.37% with Diacap Pro 19H, FX CorDiax 800 and Elisio 21H membrane respectively (p = 0.054). Albumin RR was 6.20 ? 2.12% with Diacap Pro 19H membrane, 6.01 ? 2.97% with FX CorDiax 800 membrane, and 6.46 ? 2.91% with Elisio 21H membrane (p = 0.812). Albumin loss was < 4.0g/dialysis treatment for all membranes. Conclusion. All investigated membranes effectively remove ?2-m in postdilution OL-HDF with a tolerable albumin loss. The highest ?2-m RR was determined for FX CorDiax 800 membrane, but with no statistically significant difference.

Chemical Composition and Petrogenetic Implications of Eudialyte-Group Mineral in the Peralkaline Lovozero Complex, Kola Peninsula, Russia

Lovozero complex, the world’s largest layered peralkaline intrusive complex hosts gigantic deposits of Zr-, Hf-, Nb-, LREE-, and HREE-rich Eudialyte Group of Mineral (EGM). The petrographic relations of EGM change with time and advancing crystallization up from Phase II (differentiated complex) to Phase III (eudialyte complex). EGM is anhedral interstitial in all of Phase II which indicates that EGM nucleated late relative to the main rock-forming and liquidus minerals of Phase II. Saturation in remaining bulk melt with components needed for nucleation of EGM was reached after the crystallization about 85 vol. % of the intrusion. Early euhedral and idiomorphic EGM of Phase III crystalized in a large convective volume of melt together with other liquidus minerals and was affected by layering processes and formation of EGM ore. Consequently, a prerequisite for the formation of the ore deposit is saturation of the alkaline bulk magma with EGM. It follows that the potential for EGM ores in Lovozero is restricted to the parts of the complex that hosts cumulus EGM. Phase II with only anhedral and interstitial EGM is not promising for this type of ore. Nor is the neighboring Khibiny complex despite a bulk content of 531 ppm of Zr. Khibiny only has interstitial and anhedral EGM. The evolution of the Lovozero magma is recorded in the compositions EGM up through a stratigraphy of 2400 m in Phase II and III of the complex, and distinct in elements like rare earth elements (REE), Sr, Ba, Th, U, Rb, Mn, Fe. The compositional evolution reflects primarily fractional crystallization processes within the magma chamber itself in combination with convective magma flow and layering by precipitation of minerals with different settling velocities. The suggested mechanism for the formation of the EGM deposits is flotation of very small, suspended EGM crystals in the convective magma and concentration below the roof of the magma chamber. Phase III EGM is enriched in total REE (1.3%) and in HREE (Ce/Yt = 8.8) and constitutes a world class deposit of REE in the million tons of Phase III eudialyte lujavrites.

TO014COMPARISON BETWEEN HIGH FLUX-HD AND OL-HDF ON SURVIVAL AND ADEQUACY: TEN YEARS EXPERIENCE

Background and Aims Four RCTs have been published that compared on-line HDF (Ol-HDF) with HD. However, to date, an indisputable answer in determining whether patients treated with Ol-HDF had a better survival than those treated with high-flux HD (Hf-HD) has not been reached. The aim of our study was to retrospectively evaluate the impact of the dialysis modality (Hf-HD, Ol-HDF or acetate-free biofiltration AFB) on patient survival and dialysis adequacy. Methods We retrospectively evaluated all the incident patients that started dialysis due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. Exclusion criteria were: duration of dialysis treatment less than 3 months, and previous dialytic treatment or kidney transplantation. The dialysis modality performed (Hf-HD vs Ol-HDF), the modality of infusion (pre-dilution or post-dilution) and mean total convective volume (replacement fluid volume + ultrafiltration) during last year’s dialysis session in Ol-HDF were analyzed for each patient. Results During observation 677 patients started HD treatment. 70 patients were excluded due to less than 3 months HD treatment. 607 patients (male 390, 64%) were analyzed. 467 pts (77%) were treated with Hf-HD, 103 pts (17%) with Ol-HDF, 36 pts (6%) with AFB. Median duration of HD treatment was 2.6 years (IQR 1.3; 4.7). Ol-HDF was performed in post-dilution mode in 60% of cases (total convective volume 25±4 L); pre-dilution mode was used in 40% of the cases (total convective volume 51±18 L). Patients in the Ol-HDF group were significantly younger than those in Hf-HD and AFB groups (respectively 59±15 years vs 71±15 vs 78±9, p &lt;0.05), and had less diabetes, hypertension and ischemic heart disease (p&lt;0.05) while presenting similar prevalence of cirrhosis (p=0.93) and peripheral vascular disease (p=0.09). Adequacy indices were similar between groups (eKt/V 1.39±0.02 vs 1.41±0.01 vs 1.44±0.04, p=0.47) as well as the protein intake (PCRn 0.92±0.01 vs 0.93±0.01 vs 0.90±0.03 g/Kg/d, p=0.69) and residual renal function (1.5±0.3 vs 1.6±0.1 vs 0.8±0.4 ml/min, p=0.20). Patients on Ol-HDF more frequently had an AV fistula (71% vs 58% vs 59%, p&lt;0.05). At the end of follow-up, 12% of patients had undergone kidney transplantation, 42% continued dialytic treatment while 43% died. Univariate analysis showed a better survival for Ol-HDF patients (Figure 1) (p &lt;0.05). This benefit was confirmed in multivariate analysis (Figure 2) showing that older age, cirrhosis and ischemic heart disease negatively affect survival, while a high protein intake, use of an AV fistula and Ol-HDF (HR 0.43[0.30-0.61]) are protective. Conclusions The use of Ol-HDF is associated with better survival compared to Hf-HD. This is confirmed after adjustment for demographic and comorbidities of the patients, characterizing Ol-HDF as an independent predictor of better survival.

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

Background Online 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 presentation A 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. Conclusion OL-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.

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

Background YKL-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. Methods We 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. Results The 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). Conclusions YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Differences in Dialysis Efficacy Have Limited Effects on Protein-Bound Uremic Toxins Plasma Levels over Time

The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta2-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta2-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term.

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.