Middle Molecules Research Articles

Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study.

ABSTRACTBackgroundDialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for performance during online hemodiafiltration (HDF) in a clinical setting.MethodscomPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was β2-m removal rate (β2-m RR) during online HDF. Secondary endpoints were RR and/or clearance of β2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 versus comparators were tested.ResultsFifty-two patients were included and analysed. FX CorAL 600 showed the highest β2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its comparators was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 minutes and its sieving properties changed less over time than with comparators.ConclusionsFX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in β2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane.

Comparative Effectiveness Between Novel Medium Cut-Off Membrane Hemodialysis and Mixed-Dilution Online Hemodiafiltration on Middle Molecule Uremic Toxins Reduction: A Prospective Cross-Over Study

Comparative Effectiveness Between Novel Medium Cut-Off Membrane Hemodialysis and Mixed-Dilution Online Hemodiafiltration on Middle Molecule Uremic Toxins Reduction: A Prospective Cross-Over Study

Analysis Of The Achieved Quality Of Life In Patients With End-Stage Ckd Undergoing Online Hemodiafiltration

Online hemodiafiltration (OL-HDF), as a renal replacement therapy, has gained significant momentum in recent years due to the added benefit of increased clearance of middle molecules responsible for organ damage and the development of complications in patients with end-stage CKD (ESRD). The beneficial effect of OL-HDF on mortality from a variety of causes, as well as cardiovascular mortality and morbidity, has been reported by some clinical trials. Health-related quality of life (HRQOL) is an important component of care for hemodialysis patients and is of interest to both healthcare providers and patients. Improved quality of life in hemodialysis patients has been associated with a reduced rate of hospitalizations, morbidity and mortality, as well as higher self-esteem, well-being, and psychological comfort. Data on HRQOL in ESRD patients under OL-HDF are scarce and of negligible quality. In the Clinic of Nephrology and Dialysis at the St. Marina University Hospital, Varna, we performed a comparative analysis on 41 patients with HD with an average age of 58.6 ± 12 years (36–70), divided into two groups: Group 1—undergoing conventional HD, and Group 2—undergoing online HDF for a period of 6 months. The main research method is based on a standardized questionnaire on quality of life in kidney disease (KDQOL-SF36), containing 36 elements for assessing eight health concepts of HRQOL, as well as statistics on hospitalizations, morbidity and mortality in patients. The study shows that the use of OL-HDF is associated with a better quality of life related to health in both dimensions: the scale of the physical component and the scale of mental components. There is a reduction in the number of annual hospitalizations, a lower incidence of cardiovascular events, improvement in hypertension, chronic joint pain and stiffness, itching, and improved nutritional status and response to erythropoietin therapy.

Effects of flavonol quercetin on syndrome of endogenous intoxication in experimental periodontitis

The article presents the results of study effect of quercetin on the indicators of endogenous intoxication syndrome under conditions of experimental periodontitis. One of the key links in the pathogenesis of any inflammatory disease, including maxillofacial area, is endogenous intoxication, an important pathophysiological mechanism of which is the activation of lipid peroxidation. The experimental animals were treated by intramuscular injections with water-soluble quercetin for 7 days. For further research the blood serum was selected in which was determined the content of middle molecular weight molecules and erythrocyte intoxication index. Excessive lipoperoxidation was accompanied by accumulation of peroxidation products and depletion of antioxidant reserves, which led to accumulation of toxic substances. That is why the study of the level of middle molecular weight molecules and erythrocyte intoxication index in simulated bacterial-immune periodontitis is a reliable criterion. Quercetin was able to reduce the expression of endogenous intoxication syndrome in experimental bacterial-immune periodontitis.

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle molecule clearance in hemodialysis patients: a prospective randomized controlled trial.

BackgroundThe use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF.MethodsWe conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities.ResultsA mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the β2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups.ConclusionUse of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better β2-microglobulin clearance than predilution HDF.

Similar neuroendocrine and metabolic effects of sulfate-chloride sodium-magnesium mineral waters "Myroslava" and "Khrystyna" of Truskavets’ spa in healthy female rats

Background. In order to expand the hydro-mineral base of Truskavets’ spa by diluting brine (130 g/L), two new sulphate-chloride sodium-magnesium mineral waters "Myroslava" (5 g/L) and "Khrystyna" (10 g/L) were created. This report is the first in a series of experimental studies of their physiological activity in line with the concepts of neuroendocrine-immune complex and functional-metabolic continuum. Materials and Methods. Experiment was performed on 50 healthy female Wistar rats 220-300 g divided into 4 groups. Animals of the first group remained intact, using tap water from drinking ad libitum. Rats of the control group for 6 days administered a single tap water through the tube at a dose of 1,5 mL/100 g of body mass. The rats of the main groups received the water "Myroslava" and "Khrystyna". The day after the completion of the drinking course in all rats assessed the state of autonomous regulation by parameters of the HRV. The plasma levels of the hormones of adaptation were determined: corticosterone, triiodothyronine and testosterone (by the ELISA); as well as electrolytes, nitric metabolites, lipid peroxidation products and antioxidant enzymes as well as cholesterol, glucose, amylase and middle mass molecules. Most of the listed parameters of metabolism as well as 17-ketosteroids were determined in daily urine. In the adrenal glands the thickness of glomerular, fascicular, reticular and medullar zones was measured. Results. To identify exactly those parameters, the set of which three groups of animals differ significantly from each other, the information field of the registered parameters was subjected to discriminant analysis. The program included in the model 6 endocrine and 11 metabolic parameters, as well as glomerular filtration. Conclusion. The newly created sulfate-chloride sodium-magnesium drinking mineral waters of Truskavets’ spa have similar neuroendocrine and metabolic effects on healthy old female rats significantly different from daily water.

Expanded hemodialysis as effective alternative to on-line hemodiafiltration: A randomized mid-term clinical trial.

Expanded hemodialysis (HDx), using medium cut‐off membrane, is a novel therapy that effectively clears middle molecules (MMs). We aimed to compare HDx to hemodiafiltration (HDF) in an open randomized clinical study. Patients currently on HDF (age 18–80 years; on HDF >3 months) were randomized to switch to HDx (N = 21) or continue HDF (N = 22) with a 24‐week follow‐up. Pre‐ to post‐dialysis reduction ratios (RR) and changes in pre‐dialysis levels over time were evaluated for MMs and clinical biomarkers. Use of erythropoiesis‐stimulating agents (ESAs) was assessed. HDx showed greater RR for YKL‐40 while RR appeared similar between groups for beta2‐microglobulin, FGF‐23, and free light chains. Intradialytic changes in inflammatory biomarkers (IL‐6, CRP, PTX3) did not differ between therapies. Changes from baseline to 12 and 24 weeks did not differ between groups for MMs, inflammatory markers, albumin, fibrinogen, hemoglobin, PTH, and phosphorus. Use of ESAs tended to decrease in HDx arm while remaining stable in HDF arm. HDx appeared safe with similar clinical effectiveness as HDF. With fewer requirements and resource needs, HDx provides an attractive alternative to HDF.

MO671COMPARASION OF EXPENDED HEMODIALYSIS USING A MEDIUM CUT-OFF DIALYZER VERSUS HEMODIAFILTRATION: AN OBSERVATIONAL PROSPECTIVE STUDY

Abstract Background and Aims Expended hemodialysis (HDx) with medium cut-off (MCO) membrane enables efficient depuration of middleweight uremic toxins, which play significant roles in inflammation and cardiovascular morbidity. Hemodiafiltration (HDF) is known for good removal of middle molecules but it requires more technical resources and well-functioning dialysis access. The aim of this study is to evaluate the efficacy of depuration of uremic toxins with a high-flux dialyzer during HDF session and with a MCO membrane (Theranova®) in HDx session and its impact on quality of life (QoL) in hemodialysis patients. Method In an open, single-centre, prospective observational clinical study, 28 adult stable HD patients without residual renal function were assigned to be treated by on-line HDF (HDF group) with the APS-21H dialyzer (polysulfone membrane, 2.1 m2, Asahi Kasei Medical Co., Japan) or by HDx (HDx group) with the Theranova® 400 (1.7 m2) and Theranova® 500 (2.0 m2) dialyzers (Baxter International Inc, USA). The study was conducted during 2019-2020 and completed after 12 months period. All patients were receiving maintenance high-flux membrane HDF treatment at least six months before they were enrolled in the study. Groups of patients were matched in age, sex, BMI, dialysis length and underlying disease. Complete blood count (CBC), renal function and inflammation, electrolytes, liver function tests, iron and nutritional status were evaluated at the beginning of the study and after 3, 6, 9 and 12 months. Pre and postdialysis levels for urea, creatinine, albumin, calcium, phosphorus, C-Reactive Protein, kappa and lambda free light chains (FLC), vitamin B12, β2 microglobulin levels were determined in each patient quarterly and reduction rate (RR) for uremic toxins were calculated. Furthermore single-pool Kt/V, dose of erythropoietin therapy (EPO) and vascular access were evaluated during the study, while bioimpedance analysis using Body composition monitor (Fresenius Medical Care, Germany) and QoL using SF-36 questionnaire (Kidney Disease Quality of Life Short Form-KDQOLTM-36) were evaluated at the end of observation period. The values have been reported as mean ±SD. Results There were 28 patients (14 in each group) mean age of 54.24 years (57.71±9.65 in HDx group vs 59.81±7.99 in HDF group). Median dialysis vintage was 4.77 years (5.33 in HDx group vs 6.46 in HDF group, p=0.55). Vascular access was native arteriovenous fistula in 23 patients, arteriovenous graft in 2 patients and tunnelled dialysis catheter in 3 patients (p=0.98). Kt/V was similar in both groups (1.57±0.31 vs 1.45±0.24, p=0.9), as well as weekly dose of EPO (4533.3±1922.3 vs 4233.3±1971.8, p=0.67). Patients in HDF group had a significantly higher interdialysis fluid overload (2,48±1,37 in HDx group vs 3,64±1,33 in HDF group, p=0.04), without difference in relation to the systolic and diastolic blood pressure values, as well as others BCM parameters. There were not significant differences in examined parameters of CBC, renal function and inflammation, electrolytes, liver function tests, iron and nutritional status at the beginning and at the end of the study. RR of small and middle molecules are presented in Table 1. Serum albumin level has decreased from 37.8 g/dL to 36.4 g/dL in 12 months during HDx treatment with maximal change of serum albumin level of -3.7% during that period (Figure 1). Evaluation of Kidney Disease Quality of Life Short Form at the end of study period in both groups is shown in Figure 2. Conclusion Compared to HDF, HDx with MCO membranes show greater RR for large middle molecules such as lambda FLC (45kD), while RRs for middle molecules- kappa FLC (23kD), β2 microglobulin (12kD) and small uremic toxins are similar. During one year of treatment with MCO membranes serum albumin levels remain stable. HDx treatment may improve quality of life, making an impact primarily in energy status and emotional satisfaction.

MO799IS COMBINATION OF MAINTENANCE HEMODIALYSIS WITH HEMOPERFUSION AN EFFECTIVE METHOD IN MANAGEMENT OF RENAL OSTEODYSTROPHY AND INFLAMMATION IN HEMODIALYSIS PATIENTS?

Abstract Background and Aims Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. Method A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. Results At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p&amp;lt;0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p&amp;lt;0.05), P04 (p&amp;lt;0.001), CRP (p&amp;lt;0.011), SBP and DBP (p&amp;lt;0.05). Conclusion HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.

MO902SERUM FREE LIGHT CHAINS IN HEMODIALYSIS PATIENTS: A BRIDGE BETWEEN INFLAMMATION, IMMUNE SYSTEM DYSFUNCTION AND MORTALITY RISK

Abstract Background and Aims Uremic toxins, poor removed by conventional hemodialysis (HD), represent independent risk factors for mortality in end-stage renal disease (ESRD). Middle uremic toxin molecules were associated to pathological features of uremia, such as immune dysfunction and inflammation. These two entities are not mutually exclusive, but they could represent two sides of the same coin. ESRD-associated inflammation is closely related to the activation of innate immune system. Free light chain (FLC) may be a specific assessment of inflammation, representing a direct function of adaptive immunity through B-cell lineage production rather than a general marker of inflammation. While several studies have assessed the relation between FLCs and mortality risk in chronic kidney disease (CKD), FLCs, as uremic toxins in non-multiple myeloma dialyzed patients, were marginally analyzed. The aim of this prospective study was to evaluate the clinical impact of FLCs levels in HD patients, during a 2-years follow-up analysing the relations with biomarkers of inflammation, such as C-reactive protein (CRP) and procalcitonin (PCT), main lymphocytes subsets, such as CD4+ and CD8+ T cell count and high mobility group box (HMGB) -1 levels, as expression of the innate immune system. The potential link between FLCs levels and mortality risk was assessed. Method 190 patients on chronic hemodialysis at the Nephrology and Dialysis Unit of Papardo Hospital in Messina, Italy, were enrolled and followed for 2 years. Inclusion criteria were: age &amp;gt;18 years, absence or &amp;lt;200 ml/die residual diuresis, κ/λ ratio within the renal reference range (0.37–3.1). Receiver operating characteristics (ROC) analysis was performed to estimate the cut-off points of HMGB-1 and cFLC. Kaplan-Meier survival analysis and Cox proportional multivariate hazards model were used for clinical outcome. Results HD patients were characterized by high FLC levels. κFLC values were 182.3 (IQR: 140.2 – 216.1) mg/L, whereas λFLC levels were 108.2 (IQR: 72.7 – 143.2) mg/L. The median combined (c) FLC concentration was 182.9 mg/L (IQR = 207.8 – 330.2), which was extremely greater than the median reported in the general population (normal range = 9.3 – 43.3 mg/L) and in CKD patients [68.9 mg/L (IQR = 49.4 – 100.9)]. No differences in cFLC levels were revealed according to dialysis techniques. HD patients showed significant reduction of CD4+ and CD4+/CD8+ ratio. High HMGB1 levels were detected in HD patients (161.3 ± 39.7 ng/ml) and positively related to PCT and cFLC (r = - 0.38; p &amp;lt; 0.001), with an inverse relation to CD4+/CD8+ ratio. cFLC positively correlated with β2 microglobulin, hemoglobin, and HMGB1. Conversely, an inverse correlation was revealed with surrogate markers of inflammation, such as CRP, procalcitonin, neutrophil counts. There were 49 deaths during the follow-up. The majority (23/49) of deaths were attributed to cardiovascular disease, the remainder to infection and malignancy. cFLCs and sHMGB-1 levels in this group were significantly elevated. By ROC analysis, HMGB-1 levels &amp;gt; 100.9 ng/mL and cFLC &amp;gt; 223.4 mg/l were associated with a significantly lower survival rate (p &amp;lt; 0.02 by log-rank test) than for patients with lower levels when using Kaplan-Meier analysis. After adjusting for confounding factors, by Cox proportional hazards method, the difference remained statistically significant (p = 0.02) Conclusion Our study demonstrated an independent relation between high cFLC levels and mortality in HD patients. cFLCs represent a potential biomarker of “inflammunity”, a physiopathological process playing a pivotal role in ESRD, based on a vicious circle between inflammation and immune dysfunction. Further in-depth examinations should be verify our findings, determining whether therapeutic measures targeting cFLC balance, such as hemodiafiltration and expanded dialysis, would be helpful to reduce the “inflammunity” process, characterizing dialyzed patients.

FC 093EFFICACY OF EXPANDED HEMODIALYSIS AT DIFFERENT DIALYSATE FLOWS

Abstract Background and Aims Expanded hemodialysis (HDx) is based on hollow fibre dialyzer focused on improving the clearance of middle molecules as a target for uremia treatment. According to in vitro and in vivo results, High cut off filters have high enough clearance to allow diminishing of dialysate flow. Our aim is to compare clearance of middle molecules at different dialysate flow (Qd) in HDx with TheranovaMR membranes. Our aim was to Evaluate efficacy of MCO dialyzer in terms of Kt/V and phosphorus levels at different prescribed dialysate flows (Qd) 400 vs 500 ml/min in HD patients from 10 renal clinics in Colombia. Method We performed a Prospective, observational, multicenter cohort study. Prevalent adult HD patients (&amp;gt;90 days), with weight lower or equal to 70 Kg, were included between September to November 2017 and prospectively followed for one year with routine monthly blood tests for HD adequacy and registered at both Qd groups at 1, 3, 6, 9 and 12 months. A mixed-model repeated measures analysis (MMRM) was performed to identify statistical differences over time. Socio-demographic and clinical characteristics of all patients were summarized descriptively by Qd. Results 462 patients were included: 127 with Qd 400 mL/min. We did not find statistically significative differences in serum levels of albumin, hemoglobin, calcium or phosphorus when comparing Qd 400ml/min vs 500 ml/min. We found statistically higher Kt/V in Qd 400 mL/min patients. (Table 2). In a sustainability analysis, part of Blue Planet dialysis research group, we calculated important savings in water waste in Qd 400 mL/min group. Conclusion MCO dialyzers are at least as effective in reaching HD adequacy parameters (Kt/V, PO4) at Qd 400 as 500 mL/min with interesting savings of potable water: 24 Liters were saved in each session per patient.

FC 134WATER SAVING COMPARISON AT DIFFERENT DIALYSATE FLOWS IN EXPANDED HEMODIALYSIS

Abstract Background and Aims Expanded hemodialysis (HDx) improves clearance of middle molecules as a target for uremia treatment. According to previously published results, high cut off filters have high enough clearance to allow diminishing of dialysate flow (Qd) without detrimental in HD adequacy outcomes with less water waste. According to World Health Organization (WHO), globally, almost 800 million people lack access to safe water and 2.5 billion lack access to optimal sanitation. Is our duty to search for ways to avoid water waste. Our aim is to describe the differences in water use between HDX patients receiving Qd 400 mL/min (Group 1) vs 500 ml/min (group 2) in HD patients from 10 renal clinics in Colombia as an alternative to reduce water waste in chronic HD as a strategy from Blue Planet Dialysis initiatives. Method We performed a Sub-analysis of CORHEX Study: We calculated water use at different Qd from our database: prospective, multicentre, observational cohort study of 992 adult patients undergoing chronic HD from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. All patients were prescribed with HDX three times a week for a minimum of 4 hours. We analysed patients with weight lower than 70 Kg at different Qd prescriptions to calculate water use at different Qd prescriptions and performed a prediction analysis, adjusting to Qd 400 mL/min, the whole potential population with weight lower than 70 Kg. Results 462 patients with weight lower than 70 Kg were analysed, 127 patients received Qd 400 mL/min. When diminishing Qd from 500 to 400 mL/min, 24 litres were saved per session per patient without detriment of middle molecule clearance. There were no differences in adequacy HD parameters between Qd prescriptions (Table 1 and 2). Conclusion HDX allows lowering of Qd to 400 mL/min without harm for patients and with remarkable savings of potable water: 24 Litres were saved in each session per patient that can be translated in almost 3500 Litres of water each year by patient which is enough for one year for 47 adults. (Based on the WHO minimum for basic health protection of at least 20 L per person/day) (2). We consider our results especially relevant since the World Health Organization estimates that within the next 5 years, over 50% of world population could reside in geographies lacking sufficient access to water. We hope that our results from the Blue Planet dialysis research group, alongside with Dr. Agar`s and Dr. Barraclough`s green nephrology initiatives, can help educate the nephrology community on the ecological impact of dialysis and can present an innovative solution to offer HD therapy even in countries suffering from limited access to potable water.

MO208ASSOCIATION OF SERUM BETA-2 MICROGLOBULIN LEVEL WITH DIFFERENT CARDIAC AND METABOLIC RISK FACTORS IN CKD PATIENTS

Abstract Background and Aims Serum β M is a middle molecule uremic toxin that accumulates in serum and deposits at various tissues in chronic kidney disease (CKD), especially more in dialysis patients. The βâ M is generally considered as a predictor of cardiovascular morbidity and mortality and this is more investigated in dialysis group. However its relationship with several cardiac and metabolic risk factors in all stages of CKD is still under evaluation. This study was undertaken to evaluate the association of plasma βâ M level in different stages of chronic kidney disease patients with different cardiac, renal and metabolic risk factors that can predict future cardiovascular events Method This cross-sectional study was conducted by selecting consecutive 132 CKD subjects of stages 1-5D including both patients not requiring dialysis and those on maintenance hemodialysis. Their demographic, clinical and laboratory data were recorded in a data sheet. Fasting blood samples in dialysis non requiring subjects and predialysis samples in hemodialysis group (G5D) were taken for testin in laboratory for CBC, serum βâ M, hCRP, iPTH, lipid profile, creatinine, uric acid and serum albumin as cardiac, renal and metabolic risk markers. Urine sample was taken from predialysis patients for chemical test and ACR. The CKD staging were done by MDRD criteria. Additional 25 no CKD subject was taken as healthy referents. Results Primarily Beta-2 microglobulin was higher in CKD patients than in healthy group (13.53 ± 14.74 vs. 1.81 ± 0.47, mg/l; p&amp;lt;.001). The levels were gradually rising with the advancing stages of CKD (G1&amp;2-3.46 ± 2.39, G3-3.66 ± 1.08, G4-6.51 ± 2.20, G5-11.43 ± 2.98 and G5D-41.79 ± 8.58, mg/l). A Beta-2 microglobulin cut-off of &amp;gt;7.7 vs. &amp;lt; 7.7 mg/l showed significantly increased Systolic BP (136 ±22 vs. 123 ± 22, mmHg), diastolic BP (80 ± 12 vs. 75 ± 8.96, mmHg),( p&amp;lt;0.01); CRP (6.83 ± 6.03 vs. 4.39 ± 5.35, mg/l)( p&amp;lt;0.007); serum phosphate (4.84 ± 1.79 vs. 3.85 ±.92,mg/dl)( p&amp;lt;0.001); uric acid (5.89 ± 1.41 vs. 5.01 ± 1.57,mg/dl)( p&amp;lt;0.01); TG (189± 103 vs. 155 ± 88, mg/dl),( p&amp;lt;0.04); and PTH (239.83 ± 186.50 vs. 90.52 ± 81.77, pg/ml), ( p&amp;lt;0.001) indicating higher cardio metabolic risks in higher group. Similarly renal parameters were also more altered in high Beta-2 microalbumin group for serum creatinine (6.89 ± 3.54 vs. 1.58 ± .81, mg/dl) (p&amp;lt;0.001) and ACR (824 ± 917 vs. 320 ± 753, mg/g),( p&amp;lt;0.001). B-2 microglobulin also positively correlated with systolic blood pressure (r=.295, p&amp;lt;.001), serum creatinine (r=.879, p&amp;lt;.001), serum phosphate (r=.175, p =.047), serum iPTH (r=.403, p&amp;lt;.001) , hCRP ( r=.193, p =.050) , Triglycerides (r=.196, p =.023) and urine ACR in CKD patients. Conclusion Beta-2 microglobulin level was significantly higher in CKD with an increasing pattern towards advancing stages. The higher levels positively correlated with cardio renal and metabolic risk factors. Hence measuring Beta-2 microglobulin regularly can help to take preventive measures early to manage patients at risk.

MO387CLINICAL PERFORMANCE, HEMOCOMPATIBILITY AND SAFETY OF A NEW DIALYZER WITH A MODIFIED POLYSULFONE MEMBRANE

Abstract Background and Aims Hemodialyzers containing membranes made from a blend of polysulfone and polyvinylpyrrolidone (PVP) are widely used. PVP makes the membrane material more hydrophilic to reduce interactions with plasma proteins and platelets. A modified spinning technique has been established to stabilize the PVP on the blood-side surface in the polysulfone dialysis membrane in the new dialyzer FX CorAL 600. The objective of the present study was to prove for this new dialyzer non-inferiority of performance in comparison to established dialyzers. Further, hemocompatibility and safety of the dialyzers were explored. Method In a multicenter, prospective, randomized, crossover study adult patients on online hemodiafiltration (HDF) were enrolled. They were treated for one week each with on-line HDF in post-dilution mode, and in randomized order with the dialyzers FX CorAL 600, FX 600, and FX CorDiax 600 (all Fresenius Medical Care, Bad Homburg, Germany). Blood samples were taken on the midweek session before start, at the end to analyze removal rate and at 60 min to determine clearance of ß2-microglobulin, myoglobin, urea, creatinine and phosphate. Further a pattern of hemocompatibility parameters and safety was evaluated. Assuming no carry over effect, linear mixed models were used for statistical analysis. Results The mean age of the 49 enrolled patients was 66.3±13.6 years, 76% were male. Treatments were performed in post-dilution mode with a mean blood flow &amp;gt; 300 mL/min and a substitution volume &amp;gt;19 L. The removal rate of ß2-microglobulin was 74.4, 70.4, and 73.1% for the FX CorAL 600, FX 600, and FX CorDiax 600 dialyzer, respectively. FX CorAL 600 proved to be statistically significantly non-inferior to FX 600 (p=0.0006) and to FX CorDiax 600 (p=0.036). The removal rate of FX CorAL 600 was by 4.0% (confidence interval 0.4 – 7.5%) significantly higher than with FX 600. The difference to FX CorDiax 600 was not significant. The clearance of ß2-microglobulin and myoglobin and the removal rate of myoglobin were significantly higher with the new dialyzer FX CorAL 600 than with the FX 600, and comparable to the FX CorDiax 600. Performance for small molecules was similar for all dialyzers. The complement factors C3a and C5a increased early in the treatment with a peak at 15 min, without differences between the three dialyzers for C3a, and for C5a with significantly lower increase at 15 min with FX CorAL 600 than for FX 600 (p=0.007); the difference of increase between FX CorAL 600 and FX CorDiax 600 was not significant (p=0.515). The course of sC5b9 was similar for all three dialyzers, with significantly lower increase at 15 min for both FX CorAL 600 (p=0.009) and FX CorDiax 600 (p=0.026) as compared to FX 600 and similar increase at 60 min for both FX CorAL 600 (p=0.573) and FX CorDiax 600 (p=0.386) as compared to FX 600. The area-under-the-curve for the course of sC5b-9 with FX CorAL 600 was significantly lower than with FX 600 (p=0.044) and comparable to FX CorDiax 600 (p=0.092). The leukocyte count showed a decrease in the first 15 min of the treatment, which recovered afterwards, similarly for all treatment phases with the different dialyzers. Further, the dialyzers did not differ with respect to adverse events. Conclusion All three dialyzers showed good performance, with higher removal rates for middle molecules with the new dialyzer FX CorAL 600 compared to the FX 600. Hemocompatibility profiles were mostly similar, with lower activation of C5a and of sC5b9 with FX CorAL 600 compared to FX 600. The new dialyzer provides comparable performance levels capable of delivering adequate treatment and good tolerability for the patient.

Flow Dynamic Analysis by Contrast-Enhanced Imaging Techniques of Medium Cutoff Membrane Hemodialyzer

Introduction: Medium cutoff (MCO) membranes represent an interesting innovation in the field of hemodialysis. Given the correlation between large (PM >25 kDa) middle molecules (LMM) and clinical outcomes, the possibility to broaden the spectrum of solutes removed in hemodialysis with MCO membranes introduces a new perspective for end-stage kidney disease patients. Due to low diffusion coefficients of LMM, the use of convection is required to maximize extracorporeal clearance. High convective rates are achieved with high-flux membranes in hemodiafiltration, a technique not available in the US. In case of the MCO membrane, remarkable clearances of LMM are achieved combining the permeability of the membrane with a significant amount of internal convection. The mechanism of filtration-backfiltration inside the dialyzer enables effective removal of LMM in a technique called expanded hemodialysis (HDx). Given such theoretical explanation, it is important to demonstrate the blood and ultrafiltration rheology inside the MCO dialyzer. Method: This study for the first time describes flow dynamic parameters and internal cross-filtration, thanks to specific radiology and nuclear imaging techniques. Results: Flow dynamic analysis of the blood and dialysate compartment confirms excellent distribution of velocities and an excellent matching of blood and dialysate. Average blood flow velocity allows for wall shear rates adequate to avoid protein stagnation at the blood membrane interface and increase in blood viscosity. Cross-filtration analysis demonstrates a remarkable filtration/backfiltration flux reaching values >30 mL/min at a blood flow of 300 mL/min and zero net filtration. Conclusion: The MCO dialyzer Theranova 400 appears to have a design optimized to perform expanded hemodialysis (HDx).

Study of oxygen compounds of acid character of Garbi Absheron field oil

The paper presents the results of fraction and structural-group composition of acids and phenols of Garbi Absheron field oil. Studied oil is heavy, tarry, low paraffinic. The acids and phenols have been purified from the oil with their differentiation on the free and associated (in the form of compound esters) forms. Free acids and phenols were purified from the oil via alkali extraction. Their associated forms were purified after saponification of the oil released from the samples. To study the structure-group content of acids and phenols, proton-magnetic resonance spectroscopy method was used. Obtained results showed that acidic oxygen-containing compounds in Garbi Absheron field oil predominantly consist of associated acids and phenols in the form of compound esters. Middle molecules of these phenols contain condensed naphtenic-aromatic cycles, the acids by their structure belong to the derivatives of hydrocarbons of paraffin series of CH3 residual-substitutes.

Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study

The EvoCit study was designed to evaluate performance of a heparin-grafted dialyzer during hemodialysis with and without systemic anticoagulation. Randomized, crossover, noninferiority trial. Noninferiority was defined as a difference of≤10% for the primary outcome. Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions. Hemodialysis using a heparin-grafted dialyzer combined with a 1.0mmol/L citrate-enriched dialysate ("EvoCit") without systemic anticoagulation compared with hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("EvoHep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks. The primary end point was the difference in Kt/Vurea between EvoCit and EvoHep. Secondary end points were urea reduction ratio, middle molecule removal, treatment time, thrombin generation, and reduction in dialyzer blood compartment volume. The estimated difference in Kt/Vurea between EvoCit and EvoHep was-0.03 (95% CI,-0.06 to-0.007), establishing noninferiority with mean Kt/Vurea of 1.47±0.05 (SE) for EvoCit and 1.50±0.05 for EvoHep. Noninferiority was also established for reduction ratios of urea and β2-microglobulin. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during EvoCit and no sessions during EvoHep. Effective treatment time was 236±5 minutes for EvoCit and 238±1 minutes for EvoHep. Thrombin generation was increased and there was greater reduction in dialyzer blood compartment volume after treatments with EvoCit compared with EvoHep. The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated. EvoCit is noninferior to EvoHep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting, and greater thrombin generation TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03887468.

Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin β2-Microglobulin in Spent Dialysate.

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of β2-microglobulin (β2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of β2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated β2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of β2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin β2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

Effect of a medium cut-off dialyzer on protein-bound uremic toxins and mineral metabolism markers in patients on hemodialysis.

Hemodialysis (HD) with medium cut-off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25-60 kDa). However, the impact of MCO dialyzers on long-term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) provided an opportunity to assess the effect of MCO dialyzers on protein-bound uremic toxins and novel markers of mineral metabolism. This exploratory sub-study of REMOVAL-HD evaluated changes in protein-bound solutes (total and free indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor-23 [iFGF23], fetuin-A and endogenous calciprotein particles [CPP-1 and CPP-2]). Mid-week, pre-HD serum samples were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models. Eighty-nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (-26.8% [95%CI -39.7, -11.1], p = 0.001), which was sustained at Week 24 (-21.7% [95%CI -35.7, -4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin-A, CPP-1, or CPP-2. The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.

Clinical-pathogenetic significance of middle mass molecules of different fractions in pulmonary expirates of patients with rheumatoid arthritis

Objective — to establish the clinical and pathogenetic role of the isolation of the middle mass molecules of different fractions (aminopeptide — AF, peptide — PF, nucleotide — NF, chromatophore — CF) in exhaled breath concentrate (EBC) in pneumonitis in rheumatoid arthritis (RA) patients, their relationship with the parameters of respiratory moisture excretion, spirography and pressure in the pulmonary artery. &#x0D; Materials and methods. EBC (pulmonary expirates) were studied in 31 patients with RA (mean age 46 years, the ratio of men to women 1 : 2), among whom moderate and high degree of disease activity was established in 67.7 % of cases, III and IV stages — in 54.8 %, the extra­articular form of the disease — in 61.3 %, systemic osteoporosis — in 83.9 %, seropositivity for rheumatoid factor — in 80.7 %, for antibodies to cyclic citrullined peptide — in 77.4 %. To determine the middle mass molecules in the expirates and blood serum, a screening method was used with the precipitation of proteins with trichloroacetic acid and the determination of the light absorption spectra of the acid­soluble fraction. &#x0D; Results and discussion. Interstitial pneumonitis was diagnosed in 51.6 % of the number of RA patients, which was accompanied by fibrosing alveolitis in 18.8 % of cases, rheumatoid nodules in the lungs — in 12.5 %, obliterating bronchiolitis — in 6.3 %, with the ratio of restrictive, mixed and obstructive types of dysfunctions of external respiration 6 : 2 : 1, while the disease proceeded with a significant increase in AF indicators in 74.2 % of patients and the ratio «EBC/blood» (e/b) PF level in 77.4 % against the background of a decrease in AFe/b (at 71.0 %), NFe/b (at 54.8 %, CFe/b (at 74.2 %) and the ratio of surface tension caused by high­ and low­molecular substances in 83.9 %, and the composition of expirates was closely interrelated with the state of hemodynamics of the pulmonary circulation and bronchopermeability, depended on the rate and volume of respiratory moisture release, long­term use in the complex treatment of patients with an immunosuppressant of cytotoxic action, folic acid antagonist methotrexate. Conclusions. The nature of the respiratory excretion of middle mass molecules of different fractions determines the pathogenesis of pneumopathy in RA patients, which depends on the clinical, radiological and sonographic signs of the disease, and the study of EBC can be used to predict the course of the pathological process and monitor the effectiveness of therapeutic measures.