P1072COMPARISON OF UREMIC TOXINS, INFLAMMATORY MARKERS AND VEGF LEVEL WITH MEDIUM CUT-OFF MEMBRANES AND HIGH-FLUX MEMBRANES IN HEMODIALYSIS: THERANOVA IN SISLI HAMIDIYE ETFAL (THE SHE) STUDY

Abstract Background and Aims Mortality in hemodialysis have not changed since last 30 years which may be caused by inflammation and accumulation of middle and large uremic toxins. Medium cut-off (MCO) membranes are able to perform hemodialysis as effective as hemodiafiltration. Their effect on inflammatory molecules and vascular endothelial growth factor-C (VEGF), an independent factor effective on mortality, are not well known. The aim of the study was to compare intra and inter dialyzer performances of MCO and high-flux dialyzers regarding middle and large uremic toxin, inflammatory marker, VEGF and serum albumin level. Method This is a randomized, prospective, open-label, cross-over study (ClinicalTrials.gov: NCT03836508) approved by local ethic committee. Patients had hemodialysis with either 36 sessions of high-flux dialyzer followed by 36 sessions of medium cut-off dialyzer or vice versa. Pre and postdialysis levels for urea, creatinine, albumin, total protein, free kappa light chain, free lambda light chain, beta-2 microglobulin, myoglobulin levels were determined at first and last sessions of every dialyzer. Postdialysis level of middle and large uremic molecules have been determined by a formula to prevent hemoconcentration effect. Reduction rate for uremic toxins were calculated. Serum level of human VEGF, fibroblast growth factor-23 (FGF-23), interferon gamma (IFN-g), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-17A (IL-17A) levels were determined at first and last session of the each dialyzer. Results Fifty-two patients were enrolled to the study. Median age of patients was 56.40 (43.87-67.39) years. Median dialysis vintage was 4.77 (3.08-10.09) years. Reduction rates and postdialysis levels of free kappa and lambda light chain, myoglobulin, beta-2 microglobulin were lower both at first and last sessions in medium cut-off dialyzers compared to high-flux dialyzers (p<0.05 for all) (Table 1). Last session predialysis free kappa, free lambda, beta-2 microglobulin level was lower than first session predialysis levels in medium cut-off dialyzers (p<0.05 for all) (Table 2). Last session IL-6, IL-10, IL-17, IFN-gamma levels did not differ between dialyzers (p>0.05 for all). Vascular endothelial growth factor levels were 500.91 (363.80-679.15) pg/ml in medium cut-off group and 610.60 (450.63-1021.93) pg/ml in high-flux group (p=0,043). Predialysis serum albumin level at first session for MCO and high-flux groups were 3.88 (3.71-4.04) g/L and 3.75 (3.59-3.95) g/L, respectively (p=0.086) (Figure 1). After 3 months of hemodialysis, it was 3.62 (3.45-3.88) g/L in MCO group and 3.78 (3.58-4.02) g/L in high-flux group (p=0.04). Serum albumin level has decreased from 3.88 (3.71-4.04) g/L to 3.62 (3.45-3.88) g/L in 3 months during hemodialysis with MCO dialyzers (p=0.0001). It did not change significantly in high-flux group in the same time period (p=0.861). Conclusion MCO membranes not only decrease post dialysis levels of free kappa, free lambda, beta-2 microglobulin, myoglobulin but also decrease the third month predialysis levels of free kappa, free lambda, beta-2 microglobulin. They do not let the increase in myoglobulin level as seen in high-flux dialyzers. Even though the IL-6, IL-10, IL-17, IFN-gamma, FGF-23 levels did not differ, VEGF levels were lower in MCO dialyzer. The most important side effect of hemodialysis with MCO membranes is decreased serum albumin level.

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Impact of Serum Albumin and B2-Microglobulin level on 2-Year Overall Survival among Newly Diagnosed Multiple Myeloma Patients: A retrospective Study

RAS Medical Science ◽

10.51520/2766-5240-5 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Sherian Salama ◽

Rodaina Yousef ◽

Asma Al Olama ◽

Mahmoud Marashi ◽

Hana Salama ◽

...

Keyword(s):

Multiple Myeloma ◽

Serum Albumin ◽

United Arab Emirates ◽

Staging System ◽

Albumin Level ◽

Age At Diagnosis ◽

Newly Diagnosed ◽

International Staging System ◽

Beta 2 ◽

Beta 2 Microglobulin

Background: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. Evaluation and initial staging of the disease is made once the diagnosis is confirmed. The recommended staging system is the International Staging System (ISS). Which determines the Myeloma prognosis by 2 factors: beta-2 Microglobulin and Serum albumin. Goal and Objective: The main goal of this study is to assess the effect of Beta-2 microglobulin and Serum albumin on patient’s survival rate with Multiple Myeloma. The secondary objective is to compare the age at diagnosis with other literature. Methodology: The current study was carried out in Hematology Unit, Dubai Hospital, Dubai, Dubai Health Authority (DHA), United Arab Emirates. Chart review was done retrospectively for 49 newly diagnosed patients with Multiple Myeloma diagnosed between the period 2012-2016. Purposive sample was used to those patients who met the inclusion criteria of this study, to be diagnosed and treated in DH. diagnosed and received regular treatment in Dubai Hospital. Results: Medina follow-up of the patients in this study was (12.8) months. The 2-year overall survival rate for patients with Multiple Myeloma (n = 49) was approximately 80%. While, the 2-year OS rate based on Albumin level. Patients with albumin level > 3.5 mg\dl was significantly higher compared to those who had an albumin level <3.5 mg\dl. 100%, 65% respectively, P = 0.033. Moreover, the 2-year OS rate in terms B2MG level. Patients who had a B2MG < 3.5 mg\dl OS was slightly higher compared to those who had (3.5-5.5 and 5.5 mg\dl). OS rate approximately 85 %, 80 % and 75 respectively, P = .737 Conclusion: Multiple myeloma (MM) is a very heterogeneous disease. For this reason, various prognostic factors and staging systems have been developed to predict the disease outcome. International Staging System (ISS) is very useful in determine the survival based on serum β2- microglobulin and serum albumin levels. The age at diagnosis in Dubai hospital, United Arab Emirates is much younger compared to other studies conducted worldwide. The sample used in the study was also highly diverse in terms of culture and nationality. Such diversity is largely typical in Gulf especially in United Arab Emirates. Therefore, this can play important role in age at diagnosis.

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Prognostic factors and staging in multiple myeloma: a reappraisal.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.1.80 ◽

1986 ◽

Vol 4 (1) ◽

pp. 80-87 ◽

Cited By ~ 109

Author(s):

R Bataille ◽

B G Durie ◽

J Grenier ◽

J Sany

Keyword(s):

Multiple Myeloma ◽

Serum Albumin ◽

Serum Albumin Level ◽

Albumin Level ◽

Survival Duration ◽

Instantaneous Rate ◽

Major Interest ◽

Staging Systems ◽

Beta 2 Microglobulin ◽

New Variables

To assess the important factors in the prognosis and staging of multiple myeloma (MM), we have correlated the presenting clinical features of 147 previously untreated patients with MM with the survival duration using multiple regression analyses. We have included the three major available myeloma-staging systems (MSS), ie, Durie-Salmon (DS), Medical Research Council (MRC), and Merlini-Waldenström-Jayakar (MWJ), plus two new variables related to disease activity: the serum beta 2-microglobulin level (S beta 2M) and the instantaneous rate of bone resorption. Our study confirms the validity of the three MSS in the prediction of survival duration, with a slight but significant advantage for the DS MSS. Among single variables, S beta 2M was the most powerful indicator of prognosis (P less than .0001), serum albumin level being the only variable adding to this significantly (P = .02). Of major interest, S beta 2M alone was a better indicator than MRC and MWJMSS. Finally, S beta 2M and the serum albumin level, variables not included in the three MSS, were better indicators than the classical DS MSS and could be combined simply to give a very powerful system of stratification.

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Serum Free Light Chain Ratio (FLCR) at Diagnosis Constitute a Powerful Prognostic Factor of Survival in Multiple Myeloma (MM).

Blood ◽

10.1182/blood.v108.11.3522.3522 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3522-3522

Author(s):

Marie-Christine Kyrtsonis ◽

Theodoros P. Vassilakopoulos ◽

Nicoletta Kafasi ◽

Sotirios Sachanas ◽

Tatiana Tzenou ◽

...

Keyword(s):

Prognostic Factor ◽

Serum Albumin ◽

Light Chain ◽

Bone Fractures ◽

Free Light Chain ◽

Baseline Serum ◽

Serum Free ◽

Serum Free Light Chain ◽

Beta 2 ◽

Beta 2 Microglobulin

Abstract MM is characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum, produced by neoplastic plasma cells infiltrating the bone marrow (BM). Small amounts of free light chains (FLC) are secreted in normal individuals. In case of monoclonality, the FLC ratio increased. The detection and quantification of serum FLCs and of their ratio, was recently introduced as a useful method for the diagnosis and monitoring of light chain MM, amyloidosis, non-secretory MM and MGUS. However, the possible role of FLCR as a prognostic variable has not been investigated yet. We therefore studied the relationship of baseline serum FLCR with disease characteristics and prognosis in MM patients. Eighty-six MM patients (55 kappa-, 31 lambda- ), 16 individuals with MGUS (8 kappa-, 8 lambda-) and 29 healthy individuals (HI) were studied. Serum free light chain levels were measured in frozen sera drawn at diagnosis, before treatment, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Behring BN II nephelometric analyzer. Then, the FLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Forty-nine percent of MM patients were males and 65% were ≥ 65 years old. The Ig type was IgG in 61%, IgA in 22%, BJ in 16% and IgD in 1%. Thirty-five percent of patients were in stage I, 31% in stage II and 34% in stage III according to Durie and Salmon while 36% were in stage 1, 22% in stage 2 and 42% in stage 3 of the ISS staging system. Twenty-five percent of patients had Hb < 10g/dL, 13% creatinin ≥2 mg/dl, 10% elevated LDH, 19% serum albumin < 3.5 g/dL, 45% CRP ≥4 mg/L, 41% beta-2-microglobulin ≥5.5 mg/L, 17% presented spontaneous bone fractures and 41% had ≥50% plasma cell BM infiltration. The median serum FLCR at diagnosis was 3.68 in the 55 kappa-MM patients, 38.49 in the 31 lambda-MM patients, 1.24 in kappa-MGUS, 2.14 in lambda-MGUS and 0.43 in HI (κ/λ). Differences between MM and HI and MM and MGUS were significant (p < 0.001). Baseline serum FLCR correlated with creatinin (p=0.03), LDH (p=0.003), the percentage of BM infiltration (p=0.001), the presence of spontaneous fractures (p=0.002) and Durie and Salmon staging (p=0.003). In patients with BJ MM, FLCR was higher then in the ones with other Ig types (p=0.001). Serum FLCR did not correlate with age, gender, hemoglobin, CRP, serum albumin, beta-2-microglobulin, paraprotein level nor with the ISS staging. With a median follow-up of 27.2 months (3.2–89.8), MM patients with serum FLCR < median, had a 3- and 5- year survival of 92±6 and 79±10 respectively, while the corresponding 3- and 5-year survival of patients with FLCR ≥ median were 67±8 and 32±13 (p=0.001). In multivariate analysis, serum FLCR above the median provided prognostic information independent of the value of ISS. In conclusion, baseline serum FLCR appears to be a powerful prognostic factor of survival in MM.

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Comparison of Circulating Levels of Uremic Toxins in Hemodialysis Patients Treated with Medium Cut-Off Membranes and High-Flux Membranes: Theranova in Sisli Hamidiye Etfal (THE SHE) Randomized Control Study

Blood Purification ◽

10.1159/000508061 ◽

2020 ◽

Vol 49 (6) ◽

pp. 733-742

Author(s):

Mustafa Sevinc ◽

Nuri Baris Hasbal ◽

Vuslat Yilmaz ◽

Taner Basturk ◽

Elbis Ahbap ◽

...

Keyword(s):

Serum Albumin ◽

Light Chain ◽

Interleukin 10 ◽

Uremic Toxins ◽

Interleukin 17 ◽

High Flux ◽

Before And After ◽

Inflammatory Molecules ◽

Circulating Levels ◽

First Session

Introduction: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. Objective: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. Methods: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. Results: Reduction rates were higher, and postdialysis levels of β-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of β-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45–3.88] vs. 3.78 [3.58–4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. Conclusion: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.

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Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.01210120 ◽

2020 ◽

Vol 15 (9) ◽

pp. 1310-1319 ◽

Cited By ~ 1

Author(s):

Daniel E. Weiner ◽

Luke Falzon ◽

Line Skoufos ◽

Angelito Bernardo ◽

Werner Beck ◽

...

Keyword(s):

Serum Albumin ◽

Serum Albumin Level ◽

Albumin Level ◽

Reduction Ratio ◽

Light Chains ◽

Maintenance Hemodialysis ◽

High Flux ◽

Efficacy And Safety ◽

End Point ◽

Middle Molecules

Background and objectivesExpanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer.Design, setting, participants, & measurementsClinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment.ResultsAmong 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and β2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment.ConclusionsHemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level.Clinical Trial registry name and registration numberA Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab099.0016 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Tijana Azasevac ◽

Violeta Knezevic ◽

Gordana Strazmester Majstorovic ◽

Mira Markovic ◽

Vladimir Veselinov ◽

...

Keyword(s):

Quality Of Life ◽

Renal Function ◽

Serum Albumin ◽

Serum Albumin Level ◽

Short Form ◽

Liver Function Tests ◽

Albumin Level ◽

Uremic Toxins ◽

Middle Molecules

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.

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