Current dialyzer classification in Japan and mortality risk in patients undergoing hemodialysis.

Dialyzers are classified into five types based on their ß2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a ß2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

A study of size-selective renal elimination using a novel human model.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, ß2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients.

This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+ lamivudine+ efavirenz (TLE) for 3.19 years. Renal function, including estimated glomerular filtration rate (eGFR), blood and urine ß2 microglobulin, and other parameters, was assessed every 3 months over a period of 2.5 years. The eGFR showed a slight increasement from 116.0 at month 0 to 119.7 at month 30. Blood ß2 microglobulin increased from 2.02 mg/L at month 0 to 2.77 mg/L at month 30. Compared to month 0, the difference in blood ß2 microglobulin was statistically significant at month 6 and months 12-30 (P < .05). The incidence of proximal renal tubular dysfunction fluctuated from 2% at month 0 to 2.5% at month 30. The urine ß2 microglobulin fluctuated from 0.5 (0.3-1.1) to 0.8 (0.5-1.35) mg/L at months 18-30, which was higher than 0.41 (0.18-1.1) mg/L at month 0 (P < .05). The abnormal concentration proportion of urine ß2 microglobulin fluctuated from 72.7% to 81.3% at months 18-30, which was higher than the proportion of 57.0% at month 0. The abnormal proportion of blood ß2 microglobulin, urine ß2 microglobulin, and proximal renal tubular dysfunction were not correlated with eGFR (r1 = 0.119, r2 = -0.008, r3 = -0.165, P > .05). Long-term TDF antiviral regimen in low-risk of kidney injury HIV-infected patients may lead to damage in the proximal renal tubules and glomeruli. Blood and urine ß2 microglobulin levels may be helpful in screening for renal dysfunction.

Detection of serum major histocompatibility complex I (HLA-1) and ß2-microglobulin (ß2M) in pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ).

OBJECTIVE: The purpose of this preliminary investigation into the pathogenesis of pre-eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early-onset pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre-eclampsia. METHODS: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early-onset pre-eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen-1 (HLA-1) and ß2-microglobulin (ß2M) in placental tissues was detected using western blot. RESULTS: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre-eclampsia group, and this included 24 up-regulated proteins and 39 down-regulated proteins. The western blot results of placental tissue showed reduced HLA-1 expression (1.12 ± 0.23) in the placenta in the pre-eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, ß2M in the placenta in the pre-eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05). CONCLUSION: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre-eclampsia, and that HLA-1 and ß2M, which may be involved in the occurrence of pre-eclampsia, show promise as predictive markers of pre-eclampsia.

Predictive Value of Serum NGAL and ß2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury.

OBJECTIVE: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and ß2 microglobulin (ß2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). METHODS: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and ß2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and ß2-MG in the blood and urine of patients with AKI and AP. RESULTS: The AKI group had higher serum NGAL and ß2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and ß2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. CONCLUSIONS: The increased levels of serum NGAL and ß2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI.

Predictive Value of Serum NGAL and B2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury

Objective: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and β2 microglobulin (β2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). Methods: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and β2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and β2-MG in the blood and urine of patients with AKI and AP. Results: The AKI group had higher serum NGAL and β2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and β2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. Conclusions: The increased levels of serum NGAL and β2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI (AU)

Association between serum ß2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis.

BACKGROUND: The association between serum ß2-microglobulin (ß2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum ß2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients. METHODS: In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum ß2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline. RESULTS: During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan-Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum ß2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum ß2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21-4.17) and CVD (HR = 2.54, 95% CI = 1.19-5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn't observed the significant association between serum ß2M levels and CVEs (P > 0.05). CONCLUSION: The serum ß2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.

Clinical Efficacy of Bendamustine Plus Rituximab (BR) for B-cell Relevant Indolent Non-Hodgkin's Lymphoma and Role of ß2-MG in Predicting the Efficacy of BR Regimen: A Real-World Retrospective Study in China.

BACKGROUND: Domestic bendamustine has been approved for appearing on the market in China in the past two years. The report on bendamustine plus rituximab (BR) in the treatment of Chinese B-cell-associated indolent non-Hodgkin's lymphoma (iNHL) has not yet been published. This study probed into clinical efficacy of the BR regimen for B-cell-associated iNHL in China as well as the value of ß2-microglobulin (ß2-MG) as a prognostic factor. METHODS: We retrospectively analyzed clinical data of 73 B-cell-associated iNHL patients who received BR treatment in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 2020 to January 2021, including clinical characteristics, therapies, therapeutic efficacy, and prognosis-related factors. Thirty-three patients (45.2%) did not receive any other treatment before the BR regimen, and other patients received CHOP, R-CHOP, and other regimens in the past. The cutoff date for follow-up was May 2021. Clinical characteristics of patients were analyzed. The clinical efficacy of the BR regimen was evaluated. Differences of ß2-MG expression before and after treatment were analyzed between the CR+PR group and the SD+PD group. Main outcomes were progression-free survival (PFS) and overall survival (OS). A multivariate Cox regression model was taken to analyze prognostic factors relative to survival rate of patients, and adverse events (AEs) during treatment. RESULTS: The objective response rate (ORR) of B-cell-associated iNHL patients who received BR regimen as first-/multiline treatment was 79.5%, with complete response (CR) of 37.0%, partial response (PR) of 42.5%, median PFS of 12.1 months (95% confidence interval (CI): 10.9-13.2), and median OS of 15.5 months (95% CI: 14.8-16.1). Before treatment, there was no statistical significance in the ß2-MG level between the CR+PR group and the SD+PD group (p > 0.05). After treatment, the ß2-MG level in the CR group was noticeably lower than that in the SD+PD group (p < 0.05). The ß2-MG level in the CR+PR group decreased conspicuously after treatment (p < 0.05). The ß2-MG level in the SD+PD group after treatment was not notably different from that before treatment (p > 0.05). According to the median expression level of ß2-MG before treatment, patients were divided into two groups. The average PFS of the low expression group was 12.69 ± 0.77 months, which was longer than the high expression group (10.13 ± 0.74 months), but the difference between the groups was not statistically significant (p > 0.05). Multivariate Cox regression analysis showed that B-cell-associated iNHL subtype was the independent prognostic marker most likely to affect PFS of patients (p = 0.051). Incidence of any grade of AEs in all patients was 32.9% (24/73). CONCLUSION: B-cell-associated iNHL patients who received BR regimen had favorable clinical efficacy and were tolerable to AEs. Though the ß2-MG level in this study could not be used to predict clinical outcome, a lower level before treatment seemed to be implicated in better survival outcomes of patients. Our research also unraveled that B-cell-associated iNHL subtype may be a key factor to patient's prognosis. Overall, this study offers some important insights into clinical application of the BR regimen for Chinese B-cell-associated iNHL patients.

Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.

BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. METHODS: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), ß2-microglobulin (uß2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. RESULTS: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, ß2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points. CONCLUSIONS: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

Serum Beta-2 Microglobulin: A Possible Biomarker for Atrial Fibrillation.

BACKGROUND Atrial fibrillation (AF) is the most common persistent arrhythmia that can cause complications (including stroke). Therefore, its diagnosis and treatment require increased attention. Although beta-2 microglobulin (b2-MG) is a novel marker of cardiovascular disease, its role in AF has not been evaluated. MATERIAL AND METHODS We conducted a case-control study with 61 patients who had normal heart rhythm (control group) and 60 patients with AF (research group). We analyzed the serum b2-MG levels in both groups and performed multivariate analysis to assess the correlation between b2-MG and left atrial remodeling. In addition, b2-MG levels were compared between the left atrial blood and peripheral venous blood of another set of 57 patients with AF, who underwent cryoballoon ablation. RESULTS There were no statistically significant differences in the baseline characteristics (age, sex, history of hypertension, diabetes mellitus, previous stroke, coronary heart disease, and estimated glomerular filtration rate) of the control and research groups. The left atrial anteroposterior diameters (LAD) and left ventricular end-systolic diameters in the AF group were significantly larger compared to the control group (P<0.01). Serum ß2-MG levels in patients with AF were significantly higher (P<0.01) and positively correlated with the LAD (B-coefficient 25.482, 95% CI 14.410~36.554, P<0.01), serum ß2-MG levels in the left atrial blood were significantly higher than those in peripheral venous blood (P<0.01), and serum ß2-MG levels were an independent predictor of AF. CONCLUSIONS With the development of atrial fibrillation, the serum ß2-MG levels increase and are closely related to the left atrial remodeling due to AF. Therefore, ß2-MG can be an effective biomarker for predicting AF.

Association of dialysis-related amyloidosis with lower quality of life in patients undergoing hemodialysis for more than 10 years: The Kyushu Dialysis-Related Amyloidosis Study.

BACKGROUND: Dialysis-related amyloidosis (DRA) commonly develops in patients undergoing long-term dialysis and can lead to a decline in activities of daily living and quality of life (QOL), mainly owing to orthopedic complications. METHODS: First, we determined utility scores of the EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in 1,323 patients with DRA who had undergone dialysis for more than 10 years and compared the score between those with and without DRA. Second, a 2-year follow-up was also performed, in which patients were divided into three groups: those complicated by DRA from the beginning, those with newly developed DRA within the 2-year period, and those not complicated by DRA throughout the survey period; changes in the EQ-5D-3L utility score were compared. In the group already complicated by DRA at the survey baseline, changes in the EQ-5D-3L utility score were compared according to the dialysis treatment method. RESULTS: A total of 1,314 and 931 patients were included in the first and second studies, respectively. EQ-5D-3L utility scores among patients diagnosed with DRA were significantly lower than scores in those not diagnosed with DRA. The reduction in the EQ-5D-3L utility score over the 2-year follow-up was significantly greater in patients newly complicated by DRA during the follow-up period after enrollment but not in those complicated by DRA from the beginning, as compared with patients not complicated by DRA throughout the survey period. The reduction in utility score tended to be lower in patients routinely treated with a ß2-microglobulin adsorption column than in untreated patients with DRA. CONCLUSION: Complication by DRA in patients undergoing long-term hemodialysis was significantly associated with a decline in QOL.

Disease outcomes and biomarkers of progression in smouldering Waldenström macroglobulinaemia.

Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1-11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and ß2 -microglobulin (ß2 M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT ) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7-8·7) vs. 4·7 (2·4-7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT , P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and ß2 M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.

Effect of increased blood flow rate on renal anemia and hepcidin concentration in hemodialysis patients.

BACKGROUND: Increasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia. METHODS: Between April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required. RESULTS: The increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change. CONCLUSIONS: Increasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.

Correlations between apparent diffusion coefficient values of WB-DWI and clinical parameters in multiple myeloma.

BACKGROUND: Whole-body diffusion-weighted imaging (WB-DWI) is a method for evaluating bone marrow infiltration in multiple myeloma (MM). This study seeks to elucidate the correlation between the apparent diffusion coefficient (ADC) value and some selected clinical parameters. METHODS: A total of 101 Chinese patients with MM who had undergone WB-DWI from May 2017 to May 2019 were enrolled in this study. The ADC values of the MM lesions and the clinical parameters were quantified at the first (baseline) visit and after four-course induction chemotherapy. Multiple linear regression and logistic analyses were carried out to find the implicit inherent relationships within the patients' data. RESULTS: The paired Wilcoxon test showed that the ADC values at the baseline visit (ADC0) were significantly lower than the values after four-course induction chemotherapy (ADC4 c) (p < 0.001), including different therapeutic responses. The Revised International Staging System (RISS) stage, type of MM, and ß2-microglobulin (ß2-MG) were predictors of clinically significant increases or decreases in the ADC values (p < 0.05). Multiple linear regression showed that the ADC0 was negatively associated with ß2-MG (p < 0.001) and immunoglobulin heavy chain gene rearrangement (p = 0.012), while the RISS Stage III (p = 0.001), type IgG λ (p = 0.005), and albumin were negatively associated with ADC4 c (p = 0.010). The impacts of the therapeutic response were associated with ADC0 and immunoglobulin heavy chain gene rearrangement (p < 0.001). CONCLUSION: The ADC values of WB-DWI may be associated with clinical parameters of MM including the fluorescence in situ hybridization result, and may be useful in the prognosis of patients with MM. TRIAL REGISTRATION: ChiCTR2000029587.

Efficacy and safety of the Clearum dialyzer.

The Clearum dialyzer, built by Medtronic, became commercially available in several European countries in 2020, but there are still no reports of in vivo data. The aim of this study was to evaluate the efficacy and risk of hypoalbuminemia of this dialyzer compared with previously evaluated hemodialysis (HD), expanded hemodialysis (HDx), and postdilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 15 patients. Each patient underwent seven dialysis sessions: FX80 Cordiax in HD, Clearum HS17 in HD, Phylther 17-SD in HDx, Theranova 400 in HDx, Phylther 17-G in postdilution HDF, Clearum HS17 in postdilution HDF, and FX80 Cordiax in postdilution HDF. The reduction ratios of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Comparison of dialysis techniques revealed no differences between small molecules, but HDx and HDF were significantly higher than HD with medium and large molecular weights. The Clearum dialyzer in HDF obtained similar results to FX80 Cordiax in HDF, was slightly superior to Phylther 17-G in HDF, and was statistically superior to both dialyzers in HDx. Albumin losses with the Clearum dialyzer were among the lowest, both in HD and HDF treatments. The highest global removal score (GRS) values were obtained with the helixone and Clearum dialyzers in HDF, with similar results both in HD and HDF. In addition, the GRS values with HDx treatments were statistically significantly higher than those with HD. The new Clearum dialyzer has excellent behavior and tolerance in HD and HDF. Its adequate permeability has been proven with its maximal performance in HDF, which could represent an upgrade versus its predecessor polyphenylene dialyzers.

Evaluation of beta-2 microglobulin, erythropoietin and tobacco use in polycythemic cases.

In the 2016 WHO classification, hemoglobin and hematocrit thresholds for diagnosing polycythemia vera (PV) have been lowered, increasing the number of consultations for polycythemia investigations. In PV, beta-2 microglobulin (B2m) levels are reportedly increased, whereas erythropoietin (EPO) levels are usually low. Most secondary polycythemia cases (SP) are caused by tobacco use. We decided to analyze the relevance of these three parameters in all patients seen for polycythemia investigations to help differentiate PV from SP cases. A cohort of 257 patients (123 PV; 134 SP) was identified. The median B2m level was higher for PV patients (3.16 vs 1.98 mg/l, p < 0.0001). Increased B2m levels were observed in 83.7% of PV patients (11.9% in SP). The median EPO level was lower in PV patients (4.4 vs 12.3 UI/l, p < 0.0001). Tobacco was used by 42.8% of SP patients (8% in PV, p < 0.0001). Increased B2m, low EPO and no tobacco exposure was predictive of PV (specificity and positive predictive value = 100%). Normal B2m, normal EPO and tobacco exposure was predictive of SP (positive predictive value = 100%). These simple and inexpensive parameters could be used to rapidly differentiate PV from SP cases, before prescribing time-consuming JAK2 V617F mutation analysis by specialists.

Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin ß2-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 ß2-microglobulin (ß2M), 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 ß2M 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 ß2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of ß2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin ß2M 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.

The Association of ß2-Microglobulin and Fibroblast Growth Factor 23 with Major Adverse Cardiac Event in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

BACKGROUND: chronic kidney disease (CKD) increases the severity and risk of mortality in acute coronary syndrome (ACS) patients. The role of ß2-M as a filtration and inflammation marker and FGF23 as a CKD-MBD process marker might be significant in the pathophysiology in ACS with CKD patients. This study aims to determine the association of ß2-M and FGF23 with major adverse cardiac event (MACE) in ACS patients with CKD. METHODS: we used cross sectional and retrospective cohort analysis for MACE. We collected ACS patients with CKD consecutively from January until October 2018 at Dr. Cipto Mangunkusumo General Hospital. Data were analyzed using logistic regression and Cox's Proportional Hazard Regression. RESULTS: a total of 117 patients were selected according to the study criteria. In bivariate analysis, ß2-M, FGF23, and stage of CKD had significant association with MACE (p = 0.014, p = 0.026, p = 0.014, respectively). In multivariate analysis, ß2-M - but not FGF 23- was significantly associated with MACE (adjusted HR 2.16; CI95% 1.15-4.05; p = 0.017). CONCLUSION: ß2-M was significantly associated with MACE, while FGF23 was not so. This finding supports the role of inflammation in cardiovascular outcomes in ACS with CKD patient through acute on chronic effect.

Serum ß2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

ß2-microglobulin (ß2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed ß2-m is measurable in circulation, and various disorders are accompanied by increases in ß2-m levels, including several viral infections. Therefore, we explored whether ß2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum ß2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean ß2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean ß2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean ß2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean ß2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression ß2-m levels were the only significant predictor of disease severity. Our findings suggest that higher ß2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of ß2-m measurements. The role of ß2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.