Beta 2-microglobulin Concentrations Research Articles

Are ultrasound renal aspects associated with urinary biochemistry in fetuses with lower urinary tract obstruction?

To evaluate the association between ultrasonographic renal parameters and urine biochemistry in fetuses with lower urinary tract obstruction (LUTO). Data were collected prospectively from 31 consecutive fetuses with LUTO that underwent vesicocentesis for fetal urinary biochemistry between April 2013 and September 2015. The following renal ultrasound markers were assessed immediately before the vesicocentesis: renal echogenicity, presence of cortical cysts, presence of findings suggestive of 'renal dysplasia' (hyperechogenic cystic kidneys with no cortical-medullary differentiation) and severe oligohydramnios (amniotic fluid < 5th percentile). The association of these parameters to the fetal urinary concentration of sodium, chloride, calcium, osmolality and beta2-microglobulin was investigated by logistic regression analysis. There was no relationship between any of the ultrasonographic fetal renal characteristics and fetal urinary biochemistry. In LUTO, the ultrasound appearance of the fetal kidneys and urinary biochemistry are not correlated. It may be better to take both ultrasound and biochemistry into account when evaluating fetuses with fetal LUTO. © 2016 John Wiley & Sons, Ltd.

PP.LB03.11] CAN ARTERIAL STIFFNESS PREDICT LARGE ARTERY DAMAGE IN SHORT TERM IN PATIENTS ON DIALYSIS?

Objective: To study a short term aortic pulse wave velocity measurement value for predicting cerebrovascular and cardiovascular events in patients on dialysis. Design and method: 26 stable dialysis patients (mean age 57.27 ± 13.97) without previous large artery damage were prospectively studied. Blood tests within 6 month were accomplished. All patients underwent two carotid-femoral pulse wave velocity measurements at the beginning of the study and after 6 months. Carotid-femoral PWV assessment was performed on the non dialysis day. We collected data about cerebrovascular and cardiovascular events during 6 month follow-up and according this divided patients into two groups (with and without events). Statistical analysis was performed using R Statistical Software. Results: During a 6 month follow-up, 2 non cardiovascular deaths, 7 cardiovascular events (atrial fibrillation, myocardial infarction) and 1 cerebrovascular (stroke) event were registered. Cerebrovascular and cardiovascular pathology was associated with an increase in beta2-microglobulin concentration (46.91 vs 33.51, 46.91, p = 0.0626) and in carotid-femoral PWV at the beginning of the study (11.4 vs 10.9, p = 0.6707) and during follow-up (12.55 vs 10.00, p = 0.0369). There was no difference between groups while comparing other laboratory parameters (albumin, cholesterol, parathyroid hormone concentration, CRP, hemoglobin concentration, calcium and phosphate level) and no correlation between carotid-femoral PWV and beta2-microglobulin values. Patients with carotid-femoral PWV >10 m/s had 2,6 higher event risk. Conclusions: Carotid-femoral PWV even in a short term follow-up helps indicate patients with higher cerebrovascular and cardiovascular risk.

Renal function in children treated for central nervous system malignancies.

AimThe aim of the study was to evaluate renal function and to assess the usefulness of the following nephrotoxicity markers: cystatin C (CYS C), beta-2 microglobulin (B2MG) and neutrophil gelatinase-associated lipocalin (NGAL) in 38 (18 girls, 20 boys) children previously treated for central nervous system malignancy.MaterialMedian age at evaluation was 13.7 years (range 2.1–22 years). The mean follow-up time after the completion of chemotherapy was 3.2 years (range 0.16–6.5 years).ResultsSubclinical chronic kidney disease (estimated glomerular filtration rate: eGFR 90–60 ml/min/1.73 m2) was found in 22 patients (58 %), while renal insufficiency (eGFR 30–60 ml/min/1.73 m2) was found in six children (16 %). It has been demonstrated statistically significant negative correlation between the eGFR and cystatin C concentration (p < 0.0001) and eGFR and beta-2 microglobulin concentration (p < 0.02). Conversely, there was no correlation between eGFR and NGAL. Thirteen children (34 %) developed drug-induced tubulopathy: decreased tubular reabsorption of phosphate (TRP) and renal tubular threshold for phosphate (Tmp/GFR).ConclusionChildren treated for CNS tumours often develop drug-induced chronic renal disease, involving the glomeruli and/or renal tubules. Cystatin C and beta-2 microglobulin seemed to be good markers for chronic kidney damage in these patients, which is probably not true for NGAL.

The Prognostic Significance of Beta2 Microglobulin in Patients with Hemophagocytic Lymphohistiocytosis.

Objective. To determine the prognostic significance of beta2 microglobulin (β 2-m) concentrations in patients with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. Patients and Methods. The study population consisted of 74 patients diagnosed with HLH and 35 healthy controls. Serum β 2-m levels were measured using a latex agglutination photometric immunoassay. Results. Median serum β 2-m levels were significantly higher in HLH patients than in healthy controls (4.05 versus 1.5 mg/L; P < 0.001) and were significantly higher in patients with lymphoma associated hemophagocytic syndrome (LAHS) than in patients with benign disease-associated HLH (4.2 versus 3.3 mg/L; P < 0.001). Higher serum β 2-m levels were positively correlated with LAHS (P = 0.005), abnormal lactate dehydrogenase concentrations (P = 0.009), and hypoalbuminemia (P = 0.003). ROC analysis showed that overall survival (OS) was significantly shorter in LAHS patients with serum β 2-m levels ≥4.03 mg/L compared to <4.03 mg/L (P < 0.001). Moreover, multivariate analysis showed that serum β 2-m level was an independent prognostic of OS (P = 0.034) in patients with LAHS. Conclusion. High serum β 2-m levels and LAHS were associated with markedly poorer OS in patients with HLH. Serum β 2-m concentration was a powerful and independent prognostic factor for OS in patients with LAHS.

Glucose Serum Concentrations and Cardiovascular Disease in Patients on the End Stage of Renal Disease without Diabetes Mellitus.

Background/Aim: It is still controversial whether tighter glycemic control is associated with better clinical outcomes in patients with kidney failure. We examined the association between glucose serum concentrations and cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus. Methods: We studied 76 patients on on-line hemodiafiltration. Cardiovascular disease was defined by the existence of coronary disease (CD). Arterial stiffness was measured as carotid-femoral pulse wave velocity (c-fPWV) and carotid augmentation index (AIx). The concentrations of beta2-microglobulin (β2M) and insulin were measured by radioimmunoassays and insulin resistance by HOMA-IR. We built a logistic-regression analysis to examine the role of glucose on cardiovascular disease after adjustment for the traditional and specific risk factors for dialysis patients. Results: Serum glucose was positively correlated with beta2M, insulin and HOMA-IR (r = 0.361, p = 0.002, r = 0.581, p = 0.001 and r = 0.753, p = 0.001 respectively). Logistic-regression analysis did not show significant impact of glucose concentrations on cardiovascular disease after adjustment for traditional and specific risk factors. Conclusions: The association between elevated glucose serum concentrations and represented by coronary syndrome cardiovascular disease in patients on the end stage of renal disease without diabetes mellitus was not found significant.

Beta2-microglobulin as a diagnostic marker in cerebrospinal fluid: a follow-up study.

Beta2-Microglobulin (β2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinal fluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinal fluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF β2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF.

Chronic lymphocytic leukemia in young individuals revisited

1 In studies from Europe and USA only 5%-11% of patients with CLL are younger than 50-55 years at diagnosis. 2,3 However, in view of the high incidence (4-5 cases per 100,000 inhabitants/year) and prevalence of CLL in Western countries, the absolute number of young patients with CLL is significant. Good knowledge of the factors asso - ciated with disease evolution and outcome of such patients is needed in order to be able to provide these patients appro - priate management. Our knowledge of the clinical picture and behavior of CLL diagnosed at a young age does, howev - er, come from studies conducted in the late 1980s 4,5 and 1990s, 6-9 a time when most biomarkers currently analyzed in CLL patients had not yet been discovered, 10-13 therapy was still based on alkylating agents, 14 and the role of allogeneic stem cell transplantation was not well established. 15 and should be confirmed in further studies. Additionally, young CLL patients more frequently had sever- al adverse biological features such as unmutated IGHV (54% versus 45%), positivity for ZAP-70 (45% versus 38%), and higher values of clonal B cells. In contrast, young CLL patients had significantly higher values of hemoglobin, although this difference was clinically non-relevant, lower values of beta2-microglobulin, lower expression of CD49d, and better performance status. Finally, fluorescence in situ hybridization (FISH) risk category and CD38 expression by CLL cells did not differ according to age. The paradox of hav - ing simultaneously favorable and adverse risk features deserves further confirmation, even though some of these results could be associated with age-related factors (e.g. the lower incidence of renal failure in young patients would result in lower beta2-microglobulin concentration despite having a higher tumor burden). The higher frequency of intermediate Rai stages and of unmutated IGHV in young CLL patients was maintained when the analysis was restrict - ed to local patients and when the patients were subdivided further by age ( ≤45, 46 to 50, and 51 to 55 years old). In keep - ing with this, the time to first treatment was shorter in younger patients. It could be argued that physicians looking after older (slow go 18 ) patients may delay treatment initia - tion due to co-morbidities, impaired performance status or patients' desire. However, a multivariate analysis confirmed that Rai stage and IGHV mutation status rather than age accounted for this difference in time to first treatment. In summary, younger patients with CLL followed up at the Mayo Clinic had a significantly more aggressive and advanced disease at diagnosis and, importantly, this was not due to referral bias. The long period of analysis and the observational nature of this study resulted in heterogeneity in the treatment given to patients. Moreover, young CLL patients were more likely than older patients to receive chemoimmunotherapy or purine analogs in monotherapy or in combination. Although the causes of the differential treatment applied to both groups of patients were not explored, the better performance status and the use of a treatment approach with curative intent in the subgroup of young patients could underlie the difference. In fact, the proportion of patients submitted to allogeneic transplantation was 14%, 5% and 1% for patients ≤45, 46 to 55, and >55 years old, respectively. Unfortunately, the authors did not provide information on response to treat - ment and outcome after treatment in these subgroups of young patients. CLL patients ≤55 years old at diagnosis had a longer overall survival than older patients (12.5 years versus 9.5 years), even if the comparison was restricted to patients 56 to 65 year old. At the same time, no differences in overall survival were observed among age subgroups of young patients. As differ- ent treatment modalities were given according to age sub - groups, an analysis of their impact on overall survival could have helped in the interpretation of the results. More impor- tantly, the median overall survival of young CLL patients reported in this series was very similar to the median overall survival observed in some historical studies. 6,9

AP-VAS 2012 case report: an atypical case of microscopic polyangiitis presenting with acute tubulointerstitial nephritis without glomerular change.

Renal involvement in myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis is frequently characterized by focal segmental crescentic and/or necrotizing glomerulonephritis. However, a few cases of only tubulointerstitial nephritis (TIN) involvement without any apparent glomerular lesions have been reported. Here we report just such a case. A 74-year-old woman was admitted to a nearby hospital with a 2-week history of pitting edema, fever and anemia. She developed acute renal failure without proteinuria and microscopic hematuria. The urinary excretion of N-acetyl-beta-D-glucosaminidase and beta2-microglobulin concentration were 30.3 U/ml and 42270μg/ml, respectively. Gallium-67 scintigraphy revealed abnormal concentrations on both sides of her kidneys. Her MPO-ANCA titer was 92 EU (normal range <10 EU). Skin and renal biopsies demonstrated fibrinoid vasculitis, necrotizing angiitis and TIN without glomerular change. Microscopic polyangiitis was diagnosed based on clinical and pathological criteria. No other factor that could induce TIN was detected. This case illustrates an unusual renal presentation of acute renal failure due to necrotizing arteritis and TIN, consistent with MPO-ANCA-associated vasculitis lacking crescentic glomerulonephritis. The pathogenesis is currently unclear, but the low-affinity type of MPO-ANCA was identified.

A triclonal gammopathy in a relapsing multiple myeloma patient, detected by immunosubtraction method

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the malignant proliferation of a plasma cell clone that produces a monoclonal immunoglobulin. Diagnosis and management of patients with monoclonal gammopathies depend on accurate identification and characterization of monoclonal proteins. We present a 67-year-old male patient with anaemia, weakness and weight loss for six months. His physical examination was normal with no fever, and no bone lesions were present in the imaging studies. Laboratory investigations revealed low haemoglobin and albumin concentrations with high total protein and beta 2-microglobulin concentrations. Capillary zone electrophoresis with immunosubtraction method revealed a triclonal pattern of M-protein (IgG κ + IgG λ + IgA κ) which was not prominent with immunofixation electrophoresis. After bone marrow biopsy, MM with triclonal gammopathy was diagnosed and autologous stem cell transplantation was performed. Six months later, again a triclonal M-protein was detected by immunosubtraction method, and a relapse was confirmed with a second bone marrow biopsy. The occurrence of monoclonal and biclonal gammopathies can often be seen upon diagnosis in plasma cell dyscrasias and lymphoproliferative disorders, but triclonal paraproteins are very rare and their clinical significance is unknown. In this particular patient, triclonality was detected by an alternative method called immunosubtraction by capillary electrophoresis. The patient was resistant to therapy suggesting that more than one monoclonal M protein may be a negative prognostic factor, and with new technologies and methods, the number of patients with different monoclonal patterns may increase.

Interleukin 18 as a Marker of Chronic Nephropathy in Children after Anticancer Treatment

Novel markers of nephrotoxicity, including kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and beta-2 microglobulin, were used in the detection of acute renal injury. The aim of the study was to establish the frequency of postchemotherapy chronic kidney dysfunction in children and to assess the efficacy of IL-18, KIM-1, and beta-2 microglobulin in the detection of chronic nephropathy. We examined eighty-five patients after chemotherapy (median age of twelve years). The median age at the point of diagnosis was 4.2 years, and the median follow-up time was 4.6 years. We performed classic laboratory tests assessing kidney function and compared the results with novel markers (KIM-1, beta-2 microglobulin, and IL-18). Features of subclinical renal injury were identified in forty-eight children (56.3% of the examined group). Nephropathy, especially tubulopathy, appeared more frequently in patients treated with ifosfamide, cisplatin, and/or carboplatin, following nephrectomy or abdominal radiotherapy (P = 0.14, P = 0.11, and P = 0.08, resp.). Concentrations of IL-18 and beta-2 microglobulin were comparable with classic signs of tubulopathy (P = 0.0001 and P = 0.05). Concentrations of IL-18 were also significantly higher in children treated with highly nephrotoxic drugs (P = 0.0004) following nephrectomy (P = 0.0007) and abdominal radiotherapy (P = 0.01). Concentrations of beta-2 microglobulin were higher after highly toxic chemotherapy (P = 0.004) and after radiotherapy (P = 0.02). ROC curves created utilizing IL-18 data allowed us to distinguish between children with nephropathy (value 28.8 pg/mL) and tubulopathy (37.1 pg/mL). Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.

Evaluation of salivary beta-2 microglobulin as HBV proliferation marker in HBS Ag(+), HBV DNA PCR(+) and HBV DNA PCR(-) subjects.

The aim of this study was to determine the concentration of salivary B2M as a marker of viral proliferation in HBS Ag(+), HBV DNA PCR(+) and Hbs Ag(+) and HBV DNA PCR(-) subjects. Beta-2 microglobulin (B2M) is responsible for transmission of viral antigens such as Hepatitis B (HBV) on the surface of liver cells as part of an HLA complex. In this case control study, 25 PCR(+) and 2 PCR(-) patients were included. 5 mL of the saliva sample was obtained from all patients and salivary B2M level was measured using nephelometer. The data was evaluated by the descriptive, chi square and t tests. 72% of the PCR(+) patients received medications and in contrast, 85.7% of the patients with PCR(-) did not take any medication (P < 0.001). The average salivary concentration ofBeta-2 microglobulin in the PCR(+) group (5.28 ± 5.45 mg/deciliter) was more than PCR(-) group (1.51±0.77) and this difference was statistically significant (P = 0.003). The salivary B2Mlevel can be used as a marker of viral proliferation in patients with hepatitis B.

Progression of residual renal function with an increase in dialysis: haemodialysis versus peritoneal dialysis.

The main objective of the study was to analyse the progression of residual renal function according to the dialysis technique (peritoneal dialysis or haemodialysis) and the frequency of treatment (two or three sessions of haemodialysis per week). As secondary objectives, we studied the progression of the serum concentration levels of β2 microglobulin and the response of anaemia to erythropoietic agents. 193 non-anuric patients were included and began renal replacement therapy with dialysis in our hospital between 1 January 2006 and 31 December 2011, with a follow-up period of over three months. 61 patients (32%) began treatment with two haemodialysis sessions per week, 49 patients (25%) with three haemodialysis sessions per week and 83 patients (43%) with peritoneal dialysis. The glomerular filtration rate was measured as the mean of the renal clearances of urea and creatinine. The rate of decrease in glomerular filtration was the same in patients who began treatment with two haemodialysis sessions per week and with peritoneal dialysis (median 0.18 ml/min/month) and it was higher in patients who began treatment with three sessions of haemodialysis per week (median 0.33 ml/min/month, P<.05). Throughout progression, the glomerular filtration rate did not display differences between the group that began with two weekly sessions of haemodialysis and the group on peritoneal dialysis, and it was lower in the group that began treatment with three sessions of haemodialysis per week with statistical significance during the first 24 months of follow up. In the three patient groups, β2-microglobulin concentration increased as the glomerular filtration rate decreased and it was higher in the group on three weekly haemodialysis sessions for the first 12 months of follow up. In all the controls carried out, there was a negative correlation between the beta-2 microglobulin concentration and the glomerular filtration rate (P<.001). The erythropoietin dose was negatively related to glomerular filtration. Patients who began with two sessions of haemodialysis per week required a lower dose of erythropoietin than patients that began renal replacement therapy with three weekly sessions. The erythropoietin dose in the peritoneal dialysis group was below that of the group of two weekly haemodialysis sessions despite maintaining a similar glomerular filtration rate. Patients who begin treatment with two sessions of haemodialysis per week experience the same rate of decrease in residual renal function as patients treated with peritoneal dialysis. The progression of the concentration of β2-microglobulin is parallel to that of the glomerular filtration rate. Patients treated with two haemodialysis sessions require a lower dose of erythropoietin than those who receive three sessions per week, but a significantly higher dose than those treated with peritoneal dialysis, which suggests that the response of anaemia to erythropoietic agents is not only related to residual renal function, but also to other factors that are inherent to the dialysis technique.

Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results

Patients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p-) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p- CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p- CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27-98) years at the time of fluorescence in situ hybridization analysis. After 17p- documentation, 52% received treatment, achieving an overall response rate of 50%. Median overall survival was 41 months, and was significantly shorter in patients with elevated beta(2)-microglobulin concentration (P < 0·001), B symptoms (P = 0·016), higher percentage of cells with deletion (P < 0·001), and acquired deletions (P = 0·012). These findings suggest that patients with 17p- CLL have a variable prognosis that can be refined using simple clinical and laboratory features, including 17p- clone size, beta2-microglobulin concentration, presence of B symptoms and type of deletion (de novo versus acquired).

Title: Beta2-Microglobulin (B2M) Concentrations in Cerebrospinal Fluid (CSF) Correlate with Neurodevelopmental Outcome in Newborns with Symptomatic Congenital Cytomegalovirus Infection (SCCI)

Title: Beta 2 -Microglobulin (B 2 M) Concentrations in Cerebrospinal Fluid (CSF) Correlate with Neurodevelopmental Outcome in Newborns with Symptomatic Congenital Cytomegalovirus Infection (SCCI)

Prompt Myocardial Damage Contributes to Hepatic, Renal, and Intestinal Injuries Soon After a Severe Burn in Rats

Ischemic/hypoxic myocardial damage and functional impairment of the myocardium occurs immediately after major burns. This experimental study investigated whether the prompt cardiac dysfunction initiates hepatic, renal, and intestinal injuries soon after a severe burn. Wistar rats were randomized to a sham burn group, a burn group (subjected to 30% total body surface area third-degree burn) that was subdivided into two groups: a simple burn group, observed at 0.5 hour, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours postburn and a group medicated with propranolol (a cardiac inhibitor), cedilanid (a cardiotonic agent), enalaprilat (an angiotensin converting enzyme inhibitor), and cedilanid plus enalaprilat injected at 0.5 hour postburn and observed at 6 hours later. Serum cardiac troponin I, total bile acid, beta2-microglobulin concentrations, and diamine oxidase activity were measured to reflect the severity of cardiac, hepatic, renal, and intestinal injuries that were confirmed by histopathologic observations. Cardiac function and organs' blood flow were also recorded. Histopathologic changes and serum cardiac troponin I increase occurred significantly earlier than the other organs, and the organ damage developments followed a similar pattern. Myocardial injury was significantly aggravated in rats treated with propranolol, with further decreases in myocardial function, blood flow to the liver, kidneys, and intestines significantly decreased, and injuries were aggravated. In contrast, these conditions were greatly improved in the rats treated with enalaprilat, cedilanid, or with both. The prompt cardiac dysfunction has some initiating effects on ischemic/hypoxic injury to organs such as the liver, kidneys, and intestines soon after a severe burn.

Statement on tolerable weekly intake for cadmium

The Panel on Contaminants in the Food Chain of the European Food Safety Authority (CONTAM Panel) was asked by the European Commission to confirm whether the current tolerable weekly intake (TWI) of 2.5 µg/kg body weight (b.w.) for cadmium is still considered appropriate or whether any modifications are needed in view of the provisional tolerable monthly intake (PTMI) of 25 µg/kg b.w. established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2010. Both assessments used the same epidemiological dataset and have two primary components, a concentration-effect model that relates the concentration of cadmium in urine to that of beta-2-microglobulin (B2M), a biomarker of renal tubular effects, and a toxicokinetic model that relates urinary cadmium concentration to dietary cadmium intake. The following methodological differences were identified: i) the identification of the reference point on the basis of the urinary cadmium and the B2M concentration data; ii) the statistical approach to account for the variability and uncertainty of the biomarker of exposure (urinary cadmium concentration) and the biomarker of response (B2M concentration) in the concentration-effect model; and iii) the methodology for transforming urinary cadmium concentrations into dietary intake values. Following an evaluation of the two approaches, the CONTAM Panel concluded that the approach adopted for its previous opinion on cadmium in food was appropriate and hence the current TWI for cadmium of 2.5 µg/kg b.w. was maintained.

Beta2-microglobulin causes abnormal phosphatidylserine exposure in human red blood cells

The exposure of the aminophospholipid phosphatidylserine on the external leaflet of red blood cell plasma membrane can have several pathophysiological consequences with particular regard to the processes of cell phagocytosis, haemostasis and cell-cell interaction. A significant increase in phosphatidylserine-exposing erythrocytes has been reported in chronic haemodialysis patients and found to be strongly influenced by the uraemic milieu. To identify uraemic compound(s) enhancing phosphatidylserine externalization in erythrocytes, we fractionated by chromatographic methods the ultrafiltrate obtained during dialysis, and examined by flow cytometry the effect of the resulting fractions on phosphatidylserine exposure in human red cells. Chromatographic procedures disclosed a homogeneous fraction able to increase erythrocyte phosphatidylserine exposure. The inducer of such externalization was identified by monodimensional gel electrophoresis and mass spectrometry investigations as beta2-microglobulin. To confirm the beta2-microglobulin effect and to examine the influence of protein glycation (as it occurs in uraemia) on phosphatidylserine erythrocyte exposure, erythrocytes from normal subjects were incubated with recombinant beta2-microglobulin (showing no glycation sites at mass analysis), commercial beta2-microglobulin (8 glycation sites), or with in vitro glycated recombinant beta2-microglobulin (showing multiple glycation sites). Elevated concentrations of beta2-microglobulin (corresponding to plasma levels reached in dialysis patients) increased slightly but significantly the protein's ability to externalize phosphatidylserine on human erythrocytes. Such an effect was markedly enhanced by glycated forms of the protein. Beta2-microglobulin is recognized as a surrogate marker of middle-molecule uraemic toxins and represents a key component of dialysis-associated amyloidosis. Our study adds further evidence to the potential pathophysiologic consequences of beta2-microglobulin accumulation in chronic uraemic patients.

Minimal health impact from exposure to diet-sourced cadmium on a population in central Jamaica

Elevated concentrations of naturally occurring Cd have been found mainly in the bauxitic soils of central Jamaica at levels up to 100-1,000 times higher than typical worldwide averages. Some food crops cultivated on these soils absorb significant amounts of Cd. Autopsy studies of kidney Cd concentrations confirm elevated human exposure, and some long-term residents in central Jamaica exceed the general population average by a factor of two. Diet studies have ascertained that a population in central Jamaica is at risk of being exposed to Cd levels in excess of the Provisional Tolerable Weekly Intake (PTWI) set by the WHO of 7 μgCd/kg bodyweight/week, and the EU TWI of 2.5μgCd/kg bodyweight/week. Elevated levels of urine cadmium (U-Cd) and beta-2 microglobulin (β2-MG) concentrations were confirmed with a strong correlation between soil Cd and the U-Cd. Also, higher β2-MG concentrations (>200μg/g creatinine) were found in the population with U-Cd concentrations greater than 2.5μg/L. While this identification is often taken to indicate impairment in the reabsorption capacity of the renal tubules leading to renal disease, there is no evidence in the mortality records of enhanced deaths in central Jamaica compared with the general population resulting from renal disease or diabetes related complications. The highest median age of death in the island is found in Manchester, the parish with the highest average Cd concentration. While we have identified a possible Cd linked renal dysfunction, significant indications of morbidity are not present in the general population.

Efficacy of N-acetylcysteine and aminophylline in preventing contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN. Forty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704 mg orally twice daily; NAC group, n=15), hydration and aminophylline (250 mg intraveneously 30 min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00 + or - 0.36 to 0.67 + or - 0.16 mg/dl (p<0.01), and Ccr significantly increased from 62.4 + or - 15.6 to 80.4 + or - 8.39 ml/min (p<0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94 + or - 0.21 to 1.28 + or - 0.21 mg/dl (p<0.01), and Ccr significantly decreased from 63.7 + or - 16.1 to 46.1 + or - 10.6 ml/min (p<0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38 + or - 0.58 to 1.71 + or - 0.38 mg/dl (p<0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337 + or - 31.0 to 239 + or - 34 microg/ml (p<0.01). These results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN.

Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients

Recently, serum beta2-microglobulin, an endogenous marker for renal function, has been shown to be an independent predictor of mortality in older adults. However, the prognostic role of beta2-microglobulin in heart failure has not been elucidated. We prospectively evaluated serum beta2-microglobulin and creatinine concentrations, creatinine-based renal parameters (estimated glomerular filtration rate and creatinine clearance), and echocardiographic data in 131 patients with acute heart failure and creatinine concentrations < or =3.0mg/dL admitted to our hospitals. During 2.3+/-1.3 years, 42 patients died of cardiovascular causes and 12 died of noncardiac causes. Cardiovascular events were observed in 63 patients: 53 were readmitted due to worsening heart failure, 5 readmitted for cerebral embolism, and 5 died from sudden cardiac death. According to multivariate stepwise Cox proportional hazard analysis, higher baseline serum beta2-microglobulin concentrations (X(2)=16, p<0.0001), previous congestive heart failure (X(2)=11, p<0.001), presence of chronic obstructive pulmonary disease (X(2)=8, p<0.01), and lower diastolic blood pressure (X(2)=6, p<0.05) were independent predictors of increased cardiovascular events. Also, higher baseline serum beta2-microglobulin (X(2)=20, p<0.0001), lower systolic blood pressure (X(2)=11, p<0.001), higher relative left ventricular wall thickness (X(2)=6, p<0.05), and lower body mass index (X(2)=5, p<0.05) were independent predictors of increased cardiac mortality. The adjusted hazard ratio for cardiovascular events increased with baseline serum beta2-microglobulin above 2.1 mg/L: 2.9 with beta2-microglobulin of 2.2-2.6 mg/L (95%CI 1.2-6.9, p<0.05), 2.9 with beta2-microglobulin of 2.7-3.9 mg/L (95%CI 1.2-7.2, p<0.05), and 4.7 with beta2-microglobulin of > or =4.0 mg/L (95%CI 2.0-11, p<0.001). Higher baseline serum beta2-microglobulin concentration could be a promising risk marker in acute heart failure patients with creatinine < or =3.0 mg/dL.