Urinary β2-MG Research Articles

Efficacy and safety of tailin formulation combined with continuous low-dose antibiotic therapy in patients with recurrent urinary tract infection: A multicenter, randomized, controlled clinical trial

Persistent inflammation associated with recurrent urinary tract infection (rUTI) is a crucial inducement of inflammation-driven renal fibrosis (IDRF). Although continuous low-dose antibiotic therapy (CLAT) is the common treatment for rUTI, its clinical efficacy remains unsatisfactory. Tailin formulation (TLF), a Chinese herbal formulation prescribed for treating rUTI, is effective in alleviating symptoms and reducing recurrence. This study was to evaluate the efficacy and safety of TLF combined with CLAT compared with CLAT used alone in patients with rUTI. In this multicenter, randomized, controlled clinical trial, patients were assigned (1:1) to receive either TLF + CLAT or CLAT for 12 weeks. The primary outcome was the effective rate at week 12 of the treatment. The secondary outcomes were the recurrent rate at week 4 and week 12 post treatment; the post-treatment changes in renal tubular injury markers (urinary N-acetyl-β-d-glucosaminidase (NAG) and β2-microglobulin (β2-MG)), profibrotic factors (urinary monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor beta1 (TGF-β1)), and traditional Chinese medicine (TCM) symptoms, and vital signs indicators and serious adverse events (SAEs) were also monitored throughout the trial. A total of 195 patients were included in the final analysis. The TLF + CLAT group had a higher effective rate and a lower recurrence rate than the CLAT group (p < 0.01). Significant decrease of urinary NAG and β2-MG was observed in the TLF + CLAT group vs. CLAT group (p < 0.01), and similar changes were observed in profibrotic factors (urinary MCP-1 and TGF-β1) (p < 0.05), which indicated that TLF might have potential renal tubular protection and anti-fibrosis effects. Additionally, a positive correlation within a certain range was shown in the correlation analysis of medical history (months) of rUTI patients with urinary MCP-1 (r = 0.50, p < 0.05) and TGF-β1 (r = 0.78, p < 0.01). A significant difference was also observed in TCM symptoms (p < 0.01). There were no obvious adverse reactions that occurred during this study. We conclude that TLF combined with CLAT was superior to CLAT used alone in reducing rUTI recurrence, alleviating the non-infection-related physical symptoms and protecting renal tubular and anti-fibrosis, which suggests this novel therapy might be an available treatment with great promise in treating rUTI.

Insufficient Fruit and Vegetable Intake and Low Potassium Intake Aggravate Early Renal Damage in Children: A Longitudinal Study.

Insufficient fruit and vegetable intake (FVI) and low potassium intake are associated with many non-communicable diseases, but the association with early renal damage in children is uncertain. We aimed to identify the associations of early renal damage with insufficient FVI and daily potassium intake in a general pediatric population. We conducted four waves of urine assays based on our child cohort (PROC) study from October 2018 to November 2019 in Beijing, China. We investigated FVI and other lifestyle status via questionnaire surveys and measured urinary potassium, β2-microglobulin (β2-MG), and microalbumin (MA) excretion to assess daily potassium intake and renal damage among 1914 primary school children. The prevalence of insufficient FVI (<4/d) was 48.6% (95% CI: 46.4%, 50.9%) and the estimated potassium intake at baseline was 1.63 ± 0.48 g/d. Short sleep duration, long screen time, lower estimated potassium intake, higher β2-MG and MA excretion were significantly more frequent in the insufficient FVI group. We generated linear mixed effects models and observed the bivariate associations of urinary β2-MG and MA excretion with insufficient FVI (β = 0.012, 95% CI: 0.005, 0.020; β = 0.717, 95% CI: 0.075, 1.359), and estimated potassium intake (β = −0.042, 95% CI: −0.052, −0.033; β = −1.778, 95% CI: −2.600, −0.956), respectively; after adjusting for age, sex, BMI, SBP, sleep duration, screen time and physical activity. In multivariate models, we observed that urinary β2-MG excretion increased with insufficient FVI (β = 0.011, 95% CI: 0.004, 0.018) and insufficient potassium intake (<1.5 g/d) (β = 0.031, 95% CI: 0.023, 0.038); and urinary MA excretion increased with insufficient FVI (β = 0.658, 95% CI: 0.017, 1.299) and insufficient potassium intake (β = 1.185, 95% CI: 0.492, 1.878). We visualized different quartiles of potassium intake showing different renal damage with insufficient FVI for interpretation and validation of the findings. Insufficient FVI and low potassium intake aggravate early renal damage in children and underscores that healthy lifestyles, especially adequate FVI, should be advocated.

Sex-specific differences in early renal impairment associated with arsenic, lead, and cadmium exposure among young adultsin Taiwan.

Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147–0.899) and β2MG (β = 1.502, 95% CI: 0.635–2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027–0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-022-19521-3.

Study of uric acid excretion in children with beta-thalassemia major attending Alexandria University Children’s Hospital

Background It is evident that high cell turnover rate is present in patients suffering from β-thalassemia. This is mainly the result of not only chronic hemolysis but also ineffective erythropoiesis. It is thus expected that hyperuricemia will occur. Aim Our study was conducted to study uric acid excretion in β-thalassemia major patients and to determine its relationship to tubular dysfunction in those patients. Patients and methods This case–control study was performed on 60 patients with β-thalassemia major and 15 children who were healthy and well, playing the role of the control group. Thorough history taking, review of medical records, and complete physical examination were done for all patients. Evaluation of uric acid excretion, glomerular and tubular renal functions were performed and compared between patients and the control group. Results Hyperuricemia was found in 48.8% of patients; however, none of the patients had evidence of gouty arthritis or nephrolithiasis. Serum uric acid (SUA) levels in patients who had positive correlation with serum creatinine, urine P/Cr ratio and urine uric acid/glomerular filtration rate (UUA/GFR), negative correlation with eGFR and no correlation with urine calcium/creatinine (UCa/UCr) ratio, blood urea nitrogen (BUN), urine β2 MG, and urinary uric acid/creatinine (UUa/UCr) ratio were assessed. The mean SUA level, BUN, serum creatinine, and levels of eGFR were significantly higher in β-thalassemia patients in comparison to the control group. Urinary P/Cr ratio, urine uric acid/ glomerular filtration rate (UUA/GFR) ratio, β-2 microglobulin levels, UCa/UCr, and UUa/UCr were also higher in β-thalassemia patients in comparison to the control group. The present study has a mean age of 8.62 years for the cases studied, and investigations in patients revealed the following results: mean SUA 5.17 mg/dl, mean BUN 16.58 mg/dl, mean serum creatinine 0.49 mg/dl, mean urine P/Cr ratio 1.40, mean eGFR 141.42 ml/min/1.73 m2, mean UUA/GFR 0.55, mean urine β2 MG 0.18 µg/ml, mean UCa/UCr 0.44, UUa/UCr 1.46, and these results were statistically significantly higher in patients compared with controls. Conclusion Renal dysfunction and hyperuricemia are prevalent among patients with β-thalassemia major, mostly related to hyperfiltration and tubular dysfunction. Early markers of tubular dysfunction (urine β2 MG, UCa/UCr, UUa/UCr) and glomerular dysfunction (urine P/Cr ratio and urinary uric acid/GFR ratio) should be followed up regularly in β-thalassemia major patients.

Urine β2-Microglobulin and Retinol-Binding Protein and Renal Disease Progression in IgA Nephropathy.

Background: Tubulointerstitial involvement has been reported to have a decisive influence on the progression of IgA nephropathy (IgAN). High levels of urine β2-microglobulin (β2-MG) and retinol-binding protein (RBP) were observed in patients with IgAN with tubulointerstitial lesions. However, their roles in disease progression remain unclear. This study aimed to evaluate the associations of urine β2-MG and RBP with the progression of IgAN.Methods: We retrospectively investigated a cohort of 2,153 patients with IgAN. Clinical and pathological features, outcomes, and urine β2-MG, and RBP at the time of biopsy were collected. The associations, of urine β2-MG and RBP with the composite renal outcome, defined as a decline in estimated glomerular filtration rate (eGFR) of ≥50% from baseline or end-stage renal disease (ESRD), were examined using restricted cubic splines and the Cox proportional hazards models.Results: During a median follow-up of 20.40 months, 140 (6.50%) patients reached the composite renal outcomes. Restricted cubic splines showed that patients with higher urinary β2-MG and RBP levels had worse renal outcomes. The Cox regression analysis revealed that urine β2-MG and RBP were associated with a risk of the composite renal outcome in the multivariate adjusted model [+1 SD for log β2-MG, hazard ratio (HR) = 1.462, 95% CI: 1.136–1.882, p = 0.003; +1 SD for log RBP, HR = 1.972, 95% CI: 1.486–2.617, p = 0.001]. The associations were detectable within patients with baseline eGFR <90 ml/min/1.73 m2 (+1 SD for log β2-MG, HR = 1.657, 95% CI: 1.260–2.180, p < 0.001; +1 SD for log RBP, HR = 1.618, 95% CI: 1.199–2.183, p = 0.002), but not among patients with eGFR ≥90 ml/min/1.73 m2.Conclusion: Higher levels of urine β2-MG and RBP were independent risk factors for renal disease progression in IgAN.

Predictor significance of β&lt;sub&gt;2&lt;/sub&gt;-microglobulinuria in determining the risk of cardiovascular complications in patients with chronic ischemic heart disease

BACKGROUND. The relevance of identifying new biomarkers of the cardio-renal syndrome in patients with coronary heart disease is beyond doubt. It is promising to study the indicators of tubular dysfunctions as predictors of the risk of cardiovascular complications in patients without primary kidney pathology.THE AIM. Analysis of the effect of β2-microglobulinuria on the prognosis of cardiovascular complications in patients with chronic ischemic heart disease in the long-term period after myocardial revascularization.PATIENTS AND METHODS. The study included 90 patients with coronary artery disease and indications for myocardial revascularization. Coronary bypass surgery was performed in 64 people, coronary artery stenting - in 26. Clinical and anamnestic data were collected in all patients, standard laboratory and instrumental diagnostics were performed. In addition, the level of β2-microglobulin (β2-MG) in the first morning portion of urine was determined at different study dates. The endpoint was considered to be the presence of acute forms of coronary heart disease - myocardial infarction and unstable angina. Survival after 5.8 ±0.1 years after myocardial revascularization was 69 %.RESULTS. A positive linear relationship of weak strength was established between the level of diastolic blood pressure (DBP) and β2-MG of urine obtained before myocardial revascularization (r = 0.28, p = 0.03). Moreover, the Kaplan-Meyer survival analysis showed the effect of an increase in β2-MG of urine over 0.2 ng/ml on the risk of AMI in the long-term period after myocardial revascularization (p = 0.025). It was found that an increase in the concentration of β2-MG in urine determined before myocardial revascularization is a statistically significant risk factor for the development of unstable angina in the long-term period after RM (χ2-criterion = 7.17, p = 0.007).CONCLUSION. It has been shown that an increase in the concentration of β2-MG in urine, reflecting the presence of tubular dysfunctions, can be considered as a predictor of an unfavorable cardiovascular prognosis in patients in the long-term period after myocardial revascularization.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА НАСЛЕДСТВЕННЫХ БОЛЕЗНЕЙ ПОЧЕК У ДЕТЕЙ С ИСПОЛЬЗОВАНИЕМ НЕИНВАЗИВНЫХ МАРКЕРОВ ПОВРЕЖДЕНИЯ

Aim. To develop the diagnostic method to determine the likelihood of a specific hereditary kidney disease. Material and methods. KIM-1, TGF-β1, RBP, β2-MG, creatinine, daily proteinuria (Pt) and GFR were determined in 23 patients with hereditary nephritis and 19 patients with tubulopathies. The average age at the time of the study was 13.5 (9-17) years. The ratio of boys/girls (%) was 24:18 (57.1:42.9). Results. The distribution of factors in the groups was considered. Statistically significant differences were found in terms of serum TGF-β1 and daily Pt. According to the results of mono-factor analysis, the factors that confirmed the prognostic significance were selected: urinary β2-MG (OR = 0.892 (0.696-1.175)), serum TGF-β1 (OR = 1.01 (1.002-1.018)) and daily Pt (OR = 25 (1.774-350)). For these factors the threshold values were calculated: urinary β2-MG = 0, serum TGF-β1&gt;280, daily Pt&gt;0.8. The nomogram and classification scheme were built on the basis of the mathematical model for the practical application. Conclusion. As a result of the study, 3 factors were established and 2 from these 3 markers were non-invasive (urinary β2-MG and daily proteinuria). The use of these markers makes possible to diagnose hereditary nephritis in children with high accuracy.

Urinary neutrophil gelatinase-associated lipocalin—an early biomarker for renal injury in patients with beta-thalassemia major

INTRODUCTION : The iron overload and the development of secondary hemosiderosis in patients with β-thalassemia major (β-TM) lead to organ damages, including kidney disorders from early childhood. Contemporary urinary markers such as neutrophil gelatinase-association lipocalin (NGAL), β2-microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG) could be a useful tool for clinicians in diagnosis of early tubular lesions. AIM : The aim of this article is to make an assessment of contemporary urine biomarkers β2-microglobulin, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase in the diagnosis of early renal injury in patients with β-TM. MATERIALS AND METHODS : The current study was conducted by examining 44 patients with β-thalassemia major and 30 controls. All participants were tested for NGAL, β2-MG, and NAG in the first sample morning urine using ELISA method. RESULTS : The results show statistically significant differences between the two examined groups in urinary NGAL. CONCLUSION : Urinary NGAL indicates subclinical kidney injury when the tubular reabsorption of molecules is impaired.

The Value of Electrophoresis and Chemical Detection in the Diagnosis of Hypertensive Nephropathy.

ObjectiveTo investigate the clinical value of sodium dodecyl sulfate–agarose gel electrophoresis (SDS-AGE) of urinary proteins combined with several biochemical indices in the detection of hypertensive nephropathy.Material and MethodsIn this study, 210 patients with hypertensive nephropathy were recruited as the kidney disease group, 100 patients with simple hypertension were recruited as the hypertension group, and another 100 healthy participants were recruited as the control group. We conducted SDS-AGE of urinary proteins and urinary microalbumin (mAlb), β2-microglobulin (β2-MG), retinol-binding protein (RBP), serum cystatin C (CysC), blood urea nitrogen (BUN), and creatinine tests at the same time.ResultsThe results showed that the urinary mAlb levels in the hypertension group and hypertensive nephropathy group were higher than in the control group (P<0.05). The biochemical index detection results showed that β2-MG, RBP, serum CysC, BUN, and creatinine were higher in the hypertensive nephropathy group than in the control group and hypertension group (P<0.05). The total positive rates of urinary protein SDS-AGE and urinary mAlb, urinary β2-MG, blood CysC, blood RBP, BUN, and creatinine in 210 patients with essential hypertension nephropathy were 100.0%, 98.6%, 32.8%, 98.6%, 21.0%, 2.0%, and 20%, respectively. The total positive rate of SDS-AGE urinary protein was higher than that of the other six biochemical indices.ConclusionSDS-AGE of urinary proteins, combined with urinary mAlb, β2-MG, serum CysC, RBP, BUN, and creatinine, could improve the detection sensitivity, which would be helpful for the early and accurate diagnosis of kidney damage.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan.

We evaluated the association between urinary cadmium concentration (uCd, μg/g Cr) and risk of cause-specific mortality according to urinary β2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and β2-MG were evaluated in a survey in 1981–1982, where those participants were followed-up over 35 years later. Among the participants with a urinary β2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with <5.0 for cardiovascular disease [HR 1.92 (1.08–3.40) for men, 1.71 (1.07–2.71) for women], pneumonia or influenza [2.10 (1.10–4.00) for men, 2.22 (1.17–4.19) for women], and digestive diseases [for men; 3.81 (1.49–9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary β2-MG of ≥1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

Reciprocal assessment of urinary beta-2-microglobulin and BUN levels in renal dysfunction of neonates with birth asphyxia

Objective Asphyxia at birth is one of the major causes of morbidity and mortality in all neonates due to various organ dysfunctions, for example, kidneys. Recent advances in this area have suggested new urinary proteins for the assessment of renal damage, including beta-2 microglobulin (β2-MG). The aim of this study was to investigate the changes of urinary β2-MG in asphyxiated neonates and to evaluate the value of combined detection of multiple biomarkers in the early diagnosis of acute kidney injury (AKI) in asphyxiated neonates. Study design This case-control study was performed on 84 term neonates in two control and case groups who were hospitalized at the neonatal intensive care unit. Using the Sarnat scoring system, the asphyxiated neonates were neurologically divided. Renal function tests and urinary β2-MG (uβ2-MG) levels of participants who registered based on inclusion criteria were measured. The data analyzed using descriptive and inferential statistical tests. The diagnostic value of the biomarker was determined using receiver operating characteristic (ROC) curves. Results This study showed that uβ2-MG was not a statistically significant difference in both asphyxiated neonates with AKI and non-AKI (p = .085). Whereas, uβ2-MG levels were statistically significant in neurological grading of asphyxiated infants to two groups (p = .013). A new predictor, uβ2-MG and blood urea nitrogen (BUN); named BB1, was substituted as the diagnostic value in neonates with asphyxia with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.88 (0.76–1.0). This AUC was significantly greater than the value for uβ2-MG associated with AKI (p = .003). Conclusion Our findings showed that mutual detection of uβ2-MG levels with BUN should be an early indicator for the diagnosis of renal injury with greater specificity and improved prognostic accuracy after neonatal asphyxia.

Urinary retinol binding protein and β 2 -microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients

Objective: To explore the associations of urinary retinol binding protein (RBP) and β2-microglobulin (β2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min-1·1.73m-2) and the normal eGFR group (≥90 ml·min-1·1.73m-2). Urine RBP and β2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β2-MG. Results: In all patients (n=1 030), urine RBP and β2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% (P<0.001), and 12.9%, 26.7%, 46.8% (P<0.001), respectively. In the UACR normal group (n=788), 12.2% of the patients were with eGFR<90 ml·min-1·1.73m-2. The proportion of abnormal β2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β2-MG as dependent variable, and showed that urine RBP was independently associated with UACR (β=0.0005, P<0.001), serum creatinine (β=0.006, P<0.001) and glycosylated hemoglobin A1c (β=0.050, P=0.001), and β2-MG was independently correlated with UACR (β=0.000 4, P<0.001), serum creatinine (β=0.011, P<0.001), systolic blood pressure (β=0.005, P=0.031) and fasting blood-glucose (β=0.027, P=0.046). Conclusions: Urine RBP and β2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with myocardial infarction

BackgroundRenal dysfunction, defined as a lower estimated glomerular filtration rate (eGFR), has been shown to be related to cardiovascular events in patients with myocardial infarction (MI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of cardiac death and recurrence of MI in patients who have had MI. Methods and resultsUrinary β2-microglobulin (β2MG) was measured in 681 consecutive patients with MI in our hospital. All patients were followed up for <12 years or until the occurrence of cardiac death and MI. During a median follow-up period of 6 years, the cumulative cardiac death rate was 5.4%, and the MI rate was 3.1%. When outcomes were divided into two groups according to the β2MG levels, cardiac death and MI rates were lower in patients with lower levels of β2MG (<0.319 mg/gCre: determined by receiver operating characteristic analyses) than in those with β2MG ≥0.319 mg/gCre (5.9% versus 17.1%, p<0.01). When outcomes were stratified according to the β2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that cardiac death and MI rates increased depending on an increase in the β2MG levels (p<0.05). Moreover, multivariate Cox analyses revealed that high levels of β2MG were a significant independent predictor of adverse events (hazard ratio: 1.956; 95% confidence interval: 1.014–3.774; p = 0.045). The addition of high levels of β2MG to conventional risk factors, including eGFR and urinary albumin, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.5447, p = 0.0002; IDI 0.0126, p = 0.0454). ConclusionRenal tubulointerstitial damage, as assessed by urinary β2MG, is associated with the occurrence of cardiac death and recurrence of MI independent of renal glomerular function in patients with MI.

Ginkgo Biloba Extract EGB761 Ameliorates the Extracellular Matrix Accumulation and Mesenchymal Transformation of Renal Tubules in Diabetic Kidney Disease by Inhibiting Endoplasmic Reticulum Stress.

The study is aimed at investigating the effects of Ginkgo biloba extract EGB761 on renal tubular damage and endoplasmic reticulum stress (ERS) in diabetic kidney disease (DKD). A total of 50 C57BL/6 N mice were randomly divided into the normal group, DKD group, DKD+EGB761 group (36 mg/kg), and DKD+4-phenylbutyrate (4-PBA) group (1 g/kg). The DKD model was replicated by high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). Renal tubular epithelial cells (HK-2) were divided into the control group, high-glucose group (30 mmol/L), EGB761 group (40 mg/L, 20 mg/L, 10 mg/L), TM group, and TM+4-PBA group. After 8 weeks of administration, expressions of serum creatinine (Scr), blood urea nitrogen (BUN), 24 h urinary protein (24 h Pro), fasting blood glucose (FBG), β2-microglobulin (β2-MG), and retinol binding protein 4 (RBP4) of mice were tested. The pathological changes of renal tissue were observed. The expressions of extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) markers α-smooth muscle actin (α-SMA), E-cadherin, fibronectin, and collagen IV, as well as the ERS markers GRP78 and ATF6, were tested by Western blot, qPCR, immunohistochemistry, or immunofluorescence. EGB761 could decrease the Scr, BUN, 24 h Pro, and FBG levels in the DKD group, alleviate renal pathological injury, decrease urine β2-MG, RBP4 levels, and decrease the expression of α-SMA, collagen IV, fibronectin, and GRP78, as well as ATF6, while increase the expression of E-cadherin. These findings demonstrate that EGB761 can improve renal function, reduce tubular injury, and ameliorate ECM accumulation and EMT in DKD kidney tubules, and the mechanism may be related to the inhibition of ERS.

Elevated cadmium and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in residents living near electroplating industries.

This study aims to evaluate the body burdens of cadmium (Cd) associated with potential health impairment in residents living near electroplating industries. A total of 269 residents from exposure area and 106 from control area were recruited. We measured the blood and urinary Cd levels using an inductively coupled plasma mass spectrometer (ICP-MS); performed physical examinations; determined the urinary levels of β2-microglobulin (β2-MG), Nacetyl-β-D-glucosaminidase (NAG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and evaluated the associations between Cd and these biomarkers. Blood and urinary Cd levels in exposure group were statistically higher than in control group (1.712 vs. 1.159 μg/L; 1.980 vs. 1.740 μg/L, respectively, p < 0.05). Urinary β2-MG and 8-OHdG levels in exposure group were also statistically higher (0.448 vs. 0.090 mg/L; 12.759 vs. 12.115 μg/L, respectively, p < 0.05), but urinary NAG levels showed no significant difference between the two groups (13.614 vs. 8.246 IU/L, p > 0.05). The proportion of abnormal nasal symptoms occurring in exposed subjects (88.8%) was much higher than in control subjects (78.2%, p < 0.05). Urinary Cd levels were positively correlated with blood Cd levels, urinary 8-OHdG, and NAG levels (r = 0.307, r = 0.185, r = 0.150, p < 0.05), but not correlated with urinary β2-MG levels (p > 0.05). In conclusion, our study revealed that residents living in close proximity to electroplating industries had elevated body burdens of Cd levels, as well as slight renal dysfunction and DNA oxidation damage.

Association between plasma aldosterone and markers of tubular and glomerular damage in primary aldosteronism.

Although renal impairments are observed in patients with primary aldosteronism (PA), the association between plasma aldosterone concentration (PAC) and specific structural kidney damage remains unknown. Thus, we analysed the association between PAC, and markers of glomerular and tubular damage. This was a retrospective cross-sectional study of 96 PA patients, in which we analysed the association between PAC and markers of kidney damage, including urinary albumin-creatinine ratio (ACR) for glomerular damage, and urinary liver fatty acid-binding protein (L-FABP), N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin (β2-MG) for tubular damage. In addition, we evaluated the association between PAC and N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker for body fluid volume. Urinary ACR, L-FABP, NAG, β2-MG and NT-proBNP significantly correlated with PAC. PAC (<415pmol/L, 415-550, 550-740, 740 <)-based quartile analysis revealed that both elevated markers of kidney damage and NT-proBNP could be observed in PA patients with a PAC over 550pmol/L. Logistic regression analysis showed that PAC was significantly associated with a risk of both microalbuminuria and lowered eGFR (<60mL/min/1.73m2 ), with its optimal cut-offs for predicting each, 558 and 594pmol/L, respectively. Increased PAC, especially over 550pmol/L, is associated with excessive damage to the tubule and glomerulus.

First-week urine beta-2 microglobulin levels in term healthy neonates.

Beta-2 microglobulin (β2mG) is a low-molecular-weight protein that is almost exclusively eliminated through the kidneys. It is freely filtered in the glomeruli and almost completely reabsorbed and degraded in the proximal tubules. Normal urinary β2mG levels are very low (between 0.04 and 0.22 mg/L). No reference values are known in infants and young children. Urinary β2mG levels were measured in 103 healthy term neonates during the first week of life by nephelometric technology. The average level of urinary β2mG was 0.65 mg/L (95% confidence interval between 0 and 10.8 mg/L). There was a minor difference between male and female neonates but it did not reach statistical significance. There was no effect of the gestational week, birth weight, or weight loss in the first week of life, on urinary β2mG levels. First-week urinary β2mG levels in healthy term infants were higher than adult levels. Incomplete maturation of kidney tubules in neonates could be a possible explanation. These can now be used in clinical practice and further studies that assess the degree of proximal tubular function in health and disease. Graphical abstract.

Acute Hyperglycemia May Induce Renal Tubular Injury Through Mitophagy Inhibition.

AimAcute hyperglycemia is closely related to kidney injury. Oxidative stress activation and notable mitochondria damages were found under acute hyperglycemia treatment in our previous work. In the present study, we explored the dose-effect relationship and the pivotal role of mitophagy in acute hyperglycemia induced tubular injuries.MethodsForty non-diabetic SD rats were randomly divided and treated with different concentrations of hyperglycemia respectively during the 6-h clamp experiment. Renal morphological and functional alterations were detected. Rat renal tubular epithelial cells were treated with different concentrations of glucose for 6 h. Markers and the regulation pathway of mitophagy were analyzed.ResultsSignificant tubular injuries but not glomeruli were observed under both light and electron microscope after acute hyperglycemia treatment, which manifested as enlargement of tubular epithelial cells, disarrangement of epithelial cell labyrinths and swelling of mitochondria. Urinary microalbumin, β2-MG, CysC, NAG, GAL, and NGAL were increased significantly with the increase of blood glucose (P < 0.05). ROS was activated, mitochondrial membrane potential and LC3-II/LC3-I ratio were decreased but P62 and BNIP3L/Nix were increased in hyperglycemia groups (P < 0.05), which were reversed by AMPK activation or mTOR inhibition.ConclusionAcute hyperglycemia causes obvious tubular morphological and functional injuries in a dose-dependent manner. Acute hyperglycemia could inhibit mitophagy through AMPK/mTOR pathway, which would aggravate mitochondria damage and renal tubular impairment.

Assessment of acute kidney injury by urinary β2-MG and NAG in pediatric cancer patients prescribed with Cisplatin, Carboplatin, and Ifosfamide as the chemotherapeutic agents

Background: Acute kidney injury (AKI) is defined as a failure in renal function leading to insufficiency of fluid and electrolyte homeostasis. Thus, sensitive biomarkers of renal tubular injury are needed to detect AKI earlier. In this study, urinary beta 2-microglobulin (β2-MG) and urinary N-acetyl-β-D-glucosaminidase (NAG) were evaluated for AKI prognosis/diagnosis in pediatric patients suffering different cancers prescribed with Ifosfamide, Ifosfamide plus Carboplatin, and Ifosfamide plus Cisplatin. Materials and Methods: In this prospective study done in Isfahan, Iran, urinary β2-MG, urinary NAG, blood urea nitrogen (BUN), and serum and urinary creatinine (Cr) were measured in 40 pediatric cancer patients less than 16 years old in three age groups during 61 courses of chemotherapy on day 0, three and six after the treatment. Results: Using ANOVA and t-test, the mean levels of urinary β2-MG (p= 0.001), urinary β2-MG/Cr (p= 0.003) and urinary NAG/Cr (p= 0.001), before and on day six of the treatment were statistically significant (p&lt; 0.05). Also, the mean levels of BUN (p= 0.01), urinary β2-MG (p= 0.001), β2-MG/Cr (p= 0.001) and NAG/Cr (p= 0.004) based on the gender groups, the mean levels of urinary NAG (p=0.001), NAG/Cr (p= 0.001) and β2-MG/Cr (p= 0.008) based on three age groups, and the mean levels of serum Cr (p= 0.047), urinary β2-MG (p= 0.005), β2-MG/Cr (p= 0.032) and NAG/Cr (p= 0.032) based on the Ifosfamide dosage were statistically significant during the time of the treatment. Conclusion: Urinary β2-MG, urinary β2-MG/Cr, and urinary NAG/Cr are more significant biomarkers than serum Cr in earlier diagnosis and treatment of AKI in cancer patients. However, urinary NAG should be further studied to prove its reliability for AKI prognosis/diagnosis. It is suggested that urinary NAG can be used along with other renal biomarkers such as urinary β2-MG, kidney injury molecule-1(KIM-1), or interleukin-18 (IL-18) for AKI prognosis/diagnosis.

Increased risk markers in women with polycystic ovary syndrome and gestational diabetes mellitus during mid-pregnancy.

ObjectiveThis study aimed to investigate application of the urine albumin-to-creatinine ratio (ACR), serum beta 2-microglobulin (β2-MG), and cystatin C as risk markers in a cohort of women with polycystic ovary syndrome (PCOS) for the incidence of gestational diabetes mellitus (GDM).MethodsIn this cross-sectional study, we analyzed 312 pregnant women with PCOS and classified them as those with and without GDM. For all participants, elbow venous blood and clean middle urine were collected in the morning after 8 hours of an empty stomach.ResultsLogistic regression analysis showed that the ACR, urine β2-MG levels, and serum cystatin C levels were important markers for women with PCOS concomitant with GDM. Receiver operating characteristic curve analysis showed that the area under the curve of CysC was 0.81 with the threshold based on >0.93 and that of β2-MG was 0.72 with the threshold based on >1.25.ConclusionsIncreased levels of β2-MG and cystatin C and a high ACR might be risk factors for Chinese women with PCOS and GDM during mid-pregnancy.