Urinary Beta 2-microglobulin Research Articles

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with aortic valve stenosis

Abstract Background Renal dysfunction, defined as a lower eGFR, has been shown to be related to cardiovascular events in patients with aortic stenosis treated with transcatheter aortic valve implantation (TAVI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events remains unclear. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of all death and heart failure patients who have had TAVI. Methods and results In a cohort of 155 patients, urinary beta2-microglobulin (beta2MG) levels were measured. Patients were monitored for less than three years or until experiencing all-cause mortality or hospitalization due to heart failure. The cumulative all-cause mortality was 11.5%, and heart failure admission rate stood at 5.4%. Stratifying outcomes by beta2MG levels revealed significantly lower rates of all-cause mortality and heart failure in patients with beta2MG <0.20 mg/gCre compared to those with beta2MG ≥0.20 mg/gCre (10.2% versus 24.2%, p=0.01). When outcomes were stratified according to the beta2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that all-cause mortality and heart failure rates increased depending on an increase in the beta2MG levels (p<0.05) even if eGFR is above 60 ml/min. Moreover, multivariate Cox analyses revealed that high levels of beta2MG were an independent predictor of adverse events. Conclusion Renal tubulointerstitial damage is associated with the occurrence of all death and hospitalization for heart failure independent of renal glomerular function.

Dal rene all'occhio: che cos'è la TINU?

An eight-year-old boy presenting with interstitial nephritis (abdominal pain, microhematuria, glycosuria, proteinuria, elevated urinary beta2-microglobulin levels) was eventually diagnosed with TINU syndrome (tubulointerstitial nephritis associated with uveitis) following the late onset of uveitis.

Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia–Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of − 0.9, + 1906, − 7.1, − 38.3, − 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: − 1.1, − 2.3, − 0.7, − 1.6 and − 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.

The Effect of Iron Chelators on urine Beta Microglobulin(β2M) and Serum Sodium on Patients with Thalassemia Major

Background and Objectives Thalassemia is the most common genetic disease associated with the body's recurrent blood transfusions and iron overload. Iron chelators can reduce the adverse effects of iron overload through various mechanisms. However, concerns have recently been raised about their negative impact on renal function. The current study, therefore, examined the effect of different iron chelators on renal function in patients with thalassemia major. Subjects and Methods This cross-sectional descriptive study included primary thalassemia patients (5 - 25 years) referring to Ahwaz Thalassemia Center for regular blood transfusion and regular treatment with iron chelators. They were divided into 3 groups (deferiprone 60-80 mg/kg/d, deferasirox 15-35 mg/kg/d and deferoxamine 11-48 mg/kg/d). Blood and 24-hour urine samples were collected to determine glomerular filtration rate (GFR) and biochemical factors. Results No significant difference was observed between the studied groups in terms of GFR, urine albumin, serum creatinine, serum cystatin C, serum and urine phosphorus, and urine sodium (p > 0.05), but serum sodium and urine β2microglobulin (β2M) were significantly different between the studied groups (p < 0.05). Serum sodium was significantly higher in the deferiprone group compared to the control (P=0.004). Urine β2M was significantly higher in the deferoxamine and deferasirox groups in comparison with the control group (P=0.041, P=0.013). Finally, serum sodium was significantly higher in the deferiprone and deferasirox groups than that in the deferoxamine group (P=0.001, P=0.021). Conclusion Urine beta-2 microglobulin increased in patients receiving deferoxamine and deferasirox compared to the control group, which might indicate primary kidney damage.

Comparison of Urinary Beta-2 Microglobulin Levels in Children with SSNS and Calcineurin Inhibitor-Treated SRNS.

While the utility of beta-2 microglobulin (β2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary β2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission. This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary β2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit. Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary β2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 mg/ml, P < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary β2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 mg/ml, P = 0.03). Median β2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 mg/ml). Urinary β2M levels were higher in SRNS compared to SSNS disease in remission, and β2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Background Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dl, and the Uur/Ucr and Cur/Ccr were 0.56%±0.14% and 45.7%±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Impact of Hyper- and Hypo-Uricemia on Kidney Function.

Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress.

The association between βeta 2-microglobulin and bronchopulmonary dysplasia

Abstract Objectives Previous studies showed that increased urinary Beta 2-microglobulin (β2-M) level is associated with fetal inflammatory response and successfully predict bronchopulmonary dysplasia (BPD). We aimed to investigate the clinical utility of serum β2-M levels to predict BPD in preterm infants. Method Infants born between May and November 2018 and whose gestational age (GA) was &lt;32 weeks were included into the study. During routine blood work in the first couple of hours of life an extra 0.5 mL blood was drawn to study β2-M levels later on. β2-M levels were compared between infants who developed BPD or not. Results Data analysis of 111 infants was performed. Out of 111 infants, 37 died before BPD diagnosis and out of the rest 74 infants, 38 (34.2%) were diagnosed with BPD. Mean GA was 28 ± 1.8 and 29.9 ± 1.4 weeks (p &lt; 0.01) and mean birth weights (BW) were 1,086 ± 316 and 1,395 ± 348 g (p &lt; 0.01) in BPD group and without BPD respectively. Demographic characteristics of the two groups were similar. While the white blood cell count, CRP and IL-6 levels were similar in both groups, β2-M levels were significantly higher in BPD group (4.84 ± 1.0 and 3.79 ± 0.95 mg/L, p = 0.01). Furthermore a weak correlation between β2-M level and BPD was observed (r = 0.23, p = 0.04). Conclusion Serum β2-M levels which obtained in the early postnatal life could predict developing BPD. Monitoring β2-M levels in infants who have high clinical risk factors for BPD development may provide additional benefit in predicting BPD.

Tubulointerstitial Nephritis and Uveitis Syndrome in the United Arab Emirates

ABSTRACT Purpose To report the first series of tubulointerstitial nephritis (TINU) syndrome from the Middle East. Methods We retrospectively included patients with elevated urine beta-2 microglobulin, and a diagnosis of TINU based on anterior uveitis with or without posterior involvement. Multimodal imaging, duration of follow-up, local and systemic treatment used were recorded. Results 24 eyes of 12 patients (8 male, mean age 20.3 years) met the criteria for TINU. The most common posterior segment clinical finding was optic nerve head edema (41.7%), while on fluorescein angiography 58.3% and 75% of eyes had peripheral vascular and optic disc leakage, respectively. The mean follow-up was 2.5 years and all patients required immunomodulatory treatment. Conclusions Middle Eastern patients with TINU seem to have a male predominance, a bimodal distribution in terms of age, and present with ocular involvement first. Multimodal imaging is paramount in detecting subclinical inflammation and tailoring immunomodulatory treatment.

Correlation of Renal Oxygenation with Renal Function in Chronic Kidney Disease: A Preliminary Prospective Study

Introduction: Chronic hypoxia is prevalent in chronic kidney disease (CKD), and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) provides noninvasive evaluation of renal oxygenation. This study aimed to explore the correlation of renal oxygenation evaluated by BOLD-MRI with renal function. Methods: 97 non-dialysis patients with CKD stages 1–5 and healthy volunteers (HVs) were recruited in the study, all participants without diabetes. Based on their estimated glomerular filtration rate (eGFR), the patients were divided into two groups: CKD stages 1–3 (CKD 1–3) and CKD stages 4–5 (CKD 4–5). We measured cortical and medullary T2* (COT2* and MET2*) values in all participants by BOLD-MRI. Physiological indices were also recorded and compared among three groups. Correlation of T2* values with clinical characteristics was determined. Results: The COT2* values were significantly higher than MET2* values in all participants. The COT2* and MET2* values of three groups were ranked as HV > CKD 1–3> CKD 4–5 (p < 0.0001). There were positive correlations between the COT2* values, MET2* values and eGFR, hemoglobin (r > 0.4, p < 0.01). The 24-h urinary protein (24-h Upr) showed weak correlation with the COT2* value (rs = −0.2301, p = 0.0265) and no correlation with the MET2* value (p > 0.05). Urinary microprotein, including urinary alpha1-microglobulin, urinary beta2-microglobulin (β2-MG), and urinary retinol-binding protein (RBP), showed strong correlation with COT2* and MET2* values. According to the analysis of receiver operating characteristic curve, the optimal cut-points between HV and CKD 1–3 were “<61.17 ms” (sensitivity: 91.23%, specificity: 100%) for COT2* values and “<35.00 ms” (sensitivity: 77.19%, specificity: 100%) for MET2* values, whereas COT2* values (“<47.34 ms”; sensitivity: 90.00%, specificity: 92.98%) and MET2* values (“<25.09 ms”; sensitivity: 97.50%, specificity: 80.70%) between CKD 1–3 and CKD 4–5. Conclusion: The decline of renal oxygenation reflected on T2* values, especially in cortex, may be an effective diagnostic marker for early detection of CKD.

Neurological prognostic factors for human herpes virus 6/7-associated acute encephalopathy in children: A single-center study

AimTo identify prognostic factors for severe neurological sequelae and epileptic seizures in children with human herpes virus (HHV) 6/7-associated acute encephalopathy (AE). MethodsWe retrospectively studied pediatric cases of HHV6/7-associated AE between April 2011 and March 2021. Neurological sequelae were assessed using the Pediatric Cerebral Performance Category scale (PCPC) and the presence of epileptic seizures 1 year after onset. We investigated the prognostic factors between the non-severe sequelae group (PCPC scores ≤ 2) and severe sequelae group (PCPC scores ≥ 3) in patients without severe neurological complications before onset. ResultsForty patients, ranging from 4 to 95 months old, were included. AE with biphasic seizures and late reduced diffusion were the most common types of encephalopathy (n = 28). Among the 36 patients evaluated neurological sequelae, 17, nine, eight, and two were categorized as PCPC 1, 2, 3 and 4, respectively. Epileptic seizures were observed in nine patients. In the severe sequelae group, significantly more cases with coma in the acute phase and thalamic lesions on MRI and higher serum aspartate aminotransferase, alanine aminotransferase (ALT), and lactate dehydrogenase levels were observed. Multivariate analysis showed a significant between-group difference in the rate of coma (p = 0.0405). Patients with epileptic seizures had a higher rate of coma and thalamic lesions and higher serum ALT and urinary beta 2-microglobulin levels, but there was no significant difference in the multivariate analysis. ConclusionsIn HHV6/7-associated AE, coma was a significant prognostic factor for severe neurological sequelae.

Proximal tubular renal dysfunction among HIV infected patients on Tenofovir versus Tenofovir sparing regimen in western Kenya.

Tenofovir Disoproxil Fumarate (TDF) is the most widely used Anti-Retroviral Therapy (ART) drug due to its potency, safety profile and World Health Organization (WHO) recommendation. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney disease. Modest rates (2-4%) of TDF related toxicity based on estimated Glomerular Filtration Rate (GFR) have been described, while TDF-induced PTRD has been reported to be 22%. TDF toxicity is more likely among African patients, it is reversible and TDF may be renal dosed in patients with dysfunction. The objective of this study was to assess proximal tubular renal dysfunction, global renal function, and their determinants among patients on TDF versus TDF-sparing regimen. This was a cross-sectional study among people living with HIV/AIDS (PLWHA) attending the Academic Model Providing Access to Healthcare (AMPATH) program. The primary outcome of interest in this study was PTRD while the secondary outcome of interest was estimated GFR. PTRD was defined as any two of beta-2 microglobulin in urine, metabolic acidosis, normoglycemic glucosuria and fractional excretion of phosphate. Student's t-test, chi-square and their non-parametric equivalents were used to test for statistical significance. Univariate and multivariate logistic regression analysis was carried out. A total of 516 participants were included in the final analysis, 261 on TDF while 255 were on TDF-sparing regimens. The mean (SD) age of all participants was 41.5 (12.6) years with majority being female (60.3%). The proportion of PTRD was 10.0% versus 3.1% in the TDF compared to TDF-sparing group (P<0.001). Mean estimated GFR was 112.8 (21.5) vs 109.7 (21.9) ml/min/1.73mm3 (P = 0.20) for the TDF compared to TDF-sparing group. TDF users were more likely to have PTRD compared to non-TDF users, adjusted Odds Ratio (AOR) 3.0, 95% CI 1.12 to 7.75. There was significant PTRD in the TDF compared to TDF-sparing group without significant difference in estimated GFR. The clinical significance of these findings may not be clear in the short term.

Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia.

To evaluate the role of urinary beta-2 microglobulin (B2mG) as an early predictive biomarker of acute kidney injury (AKI) in neonates with perinatal asphyxia. In this prospective cohort study, 80 term infants with perinatal asphyxia were included. The neonates were divided into AKI and no-AKI groups. Urinary B2mG levels were measured at 24h of life. The diagnostic efficacy of the biomarker was determined using receiver operating characteristic (ROC) curves. Compared to infants without AKI, infants with AKI had higher levels of urinary B2mG (mean 6.8 versus 2.6mg/L, p < 0.001). Area under the receiver operating characteristic curve (ROC curve) was 0.944. The balanced sensitivity/specificity trade-off was found at a cut-off value of 3.8mg/L (81% sensitive and 81.6% specific).Conclusion Urinary B2mG can be useful to predict AKI early in term neonates with perinatal asphyxia. What is Known: • AKI is seen in 20-40% of neonates with asphyxia. • AKI affects the treatment plan and the prognosis of such neonates. What is New: • Urinary biomarkers are the easiest way to diagnose AKI in asphyxiated neonates. • Beta 2 microglobulin is the cheapest and readily available one such urinary biomarker with good sensitivity and specificity.

COMPARATIVE EFFICACY OF EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY AND RETROGRADE INTRARENAL SURGERY IN THE TREATMENT OF CALCIUM OXALATE NEPHROLITHIASIS

Objective To evaluate the results of extracorporeal shockwave lithotripsy (ESWL) versus retrograde intrarenal surgery (RIRS) for the treatment of calcium oxalate nephrolithiasis, as well as the damaging effects on renal function, taking into account the dynamics of blood cystatin C and urine beta2-microglobulin.Material and Methods Of 94 patients with calcium oxalate nephrolithiasis aged 23–78 included in the study, 42 patients were classified as having undergone ESWL (group I) and 52 patients as having undergone RIRS (group II). Group II patients were then stratified into subset 2A (n = 32) as having undergone RIRS through rigid ureteroscope and subset 2B (n = 20) as having undergone RIRS through flexible ureteroscope. We performed plain urography and nephrosonography at 24–48 hours postoperatively and unenhanced computed tomography 4–6 weeks after surgery. We measured concentrations of serum cystatin C and urinary beta2-microglobulin as a marker for kidney damage. In group I, samples of peripheral blood andurine were taken before and after the first, third sessions and 30 days after the last ESWL session. In group II, samples were analyzed before surgery, on the first and 30th postoperative days.Results The average size of calculi in the group with RIRS was 16.91 ± 2.79 mm, in the group with ESWL 12.31 ± 2.27 mm. The need for reoperation after RIRS was 19.2%, which was lower than after ESWL. Stone-free effect (no stones, or residual stones less than 3 mm) was observed in 95% of cases in patients with RIRS, and in 78% with ESWL. Group I patients demonstrated an increase in the blood leukocytes total number more often than subsets 2A (rigid RIRS) and 2B (flexible RIRS) patients. Leukocyturia was also a more common complication in group I. In the RIRS group, there was no statistically significant change in the level of blood cystatin C and urine beta2-microglobulin, on the contrary, a moderate increase in the endogenous marker of cystatin C was noted after one ESWL session. The increase in urine beta2-microglobulin levels in patients after the first and third ESWL sessions was significantly higher than after RIRS.Conclusion Flexible RIRS may be suggested as the preferred procedure for patients requiring additional protection of renal function in the treatment of renal stones less than 20 mm. ESWL of stones less than 20 mm can be used as an alternative treatment, since it is characterized by a rather long period of stone eradication from the urinary tract, a high frequency of residual calculi after the procedure, and also has a damaging effect on the renal tissue.

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.

Investigation of Urinary Beta-2 Microglobulin Level in Neonates with Asphyxia Admitted in Alzahra Hospitals in Isfahan, 1396-1397

Background: Despite advances in perinatal care, perinatal asphyxia (PA) remains one of the most important causes of mortality and morbidity at birth. Asphyxia is associated with the dysfunction of different organs of the body. Therefore, this study aimed to investigate the urinary biomarker of beta-2 microglobulin in neonates with asphyxia. Methods: This case-control study was performed on neonates admitted to the Neonatal Intensive Care Unit of AL Zahra and Shahid Beheshti hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, during 2017-18. On the second day of birth, beta-2 microglobulin was measured in urine samples using the enzyme-linked immunosorbent assay technique. Results: The mean level of beta-2 microglobulin in the group with asphyxia (9.91±6.16) was significantly higher than that in the control group (3.83±4.03) (P=0.001). Moreover, analysis of beta-2 microglobulin level in the group with asphyxia showed that the mean serum level of neonates with acute renal failure (13.14±6.27) was significantly higher than that in newborns without acute renal failure (6.68±4.24) (P=0.02). Conclusion: The results of our study suggest that the beta-2 microglobulin level can be evaluated as a marker of neonatal asphyxia. Furthermore, its level was significantly associated with acute kidney injury. It is suggested that further studies be conducted with a larger sample size.

The impact of dyslipidemia on early markers of endothelial and renal dysfunction in children

BackgroundDyslipidemia has been associated with endothelial dysfunction in childhood. Impairment of renal function has been demonstrated in dyslipidemic adults. ObjectiveThe aim of this study was to assess markers of early endothelial and renal dysfunction in dyslipidemic children. MethodsThis was a cross-sectional study of 100 children with dyslipidemia and 100 age- and sex-matched control subjects without dyslipidemia aged 7–16 years. Renal dysfunction was assessed by measurement of serum creatinine and cystatin C levels, urinary beta 2-microglobulin levels, urinary albumin to creatinine (Alb:Cr) ratio, and by the estimated glomerular filtration rate (eGFR), based on serum creatinine or cystatin C. Endothelial dysfunction and early vascular changes were evaluated by ultrasound assessment of flow mediated dilation (FMD) of the brachial artery, and carotid intima-media thickness (cIMT), respectively. ResultsThe markers of early renal dysfunction showed no difference between the dyslipidemic children and control subjects except for the urinary Alb:Cr ratio that was higher in the dyslipidemic children (median, 0.007 mg/mg vs 0.005 mg/mg, p = 0.004). The urinary Alb:Cr ratio was positively correlated with the triglyceride to high-density lipoprotein cholesterol ratio (r = 0.28, p = 0.013). FMD values were lower in the dyslipidemic children than in the control subjects (8.504 ± 4.73% vs 10.535 ± 4.35%, p = 0.004), but cIMT did not differ between groups. This decrease in FMD values was evident in children aged ≥10 years. FMD was independently associated with the level of lipoprotein (a) (beta = −0.29, p = 0.01). ConclusionAmong markers of endothelial and renal dysfunction investigated, FMD was found to be lower and the urinary Alb:Cr ratio higher in children with dyslipidemia.

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.

Acute Focal Bacterial Nephritis Associated With Reversible Splenial Corpus Callosum Lesion

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidney, which presents as an inflammatory mass without formation of a frank abscess. Rare cases of AFBN are accompanied by neurological symptoms such as meningeal irritation, unconsciousness, and seizures. Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is characterized by transient high signal intensity splenial lesions on diffusion-weighted magnetic resonance imaging. MERS can be divided into two types: type 1 with an isolated splenium of the corpus callosum and type 2 with extensive white matter and/or entire callosal lesions. We experienced three rare cases of pediatric AFBN associated with neurological symptoms, including unconsciousness and reversible splenial corpus callosum lesion. The first case was an 8-year-old girl who had neurological symptoms, including unconsciousness, and AFBN was associated with MERS type 2. The second (5-year-old boy) and third (5-year-old girl) cases had neurological symptoms, including unconsciousness and AFBN with MERS type 1. Two of the three cases had AFBN caused by Escherichia coli . All three cases showed high levels of urinary beta 2 -microglobulin (B2MG). AFBN should be suspected in children with fever, rapid clinical deterioration, neurological symptoms including unconsciousness, and high urinary B2MG level. We recommend that abdominal enhanced computed tomography should be performed for the diagnosis of AFBN. Int J Clin Pediatr. 2020;9(3):82-86 doi: https://doi.org/10.14740/ijcp395

Ultra-widefield Fluorescein Angiography and OCT Findings in Tubulointerstitial Nephritis and Uveitis Syndrome

To report the spectrum of posterior segment findings in tubulointerstitial nephritis and uveitis syndrome (TINU) and discuss the abnormalities that can be seen on imaging. Retrospective, consecutive case series. Patients with TINU and posterior segment manifestations on examination or imaging. Patients with elevated urine beta-2 microglobulin (Uβ2M) and a diagnosis of TINU were included if they were evaluated at the Cole Eye Institute and did not have alternative etiologies for uveitis. Electronic medical records were reviewed for abnormal findings on ultra-widefield fluorescein angiography (UWFFA) and OCT. Presence of peripheral vascular leakage, optic disc leakage, chorioretinal lesions, or leakage within the macula on UWFFA. For OCT findings, patients were categorized as having intraretinal fluid, epiretinal membrane, or optic nerve edema. Twenty eyes from 10 patients (6 female, 4 male) with a bimodal age distribution (10-46 years and 77-83 years) were included. Eighteen of 20 eyes (90%) underwent UWFFA; 13 eyes demonstrated the presence of peripheral vascular leakage, 5 eyes showed optic disc leakage, and 6 eyes had leakage within the macula. All eyes underwent OCT imaging; 7 eyes demonstrated intraretinal fluid, 4 eyes were found to have an epiretinal membrane, and 1 eye had optic nerve edema. Six eyes lacked anterior uveitis on initial or follow-up examination but had abnormal findings on UWFFA or OCT. Tubulointerstitial nephritis and uveitis syndrome is under-recognized in the clinical setting. It can manifest in patients of all ages, and posterior segment involvement is not uncommon. Abnormalities may be seen on posterior segment examination or imaging in the absence of anterior segment inflammation. Tubulointerstitial nephritis and uveitis syndrome should be considered in the differential diagnosis for patients presenting with bilateral uveitis without evidence of infection or other clear etiology for intraocular inflammation.