Immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus.

OBJECTIVES: We evaluated the immunogenicity and safety of BNT162b2 vaccination in adolescents with systemic lupus erythematosus (adoSLE) receiving either high- or low-dose immunosuppressant (High-IS and Low-IS). METHODS: Patients aged 12-18 years diagnosed with SLE were enrolled. High-IS was defined as >7.5 mg/day prednisolone or with other immunosuppressant, while Low-IS was defined as only ≤7.5 mg/day of prednisolone and no immunosuppressant. Two doses of BNT162b2 vaccination were given 4 weeks apart, followed by a booster (third) dose at 4-6 months later. Anti-spike receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NT) against Wuhan and Omicron variants, and cellular immune response by IFN-γ-ELISpot assay were evaluated following vaccination. Adverse events (AEs) and SLE flare were monitored. RESULTS: A total of 73 participants were enrolled, 40 and 33 in the High-IS and Low-IS group, respectively. At 4 weeks following the 2nd dose, overall anti-RBD IgG seropositivity was 97.3%, with no difference between the groups (p = .498). AdoSLE on High-IS had lower anti-RBD IgG (p < .001), Wuhan NT (p < .001), and IFN-γ-ELISpot (p = .022) than those on Low-IS. A 3rd dose induced significantly higher antibody responses than after the 2nd dose (p < .001) in both groups and established seroconversion against Omicron variants, with persistent lower antibody levels in High-IS group. SELENA-SLEDAI scores within 12 weeks after 2-dose vaccination was higher than before vaccination (3.1 vs 2.5; p < .036); however, the occurrence of disease flare by SELENA-SLEDAI flare index was not different after vaccination compared to before vaccination, consistent across groups. Non-severe AEs occurred similarly in both groups. CONCLUSION: AdoSLE on High-IS induced lower SARS-CoV-2 vaccine immune responses than Low-IS. Vaccination can increase disease activity and requires close monitoring for disease flare.

Effect of peritoneal dialysate on bioelectrical impedance analysis variability in pediatric patients receiving peritoneal dialysis.

BACKGROUND: Previous adult studies have yielded conflicting results regarding whether the presence (D +) or absence (D-) of peritoneal dialysate affects the accuracy of bioelectrical impedance analysis (BIA) measurements. The aim of this study was to investigate whether the accuracy of BIA data varies between D + and D- measurements in children. METHODS: This cross-sectional study recruited chronic kidney disease stage 5 patients aged 3 to 18 years who received peritoneal dialysis. Body composition was assessed by multifrequency BIA, and values were compared between D + and D- measurements using the intraclass correlation coefficient (ICC). RESULTS: Fifty paired BIA measurements were collected from 18 patients with a mean age of 13.6 ± 4.1 years and a mean dialysate fill volume of 1,006 ± 239.7 ml/m2. Sixteen out of 17 BIA parameters (94.1%) exhibited excellent correlations between D + and D- measurements (ICC values = 0.954, 0.998). There was a trend of increased fluid status, including extracellular water, edema index, and overhydration, in D + measurements, with mean differences (95% CIs) of 0.5 (0.4, 0.6) L, 0.002 (0.001, 0.002), and 0.1 (0.1, 0.2) L, respectively. Soft lean mass and fat-free mass were higher in D + measurements, with mean differences (95% CIs) of 1.4 (1.2, 1.6), and 1.6 (1.4, 1.8) kg, respectively. In addition, patients older than 10 years had a stronger correlation between D + and D- measurements than younger patients. CONCLUSIONS: A total of 94.1% of BIA parameters exhibited excellent correlations between D + and D- measurements, especially patients older than 10 years. We recommend that BIA measurements be collected from children regardless of the presence of peritoneal dialysate.

Dysnatremia and subsequent sodium level changes following various intravenous treatments in infants with acute gastroenteritis.

Acute gastroenteritis is one of the main causes of electrolyte imbalance in infants. We aimed to determine the frequency of and factors associated with dysnatremia at presentation and establish the ideal intravenous treatment scheme. The records of hospitalized infants aged 1-12 months with community-acquired acute gastroenteritis between January 2017 and March 2021 were retrospectively reviewed. Factors associated with dysnatremia at presentation were analyzed by multivariable logistic regression analysis. Subsequent sodium levels 4-24 h after intravenous fluid treatments, which were categorized into 2 groups, were determined in the subgroup of infants with normal sodium levels at presentation. A total of 347 infants with a median age of 8.0 (5.0-10.0) months were included. The frequency of dysnatremia at presentation was 14% (hyponatremia 12% and hypernatremia 2.0%). Severe dehydration was associated with dysnatremia at presentation (p = 0.048). Among 68 infants with normal sodium levels at presentation, the median sodium change was highest in the 5% dextrose in saline group, with changes of + 3 (0.5-5) and + 1 (- 2 to 2) mmol/L in infants who received 5% dextrose in saline and 5% dextrose in 1/3-1/2 saline, respectively (p = 0.001). Four out of 47 infants (8.5%) developed hyponatremia while receiving 5% dextrose in 1/3-1/2 saline. None of those who received 5% dextrose in saline developed subsequent dysnatremia.   Conclusion: The frequency of dysnatremia at presentation among infants with acute gastroenteritis was 14%. Severe dehydration was associated with dysnatremia at presentation, so electrolyte levels need to be assessed in these patients. The use of isotonic solution did not promote acquired dysnatremia. This study supports once more that current guidelines recommending isotonic solution for children, and, especially, infant rehydration, are important also for infants in Thailand. What is Known: • There were a wide variation in the incidence of dysnatremia at presentation in children with acute gastroenteritis in previous pediatric series. • The AAP guidelines recommend using isotonic solution in children with acute illness from 28 days to 18 years of age to prevent acquired hyponatremia. What is New: • The incidence of dysnatremia at presentation in infants with acute gastroenteritis was 14% (hyponatremia 12% and hypernatremia 2.0%). • The use of isotonic solution did not promote acquired dysnatremia in infants with acute gastroenteritis.

Outcomes of achieving lupus low disease activity state and damage accrual in childhood-onset systemic lupus erythematosus.

INTRODUCTION: At present, the treat-to-target approach has been proposed with the lupus low disease activity state (LLDAS) as an achievable target. OBJECTIVES: To determine damage accrual and baseline clinical characteristics associated with achieving LLDAS within 12 months of treatment in patients with childhood-onset systemic lupus erythematosus (c-SLE). METHODS: This retrospective cohort study was conducted at the largest university-based tertiary referral center in Thailand. Data of c-SLE patients (≤ 18 years) at diagnosis who were followed ≥ 12 months during January 2009 to December 2019 were collected. SLE disease status was categorized into LLDAS and non-optimally controlled state. SLEDAI-2K score was used to assess disease activity. Damage accrual was assessed by a pediatric version of the SLICC/ACR damage index. RESULTS: A total of 232 c-SLE patients (85.8% female) were included. At 12 months of treatment, 109 (47%) patients achieved LLDAS. Damage accrual was observed in 93 (40.1%) patients at the mean follow-up time of 6.2 ± 3.7 years. Damage accrual was significantly lower in patients who achieved LLDAS within 12 months than in those non-optimally controlled (p = 0.002). The median time to achieving LLDAS was 12.6 months (95%CI: 11.19-13.97). The median time to achieving LLDAS was significantly shorter in those without renal involvement (10.8 months, 95%CI: 9.62-12.00 vs. 15.6 months, 95%CI: 13.76-17.52, respectively; p = 0.044). Multivariable logistic regression analysis revealed absence of renal involvement as the predictor of achieving LLDAS within 12 months of treatment (aOR: 2.430, 95%CI: 1.420-4.158; p = 0.001). CONCLUSIONS: Achieving LLDAS within 12 months of treatment was associated with lower damage accrual. Absence of renal involvement was the predictor of achieving LLDAS within 12 months of treatment. Key Points • LLDAS is a promising and achievable treatment target in c-SLE. • Achieving LLDAS within 12 months of treatment is associated with lower damage accrual. • Absence of renal involvement is the predictor of achieving LLDAS within 12 months of treatment.

Model for predicting high-grade vesicoureteral reflux in young children presenting with febrile urinary tract infection.

INTRODUCTION: High-grade vesicoureteral reflux (VUR) is associated with long-term renal outcome, and can be missed if voiding cystourethrogram (VCUG) is not performed. The current febrile urinary tract infection (UTI) guidelines have narrowed down the indications for VCUG. This study aimed to determine the predictors and develop a model to predict high-grade VUR (grade III-V) in young children presenting with febrile UTI. METHODS: We retrospectively reviewed 324 children aged 2-60 months who presented with first or recurrent febrile UTI and underwent both renal and bladder ultrasonography (RBUS) and VCUG during 2004-2013. Multivariate logistic regression was used to identify independent predictors of high-grade VUR, and a predictive model and scoring system were developed. Sensitivity and specificity of the predictors were evaluated. RESULTS: Sixty-two (67.4%) of 92 children with VUR were high-grade VUR. The independent risk factors for high-grade VUR were recurrent UTI (p < 0.001), non-Escherichia coli (non-E. coli) pathogen (p = 0.011), and abnormal RBUS (p < 0.001) including pelvicalyceal dilation only (p = 0.003), and with ureteric dilation (p < 0.001). Abnormal RBUS showed highest sensitivity (58.1%), while ureteric dilation had highest specificity (96.6%) to predict high-grade VUR. Combination of these predictors improved the specificity but decreased the sensitivity. The prediction score was calculated, as follows: recurrent UTI = 3 points + non-E. coli = 1 point + pelvicalyceal dilation only = 1 point + pelvicalyceal and ureteric dilation = 3 point. A cutoff score of 1 showed sensitivity of 82.3% and specificity of 63.7%. The specificity would increase (87.8, 92.7, 97.7, 100, 100, and 100%) for higher scores of 2, 3, 4, 5, 6 and 7, respectively. DISCUSSION: High-grade VUR could be predicted by simple model using single or combined predictors. Sensitivity and specificity varied according to each predictor. The specificity of ureteral dilation was as high as recurrent UTI. The weighing score for each presenting predictor and the summation of the scores provided more detailed in sensitivity and specificity. CONCLUSIONS: Children with febrile UTI who have the predictor(s) of high-grade VUR are recommended to undergo VCUG. The high-grade VUR prediction score may help for decision-making regarding whether to perform VCUG in a particular child.

Screening and management of bladder and bowel dysfunction in general pediatric outpatient clinic: a prospective observational study.

BACKGROUND: Bladder and bowel dysfunction (BBD) is a common disorder in children that is often associated with psychosocial and behavioral problems. Data specific to BBD in Asian children are comparatively scarce. Accordingly, this study aimed to investigate the prevalence of BBD and the response to standard urotherapy among Thai children attending the general pediatric outpatient clinic of Siriraj Hospital - Thailand's largest national tertiary referral center.  METHODS: Children aged 4-12 years were recruited to complete the Dysfunctional Voiding Symptom Score (DVSS) questionnaire to screen for BBD during 2018 to 2020. Standard urotherapy, which consists of education and behavior management, was prescribed to those with a DVSS score that suggests the presence of BBD. Enrolled children and their caregivers were followed-up at 3 and 6 months. The Strengths and Difficulties Questionnaire (SDQ) was completed at baseline. DVSS scores at baseline, and at 3 months and 6 months after standard urotherapy were compared using repeated measures analysis of variance (ANOVA). RESULTS: A total of 1,042 children completed the DVSS during the study period, and 90 (8.6%) were deemed to have BBD. The mean age of BBD children was 6.9 ± 2.2 years, and the female to male ratio was 2.9:1. The most common symptoms were defecation frequency (80.0%), difficult defecation (80.0%), curtsying (74.4%), urgency (68.9%), infrequent voiding (43.3%), and daytime incontinence (32.2%). Forty-one BBD children completed the SDQ, and 32.5% had scores suggestive of hyperactivity problems. Among the 24 BBD patients who were followed-up after 3 and 6 months of standard urotherapy, there was a significant improvement in DVSS results (9.5 ± 3.1 at baseline vs. 6.9 ± 3.4 at 3 months vs. 4.4 ± 3.9 at 6 months; p < 0.01). Nine of 12 patients with urinary incontinence showed complete response at 6 months. The overall Bristol stool score significantly improved from 2.6 ± 0.7 at baseline to 3.2 ± 1.0 at 6 months (p = 0.03). CONCLUSIONS: BBD is a prevalent condition among Thai children that is often associated with emotional and behavioral problems. Standard urotherapy prescribed in a general pediatric outpatient clinic setting yielded favorable outcomes in Thai children with BBD.

Prevalence of cognitive dysfunction and its risk factors in children with chronic kidney disease in a developing country.

BACKGROUND: Chronic kidney disease (CKD) is associated with cognitive dysfunction. Cognitive function in children with CKD residing in developing countries has not been previously reported. METHODS: This cross-sectional study included children aged 6-18 years with CKD stages 2-5D and kidney transplant. Cognitive function was assessed by WISC-V for children from 6-16 years of age. In adolescents 17-18 years of age, WAIS-III was used. Factors associated with cognitive dysfunction were identified using multivariable regression analysis. RESULTS: Thirty-seven children with median age 13.9 (11.3-15.7) years were recruited. The median full-scale intelligence quotient (FSIQ) was 83.0 (71.0-95.0). Below-average cognitive function (FSIQ <90) was identified in 24 children (64.8%), 24.3% of whom had cognitive impairment (FSIQ <70). Most children (94.6%) scored lower than average on at least 1 cognitive domain. Kidney replacement therapy (p = 0.03) and low family income (p = 0.02) were associated with below-average cognitive function in multivariable logistic regression analysis. Children who left school and low family income were significantly associated with cognitive function. The FSIQ of children who had left school was 12.94 points lower than the educated group (p = 0.046). In addition, every 10,000 Thai Baht (approximately 330 United States dollars) increase in family income correlated with 1.58 increase in FSIQ (p = 0.047). CONCLUSION: Cognitive dysfunction was commonly found in children with CKD. Socioeconomic factors, particularly school attendance and family income, were associated with cognitive dysfunction. Cognitive evaluation is suggested for children with CKD who have socioeconomic risk factors. "A higher resolution version of the Graphical abstract is available as Supplementary information."

Acute kidney injury without previous renal disease in critical care unit.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized and critically ill children. Apart from primary kidney disease, etiologies of AKI are usually related to systemic disease and nephrotoxic insult. This study examines the incidence, characteristics, and mortality risks of AKI in critically ill children without primary renal disease or previously known chronic kidney disease. METHODS: A retrospective cohort study was conducted of patients aged 1-18 years, diagnosed with AKI (excluding severe glomerulonephritis and previously known chronic kidney disease) in pediatric intensive care units between 2013 and 2016. Acute kidney injury was defined according to the Kidney Disease Improving Global Outcomes classifications. Cox proportional hazards regression analysis was employed to assess the relationship between the risk factors and mortality. RESULTS: Of 1,377 pediatric intensive care unit patients, 253 (18.4%) developed AKI and only 169 (12.3%) who did not have previously known renal disease were included. Of these 169 AKI patients, the mean age was 8.1 ± 4.7 years; 88 (52.1%) patients were male; and 60 (35.5%) patients had AKI stage 3. The most common etiologies of AKI were sepsis (76.9%) and shock (64.5%). Fifty-three (31.4%) of those patients died during admission. The risk factors for death were the need for mechanical ventilation (adjusted hazard ratio, 17.82; 95% CI, 2.41-132.06) and AKI stage 3 (adjusted hazard ratio, 2.32; 95% CI, 1.07-5.00). CONCLUSIONS: Acute kidney injury in critically ill children without previously known renal disease was approximately two-thirds of the overall incidence. The risk factors of in-hospital death were the use of mechanical ventilation, and AKI stage 3.

Takayasu arteritis with an initial presentation of chronic monoarthritis mimicking oligoarticular juvenile idiopathic arthritis.

Patients with Takayasu arteritis (TA) generally present with non-specific symptoms that, if unrecognized and untreated, may develop vessel stenosis and/or aneurysm. There is limited data regarding chronic monoarthritis as the initial presentation in children with TA. We report a 6-yearold girl diagnosed and treated as oligoarticular juvenile idiopathic arthritis (JIA). She later developed stroke with malignant hypertension and was definitively diagnosed with TA. She additionally developed proteinuria secondary to focal segmental glomerulosclerosis. This is the report of a patient with chronic monoarthritis mimicking oligoarticular JIA which chronic monoarthritis was the presentation of TA. Since JIA is a diagnosis of exclusion, any atypical features of oligoarticular JIA should illuminate the possibility of an alternative diagnosis. Our literature review focused on musculoskeletal presentations of children with TA.

Renal outcome and risk factors for end-stage renal disease in pediatric rapidly progressive glomerulonephritis.

BACKGROUND: Rapidly progressive glomerulonephritis (RPGN), defined as acute nephritic syndrome with dramatic loss of renal function within a few months, is associated with crescentic glomerulonephritis (CresGN), which requires ≥50% crescents on pathology. The disease characteristics and renal outcome in children with RPGN, however, will differ according to the percentage of crescents. METHODS: To evaluate the renal outcomes and factors associated with end-stage renal disease (ESRD), this retrospective cohort study assessed children aged ≤15 years with RPGN at a tertiary medical center. RESULTS: Of 67 patients with RPGN, 32 (47.8%) were male; mean age was 10.6 ± 3.0 years; median follow up was 1.1 years (range, 0.02-9.17 years) and 24 (35.8%) progressed to ESRD. Post-infectious glomerulonephritis was the most frequent cause of RPGN (50.7%). The incidence of ESRD was significantly higher in patients with ≥50% than <50% crescents (57.9% vs 28.6%, P = 0.029). On Cox regression analysis, disease etiology, serum creatinine >3 mg/dL, need for acute dialysis, ≥80% crescents and ≥20% tubular atrophy and interstitial fibrosis (TA/IF) were associated with ESRD. On multivariate analysis, need for acute dialysis (HR, 2.8; 95% CI: 1.1-7.3, P = 0.041) and ≥20% TA/IF (HR, 4.8; 95% CI: 1.4-16.1, P = 0.011) were independent risk factors for the development of ESRD. CONCLUSIONS: Approximately one-third of children with RPGN developed ESRD; and need for acute dialysis and TA/IF ≥20% were independent risk factors for ESRD.

Validity and Reliability of the Thai Version of Dysfunctional Voiding Symptom Score (DVSS) Questionnaire.

Background: Bladder and bowel dysfunction (BBD) is a common problem and a predisposing factor for urinary tract infection in children. Evaluation using the Dysfunctional Voiding Symptom Score (DVSS) questionnaire is widely used. The original English DVSS has been translated to several languages. Thai version of the DVSS would be helpful for early detection and management of BBD in children. Objective: To translate and adapt DVSS to Thai version and evaluate validity and reliability of this questionnaire in children aged 3-10 years. Material and Method: DVSS English version was translated into Thai according to the following methodology: translation, synthesis, back-translation, expert reviews, and pre-testing. Patients aged 3 -10 years with a history of diurnal urinary incontinence, urinary tract infection or abnormal voiding habits, presenting to pediatric nephrology or urology clinic, were recruited as study group. Age-matched children presenting to general outpatient clinic were recruited as control group. Final DVSS-Thai version was tested and re-tested at the following 1 - 2 weeks. The internal consistency and test­retest reliability was assessed with Cronbach's alpha test and intraclass correlation (ICC), respectively. The optimum cutoff score was analyzed using receiver operating characteristics (ROC) curve. Results: The back translation to English of Thai version corresponded to the original English DVSS. Age and sex between the study (n = 22) and control (n = 30) group were not different. Mean total scores of the DVSS were 11.6±4.7 VS 1.9±1.6 (p<0.001) in the study and control group, respectively. Cronbach's alpha coefficient was 0.8 and intraclass correlation coefficient (ICC) was 0.906 (p<0.001). The optimum cutoff score was 5 (sensitivity 100% and specificity 96.7%) with area under the curve of 0.998 (p<0.001). Conclusion: Thai version of the DVSS was completed by proper process and demonstrated an excellent validity and reliability. It should be used to identify BBD in Thai children.

Delayed Therapeutic Response Time Predicts Renal Damage in the First Episode of Febrile Urinary Tract Infection.

Objective: To evaluate the relationship of therapeutic delay time (TDT) and therapeutic response time (TRT) with renal damage in the first episode of febrile urinary tract infection (UTI). Material and Method: A prospective study was conducted in 67 children with the first episode of UTI at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital between 2008 and 2010. To assess for renal damage, dimercaptosuccinic acid (DMSA) renal scintigraphy was performed at one and six months after the acute episode. Results: Abnormal DMSA renal scintigraphy was detected in 20 (29.9%) patients. There was no difference in TDT but TRT was different between the patients with normal and abnormal DMSA renal scintigraphy at p-value 0.001. The area under receiver operating characteristic (ROC) curve for TRT was 0.76 (95% confidence interval (CI) 0.64-0.86) at p-value 0.001. The optimal cut-off value for TRT was 22 hours with sensitivity 80.0% (56.3-94.1) and specificity 63.6% (47.8-77.6). In 50 patients with no vesicoureteral reflux (VUR), there was difference in TRT at p-value 0.002. The area under ROC curve for TRT was 0.82 (95% CI 0.69-0.96) at p-value 0.004. The optimal cut-off value for TRT was 25 hours with sensitivity 88.9% (95% CI 51.7-98.2) and specificity 68.4% (95% CI 51.3- 82.5). Conclusion: TRT at or more than 22 hours predicts renal damage after first episode of UTI. In patients with no VUR, TRT at or more than 25 hours predicts renal damage. DMSA renal scintigraphy in the first episode of UTI should be considered in these patients.

Tacrolimus in steroid resistant and steroid dependent childhood nephrotic syndrome.

OBJECTIVE: To evaluate the efficacy of tacrolimus (Tac) in steroid resistant and steroid dependent nephrotic syndrome (NS) in children. MATERIAL AND METHOD: Retrospective chart reviews of 18 children from outpatient clinic at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital were diagnosed with steroid resistant (SR) and steroid dependent (SD) NS during 2002-2008 were enrolled in the present study RESULTS: The boy to girl ratio was 2:1. The mean age at diagnosis was 6.0 years (1-14.4 years). There were nine SR and nine SDNS. Nine patients had focal segmental glomerulosclerosis (FSGS), 4 IgMnephropathy and two had minimal change diseases (MCD). Three children did not receive renal biopsy. All patients received prednisolone at the start of Tac. The average time from the diagnosis to initiation of Tac was 3.5 years (0.2-14years). The mean duration of Tac treatment was 1.3 year (0.3-6.2 years). The average Tac trough blood level was 4.09 mcg/L (1.3-9.9 mcg/L). The average dosage of Tac was 0.09 mg/kg/day (0.03-0.2 mg/kg/day). Thirteen (72.2%) children achieved complete response (CR). Five (27.80%) children did not respond to Tac. Nine (69.2%) children could stop prednisolone whereas four (30.8%) could lower prednisolone doses. The mean time to achieve CR was 24.6 days (0.1-3 months). The mean follow up period was 3.1 years (0.2-6.4 years). There was no change in an estimation of glomerular filtration rate (eGFR). In SRNS, there were CR in four (44.4%) and five (55.6%) children that FSGS did not respond to Tac. In SDNS, all responded to Tac and four (44.4%) children relapsed while on Tac and had upper respiratory tract infection (URI). CONCLUSION: Tac is well-tolerated and effective treatment for SR and SDNS.

NGAL distinguishes steroid sensitivity in idiopathic nephrotic syndrome.

BACKGROUND: Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Invasive biopsy remains the diagnostic method of choice for NS. Prognosis correlates with steroid responsiveness, from sensitive (SSNS) to resistant (SRNS). Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a powerful risk marker of chronic kidney disease progression. We set out to determine if urine NGAL can distinguish between patients with SRNS, SSNS, and healthy controls. METHODS: Urine and clinical data were collected from patients at Cincinnati Children's Hospital who were recently diagnosed with active nephrotic syndrome as well as healthy controls. Participants included SRNS (n = 15), SSNS (n = 14), and healthy controls (n = 10). Urinary NGAL was measured by ELISA and normalized to creatinine. RESULTS: Median NGAL was significantly (p < 0.001) higher in SRNS (172.3 ng/ml, IQR 18.8-789) than both SSNS (6.3 ng/ml, IQR 4.9-9.9) and healthy controls (6.5 ng/ml, IQR 4.2-9.1). The area under the curve (AUC) for NGAL to distinguish SRNS from SSNS was 0.91 (p < 0.0001). NGAL levels demonstrated a significant negative correlation with glomerular filtration rate (r = -0.5, p < 0.001). Results did not change with NGAL corrected for urine creatinine and were independent of the degree of proteinuria. CONCLUSIONS: NGAL levels differentiate SSNS from SRNS and correlate with disease severity in SRNS.

Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass.

OBJECTIVES: We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI). BACKGROUND: Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. METHODS: Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a ≥50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement. RESULTS: AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction. CONCLUSIONS: Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.

Discovery and initial validation of α 1-B glycoprotein fragmentation as a differential urinary biomarker in pediatric steroid-resistant nephrotic syndrome.

PURPOSE: In this cross-sectional pilot study we set out to discover a non-invasive biomarker that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). EXPERIMENTAL DESIGN: Urine and clinical data were collected from patients with idiopathic nephrotic syndrome and healthy controls. Using SELDI-TOF-MS, we identified an 11-fold upregulated 13.8 kDa fragment of α 1-B glycoprotein (A1BG) in urine in SRNS. To validate our findings, A1BG was detected by Western blot. Creatinine was measured and transformed to glomerular filtration rate (GFR) by the new Schwartz formula and classified to chronic kidney disease (CKD) stage. p-Values were determined by unpaired t-test and Mann-Whitney rank sum test. Microalbumin was also measured to determine albumin/creatinine ratios. RESULTS: The 13.8 kDa A1BG was present in 7 of 19 patients with SRNS; but absent in all SSNS (n=15) and controls (n=10). The A1BG(+) patients had lower GFR than A1BG(-) patients (p<0.009) and tended to have higher CKD stage. CONCLUSION AND CLINICAL RELEVANCE: The 13.8 kDa A1BG fragment had a high discriminatory power for steroid resistance in pediatric nephrotic syndrome, but is only present in a subset of patients. Additional longitudinal studies are required to determine the usefulness of this biomarker as a non-invasive predictive marker of therapeutic response.

Renal tubule function in beta-thalassemia after hematopoietic stem cell transplantation.

Advances in hematopoietic stem cell transplantation (HSCT) for beta-thalassemia major make the long-term outcome of these patients very important. Few data on long-term renal function of thalassemia patients are available. We evaluated the renal function in children after successful allogeneic HSCT for beta-thalassemia. Twenty-nine patients were included; the mean age at HSCT was 4.9 years. Mean follow-up time was 7.6 years. After HSCT, two patients developed acute renal failure and two had graft versus host disease. At last follow up, height standard deviation score (SDS) remained the same, but weight SDS had improved. Mean hemoglobin was 12.5 g/dl, and serum ferritin level was 545 ng/ml. All children had normal estimated glomerular filtration rate (GFR). One patient had hypertension and proteinuria, 10 years after HSCT. When comparing 39 children of the same age with beta-thalassemia of similar disease severity but who had not experienced HSCT, we found that the parameters of renal tubule function were better in patients that had undergone HSCT, as demonstrated by urine protein level (0.36 mg/mg creatinine vs 3.03 mg/mg creatinine, P < 0.001), osmolality (712 mosmol/kg vs 573 mosmol/kg, P = 0.006), N-acetyl-beta-D: -glucosaminidase (17.7 U/g creatinine vs 42.9 U/g creatinine, P = 0.045), and beta 2 microglobulin (0.09 microg/mg creatinine vs 0.13 microg/mg creatinine, P = 0.029). This study showed a low incidence of long-term renal impairment after HSCT and indicated that renal tubule function may be better in beta-thalassemia patients after HSCT.

Features of patients with anaphylaxis admitted to a university hospital.

BACKGROUND: Anaphylaxis in hospitalized patients has been infrequently reviewed. There are few studies of anaphylaxis from Asian countries. OBJECTIVE: To describe the clinical characteristics of patients with anaphylaxis admitted to Siriraj Hospital. METHODS: The medical records of 101 patients admitted with clinical anaphylaxis between January 1, 1999, and December 31, 2004, were reviewed. Data were analyzed using the chi2 test. RESULTS: The annual occurrence of anaphylaxis increased from 9.16 per 100,000 admitted persons in 1999 to 55.45 per 100,000 admitted persons in 2004. The case fatality rate was 0.19 per 100,000 admitted persons. The mean +/- SD age was 23.73 +/- 21.84 years. Males experienced more anaphylaxis than females in pediatric patients and vice versa in adult patients. Biphasic anaphylaxis was found in 7% of pediatric and 2% of adult patients. Anaphylaxis occurred in the hospital in 37% of patients. Involved systems were cutaneous (86%), respiratory (80%), cardiovascular (52%), and oral and gastrointestinal (36%). Identifiable causes were drugs (50%), foods (24%), idiopathic (15%), and insect stings/bites (11%). Epinephrine was given to 77% of the patients. CONCLUSIONS: We report the clinical characteristics of patients with anaphylaxis admitted to a university hospital. Knowing the clinical features will raise physician awareness of this condition.