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Background To determine whether urine neutrophil gelatinase-associated lipocalin (uNGAL) might be superior to pyuria for detecting urinary tract infection (UTI) regardless of urine specific gravity (SG) in young children. Methods We conducted a retrospective analysis of children aged < 3 years who were evaluated for UTI with urinalysis, urine culture, and uNGAL measurements during a 5-year period. Sensitivity, specificity, likelihood ratios (LRs), predictive values (PVs), area under the curves (AUCs) of uNGAL cut-off levels, and various microscopic pyuria thresholds for detecting UTI were calculated for dilute (SG < 1.015) and concentrated urine (SG [greater than or equal to] 1.015). Results Of 456 children included, 218 had UTI. The diagnostic value of urine white blood cell (WBC) concentration to define UTI changed with urine SG. For detecting UTI, uNGAL cut-off of 68.4 ng/mL had higher AUC values than pyuria [greater than or equal to] 5 WBCs/high power field (HPF) for dilute and concentrated urine samples (both P 0.05). Positive LR and PV and specificity of uNGAL were all greater than those of pyuria [greater than or equal to] 5 WBCs/HPF regardless of urine SG, although the sensitivity of pyuria [greater than or equal to] 5 WBCs/HPF was higher than that of uNGAL cut-off for dilute urine (93.8% vs. 83.5%) (P < 0.05). At uNGAL [greater than or equal to] 68.4 ng/mL and [greater than or equal to] 5 WBCs/HPF, posttest probabilities of UTI were 68.8% and 57.5% for dilute urine and 73.4% and 57.3% for concentrated urine, respectively. Conclusions Urine SG can affect the diagnostic performance of pyuria for detecting UTI and uNGAL might be helpful for identifying UTI regardless of urine SG in young children. Graphical abstract, Author(s): Do Young Kim [sup.1] , Hyung Eun Yim [sup.1] , Min Hwa Son [sup.1] , Kee Hwan Yoo [sup.2] Author Affiliations: (1) grid.411134.2, 0000 0004 0474 0479, Department of [...]

Background Children with nephrotic syndrome (NS) are at an increased risk of acute kidney injury (AKI) and the incidence of AKI in this population is reportedly increasing. This study aimed to investigate the incidence, clinical profiles, and risk factors of AKI in hospitalized children with NS through a nationwide study. Methods This retrospective multicenter study included 14 pediatric nephrology centers in Korea. From 2013 to 2017, a total of 814 patients with idiopathic NS were cared for at participating centers. Among them, 363 patients were hospitalized for NS and investigated in this study. Results A total of 363 children with NS were hospitalized 574 times. AKI occurred in 93 admissions (16.2%) of 89 patients: 30 (32.3%) stage 1; 24 (25.8%) stage 2; and 39 (41.9%) stage 3. Multivariate logistic regression analysis showed that longer disease duration, lower albumin level, and methylprednisolone pulse treatment were significantly associated with AKI development in hospitalized children with NS. AKI was associated with a longer hospital stay than non-AKI (median 10 vs. 7 days, P = 0.001). Among 93 admissions, 85 (91.4%) episodes recovered from AKI without complication, whereas 6 (6.5%) progressed to advanced chronic kidney disease (CKD). Conclusions AKI is not uncommon in hospitalized children with NS, and its incidence in this nationwide study was 16.2%. Risk factors for AKI in hospitalized children with NS include longer disease duration, lower albumin level, and methylprednisolone pulse therapy. Pediatric NS patients with these characteristics should be under more strict scrutiny for the occurrence of AKI., Author(s): Eun Mi Yang [sup.1] , Kee Hwan Yoo [sup.2] , Yo Han Ahn [sup.3] , Seong Heon Kim [sup.4] , Jung Won Lee [sup.5] , Woo Yeong Chung [sup.6] [...]

Objectives This study was designed to compare the diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin (NGAL) with procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) for predicting acute pyelonephritis (APN) in children with febrile urinary tract infections (UTIs). Materials and methods In total, 138 children with febrile UTIs (APN 59, lower UTI 79) were reviewed retrospectively. Levels of NGAL, PCT, CRP, and WBCs in blood were measured on admission. The diagnostic accuracy of the biomarkers was investigated. Independent predictors of APN were identified by multivariate logistic regression analysis. Results Receiver operating curve (ROC) analyses showed good diagnostic profiles of NGAL, PCT, CRP, and WBCs for identifying APN [area under the curve (AUC) 0.893, 0.855, 0.879, and 0.654, respectively]. However, multivariate analysis revealed only plasma NGAL level was an independent predictor of APN (P = 0.006). At the best cutoff values of all examined biomarkers for identifying APN, sensitivity (86 %), specificity (85 %), positive predictive value (81 %), and negative predictive value (89 %) of plasma NGAL levels were the highest. The optimal NGAL cutoff value was 117 ng/ml. The positive likelihood ratio [odds ratio (OR) 5.69, 95 % confidence interval (CI) 3.56-8.78], and negative likelihood ratio (OR 0.16, 95 % CI 0.08-0.29) of plasma NGAL for APN diagnosis also showed it seemed to be more accurate than serum PCT, CRP, and WBCs. Conclusion Plasma NGAL can be more useful than serum PCT, CRP, and WBC levels for identifying APN in children with febrile UTIs., Author(s): Byung Kwan Kim [sup.1] , Hyung Eun Yim [sup.2] , Kee Hwan Yoo [sup.1] Author Affiliations: (1) 0000 0004 0474 0479grid.411134.2Department of Pediatrics, Korea University Guro Hospital, 148 Gurodong-ro, [...]

The prevalence of chronic kidney disease (CKD) has increased considerably with a parallel rise in the prevalence of obesity. It is now recognized that early life nutrition has life-long effects on the susceptibility of an individual to develop obesity, diabetes, cardiovascular disease and CKD. The kidney can be programmed by a number of intrauterine and neonatal insults. Low birth weight (LBW) is one of the most identifiable markers of a suboptimal prenatal environment, and the important intrarenal factors sensitive to programming events include decreased nephron number and altered control of the renin-angiotensin system (RAS). LBW complicated by accelerated catch-up growth is associated with an increased risk of obesity, hypertension and CKD in later life. High birth weight and exposure to maternal diabetes or obesity can enhance the risk for developing CKD in later life. Rapid postnatal growth per se may also contribute to the subsequent development of obesity and CKD regardless of birth weight and prenatal nutrition. Although the mechanisms of renal risks due to early life nutritional programming remain largely unknown, experimental and clinical studies suggest the burdening role of early life obesity in longstanding cardiovascular and renal diseases., Author(s): Hyung Eun Yim[sup.1] , Kee Hwan Yoo[sup.1] [sup.2] Author Affiliations: (1) Department of Pediatrics, College of Medicine, Korea University, 152-703, Seoul, South Korea (2) Department of Pediatrics, Korea University [...]

Background Early predictive biomarkers for the diagnosis and management of febrile urinary tract infections (UTIs) can be valuable diagnostic tools in children. Methods The study cohort comprised 73 pediatric patients with febrile UTIs [46 with acute pyelonephritis (APN) and 27 with lower UTIs] and 56 healthy children. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) levels and serum cystatin C (sCysC) levels were measured. Results The uNGAL/creatinine (Cr) and uKIM-1/Cr levels were higher in the UTI group than in the controls (P < 0.05). uNGAL/Cr and sCysC levels were higher in patients with APN than in those with lower UTIs (P < 0.05). uNGAL/Cr levels in both the APN and UTI groups decreased following the administration of antibiotics compared to those before treatment (P < 0.05). The uNGAL/Cr level was correlated with serum levels of white blood cells, C-reactive protein, CysC and with uKIM-1/Cr (P < 0.05). uKIM-1/Cr was also correlated with sCysC (P < 0.05). Receiver operating curve analyses showed good diagnostic profiles of uNGAL/Cr and uKIM-1/ Cr for identifying UTIs [area under the curve (AUC) 0.9 and 0.66, respectively) and of uNGAL/Cr and sCysC for predicting APN (AUC 0.78 and 0.72, respectively). Conclusions Our results suggest that uNGAL, uKIM-1 and sCysC levels may be useful for predicting and managing febrile UTIs in children. Keywords Acute kidney injury * Bacterial infections * Biomarkers * Child * Pyelonephritis, Introduction Febrile urinary tract infection (UTI) has long been considered the most common serious bacterial infection in childhood, with a potential for consequent renal scarring [1]. While the guidelines for [...]

Am J Physiol Renal Physiol 298: F62-F71, 2010. First published November 4, 2009; doi: 10.1152/ajprenal.00234.2009.--To investigate the role of endogenous inducible nitric oxide synthase (iNOS) in the response of the developing kidney to unilateral ureteral obstruction (UUO), neonatal iNOS null mutant (-/-) and wild-type (WT) mice were subjected to partial or complete UUO. At 7 and 21 days of age, apoptosis, renin, vascular endothelial growth factor (VEGF), fibroblasts (anti-fibroblast-specific peptide 1), myofibroblasts ([alpha]-smooth muscle actin), macrophages (F4/80), and collagen were measured in kidney tissue. Compared with WT, renal parenchymal thickness was increased, with preservation of the papilla, in -/- mice with partial UUO, but decreased in -/- mice with complete UUO. Ureteral peristalsis increased with severity of pelvic dilatation in WT, and increased further in -/- mice with partial UUO. Apoptosis, fibroblasts, and macrophages were increased in -/- mice with complete UUO, but there was no effect of iNOS on other histological parameters following complete UUO. Renin was decreased in -/- mice with partial UUO. There was no effect of iNOS genotype on renal collagen accumulation at either 7 or 21 days of age. These results are consistent with an injurious role for endogenous iNOS following partial UUO by inhibiting ureteral peristalsis and increasing renal renin although renal fibrosis is not affected. In contrast, in mice with complete UUO, iNOS attenuates apoptosis and enhances renal parenchymal thickness. Alterations in the severity of ureteral obstruction may therefore influence the effect of iNOS on long-term renal injury. apoptosis; collagen; fibrosis; macrophages; ureteral peristalsis

Congenital urinary tract obstruction is the most important cause of renal insufficiency in infants and children, and angiotensin-converting enzyme (ACE) inhibitors attenuate the progression of renal disease in adults. ACE inhibitors are increasingly utilized in children with progressive renal disease. Because angiotensin is necessary for normal renal development, we examined the effects of ACE inhibition both during and immediately following the period of postnatal nephrogenesis in the neonatal rat subjected to sham operation or partial unilateral ureteral obstruction (UUO) under general anesthesia within the first 48 h of life. Rats in group I received enalapril 30 mg/kg body wt (or vehicle) daily for the first 10 days, while in group II, the l0 days of treatment began 10 days after surgery. Kidneys were harvested at day 21 and analyzed for apoptosis (TUNEL), interstitial macrophages (ED-1 immunohistochemistry), myofibroblasts ([alpha]-smooth muscle actin), and collagen (Sirius red). Partial UUO delayed glomerular maturation and increased ipsilateral renal macrophage infiltration, [alpha]-smooth muscle actin and Sirius red staining. In group I, enalapril increased myofibroblast accumulation in sham-operated kidneys, but not in obstructed kidneys. In contrast, in group II, enalapril further increased macrophage, myofibroblast, and collagen accumulation following partial UUO. The relative abundance of components of the kallikrein-kinin system, measured by Western blot, was not altered by partial UUO in the 14- and 28-day-old rat. Thus, in contrast to its salutary effects at later ages, ACE inhibition can worsen injury to the partially obstructed kidney during renal maturation even after the completion of nephrogenesis. fibrosis; kidney development; apoptosis; macrophages

Abstract Previous studies by our group have demonstrated that angiotensin-converting enzyme (ACE) inhibition in the developing kidney modulates transforming growth factor-[beta] receptors. Blocking of angiotensin II (ANG II) mainly through [...]

An investigation of the developmental regulation of angiostensin II AT1 and AT2 receptor genes in neonatal uretal osbtruction was conducted by subjecting Sprague-Dawley rats to control sham operation. Results of the experiment revealed that increased renal AT1 messenger RNA and receptor binding are likely to influence vasoconstriction and interstitial fibrosis. The early downregulation of renal angiotensin II receptors represents an adaptive response to the activation of the intrarenal renin-angiotensin system.

Objectives: We aimed to evaluate the association between early-life weight status and urinary tract infection (UTI) risk in children.Methods: A nationwide study was conducted using Korean National Health Screening (NHS) data and National Health Insurance Service data. A sample cohort was selected using data from the 2014 and 2015 NHS for infants and children (4-71 months) and followed up until the end of 2017. Participants were divided into 4 groups (underweight, normal weight, overweight, and obese) based on the weight-for-age (< 2 years) or body mass index (≥ 2 years). Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing UTIs, cystitis, and acute pyelonephritis (APN) were calculated using a Cox proportional hazard model.Results: Of 1,653,106 enrolled children, 120,142 (7.3%) developed UTIs, cystitis, and APN during follow-up. The underweight, overweight, and obese groups had higher risks of UTIs than the reference group after adjusting for age, sex, birth weight, and preterm birth. Between 2 years and 6 years of age, boys with underweight had a high risk of UTI and APN, while girls with overweight and obesity revealed elevated risks of UTIs, cystitis, and APN. The HRs for APN in boys with underweight and in girls with obesity were 1.46 (95% CI, 1.03 to 2.07) and 1.41 (95% CI, 1.13 to 1.75), respectively, after adjusting for age, sex, birth weight, and preterm birth. The incidence of APN did not decrease with age in underweight and obese children aged 2-6 years.Conclusions: Children with underweight, overweight, and obesity may be at high risk for UTIs. [ABSTRACT FROM AUTHOR]