Search

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 ≥ 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 ≥ 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 ≥ 5 WBCs/HPF regardless of urine SG, although the sensitivity of pyuria ≥ 5 WBCs/HPF was higher than that of uNGAL cut-off for dilute urine (93.8% vs. 83.5%) (P < 0.05). At uNGAL ≥ 68.4 ng/mL and ≥ 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. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype-phenotype correlation not only in male patients but also in female patients with XLAS., (© 2023. The Author(s).)

Background: Exposure to air pollution can interfere with the vitamin D endocrine system. This study investigated the effects of airborne particulate matter (PM) on renal tubular cell injury in vitro and explored the underlying mechanisms., Methods: HK-2 human renal proximal tubule cells were treated with PM with or without 1,25(OH) 2 D 3 analog, 19-Nor-1,25(OH) 2 D 2 (paricalcitol, 10 nM) for 48 h. The dose- and time-dependent cytotoxicity of PM with or without paricalcitol was determined via cell counting kit-8 assay. Cellular oxidative stress was assessed using commercially available enzyme-linked immunosorbent assay kits. The protein expression of vitamin D receptor (VDR), cytochrome P450(CYP)27B1, CYP24A1, renin, angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was determined., Results: PM exposure decreased HK-2 cell viability in a dose- and time-dependent manner. The activities of superoxide dismutase and malondialdehyde in HK-2 cells increased significantly in the group exposed to PM. PM exposure decreased VDR and Nrf2, while increasing CYP27B1, renin, ACE, AT1, NF-kB, TNF-α, and IL-6. The expression of VDR, CYP27B1, renin, ACE, AT1, and TNF-α was reversed by paricalcitol treatment. Paricalcitol also restored the cell viability of PM-exposed HK-2 cells., Conclusion: Our findings indicate that exposure to PM induces renal proximal tubular cell injury, concomitant with alteration of vitamin D endocrine system and renin angiotensin system. Vitamin D could attenuate renal tubular cell damage following PM exposure by suppressing the renin-angiotensin system and by partially inhibiting the inflammatory response., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases., Methods: This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016., Results: Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels., Conclusions: Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

The prevalence of childhood obesity is increasing worldwide at an alarming rate. While obesity is known to increase a variety of cardiovascular and metabolic diseases, it also acts as a risk factor for the development and progression of chronic kidney disease (CKD). During childhood and adolescence, severe obesity is associated with an increased prevalence and incidence of the early stages of kidney disease. Importantly, children born to obese mothers are also at increased risk of developing obesity and CKD later in life. The potential mechanisms underlying the association between obesity and CKD include hemodynamic factors, metabolic effects, and lipid nephrotoxicity. Weight reduction via increased physical activity, caloric restriction, treatment with angiotensin-converting enzyme inhibitors, and judicious bariatric surgery can be used to control obesity and obesity-related kidney disease. Preventive strategies to halt the obesity epidemic in the healthcare community are needed to reduce the widespread deleterious consequences of obesity including CKD development and progression.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a valuable biomarker of urinary tract infection (UTI) in children., Purpose: This study aimed to compare the diagnostic accuracy of urinary NGAL (uNGAL) with those of serum C-reactive protein (CRP) and white blood cell (WBC) count for predicting UTI and acute pyelonephritis (APN) in febrile children., Methods: The medical charts of children undergoing uNGAL measurements between November 2017 and August 2019 were retrospectively reviewed. Patients with a suspected or diagnosed UTIs were included. The diagnostic accuracies of uNGAL, serum CRP, and WBC count for detecting UTI and APN were investigated. Independent predictors of UTI and APN were investigated using multivariable logistic regression analyses., Results: A total of 321 children were enrolled in this study. The uNGAL levels were higher in the UTI group (n=157) than in the non-UTI group (n=164) (P<0.05). Among children with a UTI, uNGAL levels were higher in the APN group (n=70) than, the non-APN group (n=87) (P<0.05). In the multivariate analysis, uNGAL was independently associated with UTI and APN (both P<0.05). Serum CRP and WBC count were not correlated with the presence of UTI and APN. Receiver operating curve analyses showed that the uNGAL level had the highest area under the curve (AUC) for predicting UTI and APN, respectively (AUC, uNGAL vs. CRP vs. WBC count, 0.860 vs. 0.608 vs. 0.669 for UTI; 0.780 vs. 0.680 vs. 0.639 for APN, all P<0.05, respectively). The predictive values and likelihood ratios of uNGAL were superior to those of serum CRP and WBC count for detecting UTI and APN at each cutoff level., Conclusion: UNGAL may be more useful than serum CRP and WBC count for identifying and assessing UTI in febrile children.

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. Graphical abstract.

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.

Cellular senescence is important for the maintenance of tissue homeostasis during normal development. In this study, we aimed to investigate the effect of renin angiotensin system (RAS) blockade on renal cell senescence in the developing rat kidney. Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for seven days after birth. We investigated the intrarenal expressions of cell cycle regulators p21 and p16 with immunoblots and immunohistochemistry at postnatal day 8. For the determination of renal cellular senescence, immunostaining for senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) was also performed. Enalapril treatment showed significant alterations in cellular senescence in neonatal rat kidneys. In the enalapril-treated group, intrarenal p16 and p21 protein expressions decreased compared to controls. The expressions of both p21 and p16 were reduced throughout the renal cortex and medulla of enalapril-treated rats. The immunoreactivity of TERT in enalapril-treated kidneys was also weaker than that in control kidneys. Control kidneys revealed a clear positive SA-β-gal signal in the cortical tubules; however, SA-β-gal activity was noticeably lower in the enalapril-treated kidneys than in control kidneys. Interruption of the RAS during postnatal nephrogenesis may disrupt physiologic renal cellular senescence in the developing rat kidney., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulopathies diagnosed in children and adolescents. This study aimed to evaluate the clinical features in and outcomes of pediatric IgAN over the last 30 years. Patients who were diagnosed before age of 18 at 20 centers in Korea were evaluated retrospectively. Of the 1154 patients (768 males, 386 females) with a median follow-up of 5 years, 5.6% ( n = 65) progressed to stage 3-5 chronic kidney disease (CKD). The 10- and 20-year CKD-free survival rates were 91.2% and 75.6%, respectively. Outcomes did not differ when comparing those in Korea who were diagnosed prior to versus after the year 2000. On multivariate analysis, combined asymptomatic hematuria and proteinuria as presenting symptoms and decreased renal function at the time of biopsy were associated with progression to CKD, while remission of proteinuria was negatively associated with this outcome. Patients who presented with gross hematuria or nephrotic syndrome tended toward positive outcomes, especially if they ultimately achieved remission. While remission of proteinuria might imply that the disease is inherently less aggressive, it also can be achieved by management. Therefore, more aggressive management might be required for pediatric-onset IgAN.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage renal disease (ESRD) in childhood and is mostly associated with focal segmental glomerulosclerosis (FSGS). More than 50 monogenic causes of SRNS or FSGS have been identified. Recently, the mutation detection rate in pediatric patients with SRNS has been reported to be approximately 30%. In this study, genotype-phenotype correlations in a cohort of 291 Korean pediatric patients with SRNS/FSGS were analyzed. The overall mutation detection rate was 43.6% (127 of 291 patients). WT1 was the most common causative gene (23.6%), followed by COQ6 (9.4%), NPHS1 (8.7%), NUP107 (7.1%), and COQ8B (6.3%). Mutations in COQ6 , NUP107 , and COQ8B were more frequently detected, and mutations in NPHS2 were less commonly detected in this cohort than in study cohorts from Western countries. The mutation detection rate was higher in patients with congenital onset, those who presented with proteinuria or chronic kidney disease/ESRD, and those who did not receive steroid treatment. Genetic diagnosis in patients with SRNS provides not only definitive diagnosis but also valuable information for decisions on treatment policy and prediction of prognosis. Therefore, further genotype-phenotype correlation studies are required.

Background: Neutrophil gelatinase-associated lipocalin (NGAL), a bacteriostatic agent, is known to inhibit erythropoiesis leading to anemia. We aimed to investigate the associations of NGAL, anemia, and renal scarring in children with febrile urinary tract infections (UTIs)., Methods: We retrospectively reviewed the medical records of 261 children with febrile UTIs. The relationship between the presence of anemia and plasma NGAL levels was investigated. NGAL performance in comparison with serum C-reactive protein (CRP) at admission and after 72 hours of treatment was also evaluated for the prediction of renal scarring as well as acute pyelonephritis (APN) and vesicoureteral reflux (VUR)., Results: Plasma NGAL levels were elevated in patients with anemia compared with those without anemia. Multiple linear regression analysis showed an inverse relationship between NGAL levels and erythrocyte counts (standard β = -0.397, P < 0.001). Increased NGAL, but not CRP, was independently associated with the presence of anemia (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.07-5.27; P < 0.05). Receiver operating curve analyses showed good diagnostic profiles of pre- and post-treatment NGAL for identifying APN, VUR, and renal scarring (all P < 0.05). For detecting renal scars, the area under the curve of post-treatment NGAL (0.730; 95% CI, 0.591-0.843) was higher than that of post-treatment CRP (0.520; 95% CI, 0.395-0.643; P < 0.05). The presence of anemia and elevated NGAL at admission (> 150 ng/mL) were independent risk factors for renal scarring in children with febrile UTIs. With anemia, NGAL levels increased consecutively in children with febrile UTI without renal involvement, with APN without scar, and with APN with renal scarring., Conclusion: Increased plasma NGAL levels may be associated with the presence of anemia and renal scarring in children with febrile UTIs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: Renin-angiotensin system (RAS) blockade during nephrogenesis causes a broad range of renal mal-development. Here, we hypothesized that disruption of renal lymphangiogenesis may contribute to tubulointerstitial alterations after RAS blockade during kidney maturation., Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for 7 days after birth. Lymphangiogenesis was assessed via immunostaining and/or immunoblots for vascular endothelial growth factor (VEGF)-C, VEGF receptor (VEGFR)-3, Podoplanin, and Ki-67. The intrarenal expression of fibroblast growth factor (FGF)-1, FGF-2, FGF receptor (R)-1, α-smooth muscle actin (α-SMA), and fibroblast-specific protein (FSP)-1 was also determined. Sirius Red staining was performed to evaluate interstitial collagen deposition., Results: On postnatal day 8, renal lymphangiogenesis was disrupted by neonatal enalapril treatment. The expression of podoplanin and Ki-67 decreased in enalapril-treated kidneys. While the expression of VEGF-C was decreased, the levels of VEGFR-3 receptor increased following enalapril treatment. Enalapril treatment also reduced the renal expression of FGF-1, FGF-2, and FGFR-1. Enalapril-treated kidneys exhibited profibrogenic properties with increased expression of α-SMA and FSP-1 and enhanced deposition of interstitial collagen., Conclusion: Enalapril treatment during postnatal renal maturation can disrupt renal lymphangiogenesis along with tubulointerstitial changes, which may result in a pro-fibrotic environment in the developing rat kidney.

Proper and timely assembly of the kidney vasculature with their respective nephrons is crucial during normal kidney development. In this study, we investigated the effects of enalapril (angiotensin-converting enzyme inhibitor) on angiogenesis-related gene expression and microvascular endothelium related to glomeular and tubular changes in the neonatal rat kidney. Enalapril-treated rats had higher tubular injury scores and lower glomerular maturity grades than those of untreated rats. In the enalapril-treated group, intrarenal angiopoietin-2, Tie-2, and thrombospondin-1 protein expression increased, whereas intrarenal angiopoietin-1 protein expression decreased. JG12-positive glomerular and peritubular capillary staining was reduced in the enalapril-treated rat kidney. The number of JG12-positive capillary endothelial cells was directly correlated with glomerular maturation grade and was inversely related with the tubular injury. Our findings suggest the imbalance between pro- and anti-angiogenic factors may be implicated in the loss of capillaries in associated with impaired nephrogenesis after angiotensin II blockade in the developing rat kidney.

This study was aimed to investigate the association of candidate gene polymorphisms and obesity or overweight in young Korean children. A total of 190 Korean preschool children (96 control, 48 overweight, and 46 obese children) were genotyped for the angiotensin converting enzyme (ACE) insertion (I)/deletion (D), angiotensin II type 2 receptor (AT2) C3123A, transforming growth factor (TGF)-β1 T869C, vascular endothelial growth factor (VEGF) T460C, and tumor necrosis factor (TNF)-α G308A polymorphisms. No differences were found among the groups with respect to age, sex, birth weight, blood pressure levels, and serum concentrations of glucose and total cholesterol. Obese children showed a higher incidence of ACE DD genotype and D allelic frequency compared to the controls (odds ratio [OR], 2.7, 95% confidence interval [CI], 1.01-7.21; OR, 2.5, 95% CI, 1.49-4.19; all P < 0.05). The frequency of TC genotype and C allele in the TGF-β1 T869C polymorphism (OR, 2.08, 95% CI, 1.01-4.27; OR, 1.93, 95% CI, 1.15-3.21) and that in the VEGF T460C polymorphism (OR, 2.5, 95% CI, 1.19-5.28; OR, 2.15, 95% CI, 1.26-3.68) was also higher in obese children than in control subjects (all P < 0.05). Overweight children exhibited a higher frequency of the A allele in the AT2 C3123A polymorphism compared to the controls (OR, 1.72, 95% CI, 1.03-2.88, P < 0.05). There were no differences in the TNF-α G308A polymorphism among the groups. The ACE I/D, AT2 C3123A, TGF-β1 T869C, and VEGF T460C polymorphisms can affect susceptibility to obesity or overweight in Korean children., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

The phenotypic combination of steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) and sensorineural hearing loss has been mainly reported in patients with mitochondrial cytopathies, including primary coenzyme Q10 (CoQ10) deficiency. In this report of 10 children with SR-FSGS and sensorineural hearing loss, we found 6 patients with biallelic COQ6 mutations. Median age at the onset of nephrotic syndrome was 29 (range, 15-47) months. All patients progressed to end-stage renal disease within a median of 13 (range, 1-27) months after the onset. Kidney biopsy revealed abnormal mitochondrial proliferation in podocytes in all 6 patients. None of the 5 patients who underwent kidney transplantation developed recurrence of FSGS. Primary CoQ10 deficiency due to COQ6 mutations should be considered in children presenting with both SR-FSGS and sensorineural hearing loss. An early diagnosis of COQ6 mutations is essential because the condition is treatable when CoQ10 supplementation is started at the early stage. We recommend early kidney biopsy because detection of abnormal mitochondrial proliferation in podocytes might provide an earlier diagnostic clue., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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.

Obesity-related kidney disease should be prevented or retarded. We aimed to investigate whether early treatment with enalapril ameliorates later renal injury induced by early postnatal overnutrition. Three or ten male pups per mother were assigned to either the Obese or Lean group during the first 21 days of life. These pups were treated with enalapril (Obese enalapril, OE; Lean enalapril, LE) or vehicle (Obese control, OC; Lean control, LC) for 15-28 days. Body weight, blood pressure (BP), and renal alterations were determined at 3 months. Enalapril decreased body weight only in the Lean group at 3 months (P < 0.05). Systemic BP levels were higher in the LE, OC, and OE groups than in the LC group at 3 months (P < 0.05). Fewer glomeruli per section area were found in the LE, OC, and OE groups than in the LC group and in the OE group than in the OC group (P < 0.05). The LE and OE groups had higher index scores of glomerulosclerosis and tubulointerstitial fibrosis than the controls (P < 0.05). LE pups showed increased intrarenal angiotensin II receptor type (AT)2 and matrix metalloproteinase (MMP)-9 and decreased renin and tissue inhibitor of MMP (TIMP)-1 expression than the LC rats (P < 0.05). OE pups showed increased intrarenal AT2 and decreased AT1 and TIMP-1 expression than the OC rats (P < 0.05). In conclusion, early treatment with enalapril can induce detrimental renal effects in later life and may not be renoprotective in programmed obese adult rats. J. Cell. Physiol. 232: 447-455, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Pseudohypoaldosteronism (PHA) type 1 is a rare, heterogeneous disease characterized by hyponatremia and hyperkalemia due to mineralocorticoid resistance. The clinical features of PHA are usually failure to thrive, vomiting, and dehydration in the neonatal period. Heterozygous mutations in the Nuclear receptor subfamily 3, group C, member 2 (NR3C2) gene result in the dominant renal form of PHA type 1. Mutations in the epithelial sodium channel gene result in the more severe, recessive, systemic form of PHA type 1. Here, we describe the clinical and biochemical characteristics of three sporadic cases from two Korean families diagnosed with the renal form of PHA type 1. Mutation analysis of the NR3C2 gene revealed one novel mutation in twin patients and two functional polymorphisms in one patient with unusual clinical symptoms. Our data contribute to a better understanding of the distinct mutations and clinical manifestations of the renal form of PHA type 1., (© 2017 by the Association of Clinical Scientists, Inc.)

Eosinophilic gastroenteritis is a rare disease characterized by prominent eosinophilic tissue infiltration of the gastrointestinal tract. Here, we report a case of eosinophilic gastroenteritis in an 18-year-old patient with prolonged nephrotic syndrome who presented with abdominal pain and peripheral hypereosinophilia. During the previous 2 years, he had visited local Emergency Department several times because of epigastric pain and nausea. He had been treated with steroid-dependent nephrotic syndrome since 3 years of age. Tests ruled out allergic and parasitic disease etiologies. Gastroduodenoscopy with biopsy revealed marked eosinophilic infiltration in the duodenum. Renal biopsy findings indicated minimal change disease spectrum without eosinophilic infiltration. The oral deflazacort dosage was increased, and the patient was discharged after abdominal pain resolved. To our knowledge, this is the first report of eosinophilic gastroenteritis in a patient with minimal change disease., Competing Interests: No potential conflict of interest relevant to this article was reported.

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population., Competing Interests: The authors have no potential conflicts of interest to disclose.

Objectives: To compare the diffusion parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) between the "reflux" and the "non-reflux" kidneys, and to evaluate the feasibility of using IVIM DWI to predict vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI)., Methods: Eighty-three kidneys from 57 pediatric patients with a UTI were classified into "reflux" and "non-reflux" groups according to voiding cystourethrography (VCUG) results. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (PF) were measured and compared in the renal pelvis of both groups. Four indices (D*/ADC, PF/ADC, D*/D, and PF/D) were calculated and receiver operating characteristic (ROC) curve analyses were performed., Results: VURs were detected on VCUG in 21 kidneys. PF and D* were significantly higher in the "reflux" group than in the "non-reflux" group. The indices were all significantly higher. The PF/D index showed the best diagnostic performance in predicting VUR in children with UTI (Az = 0.864)., Conclusion: PF and D* were significantly higher in the "reflux" kidney than in the "non-reflux" kidney. Our new index (PF/D) could prove useful for predicting VUR., Key Points: • IVIM DWI is both radiation-free and contrast media-free. • IVIM DWI index is easily calculated by combining diffusion parameters. • IVIM DWI may help predict VUR in children with UTI. • PF is significantly higher in the "reflux" than the "non-reflux" kidneys. • A new VUR index, PF/D could prove useful for predicting VUR.

Purpose: Foreign body (FB) ingestion is common in children, and button battery (BB) ingestion has been increasing in recent years. This study was to identify factors related to outcomes of FB ingestion, particularly BBs in the stomach. We evaluated whether the current recommendations are appropriate and aimed to suggest indications for endoscopic removal of BB in the stomach in young children., Methods: We investigated patient age, shape, size, location of FBs, spontaneous passage time and resulting complications among 76 children. We observed types, size, location of BB and outcomes, and analyzed their associations with complications., Results: Coins and BB were the two most common FBs. Their shapes and sizes were not associated with the spontaneous passage time. Size, spontaneous passage time, and age were also not associated with any specific complications. For BB ingestion, all 5 cases with lithium batteries (≥1.5 cm, 3 V) presented moderate to major complications in the esophagus and stomach without any symptoms, even when the batteries were in the stomach and beyond the duodenum, while no complications were noted in 7 cases with alkaline batteries (<1.5 cm, 1.5 V) (p=0.001). All endoscopies were conducted within 24 hours after ingestion., Conclusion: The type and voltage of the battery should be considered when determining whether endoscopy is required to remove a BB in the stomach. For lithium battery ingestion in young children, urgent endoscopic removal might be important in order to prevent complications, even if the child is asymptomatic and the battery is smaller than 2 cm.

Purpose: Nephrogenesis is normally accompanied by a tightly regulated and efficient vascularization. We investigated the effect of angiotensin II inhibition on angiogenesis in the developing rat kidney., Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle (control) for 7 days after birth. Renal histological changes were checked using Hematoxylin & Eosin staining. We also investigated the intrarenal expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), VEGFR2, platelet-derived growth factor (PDGF)-B, and PDGF receptor-β with Western blotting and immunohistochemical staining at postnatal day 8. Expression of the endothelial cell marker CD31 was examined to determine glomerular and peritubular capillary density., Results: Enalapril-treated rat kidneys showed disrupted tubules and vessels when compared with the control rat kidneys. In the enalapril-treated group, intrarenal VEGF-A protein expression was significantly higher, whereas VEGFR1 protein expression was lower than that in the control group (P<0.05). The expression of VEGFR2, PDGF-B, and PDGF receptor-β was not different between the 2 groups. The increased capillary CD31 expression on the western blots of enalapril-treated rat kidneys indicated that the total endothelial cell protein level was increased, while the cortical capillary density, assessed using CD31 immunohistochemical staining, was decreased., Conclusion: Impaired VEGF-VEGFR signaling and altered capillary repair may play a role in the deterioration of the kidney vasculature after blocking of angiotensin II during renal development.

Purpose: To evaluate the practical applications of the diagnosis algorithms recommended by the American Academy of Pediatrics urinary tract infection (UTI) guideline., Methods: We retrospectively reviewed the medical records of febrile UTI patients aged between 2 and 24 months. The patients were divided into 3 groups: group I (patients with positive urine culture and urinalysis findings), group II (those with positive urine culture but negative urinalysis findings), and group III (those with negative urine culture but positive urinalysis findings). Clinical, laboratory, and imaging results were analyzed and compared between the groups., Results: A total of 300 children were enrolled. The serum C-reactive protein level was lower in children in group II than in those in groups I and III (P<0.05). Children in group I showed a higher frequency of hydronephrosis than those in groups II and III (P<0.05). However, the frequencies of acute pyelonephritis (APN), vesicoureteral reflux (VUR), renal scar, and UTI recurrence were not different between the groups. In group I, recurrence of UTI and presence of APN were associated with the incidence of VUR (recurrence vs. no recurrence: 40% vs.11.4%; APN vs. no APN: 23.3% vs. 9.2%; P<0.05). The incidence of VUR and APN was not related to the presence of hydronephrosis., Conclusion: UTI in febrile children cannot be ruled out solely on the basis of positive urinalysis or urine culture findings. Recurrence of UTI and presence of APN may be reasonable indicators of the presence of VUR.

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.

Background: The identification of acute pyelonephritis (APN) is still a challenge., Methods: Patients admitted for their first urinary tract infection (UTI) were enrolled. Plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at admittance and after treatment. Laboratory, clinical, and imaging results were compared between children with and without APN., Results: A total of 123 patients were enrolled (53 APN and 70 lower UTI). After adjusting for age and gender, plasma NGAL levels were higher in the APN group than in the lower UTI group (233 (129-496) ng/ml vs. 71 (50.8-110) ng/ml, P < 0.001). NGAL levels were correlated with the serum levels of leukocytes, C-reactive protein, and creatinine, as well as fever duration (P < 0.05). Multivariable analysis revealed that log-transformed plasma NGAL was an independent predictor of APN (P < 0.05). Receiver operating curve analysis showed a good diagnostic profile of NGAL for identifying APN (area under the curve 0.864) with a best cut-off value of 102.5 ng/ml. The NGAL levels in both two groups decreased after treatment compared to levels before treatment (P < 0.001)., Conclusion: Plasma NGAL can be a sensitive predictor for identifying APN and monitoring the treatment response of pediatric UTI.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes., Methods: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test., Results: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively., Conclusions: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children., (© 2014 Japan Pediatric Society.)

Objective: We investigated whether enalapril treatment could have beneficial effects on nutritionally-programmed renal changes in postnatally overfed young rats., Methods: Three or 10 male pups per mother were assigned to either the Obese or Lean groups during the first 21 days of life. These pups were treated with enalapril (Obese enalapril, OE; Lean enalapril, LE) or vehicle (Obese control, OC; Lean control, LC) between 15 and 28 days. All pups had their kidneys examined at 29 days., Results: OC pups weighed more than those in the LC group between 7 and 28 days of age (P<0.05). Enalapril reduced body weights in rats from both the Obese and Lean groups between 22 and 28 days (P<0.05). Renal cell proliferation and apoptosis, glomerulosclerosis, and tubulointerstitial fibrosis were all increased by enalapril (P<0.05). Among the groups, renal cell apoptosis and serum creatinine were the highest in OE pups (P<0.05). Enalapril treatment resulted in contrasting molecular expression profiles involved in renal maturation and repair in the kidneys of the rats from the Lean and Obese groups., Conclusion: Enalapril can differentially modulate renal molecular alterations in lean and postnatally overfed rats and may be not beneficial in obese young male rats., (Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

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.

Purpose: To compare intravoxel incoherent motion diffusion weight imaging IVIM-DWI MRI with DMSA for the evaluation of cortical defect in pediatric upper urinary tract infection (UTI) patients., Materials and Methods: Forty-three kidneys of 22 pediatric patients with the first episode of febrile upper UTI were evaluated. DWI using IVIM model was performed with eight b factors. The presence of cortical defect was evaluated on apparent diffusion coefficient (ADC) map. DMSA was used as the standard of reference. ADC, true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (F) in both defect and nondefect area were calculated and compared., Results: Cortical defects were detected in 14 kidneys by IVIM-DWI. The sensitivity, specificity, positive predictive value, and negative predictive value of IVIM-DWI MRI for the detection of defects was 93.3%, 100%, 100%, and 96.5%, respectively. Mean values of ADC, D, D*, and F were 1.12 ± 0.15, 1.05 ± 0.10, 33 ± 17 (× 10(-3) mm(2) /s), and 0.14 ± 0.09 in the defect foci. In normal foci, ADC, D, D*, and F were 1.37 ± 0.09, 1.31 ± 0.10, 43 ± 19 (× 10(-3) mm(2) /s), and 0.12 ± 0.04, respectively. ADC and D were significantly lower in defect group than nondefect group (P < 0.01)., Conclusion: IVIM-DWI can allow both direct visualization and quantitative measurement of cortical defects., (© 2013 Wiley Periodicals, Inc.)

Objective: To determine the relationship between obesity and febrile urinary tract infection (UTI) in young children., Methods: We reviewed all medical records of children aged <3 years who visited our institution for febrile UTIs and infant national health checkups (controls) between January 2008 and February 2012. All subjects were subcategorized into 3 groups of lean, overweight, and obese using weight-for-length measurements. The effect of obesity on UTI risk was evaluated and odds ratios were calculated., Results: We analyzed 465 patients with UTIs and 812 controls. The proportion of overweight and obese children was higher in patients with UTIs (22.8%) and acute pyelonephritis (APN; 31.1%) compared with those in the control (11.7%; P <.05). After adjusting for age and gender, the odds ratio (OR) of UTI in obese relative to lean children was 1.84 (95% confidence interval [CI], 1.11-3.05) and that of APN was 2.43 (95% CI, 1.27-4.62). The OR of APN in overweight relative to lean children was 1.96 (95% CI, 1.11-3.46). After adjusting for age, the OR of APN in obese relative to lean boys was 2.74 (95% CI, 1.11-6.77) and that in overweight to lean girls was 2.48 (95% CI, 1.05-5.83). Within patients with UTIs, compared with lean children, the obese showed a longer duration of fever and a higher frequency of APN and the overweight had a higher incidence of hydronephrosis (P <.05)., Conclusion: Obesity may be associated with higher odds of a febrile UTI and APN in young children., (Copyright © 2014 Elsevier Inc. All rights reserved.)

There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children ≤ 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of the patients received oseltamivir monotherapy. The mean treatment-related charges for hospitalizations treated with antibiotics, alone or with oseltamivir, were significantly higher than those treated with oseltamivir-only (P < 0.001). Influenza patients treated with antibiotics-only and antibiotics/oseltamivir combination therapy showed 44.9% and 28.2%, respectively, longer duration of hospitalization compared to those treated with oseltamivir-only. Patients treated with antibiotics, alone or combined with oseltamivir, were associated with longer hospitalization and significantly higher medical charges, compared to patients treated with oseltamivir alone. In Korea, there is a need for more judicious use of antibiotics, appropriate use of influenza rapid testing.

Background: We evaluated the influence of postnatal early overnutrition on renal pathophysiological changes in aging rats., Methods: Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (control) groups, respectively, during the first 21 d of life. The effects of early postnatal overnutrition were determined at 12 mo., Results: SL rats weighed more than controls between 4 d and 6 mo of age (P < 0.05). However, between 6 and 12 mo, body weights in both groups were not different. In the SL group, at 12 mo, systolic blood pressure was higher and creatinine clearance was lower than the same in controls (P < 0.05). Numbers of CD68 (ED1)-positive macrophages and apoptotic cells in renal cortex were higher in SL rats (P < 0.05). Furthermore, index scores for glomerulosclerosis and tubulointerstitial fibrosis were higher in the SL group (P < 0.05). Significantly less glomeruli per section area were found in aging SL rats (P < 0.05). Immunoblotting and immunohistochemistry showed decreased intrarenal renin expression in SL rats (P < 0.05)., Conclusion: Early postnatal overnutrition can potentiate structural and functional abnormalities in the aging kidney and can lead to systolic hypertension with reduced intrarenal renin activity.

Objective: To assess the reliability and negative predictive value of voiding cystourethrogram (VCUG) performed within 24 hours postoperatively., Methods: Forty patients (56 ureters) who underwent first injection of dextranomer/hyaluronic acid (Dx/HA) because of vesicoureteral reflux (VUR) were enrolled. Patients with previous reflux operation or neurogenic disorders were excluded. All patients underwent the hydrodistention implantation technique (HIT). Patients underwent VCUG within 24 hours postoperatively and after 6 months. Grade 0 and grade 1 were considered to be cured. Negative predictive values of VCUG performed within 24 hours postoperatively were assessed., Results: The mean age of the patient was 98 ± 45.8 months. Twenty-seven patients were male and 13 patients were female. The number of refluxing ureters was 4, 12, 14, 12, and 14 in ascending order of VUR grade. Overall success rate of single injection therapy was 66.07%. Only 2 ureters with grade IV and 1 patient with grade V VUR showed failure on 24-hour VCUG. The success rates on 6 months VCUG were 100%, 83.3%, 78.57%, 50%, and 42.85% according to ascending order of VUR grade.The negative predictive value of 24-hour VCUG were 100%, 83.3%, 78.57%, 60.0%, and 46.15% according to ascending order of VUR grade. VUR grade was the only factor associated with the discrepancy. Positive but weak correlation was noted between the preoperative grade of VUR and the rate of discrepancy on Spearman correlation analysis (Spearman correlation coefficient = 0.303, P value = .018)., Conclusion: Twenty-four hour VCUG cannot replace follow-up VCUG usually performed beyond 3 months postoperatively. Further studies are needed for confirmation of cure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Accelerated growth in early infancy has been associated with later cardiovascular and metabolic diseases. We investigated the influence of overnutrition during neonatal periods on the development of renal pathophysiological changes in adult offspring rats. Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (NL) control groups during the first 21 days of life. The effects of early postnatal overnutrition on body weight, blood pressure and renal changes were determined at 3 and 6 months. Pups in the SL group weighed more than controls between 7 days and 6 months of age (P<.05). In the SL group, serum creatinine levels were higher at 3 and 6 months (P<.05), and at 6 months, blood pressure levels were higher than those of the controls (P<.05). The number of ED-1 positive macrophages in renal cortex and glomerulosclerosis index increased in the SL group at 3 and 6 months (P<.05). Additionally, cortical apoptotic cells increased in the SL group at 6 months (P<.05). Immunoblotting and immunohistochemistry showed that matrix metalloproteinase (MMP)-9 protein expressions decreased and tissue inhibitor of MMP-1, tumor necrosis factor-α, osteopontin and adiponectin expressions increased in the SL group at 3 months (P<.05). However, at 6 months, MMP-9 expression was elevated, and osteopontin expression remained elevated in the SL group (P<.05). Early postnatal overfeeding can lead to lasting overweight, hypertension and renal dysfunction and place a greater burden on the kidney., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Various forms of hypogammaglobulinemia can occur in patients with autoimmune diseases and vice versa. We report a 13-yr-old boy with membranous nephropathy and common variable immunodeficiency. He presented with the nephrotic syndrome, pneumonia with bronchiectasis, and profound hypogammaglobulinemia. Renal biopsy showed diffusely thickened glomerular capillary walls with 'spikes' suggesting a membranous nephropathy. Secondary causes were ruled out by laboratory studies; however, heavy proteinuria persisted with steroid therapy. Cyclosporine and intravenous immunoglobulin were added, and the patient was discharged with decreased proteinuria. Hypogammaglobulinemia may have a deleterious impact on the immune dysregulation in some patients with membranous nephropathy.

Overnutrition during the perinatal period has been associated with susceptibility to obesity and related comorbidities. We examined the effects of postnatal early overnutrition on the development of juvenile obesity and the associated renal pathophysiological changes. Three or 10 pups per mother from rat pup litters were assigned to either the overnutrition or control groups during the first 21 days of life. The effects of overfeeding were measured at 28 days. The smaller male litter pups were heavier than the controls between 4 and 28 days after birth (P<.05). By 28 days of age, the kidney weight per body weight ratio decreased in the small litter group (P<.05). Circulating leptin levels increased in the small litter rats (P<.05). Overnutrition had no effect on renal cell proliferation, apoptosis, macrophages and glomerulosclerosis. In the immunoblots and immunohistochemistry, renin and angiotensin II type (AT) 2 receptor expression increased in the overfed rats (P<.05). By contrast, the plasminogen activator inhibitor (PAI)-1 and matrix metalloproteinase (MMP)-9 expression decreased in the overnutrition group (P<.05). The AT 1 receptor, tissue inhibitor of MMP-1, monocyte chemoattractant protein-1, tumor necrosis factor-α, osteopontin and adiponectin expression was not changed. Our data showed that postnatal early overfeeding led to hyperleptinemia, juvenile obesity and the acquired reset of renal maturation. Up-regulation of renin and AT2 and down-regulation of PAI-1 and MMP-9 might contribute to abnormal programming of renal growth in rats exposed to postnatal early overnutrition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We assessed the role of therapeutic delay time (TDT) in acute renal cortical scintigraphic lesion (ASL) and ultimate scar formation (USF) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux (VUR). 230 children, 90 girls and 140 boys with first febrile UTI were included. Radiologic (USG, DMSA, and VCUG), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (CBC with differential count, ANC (absolute neutrophil count), BUN, Creatinine, urine analysis, gram stain, culture, CRP and ESR) variables were analysed. DMSA was performed within 5 days and after six months. VCUG was performed after acute phase of UTI. The differences in TDT according to the presence of ASL, USF and VUR were assessed. And the correlation between ASL or USF with the duration of TDT was assessed. Of 230 patients enrolled, 142 patients had refluxing UTI and 88 patients had non-refluxing UTI. TDT was the risk factor associated with ASL and USF along with presence of VUR. TDT was longer in ASL positive group compared with the ASL negative group. Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI. The TDT was significantly shorter in USF group with the presence of VUR. Positive linear association was noted between prevalence of ASL and USF and duration of TDT. In conclusion, the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT.

Obesity during childhood increases the risk of cardiac disease, hypertension, and other complications in adulthood. We investigated the cellular and renin-angiotensin system changes of the heart in obese young rats. We used Sprague-Dawley rats and early obesity was induced by overfeeding through adjusting the number of male pups per dam during the first 28 days of life. The body weight, heart weight, blood pressure, serum glucose, and blood pressure were assessed and we performed echocardiography, proliferating cell nuclear antigen (PCNA); assessment, apoptosis and Masson's trichrome staining, and Western blotting and the results were compared between the normal litter (NL, control) and the small litter (SL, obesity). There were no differences in blood pressure and serum glucose, but the body weight increased 61.2% and the interventricular septal thickness in diastole on the echocardiography was increased in the SL. There was hyperplasia of the PCNA cells and apoptotic cells without cellular hypertrophy or change of the amount of collagen in the SL. On Western blotting, rennin, and angiotensin II type 2 receptor (AT2R) were increased without a change of angiotensin II type 1 receptor (AT1R) in the SL. Early obesity caused echocardiographically detected septal hypertrophy and an increase of cellular turnover. Renin and AT2R were upregulated without a change of AT1R and the increase of AT2R was regarded as a cardioprotective effect against the pathologic conditions caused by the early obesity.

Both the renin-angiotensin-aldosterone system (RAAS) and hypoxia are vital physiological factors involved in the control of nephrogenesis and vascularization. We investigated the relationship between RAAS and hypoxia in the developing kidney. The expression of VEGF and heme oxygenase (HO)-1 related with the oxygen was analyzed in the enalapril- or spironolactone-treated neonatal rat kidneys. Enalapril (30 mg/kg/d) or spironolactone (200 mg/kg/d) was administered to newborn rat pups for 7 d. The newborn rats were injected i.p. with pimonidazole (200 mg/kg), a marker of severe tissue hypoxia, 1 h before killing. VEGF and HO-1 protein expression was significantly increased by immunoblots and immunohistochemistry in both the enalapril- and spironolactone-treated kidneys, compared with the controls (p < 0.05). HO-1 mRNA expression was increased in the spironolactone-treated group (p < 0.05). The immunoactivity of pimonidazole was not different from that of the controls in the enalapril-treated group, whereas it was increased in the spironolactone-treated group. The results of this study indicate that aldosterone blockade or angiotensin II inhibition in the developing rat kidney up-regulated renal VEGF and HO-1 expression regardless of the hypoxic conditions and may differentially modulate VEGF and HO-1 production.

One of the major goals in investigating children with urinary tract infection (UTI) is to recognize patients at risk of further UTI-related problems. This study reports the clinical features of 19 pediatric patients with UTIs in whom associated hepatic and/or pulmonary nodules were incidentally diagnosed by the imaging tests performed for the UTI. Hepatic nodules in five patients were detected on ultrasound scans, and pulmonary nodules and both hepatic and pulmonary nodules were detected in 12 and two children by dimercaptosuccinic acid scintigraphy. The mean age of the patients was 24.5 months. Vesicoureteral reflux (VUR) was detected in nine of 17 patients (52.9%), acute pyelonephritis was identified in nine of 18 patients, and renal scarring was found in 57.1% patients with pyelonephritis. On follow-up, the hepatic and/or pulmonary nodules regressed in all patients. About 85.7% of patients experienced a recurrence of UTI within 1 year. In comparison with age- and sex-matched controls with UTIs without pulmonary or hepatic nodules, the presence of VUR and the recurrence of UTI within 1 year were higher in patients with UTIs and nodules (P<0.05). The hepatic and/or pulmonary nodules identified on the ultrasound scan and by dimercaptosuccinic acid scintigraphy may provide a valuable diagnostic marker for the proper management of patients with an UTI.

In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-beta2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-beta2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.

Background: Hypertension (HTN) is no longer viewed as an adult disease. The purpose of the present study was to understand how hypertensive children are evaluated and managed, by surveying pediatricians in Japan and South Korea., Methods: A questionnaire was mailed to 109 Japanese (JA) and 159 Korean (KO) pediatric cardiologists, pediatric nephrologists, and other pediatricians., Results: A total of 127 replies were received (response rate 47%). Most of respondents did not check blood pressure (BP) routinely in outpatient clinics (JA 77%, KO 88%). A mercury sphygmomanometer was the most commonly used method for BP measurements (JA 72%, KO 62%). BP treatment goals were usually set at the 95th percentile for age, gender, and height (JA 47%, KO 54%). More KO used a lower goal in children with primary HTN than JA. KO respondents preferred angiotensin-converting enzyme inhibitors (ACEI) as initial agents regardless of underlying diseases whereas JA respondents chose various medications, that is, calcium channel blockers, diuretics, and ACEI. For BP monitoring, self-monitoring was found to be most frequent in both countries (JA 80%, KO 57%). Ambulatory BP monitoring was not frequently utilized in both countries (JA 33% KO 34%)., Conclusion: The current assessment, management and differing trends in pediatric HTN in Japan and Korea have been identified in the present study. Pediatricians should be aware of the growing implications of HTN in children.

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.