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A 2-month-old Taiwanese term baby boy was referred to us for feeding intolerance and failure to thrive. He weighed 2700 g at birth but only gained 600 g in 2 months (

BACKGROUND: Deferasirox (DFRA) is a new approved oral iron chelator. Its advantages are that it is convenient and better tolerated and adhered to due to “once-daily” oral dosage. However, its use in the field is limited and it is yet to be subjected to postmarketing surveillance. CASE REPORT: A 18.75-year-old male with β-thalassemia major received oral DFRA therapy due to transfusional iron overload for 27 months. He had received iron chelation therapy with deferoxamine injection together with oral deferiprone. However, his compliance was poor (very high routine serum ferritin level, ranging from 1059 to 6030 ng/mL). After 25 months of DFRA therapy, the serum ferritin level declined from 4097 to 1343 ng/mL. He experienced five hospital admissions including coma, Fanconi syndrome, hepatic dysfunction, and thrombocytopenia after using DFRA as oral iron chelator. After we discontinued DFRA, he recovered fully without hepatic dysfunction, thrombocytopenia, proteinuria, glucosuria, and hypophosphatemia. CONCLUSIONS: Our case illustrates the potential risks of DFRA-induced renal toxicity, hepatic dysfunction, and thrombocytopenia. Meticulous monitoring of kidney, liver, and hematopoietic function is mandatory for patients undergoing treatment with DFRA. Further investigation of the potential risk and adverse effects of long-term DFRA use is necessary.

Background: Despite recent advances in molecular epidemiology and pathogenecity analyses of extraintestinal Escherichia coli infections, detailed analyses identifying virulence factors of E. coli isolates from pediatric urosepsis patients have not been reported. This study was conducted to explore and differentiate bacterial virulence factors associated with urosepsis and 2 other severe parenchymal infections, acute pyelonephritis (APN) and acute lobar nephronia (ALN), in pediatric patients. Methods: Patients included in this study were those who fulfilled the diagnostic criteria of urosepsis, APN, and ALN, without underlying disease or structural anomalies, excluding those with vesicoureteral reflux. Patients with cystitis were included as controls. E. coli isolates from urine (cystitis, APN, and ALN) or blood (urosepsis) specimens were analyzed using polymerase chain reaction (PCR) for 25 virulence genes. Results: A total of 147 children (24 cystitis, 45 APN, 48 ALN, and 30 urosepsis) were enrolled in the study. Distinct syndrome-specific differences in the distribution for certain virulence genes, but conservation across syndromes for others, were found. In addition, urosepsis isolates presented higher aggregate virulence factor scores (P < 0.0001) compared with cystitis, APN, and ALN isolates. By contrast, cystitis isolates showed significantly lower aggregate virulence factor scores than all 3 invasive urinary bacterial infections; APN (P < 0.01), ALN (P < 0.01), and urosepsis (P < 0.0001). Conclusions: Our findings suggested that urosepsis isolates carry more virulence factors and are likely more urovirulent compared with cystitis, APN, and ALN isolates.

Acute lobar nephronia (ALN) is a complicated acute renal infection that is part of the progression of the inflammatory process of acute pyelonephritis that can progress to renal abscess if left untreated. We examined the place of ALN in the spectrum of upper urinary tract infections.: The medical records of all patients diagnosed with ALN by computed tomography (CT) were reviewed retrospectively in terms of their demographic characteristics, clinical presentations, and laboratory findings. The patterns of the ALN lesions were checked on all contrast-enhanced CT films and the volume of the CT lesions (the extent of renal involvement) was estimated in every patient. Then, the correlation between the clinical presentation and CT lesions was examined.: Two distinct CT patterns of ALN lesions were observed in 127 patients: 94 simple ALN and 33 complicated ALN. Simple ALN appeared as striated or wedge-shaped, poorly defined regions of homogeneously decreased nephrographic density, whereas the lesions of complicated ALN showed heterogeneously decreased nephrographic density after contrast enhancement. The volume fraction of the CT lesions correlated well with the duration of fever before (P = 0.006) and after (P0.001) treatment in patients with simple ALN, while only the correlation between the fever duration after treatment and the volume fraction of the CT lesions (P0.001) was significant in patients with complicated ALN. Patients with complicated ALN were generally older (P = 0.004) and febrile longer after starting antibiotic treatment (P0.001). All treatment failures were in the complicated ALN group.: Children with ALN comprise 2 groups with different clinical presentations and treatment responses: simple ALN and complicated ALN. We suggest that simple ALN be regarded as a continuation of acute pyelonephritis and require 2 weeks of antibiotic treatment, while complicated ALN is a distinct more severe form requiring a 3-week or longer therapy regimen as the treatment of choice.

SUMMARY: Aims: To assess postnatal kidney volume development and to compare the intrauterine and extrauterine kidney growth curves of premature infants. Methods: One hundred neonates were enrolled in this study, and all infants had their kidney volumes measured by renal ultrasound examination. Group GA consisted of 44 neonates who were evaluated within 48 h after birth, and their gestational ages were used in the analysis. Group CA included 56 premature infants born before 34 weeks of gestation and was evaluated 14–96 days after birth, and their conceptional ages were used in the analysis. Left kidney volume, body weight, body height and age were used in the correlation analysis. Results: There was a better kidney growth rate for Group GA infants than for Group CA infants (P = 0.001). Kidney volumes in Group CA infants were thus apparently larger than those of the Group GA infants before 31 weeks of age, but they were smaller after 31 weeks of age. Group GA infants had a significantly faster growth in body weight (P = 0.001) and body height (P

Background: Acute lobar nephronia (ALN) is a severe renal parenchymal inflammatory disease that has been diagnosed with increasing frequency as a result of newer noninvasive diagnostic modalities. Escherichia coli is the most common bacterial pathogen isolated from the urine samples of ALN patients. This prospective study was conducted to elucidate and distinguish the bacterial virulence factors associated with ALN and acute pyelonephritis (APN) in pediatric patients. Methods: Patients included in the present study were those suspected of an upper urinary tract infection who underwent ultrasonographic, computed tomographic and technetium 99m-dimercapto-succinic acid scintigraphic evaluation to distinguish between ALN and APN. The E. coli isolates from the urine samples of patients were screened with polymerase chain reaction analysis for various urovirulence genes. Pulsed-field gel electrophoresis was used to analyze the genetic association of the isolates. Results: A total of 88 patients were enrolled. Forty-six patients were diagnosed with ALN and 42 with APN. Demographic characteristics and clinical results were similar except for longer fever duration before admission, longer fever continuation following antibiotic treatment and higher C-reactive protein values noted in the ALN group. Diverse genotypes were found among the E. coli isolates in both groups. Among the pathogenetic determinants examined, multivariate logistic regression analysis indicated that a papG II allele was the only significant urovirulence factor associated with ALN (P < 0.005; odds ratio, 17.16). This association was independent of the presence of VUR. Conclusions: While no specific genetic lineage was identified among the E. coli isolates studied, a papG II gene was found to be strongly associated with the cause of ALN among pediatric patients.

Renal abscess is a rare disease in childhood and early diagnosis is essential to minimize the renal damages. Experiences gained from this 10-year study on patients with CT-proved diagnosis include the varied clinical presentations and use of sonographic-marked nephromegaly and focal mass as indications for further CT diagnosis.

Chi-Hui Cheng1, 3, Yong-Kwei Tsau4 and Tzou-Yien Lin2, 3 1Division of Pediatric Nephrology and 2Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, Taoyuan, 3College of Medicine, Chang Gung University, Taoyuan, 4Division of Pediatric Nephrology, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

We determined whether nephromegaly on ultrasound can be used to identify patients with urinary tract infection at increased risk for renal scarring, and we investigated the effect of vesicoureteral reflux on renal scarring.We enrolled hospitalized patients with a first febrile urinary tract infection. All patients underwent renal ultrasound and most patients underwent voiding cystourethrography. Renal scarring was assessed using (99m)technetium dimercapto-succinic acid renal scintigraphy at least 6 months after treatment. Children with recurrent urinary tract infections before scintigraphy were excluded from the study.A total of 545 children (80 with and 465 without nephromegaly) were enrolled. Infection was more severe in patients with than without nephromegaly. The incidence of renal scarring was significantly higher in patients with nephromegaly (90% vs 32%, p0.001), in kidneys with nephromegaly (80.5% vs 18.7%, p0.001) and in kidneys with vesicoureteral reflux (41.5% vs 22.2%, p0.001). Kidneys with nephromegaly had a greater incidence of reflux. The finding of nephromegaly is associated with a greatly increased likelihood of renal scarring in patients with vesicoureteral reflux.Our results indicate that ultrasound diagnosis of nephromegaly at onset is associated with a high incidence of renal scarring, and identification of nephromegaly at onset and vesicoureteral reflux are significant risk factors for renal scarring in children with a first febrile urinary tract infection. Nephromegaly is associated with an increased frequency of vesicoureteral reflux and increased likelihood of renal scarring in patients with reflux.

Background: Patient susceptibility to bacterial urinary tract infections, which is determined by complex pathogen-host interactions, varies between individuals due to genetic variation. The neutrophil-dependent innate immune system is an important part of keeping the urinary tract sterile. This study was performed to explore single nucleotide polymorphisms (SNPs) in genes associated with neutrophil-dependent immunity in pediatric patients with severe parenchymal infections. Methods: The subjects included patients who fulfilled the diagnostic criteria of acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying disease or structural anomalies (excluding vesicoureteral reflux). Genotyping of the genes encoding toll-like receptor 4 (TLR-4), interleukin-8 (IL-8), and IL-8 receptors CXCR1 and CXCR2 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis. Results: A total of 17 SNPs, including missense SNPs and those located in promoter regions, were initially selected for genotyping. Only 4 SNPs with a heterozygosity rate >0.01 were evaluated further. The observed genotype frequencies satisfied Hardy-Weinberg equilibrium. Statistical analysis revealed that only IL-8 (rs4073, −251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases. Following the elimination of vesicoureteral reflux, which is a significant risk factor for severe parenchymal infection, a single SNP in IL-8 (rs4073) was found to be associated with clinically severe ALN. Conclusions: The AA genotype and A allele of the IL-8 SNP is related to patient susceptibility to parenchymal infection and is correlated with the severity of infection in pediatric APN and ALN patients, probably due to the upregulation of IL-8 expression.

Background The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. To evaluate the effect of the vaccination, we conducted an active, prospective, large-scale, long-term, and multicenter study to assess the prevalence of nasopharyngeal Streptococcus pneumoniae carriage in Taiwanese children. Methods This study was performed at three tertiary teaching hospitals in northern, central, and southern Taiwan. Questionnaires provided demographic, family/household, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and serotypes. In addition, influenza virus and Staphylococcus aureus were recovered from nasopharyngeal and nasal swabs, respectively. Results Between July 2005 and July 2008, 857 pneumococcal strains were recovered from a total of 6057 children aged >2 months to 5 years (carriage rate, 14.1%). Carriage rates differed geographically and varied with subject age. In a multivariate analysis, having at least one sibling, attendance at day-care centers, a history of otitis media, and history of upper respiratory tract infection in the previous 2 weeks were each associated with a higher risk of pneumococcal colonization of the nasopharynx. Staphylococcus aureus nasal colonization was inversely associated with nasopharyngeal carriage of pneumococcus ( p = 0.000; odds ratio [OR]: 0.48; 95% CI: 0.39–0.58). Daycare attendance was the only risk factor for carriage of penicillin non-susceptible S. pneumoniae (OR: 2.37; 95% CI: 1.22–4.88). Although vaccination rates rose from 2005 to 2008, no concomitant decrease in S. pneumoniae carriage occurred. The rate of penicillin resistance among S. pneumoniae isolates was 92.8% (using the meningitis criteria). The prevalence of cefotaxime resistance (21.6%) was higher than that of penicillin (6.9%; non-meningitis criteria). Slightly more than half (57.4%) of the isolates belonged to strains covered by the heptavalent pneumococcal conjugate vaccine when both vaccine and vaccine-related serotypes were included. Conclusions Although vaccination rates rose from 2005 to 2008, no concomitant decrease occurred in S. pneumoniae carriage. Interaction between S. aureus and S. pneumoniae may influence vaccination efficacy. These findings provide baseline data to further compare pneumococcal carriage rates and antibiotic resistance patterns in Taiwanese children as vaccination rates continue to increase.

OBJECTIVE. The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux.METHODS. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded.RESULTS. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum β-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups.CONCLUSIONS. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum β-lactamase-producing bacteria or multidrug-resistant uropathogens other than E coli for breakthrough urinary tract infections; therefore, these antibiotics are not appropriate for prophylactic use in patients with vesicoureteral reflux. Co-trimoxazole remains the preferred prophylactic agent for vesicoureteral reflux.

To measure the kidney size in children with Kawasaki disease (KD) and to delineate the condition of nephromegaly, 20 children with KD were enrolled in our study. Kidney sizes were measured during acute stage in these patients. Twenty healthy children and 15 febrile children served as healthy controls and fever controls, respectively. To delineate the possible mechanism, we also evaluated kidney volume (KV) in 13 other patients with KD during the acute phase and after the recovery phase as well as 26 healthy children. Plasma hepatocyte growth factor (HGF) and transforming growth factor-beta1 (TGF-beta1) levels were determined for all children. Kidney lengths and KV in patients with KD during the acute phase were significantly larger than those of healthy children. There was no kidney enlargement in healthy controls and after the recovery phase. The ratio of patient plasma HGF/TGF-beta1 during the acute phase and after the recovery phase correlated positively with the degree of nephromegaly in all patients. These results confirm the presence of large kidneys in children with KD. Our data also suggest that an elevated HGF/TGF-beta1 ratio may be responsible for the transient nephromegaly in these children.

OBJECTIVE. Effective treatment of acute lobar nephronia (ALN) can prevent its progression to renal abscess. The goal of this prospective study was to compare the treatment efficacy for pediatric patients who had ALN with a 3- vs 2-week intravenous plus oral antimicrobial-therapy regimen.METHODS. Patients who were suspected of having an upper urinary tract infection underwent a systematic scheme of ultrasonographic and computed tomographic (CT) evaluation for ALN diagnosis. Patients with positive CT findings were enrolled and randomly allocated with serial entry for either a total 2-week or a 3-week antibiotic treatment regimen. Antibiotics were changed from an intravenous form to an oral form 2 to 3 days after defervescence of fever. Follow-up clinical evaluations and urine-culture analyses were performed 3 to 7 days after cessation of antibiotic treatment. Patients with persistent infection or relapse were considered as treatment failures.RESULTs. A total of 80 patients with ALN were enrolled. Forty-one patients were treated with a 2-week antimicrobial protocol, and the other 39 patients were treated with a 3-week course. Seven treatment failures, 1 persistent infection, and 6 infection relapses were identified, all of which were in the 2-week treatment group. Prolonged fever before admission and positive Escherichia coli growth (>105 colony-forming units per mL) in urine culture were noted as risk factors for treatment failure. All treatment failures were managed successfully with an additional 10-day antibiotic course.CONCLUSION. A total of 3 weeks of intravenous and oral antibiotic therapy tailored to the pathogen noted in cultures should be the treatment of choice for pediatric patients with ALN.

We previously showed a positive correlation between nephromegaly and plasma hepatocyte growth factor (HGF)/transforming growth factor beta1 (TGF-beta1) ratio in children with biliary atresia. The purpose of this study is to examine the possible reversibility of nephromegaly in patients with biliary atresia.We evaluated kidney volume in 13 patients with biliary atresia before and after liver transplantation, 6 patients with hepatoblastoma, and 26 healthy children. Plasma HGF and TGF-beta1 levels were determined for all children.We noted significant nephromegaly in children with biliary atresia before liver transplantation compared with healthy children and children after liver transplantation (P0.001 and P = 0.006 for intercepts, P = 0.064 and P = 0.753 for slopes by analysis of covariance, respectively). The highest plasma HGF levels and HGF/TGF-beta1 ratios and the lowest TGF-beta1 concentrations were found in children with biliary atresia before liver transplantation (P0.001). No statistically significant nephromegaly was observed in children with biliary atresia after liver transplantation or those with hepatoblastoma despite the presence of a mildly increased plasma HGF level and HGF/TGF-beta1 ratio. Plasma HGF/TGF-beta1 ratio correlated positively with degree of nephromegaly in all patients (r = 0.717; P0.001).Our data suggest that liver transplantation reverses the nephromegaly present in children with biliary atresia and that plasma HGF/TGF-beta1 ratio may be associated with the development of nephromegaly in patients with biliary atresia.

Correct identification of acute lobar nephronia (ALN) is necessary to prevent progression to renal abscess. The goal of this retrospective study was to determine whether the sonographic finding of severe nephromegaly (i.e. renal length greater than mean + 3 sd) is a preselection criterion for computed tomographic (CT) scanning in diagnosing pediatric ALN among children with an acute upper urinary tract infection.We evaluated a new imaging work-up scheme to detect pediatric ALN. All patients with urinary tract infection were evaluated with ultrasonography. If a markedly enlarged kidney or focal mass was present sonographically, CT scanning was done immediately. CT scanning was also performed when the patient had borderline nephromegaly and remained febrile for 72 h after start of antibiotic treatment. ALN diagnosis was made on the basis of positive CT findings.Thirty patients with ALN (13 left, 7 right, 10 bilateral) and one with acute pyelonephritis were identified. ALN in all patients resolved after 3 weeks of antibiotic treatment. Thirty-nine of the 62 kidneys evaluated showed severe nephromegaly, and 10 had focal renal masses. With CT diagnosis of ALN as the reference standard, the sensitivity of severe nephromegaly was 90.0% and the specificity was 86.4%. When the focal renal mass was added as a combining predictor, the sensitivity further increased to 95%.Pediatric ALN was effectively predicted using sonographic findings of severe nephromegaly and/or focal mass before CT scanning.