Prevalence of Vesicoureteral Reflux in Children with Urinary Tract Infection.

Vesicoureteral reflux (VUR) is reported in 30%-50% of children affected by urinary tract infection (UTI). We aimed to investigate the frequency of VUR in children presenting with UTI and the changes in its prevalence from birth up to 18 years. This research was an observational retrospective study in the nephrology clinic of an academic tertiary hospital during 2003-2016. Patients with UTI subjected to direct cystourethrography were enrolled (908 patients, 86.23% of girls and 13.77% of boys). They were aged from 3 days to 214 months (33 ± 33.2 months). VUR was observed in 419 of 908 (46.14%) cases. High-grade VUR (VUR Grades IV-V) and VUR were significantly more prevalent in boys (P = 0.001 for both). Only 9.2% of the VUR subjects were diagnosed after 5 years of age. The patients with VUR developed UTI at a significantly younger age compared with those without VUR (P = 0.0001). Abnormal kidney ultrasound results were significantly more common in patients with VUR than in those without VUR (P = 0.0001). The prevalence of VUR in the 1st, 2nd, 3rd, 4th, and 5th years of life was estimated to be 56.64%, 48.2%, 49.46%, 35.8%, and 45.07%, respectively. The highest and lowest VUR prevalence was 56.64% (1st year of life) and 0% (13-18 years). In addition, severe VUR was not an uncommon finding, and affected 10.7% of the total population. The results indicated a decrease in the prevalence of VUR with increased age when considering the five main age subgroups of childhood.

Diagnostic Values of Kidney Ultrasonography for Vesicoureteral Reflux (VUR) and High Grade VUR.

INTRODUCTION: Vesicoureteral reflux (VUR) is a well-known risk factor for urinary tract infection (UTI). We aim to define diagnostic values of kidney ultrasonography (US) as a predictor of VUR and high grades VUR in children presented by UTI. METHODS: This retrospective study was conducted during October 2003 to 2016. Children aged ≤ 18 years with history of UTI who had underwent kidney US and direct cystography [voiding cystourethrography (VCUG) or radionuclide cystography (RNC)] enrolled in the study. Diagnostic values of hydronephrosis, hydro ureter, renal scaring, hydroureteronephrosis, decreased kidney size and abnormal kidney US for diagnosis of VUR and high grades VUR (grades IV-V) were evaluated. RESULTS: Hydro-ureter, renal scaring, and hydroureteronephrosis were significantly more prevalent in VUR+ versus VUR- cases, also in higher grades compared with lower grades (grades I-III) VUR (P < .05 for all). Additionally, hydronephrosis was more common in VUR+ compared with VUR- patients (P < .0001). As a predictor of VUR and higher grades of VUR, abnormal kidney US had the highest sensitivity (24.87% and 40.84%, respectively), abnormal kidney US and hydro ureter reached the highest NPV (70.42% and 81.27%, respectively), hydroureteronephrosis and hydro ureter showed the highest accuracy (68.51% and 82.21%, respectively) . CONCLUSION: Kidney US is a valuable screening test, abnormal renal US significantly increases the probability of VUR and high grades VUR , but if used as the only screening test , about 2/3 and 1/3 and 20% of VUR , high grades VUR and grade V VURs will be missed. DOI: 10.52547/ijkd.5966.

A Case of Recurrent Urinary Tract Infections With Neurogenic Bladder Due to Spinal Tumors.

Neuroblastic tumors are the most common extracranial solid tumors in children. They are manifested by different clinical presentations ranging from cord compression symptoms to asymptomatic cases. A 2.5-year girl with a history of vaginal delivery at 39 gestational weeks and low Apgar score presented by repeated episodes of urinary tract infections and progressive paraplegia started at the age of 8 months. Brain MRI and EEG were normal. Voiding cystourethrography revealed grade II vesicoureteral reflux in the left kidney. Lumbar MRI with and without contrast showed a dumbbell shape mass, the hyper signal in T2 -weighted image and low signal in T1 -weighted image, extramedullary, and intramural with mass effect on the cord. Microscopic examination of tissue obtained by surgery reported ganglioneuroma. Our case was interesting because of her presentation, neurogenic bladder associated with repeated episodes of urinary tract infections, and secondary paraplegia. Neurogenic bladder dysfunction is rarely reported in cases with ganglioneuroma.

p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and neck squamous cell carcinoma cells.

The platinum-based DNA damaging agent cisplatin is used as a standard therapy for locally advanced head and neck squamous cell carcinoma (HNSCC). However, the mechanisms underpinning the cytotoxic effects of this compound are not entirely elucidated. Cisplatin produces anticancer effects primarily via activation of the DNA damage response, followed by inducing BCL-2 family dependent mitochondrial apoptosis. We have previously demonstrated that cisplatin induces the expression of proapoptotic BCL-2 family protein, Noxa, that can bind to the prosurvival BCL-2 family protein, MCL-1, to inactivate its function and induce cell death. Here, we show that the upregulation of Noxa is critical for cisplatin-induced apoptosis in p53-null HNSCC cells. This induction is regulated at the transcriptional level. With a series of Noxa promoter-luciferase reporter assays, we find that the CRE (cAMP response element) in the promoter is critical for the Noxa induction by cisplatin treatment. Among the CREB/ATF transcription factors, ATF3 and ATF4 are induced by cisplatin, and downregulation of ATF3 or ATF4 reduced cisplatin-induced Noxa. ATF3 and ATF4 bind to and cooperatively activate the Noxa promoter. Furthermore, ERK1 is involved in cisplatin-induced ATF4 and Noxa induction. In conclusion, ATF3 and ATF4 are important regulators that induce Noxa by cisplatin treatment in a p53-independent manner.

Venetoclax Is Effective in Small-Cell Lung Cancers with High BCL-2 Expression.

Purpose: Small-cell lung cancer (SCLC) is an often-fatal neuroendocrine carcinoma usually presenting as extensive disease, carrying a 3% 5-year survival. Despite notable advances in SCLC genomics, new therapies remain elusive, largely due to a lack of druggable targets.Experimental Design: We used a high-throughput drug screen to identify a venetoclax-sensitive SCLC subpopulation and validated the findings with multiple patient-derived xenografts of SCLC.Results: Our drug screen consisting of a very large collection of cell lines demonstrated that venetoclax, an FDA-approved BCL-2 inhibitor, was found to be active in a substantial fraction of SCLC cell lines. Venetoclax induced BIM-dependent apoptosis in vitro and blocked tumor growth and induced tumor regressions in mice bearing high BCL-2-expressing SCLC tumors in vivo BCL-2 expression was a predictive biomarker for sensitivity in SCLC cell lines and was highly expressed in a subset of SCLC cell lines and tumors, suggesting that a substantial fraction of patients with SCLC could benefit from venetoclax. Mechanistically, we uncover a novel role for gene methylation that helped discriminate high BCL-2-expressing SCLCs.Conclusions: Altogether, our findings identify venetoclax as a promising new therapy for high BCL-2-expressing SCLCs. Clin Cancer Res; 24(2); 360-9. ©2017 AACR.

Cross-fused renal ectopia associated with vesicoureteral reflux; a case report.

Crossed renal ectopia is a rare urinary system anomaly which mostly is asymptomatic and is diagnosed incidentally. Urinary obstruction, infection, and neoplasia of the urinary system and nephrolithiasis are main complications of this anomaly. A 6-year-old boy admitted to the hospital with colicky abdominal pain and nausea. Abdominal examination revealed tenderness in right lower quadrant. Urine analysis and culture were normal. Kidney ultrasonography showed right kidney in pelvis cavity with no kidney tissue in left side. TC 99-DMSA scan demonstrated no radiotracer accumulation in the normal renal area. Radiotracer accumulation was seen in the pelvis area with a deviation to the left. Voiding cystoureterogram revealed right sided grade II vesicoureteral reflux. Severe urological anomalies in children may be asymptomatic or have nonspecific symptoms such as abdominal pain.

Urolithiasis in the First 2 Months of Life.

INTRODUCTION: There is limited data about urolithiasis in young infants. We reviewed clinical, imaging, and biochemical data of urolithiasis in the first 2 months of life. MATERIALS AND METHODS: In an 11-year period, 77 of the 1172 children diagnosed with urolithiasis (6.8%) were 60 days old and younger (64.9% boys and 35.1% girls). Routine diagnostic assessments included urinalysis and urine culture; measurement of calcium, uric acid, oxalate, and creatinine in nonfasting random urine; measurement of blood urea nitrogen and serum creatinine, sodium, potassium, calcium, and phosphorus levels; and venous blood gasometry. Urinary calculi were diagnosed using tridimensional ultrasonography with 5-MHz, 7.5-Mhz, and 10-MHz probes. RESULTS: The most common symptom was irritability (37.6%). A family history of urinary calculi was documented in 49.4% of the patients. The calculi were 0.5 mm to 6 mm in length. Eight infants (10.4%) had urinary tract infection. Hypercalciuria was found in 21 of 62 patients (33.8%). There were no cases of hyperuricosuria, hyperoxaluria, or struvite calculus. Vesicoureteral reflux was reported in 9 of 20 patients who underwent voiding cystourethrography. Two-thirds of asymptomatic and 85% of symptomatic infants were diagnosed during summer and autumn, and the peaks of calculus visits were in September, October, and November. Of 43 infants (55.8%) who were followed up (Mean, 16.2 ± 15.2 months), none needed calculus removal interventions. CONCLUSIONS: Hypercalciuria is the most common urinary metabolic abnormality in young infants with urinary calculus. Infection was not an important factor for our cohort in the pathogenesis of the disease.

Lower Urinary Tract Urological Abnormalities and Urodynamic Findings of Physiological Urinary Incontinence Versus Non-mono Symptomatic Nocturnal Enuresis in Children.

BACKGROUND: Although 98% of children attain daytime bladder control by three years of age, urinary incontinence is regarded physiological up to the fifth year of life. OBJECTIVES: This study aimed to assess whether lower urinary tract urological abnormalities and abnormal urodynamic findings are infrequent in children with physiological urinary incontinence in contrast to those with non-monosymptomatic nocturnal enuresis (NMNE). PATIENTS AND METHODS: During a three-year period (2007-2009), 66 neurologically normal children including 51 children (34 girls, 17 boys) older than five years of age with NMNE and intermittent daytime incontinence, and 15 children with physiological urinary incontinence (eight girls and seven boys) aged four to five years of age without any known urological abnormalities were enrolled in the study. Patients with neurologic deficits or known urological anomalies were excluded from the study. Kidney-bladder ultrasonography, voiding cystourethrography (VCUG), and urodynamic studies were performed to evaluate the anatomy of urinary tract and bladder function. RESULTS: Urinary tract infection was found in 23 (34.8%) children, 17 (33.3%) and 6 (40%) patients with NMNE and physiological urinary incontinence, respectively. Out of 48 patients who underwent VCUG, vesicoureteral reflux (VUR) was found in seven and eight children younger and older than five years of age, respectively. Abnormal urodynamic findings were reported in 5 (62.5%) of eight children younger than five-year-old, and 14 (63.6%) of 22 patients older than 5-year-old. CONCLUSIONS: VUR might be more frequent in children with physiological urinary incontinence than the normal population, and might be as common as NMNE with intermittent daytime incontinence.

Monosymptomatic and non-monosymptomatic nocturnal enuresis: a clinical evaluation.

BACKGROUND: Nocturnal enuresis is divided into monosymptomatic nocturnal enuresis (MNE) and non-monosymptomatic nocturnal enuresis (NMNE). This study reviews clinical and ultrasonography (US) findings in enuretic children, and compares the organic and functional pathologies of the lower urinary tract (LUT) in children with MNE to those who have NMNE. METHODS: We enrolled 111 neurologically normal children with chief complaints of enuresis in this study. Participants included 60 boys and 51 girls, aged 5 - 17 years. There were 43 (38.8%) patients diagnosed with MNE and 68(61.2)% with NMNE. Urine analysis, urine culture and kidney-bladder US were performed for patients. Some patients underwent a voiding cystoureterography (VCUG), urodynamic study (UDS), or both.  RESULTS: Patients were divided into three groups: i) MNE, ii) NMNE without daytime incontinence (NMNE - daytime incontinence), and iii) NMNE plus daytime incontinence (NMNE + daytime incontinence). Constipation (P = 0.011), encopresis (P = 0.003) and urge incontinence (P = 0.001) were significantly more frequent in patients with NMNE +daytime incontinence. Bladder wall thickness (BWT) was the most common US finding. One patient with MNE and 9 with NMNE+ daytime incontinence had vesicoureteral reflux (VUR; P = 0.016). Posterior urethral valve (PUV) was reported in one patient with NMNE.  Evidence of bladder dysfunction was noted in about half of the patients who underwent UDS, with a higher prevalence in cases that had NMNE +daytime incontinence (P = 0.297). Bowel symptoms and VUR were significantly more prevalent in cases with NMNE + daytime incontinence.  CONCLUSION: We recommend VCUG in enuretic children who have daytime incontinence. In addition our study has revealed that symptoms suggestive of an overactive bladder (OAB) are not good indicators for bladder dysfunction.

Association of nocturnal enuresis with vesicoureteral reflux and renal cortical damage.

BACKGROUND: The prevalence of vesicoureteral reflux (VUR) is higher in enuretic children than in non-enuretic children. Recent studies have reported VUR in 6-23% of children with enuresis. OBJECTIVES: To clarify the association of nocturnal enuresis with vesicoureteral reflux (VUR) and to identify children who are at risk for VUR. PATIENTS AND METHODS: During 2007-2009, neurologically normal children who were referred with a chief complaint of nocturnal enuresis and had abnormal renal ultrasonography (US) results, daytime incontinence, abnormal results in urodynamic studies, urinary tract infection, or a history of VUR in their siblings were prospectively evaluated for VUR by voiding cystourethrography (VCUG). RESULTS: A total of 60 children (26 boys and 34 girls) aged 5-17 (mean ± SD: 8.46 ± 2.45) years met the inclusion criteria and were enrolled in the study. Twenty-eight (46.7%) patients had mono-symptomatic nocturnal enuresis (MNE), and 32 (53.3%) had non-mono symptomatic nocturnal enuresis (NMNE). VUR was reported in 10 (16.7%) patients and posterior urethral valve (PUV) was found in 1 (1.7%) patient. The prevalence of VUR was significantly higher in patients with daytime incontinence and in girls (P = 0.016 and 0.003 respectively). We did not find any significant correlations between VUR and the form of enuresis (primary versus secondary), urinary tract infection, or any diurnal urinary symptoms other than daytime incontinence (P > 0.05 for all). of 10 renal scintigrams, 5 (50%) showed renal cortical defects. CONCLUSIONS: VUR is uncommon in children with MNE and in those with NMNE who do not wet themselves during the day; however, it is a relatively common finding in enuretic children who have daytime incontinence. We recommend VCUG in all enuretic children who have daytime incontinence.

Comparison between patient dose arising from photofluorographic and standard fluoroscopic voiding cystourethro graphy in children with urinary tract infection [corrected].

BACKGROUND: Imaging of the urinary system is considered to be responsible for significant radiation in children. OBJECTIVES: This study was conducted to measure and compare the radiation dose in spot films with photofluorography voiding cystourethrography (VCUG) in children. PATIENTS AND METHODS: 111 [222 Kidney Urinary Unit (KUU)] pediatric patients, aged 1 month to 5 years, with symptomatic urinary tract infection were enrolled in the study. Peak tube voltage (kVp), exposure setting (mAs), focus film distance (FFD), film size and DAP (after the exam) were recorded for all patients. To evaluate the validity of the photographs, we calculated sensitivity, specificity, predictive values and agreement between the two methods using the kappa statistic. If the kappa was greater than 0.75, between 0.4-0.75 or less than 0.4, then the agreement was excellent, good or poor, respectively. P values less than 0.05 were statistically significant. RESULTS: Vesicoureteral reflux (VUR) was detected in 74 KUU (33.3%) in standard films and in 71 (32%) in photographic images. The photographs had no false positives and 3 false negatives. Therefore, the new method had a sensitivity of 96%, a specificity of 100%, a negative predictive value of 98% and a positive predictive value of 100%. The two-method agreement in the VUR diagnosis for grades 1, 4, 5 and the overall grading were excellent (kappa > 0.83); however, for grades 2 and 3, agreement was 80%, which was good (kappa = 0.64). CONCLUSIONS: Our study suggests that the high validity and excellent agreement of the photofluorography method in the diagnosis and grading of VUR, which is comparable to spot films and represents a 50%-90% reduction in radiation, makes it the preferred method.

Metabolic factors associated with urinary calculi in children.

INTRODUCTION: We aimed to identify metabolic and anatomical abnormalities present in children with urinary calculi. MATERIALS AND METHODS: Metabolic evaluation was done in 142 pediatric calculus formers. Evaluation included serum biochemistry; measurement of daily excretion of urinary calcium, uric acid, oxalate, citrate, and magnesium (in older children); and measurement of calcium, uric acid, oxalate, and creatinine in random urine samples in nontoilet-trained patients. Urinary tests for cystinuria were also performed. All of the patients underwent renal ultrasonography. RESULTS: Sixty-one patients (42.7%) had metabolic abnormalities. Anatomical abnormalities were found in 12 patients (8.4%). Three children (2.1%) had infectious calculi, and 3(2.1%) had a combination of metabolic and anatomic abnormalities. In 66 children (46.2 %) we did not find any reasons for calculus formation (idiopathic). Urinalysis revealed hypercalciuria in 25 (17.6%), hyperuricosuria in 23 (16.1%), hyperoxaluria in 17 (11.9%), cystinuria in 9 (6.3%), hypocitraturia in 3 (2.1%), and low urinary magnesium level in 1 (0.7%) patients. Sixteen patients (11.2%) had mixed metabolic abnormalities. CONCLUSIONS: Metabolic abnormalities are common in pediatric patients with urinary calculi. In our study, calcium and uric acid abnormalities were the most common, and vesicoureteral reflux seemed to be the most common urological abnormality which led to urinary stasis and calculus formation.

Five cases of severe vesico-ureteric reflux in a family with an X-linked compatible trait.

Vesico-ureteric reflux (VUR) is one the most common inherited disorder in humans. Even though this defect is common among siblings and parents of index patients (27-40%), the mode of inheritance is not well defined. Parents and siblings (three female and two male) of a 13-year-old girl with end-stage renal failure (ESRF) due to reflux nephropathy were screened for VUR although they had not presented episodes of urinary tract infection. VUR was identified in the father (44 years old) and in all the three sisters (aged 15 years, 16 years and 18 years) while the two brothers (aged 5 years and 8 years) had normal renal ultrasonograms and cystograms. A technetium-99m di-mercapto-succinic acid ((99m)Tc-DMSA) scan demonstrated renal scars in the father and in two of the sisters with VUR. No episodes of urinary infection had been documented for any relatives. Haplotype analysis on the X-chromosome confirmed paternity. This is the first description of VUR compatible with an X-dominant trait. This mode of inheritance must be added to what is already known on familial VUR, and future studies should also consider this possibility.

The outcome of Iranian children on continuous ambulatory peritoneal dialysis: the first report of Iranian National Registry.

BACKGROUND: Continuous ambulatory peritoneal dialysis is not a very common modality to treat Iranian children with end-stage renal disease; however, there is sometimes no choice but to offer this therapy to salvage the patient. Obviously, promotion in each program needs re-evaluation to find the pitfalls. Therefore, a nation-wide survey on pediatric continuous ambulatory peritoneal dialysis was conducted to find the cause of death or termination of dialysis. METHODS: All children, younger than 14 years old, treated by continuous ambulatory peritoneal dialysis in nine main pediatric nephrology wards in Iran between 1993 and 2006 were included in this historical cohort study. Patient and technique survival rates were determined. Kaplan-Mayer and Cox-regression analysis were used to compare the survival. 2 x 2 table was used to calculate the risk ratio. A P<0.05 was considered significant. RESULTS: One hundred twenty children with a mean age of 47.6 months were on continuous ambulatory peritoneal dialysis. The most frequent cause of renal failure was hereditary-metabolic-cystic disease. One hundred eighty-two peritoneal dialysis catheters were inserted surgically. The median first catheter exchange was 0.74 year (95%CI: 0.5 - 0.98). The most frequent cause of catheter replacement was catheter outflow failure due to displacement, adhesion, and infection (persistent peritonitis or tunnel infection). The mean patient survival was 1.22 years (95%CI: 0.91 - 1.53). The mortality rate was 55% before 1997, and 60% between 1998 and 2001, which declined to 23% after 2002 (P<0.05). Young age (<24 months) was the only independent factor that predicted mortality (P<0.05). The outcome of children was as follows: recovery of renal function (6.7%), renal transplantation (8.3%), switch to hemodialysis (16.7%), still on continuous ambulatory peritoneal dialysis (23.3%), death (43.3%), and lost to follow-up (1.7%). CONCLUSION: The mortality is still high among Iranian children on peritoneal dialysis. Young age is the most important factor influencing on survival and mortality.