Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux.

BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

Extra-Renal manifestations of atypical hemolytic uremic syndrome in children.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood. METHODS: This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded. RESULTS: The most common extrarenal manifestation was neurological system involvement (n = 46 [27.2%]), followed by gastrointestinal (n = 20 [11.8%]), cardiovascular (n = 12 [7%]), and respiratory (n = 12 [7%]) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates. CONCLUSIONS: The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.

LRIG2 mutations cause urofacial syndrome.

Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.

Mayer-Rokitansky-Küster-Hauser syndrome accompanied by renal cell carcinoma: a case report.

Mayer-Rokitansky-Küster-Hauser anomaly originates from agenesis of the Müllerian duct including agenesis of the uterus and the vagina because of abnormal development of the uterine ducts. This syndrome may be accompanied by the upper urinary tract anomalies such as unilateral renal agenesis, ectopia of 1 or both kidneys, renal hypoplasia, horseshoe kidney, and hydronephrosis. We report a 16-year-old girl, with unilateral renal agenesis, herniating ovary, and renal cell carcinoma in her solitary kidney, associated with Mayer-Rokitansky-Küster-Hauser syndrome-the first case in the literature to our knowledge.

Stricter Blood Pressure Control Is Associated With Lower Left Ventricular Mass in Children After Kidney Transplantation: A Longitudinal Analysis of the 4C-T Study.

BACKGROUND: We assessed the effect of blood pressure (BP) control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH). METHODS: Ninety-six patients (64 males) ≥9 months post-kidney transplantation from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease and Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic BP exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively. RESULTS: At baseline, LVMI was 49.7±12.7g/m2.16 with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of -5.24g/m2.16 (P=0.007). A similar tendency was seen for cumulative SBP≤50th (ß=-3.70 g/m2.16; P=0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic BP, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic BP ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03-1.07). CONCLUSIONS: Stricter BP control led to regression of LVMI and LVH. Our data suggest a BP target below the 60th pct, which needs to be substantiated in a randomized controlled trial.

Clinical characteristics and outcome of childhood vesicoureteral reflux. / Características clínicas y evolución del reflujo vesicoureteral en la infancia.

INTRODUCTION: The aim of the study was to assess the clinical features and outcome parameters of children with vesicoureteral reflux (VUR) based on gender and VUR grade. POPULATION AND METHODS: Patients with VUR who were seen during routine follow-up visits at Ankara University Children's Hospital between January 2014-January 2015 were included in this retrospective study. Patient demographics, clinical course, laboratory investigations, imaging were noted. RESULTS: Two hundred and twenty patients were recruited. Mean age at the time of diagnosis was 3,17 ± 3,08 years. Boys were diagnosed at younger ages as compared to girls (2.00 ± 2,59 vs. 3,81 ± 3.15, p < 0.001). Urinary tract infection (UTI) was the most common presentation. The second presentation form was antenatal hydronephrosis (AHN) which was more common in males (25.6 %, p < 0.001). Twenty-two percent of the patients had grade 1-2, 51 % grade 3 and 27 % grade 4-5 reflux. Patients with grade 4-5 reflux had more abnormal ultrasound (US) and Tech 99m dimercaptosuccinic acid scintigraphy (DMSA) findings and surgery was performed more frequently in this group (p < 0.001). In males, grade 4-5 reflux (43.6 % vs. 18.3 %), abnormal US (77 % vs. 54 %) and DMSA (77 % vs. 59 %) findings were more frequent (p < 0.05). In girls higher rates of UTIs, lower urinary tract dysfunction (LUTD) and spontaneous reflux resolution were seen (p < 0.05). CONCLUSIONS: Despite younger age at diagnosis, spontaneous resolution was found lower in boys and they had more frequent AHN, more severe reflux, and radiological abnormalities.

Introducción: El objetivo fue evaluar las características clínicas y la evolución del reflujo vesicoureteral (RVU) según el sexo y grado de RVU. Población y métodos: Se incluyeron pacientes con RVU vistos durante el seguimiento de rutina entre enero de 2014 y enero de 2015. Se registraron las características demográficas, la evolución, los laboratorios y las imágenes. Resultados: Se seleccionó a 220 pacientes, cuya media de edad del diagnóstico era 3,17 ± 3,08 años; en ese momento, los varones eran menores que las niñas (2,00 ± 2,59 vs. 3,81 ± 3,15, p < 0,001). La infección urinaria fue la presentación más frecuente, seguida de hidronefrosis prenatal (HNP). El 22 % de los pacientes tuvo reflujo de grado 1-2; el 51 %, de grado 3; y el 27 %, de grado 4-5. En el reflujo de grado 4-5, las ecografías y gammagrafías con ácido dimercaptosuccínico (DMSA) marcado con 99mTc presentaron más anomalías, y se realizaron más cirugías (p < 0,001). En los varones, fueron más comunes el reflujo de grado 4-5 (43,6 % vs. 18,3 %) y las anomalías ecográficas (77 % vs. 54 %) y en la DMSA (77 % vs. 59 %) (p < 0,05). En las niñas, hubo mayores tasas de infección urinaria, disfunción de las vías urinarias inferiores y resolución espontánea (p < 0,05). Conclusiones: A pesar de la menor edad al momento del diagnóstico, la resolución espontánea fue menor en los varones, y estos presentaron HNP, reflujo grave y anomalías radiológicas más frecuentemente.

Características clínicas y evolución del reflujo vesicoureteral en la infancia / Clinical characteristics and outcome of childhood vesicoureteral reflux

Introducción. El objetivo fue evaluar las características clínicas y la evolución del reflujo vesicoureteral (RVU) según el sexo y grado de RVU.Población y métodos. Se incluyeron pacientes con RVU vistos durante el seguimiento de rutina entre enero de 2014 y enero de 2015. Se registraron las características demográficas, la evolución, los laboratorios y las imágenes.Resultados. Se seleccionó a 220 pacientes, cuya media de edad del diagnóstico era 3,17 ± 3,08 años; en ese momento, los varones eran menores que las niñas (2,00 ± 2,59 vs. 3,81 ± 3,15, p < 0,001). La infección urinaria fue la presentación más frecuente, seguida de hidronefrosis prenatal (HNP). El 22 % de los pacientes tuvo reflujo de grado 1-2; el 51 %, de grado 3; y el 27 %, de grado 4-5. En el reflujo de grado 4-5, las ecografías y gammagrafías con ácido dimercaptosuccínico (DMSA) marcado con 99mTc presentaron más anomalías, y se realizaron más cirugías (p < 0,001). En los varones, fueron más comunes el reflujo de grado 4-5 (43,6 % vs. 18,3 %) y las anomalías ecográficas (77 % vs. 54 %) y en la DMSA (77 % vs. 59 %) (p < 0,05). En las niñas, hubo mayores tasas de infección urinaria, disfunción de las vías urinarias inferiores y resolución espontánea (p < 0,05).Conclusiones. A pesar de la menor edad al momento del diagnóstico, la resolución espontánea fue menor en los varones, y estos presentaron HNP, reflujo grave y anomalías radiológicas más frecuentemente.

Introduction. The aim of the study was to assess the clinical features and outcome parameters of children with vesicoureteral reflux (VUR) based on gender and VUR grade.Population and methods. Patients with VUR who were seen during routine follow-up visits at Ankara University Children's Hospital between January 2014-January 2015 were included in this retrospective study. Patient demographics, clinical course, laboratory investigations, imaging were noted.Results. Two hundred and twenty patients were recruited. Mean age at the time of diagnosis was 3,17 ± 3,08 years. Boys were diagnosed at younger ages as compared to girls (2.00 ± 2,59 vs. 3,81 ± 3.15, p < 0.001). Urinary tract infection (UTI) was the most common presentation. The second presentation form was antenatal hydronephrosis (AHN) which was more common in males (25.6 %, p < 0.001). Twenty-two percent of the patients had grade 1-2, 51 % grade 3 and 27 % grade 4-5 reflux. Patients with grade 4-5 reflux had more abnormal ultrasound (US) and Tech 99m dimercaptosuccinic acid scintigraphy (DMSA) findings and surgery was performed more frequently in this group (p < 0.001). In males, grade 4-5 reflux (43.6 % vs. 18.3 %), abnormal US (77 % vs. 54 %) and DMSA (77 % vs. 59 %) findings were more frequent (p < 0.05). In girls higher rates of UTIs, lower urinary tract dysfunction (LUTD) and spontaneous reflux resolution were seen (p < 0.05).Conclusions: Despite younger age at diagnosis, spontaneous resolution was found lower in boys and they had more frequent AHN, more severe reflux, and radiological abnormalities.