Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

Bilateral subdiaphragmatic kidneys with right-sided renal malrotation

Background The subdiaphragmatic kidney is a positional variant of the uncommon cephalad renal ectopia, whereas renal malrotation refers to the anomalous renal hilar position. Both anomalies are rare, possibly under-reported, discovered incidentally on radiological examinations since patients are often asymptomatic. Case presentation This case report presents a unique renal anatomical variation in a 71-year-old female patient. A bilateral subdiaphragmatic renal ectopia coupled with right-sided renal malrotation, discovered accidentally on abdominal ultrasound (US), and confirmed by abdominal magnetic resonance imaging (MRI). Conclusions The presented case of bilateral subdiaphragmatic kidneys associated with right-sided renal malrotation is rare and not previously described in the literature. Radiologists must be familiar with these renal anomalies that can be discovered on imaging performed for other indications. MRI can provide more anatomical data compared to US.

Genetic and Phenotypic Variability in Chinese Patients With Branchio-Oto-Renal or Branchio-Oto Syndrome

Background: Branchio-oto-renal syndrome (BOR) and branchio-oto syndrome (BOS) are rare autosomal dominant disorders defined by varying combinations of branchial, otic, and renal anomalies. Here, we characterized the clinical features and genetic etiology of BOR/BOS in several Chinese families and then explored the genotypes and phenotypes of BOR/BOS-related genes, as well as the outcomes of auditory rehabilitation in different modalities.Materials and Methods: Probands and all affected family members underwent detailed clinical examinations. Their DNA was subjected to whole-exome sequencing to explore the underlying molecular etiology of BOR/BOS; candidate variants were validated using Sanger sequencing and interpreted in accordance with the American College of Medical Genetics guidelines. In addition, a literature review concerning EYA1 and SIX1 alterations was performed to explore the genotypes and phenotypes of BOR/BOS-related genes.Results: Genetic testing identified the novel deletion (c.1425delC, p(Asp476Thrfs*4); NM_000,503.6), a nonsense variant (c.889C > T, p(Arg297*)), and two splicing variants in the EYA1 gene (c.1050+1G > T and c.1140+1G > A); it also identified one novel missense variant in the SIX1 gene (c.316G > A, p(Val106Met); NM_005,982.4). All cases exhibited a degree of phenotypic variability between or within families. Middle ear surgeries for improving bone-conduction component hearing loss had unsuccessful outcomes; cochlear implantation (CI) contributed to hearing gains.Conclusion: This is the first report of BOR/BOS caused by the SIX1 variant in China. Our findings increase the numbers of known EYA1 and SIX1 variants. They also emphasize the usefulness of genetic testing in the diagnosis and prevention of BOR/BOS while demonstrating that CI for auditory rehabilitation is a feasible option in some BOR/BOS patients.

1423. Overview of Paediatric Urinary Tract Infections in the Gulf Co-operation Council (GCC) Countries, A Literature Review

Background Urinary tract infections (UTIs) are among the most frequent infections in the pediatric population, occasionally associated with concealed renal anomalies. Hence, early treatment is pertinent to reduce morbidities for better patient outcomes. The study aimed to review published literature from the gulf region in the last decade on UTIs etiology, common risk factors, current antimicrobial management, outcomes, and common resistance patterns. Methods This narrative literature review was conducted by evaluating articles published for a 10-years period from 2011 to 2021 using “Google Scholar” and “PubMed” databases. The search included regional clinical practice guidelines, systematic review and meta-analysis conducted across Gulf Cooperation Council countries (GCC). The search was limited to English literature and patients below 18 years old. Results The prevalence of UTIs among pediatrics in the age group of 0 to18 years ranged from 9.9% to 50.8% across the region. Data obtained from 11,092 children revealed that Escherichia coli was the primary cause of UTI (26% to 93.5%), followed by Klebsiella pneumoniae (3.8% to 76.4%). Furthermore, Extended-spectrum beta-lactamases (ESBLs) producing pathogens were observed in 7% to 35.2%. Higher ESBL rates were observed in patients with recurrent UTIs. Ampicillin and Co-trimoxazole, and 3rd generation cephalosporins were mainly prescribed as first-line antibiotics. Increased resistance to Ampicillin, Co-trimoxazole, and 3rd generation cephalosporins while low resistance to Nitrofurantoin, Amikacin, and Meropenem was documented. Vesicoureteral reflux was the most common risk factor for UTIs. Renal abnormalities were also observed to provide a nidus for bacterial growth. There is an evident lack of data in the region on antimicrobial treatment duration, possible predictors of treatment failure, and epidemiological data on multidrug resistance. Conclusion Urinary tract infections (UTIs) in pediatrics are a common therapeutic challenge in the region. Larger scale multicenter national and regional epidemiology studies are a prerequisite in the region. There is a need to monitor antimicrobial resistance in pediatrics & enhance surveillance for the advancement of management. Disclosures Nervana Habashy, B. Pharm, Pfizer (Employee) Ashraf Hassanien, MD, Pfizer (Employee) Ayman Kurdi, MD, Pfizer (Employee)

Wolf-Hirschhorn Syndrome: Clinical and Genetic Study of 7 New Cases, and Mini Review

Wolf–Hirschhorn syndrome (WHS), a rare disorder determined by distal 4p deletion, is characterized by a pre and postnatal growth retardation, hypotonia, intellectual disability, epilepsy, craniofacial dysmorphism, and congenital fusion anomalies. The clinical aspects are dependent on the deletion’ size. Our aim was to identify rare specific characteristics in a cohort of seven cases with 4p deletion and to assess the utility of Multiplex ligation-dependent probe amplification (MLPA) (cheap and sensitive test)—combined kits—as a diagnostic test and selection tool for cases that require other investigations (chromosomal microarray analysis—CMA, karyotype). For all cases we conducted a clinical examination with the main features identified: facial dysmorphism, intellectual disability, postnatal development delay, cardiac defects and hypotonia. In some cases, we observed seizures, structural brain abnormalities, immunodeficiencies, and renal anomalies. Prenatal growth retardation was detected in a relatively small number of cases, but postnatal growth failure was a constant feature. In all cases, the clinical diagnosis was confirmed by genetic analyses: karyotype and/or MLPA. In conclusion, renal and brain defects, as well as immunodeficiency are rare manifestations and should be looked for. Although CMA is the standard test, in our experience, MLPA is also a reliable screening method as the identified cases were either confirmed by MLPA or selected for further investigations.

Frequency of Confirmed Congenital Renal Malformations in Neonates with Antenatal Diagnosis of Renal Anomalies Presenting In Neonatal Intensive Care Unit of a Tertiary Care Setting of a Low Income Country.

INTRODUCTION:: Approximately 20 to 30% of all anomalies identified in the prenatal period are congenital anomalies of the kidney and urinary tract (CAKUT). Widespread antenatal screening has resulted in increased detection of anomalies of the kidneys and urinary tract. There are limited studies on the postnatal confirmation of these antenatally detected renal malformations. Moreover, there is no local data available in this regard. So, we conducted the study so that we can obtain local data as well as we can plan management and prevention protocols for such chronically, and sometimes critically, ill neonates. MATERIALS AND METHODS:: It was a cross-sectional study conducted at the neonatal intensive care unit (NICU) at the National Institute of Child Health, Karachi during 2017-2018. The sample size was 100 cases. The sampling technique was non-probability consecutive sampling. All neonates aged 1-28 days of either gender admitted in NICU with antenatal diagnosis of congenital renal anomalies on anomaly scan were included in the study. Preterm neonates (gestational age below 34 weeks) and neonates having siblings with similar congenital problems were excluded. RESULTS:: The mean age of the neonates in our study was 10.17 ±9.30 days and the mean gestational age at birth was 36.65 ±1.16 weeks. The majority of the neonates, that is 65%, were males while 35% were females. Sixty-six per cent (66%) neonates were ≤10 days of age while 34% were >10 days of age. Fifty five% of the neonates were ≤36 weeks of gestation at birth while 45% were >36 weeks of gestation at birth. Frequency of postnatally confirmed congenital renal malformation was observed in 78 (78%) neonates. Neonates whose age at presentation was >10 days were slightly more likely to have confirmed congenital renal malformation as compared to neonates with ≤10 days of age, which is 85.3 % vs 74.2 % (p-value 0.206). Males and females were found to have almost equal postnatally confirmed congenital renal malformations (78.5 % in males and 77.1% in females) (p-value 0.879). Postnatally confirmed congenital renal malformations were observed more commonly in neonates who were >36 weeks of gestational age (80%) as compared to those ≤36 weeks of gestational age (76.4%) (p-value 0.662). CONCLUSION::The frequency of confirmed congenital renal malformation was found higher in neonates presenting with antenatal diagnosis of renal anomalies presenting in the neonatal intensive care unit.

Main Physical Features, Echocardiographic and Renal Ultrasonographic Findings of Turner Syndrome in 107 Pediatric Patients

Turner syndrome (TS) is one of the most common malformation syndromes in females. A total number of 107 TS patients, diagnosed between 2000 and 2018, were evaluated for their phenotypic features, and cardiac and renal findings. The mean age of patients at admission was 10.08 ± 4.9 years (range, newborn to 18 years). Four different karyotype groups were encountered, and the most common findings in all groups were short stature, followed by cubitus valgus. Echocardiographic findings of 85 patients were available among which 63 (<i>n</i> = 63/85, 74.1%) were found to be normal. The most common cardiac anomaly was left ventricular outflow tract/aortic arch pathology detected in 9 patients (<i>n</i> = 9/22, 40.9%). Renal malformations were detected in 15 patients (<i>n</i> = 15/84, 17.9%) by renal ultrasonography, and horseshoe kidney was the most common renal malformation, followed by left multicystic dysplastic kidney. There was no significant difference in the frequency of renal malformation and cardiac anomalies among the 4different karyotype groups (χ² exact test, <i>p</i> &#x3e; 0.05). Compared with the literature, the frequency of renal anomalies was detected at a lower rate. Karyotype analysis should be carried out in all female patients with short stature, even if there are no associated phenotypic findings suggestive of TS. Since cardiac anomalies are frequently seen in TS patients and they represent a common cause of mortality, echocardiography should be carried out as soon as the definite diagnosis is established. Renal anomalies may be less frequent than cardiac anomalies; however, evaluation of TS patients with renal ultrasonography should be done at the time of diagnosis. Although renal ultrasonography can be used as the initial renal screening in TS patients, it may underestimate the frequency of renal malformation; hence, further management may be required.

Co-Existence of a Rudimentary Non-Communicating Horn with a Unicornuate Uterus in Association with 2 Components of the VACTERL Association: A Case Report

The prevalence of congenital uterine anomalies has been reported as 6.7% in the general population. The unicornuate uterus accounts for 2.4-13% of all Mullerian anomalies and has a prevalence of 1:1000. A unicornuate uterus may be present alone or with a rudimentary horn and 75-90% of rudimentary horns are non-communicating. A pregnancy in the rudimentary horn may lead to uterine rupture, haemoperitoneum with a high risk of maternal mortality. The association of a unicornuate uterus with a non-communicating uterine horn to the VACTERL association of defects (vertebral anomalies, anorectal malformations, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal anomalies and limb defects) has been described only twice in the literature. We report a patient who was born with an extra thumb and had a trachea-bronchial remnant with oesophageal stenosis that were both operated on earlier, and they were associated with a non-communicating rudimentary uterine horn. To the best of our knowledge, this is the third case reported in the literature of a VACTERL association to a unicornuate uterus with a non-communicating functional rudimentary horn. Given the high risk for the patient if pregnant an early diagnosis is paramount. This case highlights the importance of considering Mullerian defects in the young patient born with components of the VACTERL association.

BRANCHIO-OTO-RENAL (BOR) SYNDROME

Introduction. This work is devoted to the problem of embryology of the ears and kidneys. First ear and kidney abnormalities were reported in 1946 by Edith Potter’s association of crumpled and flattened ears with bilateral kidney agenesis. Ear malformations are associated with an increased frequency of clinically significant structural renal anomalies compared with the general population. These include specific multiple congenital anomaly syndromes, Townes-Brocks syndrome, branchio-oto-renal syndrome.The link can be explained by structural and functional similarities between tissues in the inner ear and in the kidney. Also, toxins that accumulate in kidney failure can damage nerves, including those in the inner ear.Goal. To study the causes, clinical manifestations of Branchio-oto-renal (BOR) syndrome. Materials and Methods. Review of modern and foreign literary sources; methods - description, analysis, abstracting.Results and discussion. Mutations in three genes, EYA1, SIX1, and SIX5, have been reported in people with BOR/BO syndrome. About 40 percent of people with this condition have a mutation in the EYA1 gene. SIX1 gene mutations are a much less common cause of the disorder. SIX5 gene mutations have been found in a small number of people with BOR syndrome, although researchers question whether mutations in this gene cause the condition. Some affected individuals originally reported to have SIX5 gene mutations were later found to have EYA1 gene mutations as well, and researchers suspect that the EYA1 gene mutations may be the actual cause of the condition in these people.The proteins produced from the EYA1, SIX1, and SIX5 genes play important roles in development before birth. The EYA1 protein interacts with several other proteins, including SIX1 and SIX5, to regulate the activity of genes involved in many aspects of embryonic development. Research suggests that these protein interactions are essential for the normal formation of many organs and tissues, including the second branchial arch, ears, and kidneys. Mutations in the EYA1, SIX1, or SIX5 gene may disrupt the proteins’ ability to interact with one another and regulate gene activity.Conclusions. The link between ear anomalies and kidney function can be explained by structural and functional similarities between tissues in the inner ear and in the kidney. Additionally, toxins that accumulate in kidney failure can damage nerves, including those in the inner ear.