DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk.

Urinary tract infections (UTI), associated with vesicoureteral reflux (VUR), can lead to chronic kidney disease. Genetic alterations in the innate immune defenses contribute to UTI risk. We investigated a novel gene, Dachsous Cadherin-Related 1 (DCHS1), in children with UTI. We determined absolute DNA copy number (CN) of DCHS1 in children with UTI. In this case-control study, we utilized multiple complementary methods to determine the genomic CN of DCHS1. Children with (n = 370) and without (n = 71) VUR from two well-phenotyped clinical trials of UTI were copy-typed and compared to 491 healthy controls with no known history of VUR or UTI. Less than 1% of controls had a single copy of DCHS1, while 31% of children with UTI and no VUR and 7% of children with UTI and VUR had a single copy of the DCHS1 gene. Using immunostaining, we localized expression postnatally to the bladder and renal epithelia. Mice were also challenged with two uropathogenic Escherichia coli strains, and Dchs1 mRNA was quantified. This study represents the first report of DCHS1 in association with pediatric UTI. We hypothesize that its role in innate immunity is critical to lower urinary tract defense. Further investigation is required to determine the role of DCHS1 in innate immunity.

Elucidation of Renal Scars in Children With Vesicoureteral Reflux Using Contrast-Enhanced Ultrasound: A Pilot Study.

INTRODUCTION: Vesicoureteral reflux is a common disorder in children but can result in kidney scarring following acute pyelonephritis. The gold standard diagnostic to detect renal scars in children is 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. DMSA has a number of limitations including radiation exposure, need for sedation, and radiotracer supply shortages. Contrast-enhanced ultrasound (CEUS) is a technique whereby biocompatible microspheres of inert gas are administered i.v. that reflect ultrasonography sound waves and do not involve radiation. Because the contrast agent is rapidly cleared, contrast images must be obtained within minutes of administration. CEUS has been used in a variety of organ systems, but its use in pediatric kidney diseases is limited. METHODS: In this study, we performed CEUS in 7 children with documented renal scars by radiographic imaging consistent with reflux nephropathy. RESULTS: In all subjects, CEUS detected all previously known radiologic abnormalities as well as detecting new areas of hypoenhancing renal parenchyma. None of the patients experienced any serious adverse events. DISCUSSION: This study represents the first report of using CEUS to characterize renal scars in children with reflux nephropathy. We conclude that CEUS is a highly sensitive, rapid, and cost-effective diagnostic imaging modality for detecting and monitoring renal scars in children with vesicoureteral reflux.

Effect of Severity of Esophageal Acidification on Sleep vs Wake Periods in Infants Presenting with Brief Resolved Unexplained Events.

OBJECTIVES: To describe the pattern of gastroesophageal reflux (GER) events in wake and sleep states with increasing acid reflux index (ARI) in neonates and to test the hypothesis that GER-related symptoms are frequent in ARI >7% in wake state. STUDY DESIGN: Infants underwent 24-hour pH-impedance studies with 6-hour concurrent video-polysomnography studies. Data were stratified based on the 24-hour ARI (% duration that esophageal pH is <4) into ARI < 3% (normal), ARI 3 ≥ to ≤7% (intermediate), and ARI >7% (abnormal). GER frequency, clearance mechanisms, and symptoms were distinguished during wake state and sleep state. RESULTS: Total wake and sleep duration was similar (P ≥ .2) in all ARI groups. Acidic events were frequent with increasing ARI in wake state vs sleep state (P ≤ .03). The symptom index increased with increasing ARI (P ≤ .02) in both wake state and sleep state. Acid clearance time increased with increasing ARI in wake state (P ≤ .02). In ARI > 7% vs ARI ≤ 7%, frequency of acidic GER events was higher (P ≤ .02) in wake state and sleep state; proximal migration of acid (P = .03) and acid clearance time were higher in wake state (P = .0005) only. Symptom index was higher in ARI >7% vs ARI ≤ 7% in wake state (P < .0001), comparable in normal vs intermediate (P = .4), and higher in abnormal vs intermediate (P = .0004) groups. CONCLUSIONS: Severe esophageal acid exposure (ARI >7%) is associated with increased reflux-associated symptoms in wake state. Sleep state appears to be protective regardless of ARI, likely because of greater chemosensory thresholds. Attention to posture and movements during wake state can be helpful. Scrutiny for non-GER etiologies should occur for infants presenting with life-threatening symptoms.

Contemporary Management of Vesicoureteral Reflux.

The past 30 years have seen broad changes in the diagnosis and management of vesicoureteral reflux (VUR). Recently, a clinical debate has generated an open discussion in academic circles. New evidence has shifted treatment patterns away from widespread surgical management and recently brought into question some pharmacologic treatments. VUR is usually not hazardous by itself but is a significant risk factor for urinary tract infection (UTI) and less commonly, renal scarring and insufficiency. Given the costs and morbidity of UTI as well as the potential for significant renal injury, our approach remains conservative. Careful follow-up, parental education about pathophysiology and management of VUR and UTI, and management of bowel and bladder dysfunction (BBD) when present, are the foundation of treatment. Additionally, though we recognize the limitation of continuous antibiotic prophylaxis (CAP), we believe the benefits outweigh the risks and costs for many patients. Careful observation can be considered in patients with a single medical home, parental understanding of what UTI signs and symptoms are, low grade VUR, no history of complicated UTIs and close follow-up. Surgical management remains a relevant option for select patients who fail conservative measures with breakthrough UTIs or failure to resolve. Minimally invasive surgical options are available with acceptable outcomes though open ureteroneocystostomy still carries the highest success rate.