Nephrology and Urology Affinity Group Publications :: Nationwide Children's Hospital

Selected NURAG Publication Summaries: 2012-2013

Omitting VCUG Following a Normal Ultrasound for First UTI in Boys

When young boys first contract a UTI, a renal and bladder ultrasonogram and a voiding cystourethrogram (VCUG) are often performed to check for abnormalities that can lead to infection and kidney damage. A study of 77 boys under the age of 10, however, demonstrated that the VCUG may not offer an additional diagnostic benefit in children with normal ultrasound results. The study, led by V. Rama Jayanthi, MD, chief of Urology and a member of NURAG at Nationwide Children’s, demonstrated that omitting the VCUG in young boys with a normal ultrasound after their first urinary tract infection is unlikely to cause physicians to miss an important diagnosis. In addition, avoiding potential morbidities from the VCUG may enable clinicians to offer more appropriate care for such a common condition.

Citation: Berry CS, Vander Brink BA, Koff SA, Alpert SA, Jayanthi VR. Is VCUG still indicated following the first episode of urinary tract infection in boys? Urology. 2012 Dec, 80(6):1351-5. PMID: 23206783.

Battling UTI with Innate Immune Response

John David Spencer, MD, and Andrew Schwaderer, MD, members of NURAG at Nationwide Children’s, and colleagues discovered that the body’s urinary tract naturally produces a compound called Ribonuclease 7 (RNase 7), an antimicrobial peptide that fights bacteria. RNase 7 is now considered the most prevalent and potent known antimicrobial peptide in the human urinary tract. This research suggests that the broad-spectrum antimicrobial activity of RNase 7 may even be effective against uropathogenic bacteria that are resistant to conventional antibiotics. The peptide appears to work by binding to the bacterial cell and disrupting its microbial membrane, causing death of the bacterial cell. Learning to manipulate the production of RNase 7 could open doors for the development of novel treatments for urinary tract infections.

Citation: Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, DeSouza KR, Sims-Lucas S, Baker P, Hains DS. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney International. 2013 Apr, 83(4): 615-625. PMID: 23302724.

Urine Biomarkers to Predict Severity of Pediatric Kidney Damage

A study of the megabladder mouse model suggests that tracking changes in the expression of key genes involved in kidney disease could help physicians identify children at the greatest risk of chronic kidney disease and permanent organ damage.
The work, led by Brian Becknell, MD, PhD, clinician member of NURAG at Nationwide Children’s, and Kirk M. McHugh, PhD, director of NURAG, found that changes in the expression of certain genes, depending on the type and amount of kidney damage present, were primarily restricted to a single cell layer—in this case, the renal urothelium, which underwent significant cell division while producing important proteins that may protect the obstructed kidney from damage caused by backed-up urine. The team expects that alterations in gene expression may eventually serve as urine laboratory markers in patients with urinary tract obstruction to help determine who needs surgery and who does not.

Citation: Becknell B, Carpenter AR, Allen JL, Wilhide ME, Ingraham SE, Hains DS, McHugh KM. Molecular basis of renal adaptation in a murine model of congenital obstructive nephropathy. PLoS ONE. 2013 Sept 4, 8(9): e72762. PMID: 24023768.

Urinary Tract Beta Defensins vs. E. Coli

Dr. Becknell and other members of NURAG at Nationwide Children’s have become the first team to identify that multiple beta defensins are present in the urinary tract and are capable of killing uropathogens. Their study, initially targeted at characterizing the antimicrobial role of beta defensin-1 (BD-1) in the urinary tract, partially characterizes the role of two other beta defensins. Both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward E. coli in the mouse model of the lower urinary tract. Although other beta defensins were present, they did not observably demonstrate antimicrobial activity against E. coli. The team anticipates that beta defensins could eventually serve as novel biomarkers to assist clinicians in UTI diagnosis and as novel antibiotics for treatment of complicated UTI in the setting of antibiotic resistance.

Citation: Becknell B, Spencer JD, Carpenter AR, Chen X, Singh A, Ploeger S, Kline J, Ellsworth P, Li B, Proksch E, Schwaderer AL, Hains DS, Justice SS, McHugh KM. Expression and antimicrobial function of Beta-Defensin 1 in the lower urinary tract. PLoS One. 2013 Oct 21, 8(10):e77714. PMID: 24204930.

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