Prevalence and risk factors for renal scars in children with febrile UTI and/or vesicoureteral reflux, "Beyond the Abstract," by Nicol Corbin Bush, MD, MSc

BERKELEY, CA (UroToday.com) - We laid the foundation for this report when Dr. Warren Snodgrass, my co-author, served on the AUA Reflux Guidelines panel, and I was enrolled in the Master’s of Clinical Science program at UT Southwestern Medical Center. At a time when pediatricians and pediatric nephrologists were starting to question the clinical significance of vesicoureteral reflux (VUR) in children, we decided to focus on the risk it poses for renal scarring - realizing this is a major reason to detect VUR, yet noticing there were few publications specifically addressing this subject. So, we agreed that children who were referred to us for management of their VUR and/or febrile urinary tract infections (UTIs) would be offered dimercaptosuccinic acid (DMSA) renography to help us identify which patients had evidence of renal damage. With help from mentors and the formal curriculum in my Master’s program, I created a datasheet of the potential risk factors contributing to renal damage. We wanted to be certain we consistently captured this important information for each patient in clinic, anticipating that multiple logistic regression could help sort out the individual contributions, and we carefully defined these potential risk factors from the onset (non-febrile UTIs, febrile UTIs, overactive bladder, infrequent voiding, etc.) so that there was consistency between providers. Identifying DMSA as the gold-standard study with which to evaluate renal health, we found parents readily understood and accepted a VUR-management strategy based on stopping antibiotics and yearly voiding cystourethrograms (VCUGs) unless their child’s kidneys were scarred and/or they had recurrent UTIs. With the assistance of our co-authors, statistician Paul Nakonezny and epidemiologist Robert Haley, we then used SAS to analyze our observations.

"Ongoing analyses of our data suggest that renal ultrasound, combined with delayed DMSA, is the best screening combination to identify those children with focal and/or global renal damage after febrile UTI."
As stated in the abstract, we found only 15% of 565 consecutive children evaluated with DMSA for febrile UTI and/or VUR had renal cortical defects that we presumed were scars. These were more likely in patients with VUR, but our data revealed several important insights that challenge conventional thinking. For example, grade 1 VUR, that many dismiss as insignificant, conferred the same odds for renal damage as did grade 2, and even grade 3, which some consider more worrisome since it is “dilating reflux.” The greatest likelihood for cortical defects was found in those with grades 4 and 5 VUR, yet nearly half these patients had a normal scan. In addition, younger children had less renal scarring than did older children, which was unexpected given the frequent assertion that infants are at greatest risk for renal damage. Furthermore, while bowel and bladder dysfunction (BBD) increased risk for UTI, it was not an independent risk factor for renal scarring.

Despite the prospective nature of this cross-sectional, observational study, the large number of consecutive patients evaluated, and the statistical analysis using logistic regression to isolate factors associated with renal scars, this manuscript faced significant hurdles, and even a few rejections, before finally being accepted for publication! Many of the criticisms are summarized in the editorial comments and our responses that accompany the article. In the midst of innumerable revisions, each of which required time consuming re-analysis of various aspects of our dataset, I finally exclaimed that we didn’t need to publish it, as every pediatric urologist had already reviewed it! But despite the time and work needed for revisions, this academic process greatly strengthened the final version, as it is designed to do. For example, the original manuscript did not include data regarding BBD, which was appropriately added at the insistence of a reviewer.

Most importantly, this article has significantly changed our entire approach to VUR diagnosis and management. Ongoing analyses of our data suggest that renal ultrasound, combined with delayed DMSA, is the best screening combination to identify those children with focal and/or global renal damage after febrile UTI. These children may benefit from subsequent VCUG to diagnose VUR because they are at greater risk for UTI recurrence compared to children with normal DMSA. In contrast, ultrasound alone misses patients with cortical defects and/or poor renal function (the false negative rate is 19%), and routine VCUG diagnoses VUR in many children in whom it will likely never present a health risk. An abnormal DMSA prompts VCUG, and in those patients with VUR, we now recommend surgical correction by reimplantation or endoscopic injection given strong evidence that antibiotic prophylaxis is minimally effective in preventing UTI recurrence combined with data showing successful correction of VUR statistically significantly decreases risk for subsequent febrile UTIs. Females with a normal DMSA are followed through toilet training with bi-annual clinic visits to monitor for UTI recurrence. Males with a normal DMSA are followed to age 18 months, given that most experience febrile UTIs in the first 6 months of life. Repeat VCUG in those with known VUR is no longer obtained in the absence of additional febrile UTIs, which occurred in approximately 20% of our patients with 1.4 years median follow up. We have recently submitted a manuscript analyzing the AAP imaging guidelines for evaluation of infants < 2 years of age after their first known febrile UTI, using our DMSA data. We have also reported that children observed without antibiotic prophylaxis, despite known VUR, who have a negative baseline DMSA, have low risk for new scarring if recurrent febrile UTI occurs.

Taken together, our data suggests delayed DMSA can play a pivotal role in identifying those children who are most likely to benefit from diagnosis and intervention for VUR and those at low risk for renal damage, even when VUR is not sought after, or is only observed without antibiotics or repeat cystography.

Written by:
Nicol Corbin Bush, MD, MSc as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Division of Pediatric Urology, Department of Urology, University of Texas Southwestern Medical Center, 2350 Stemmons Frwy, Suite D-4300, MC F4.04, Dallas, TX 75207  USA

Prevalence and risk factors for renal scars in children with febrile UTI and/or VUR: A cross-sectional observational study of 565 consecutive patients - Abstract

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