The diagnosis and treatment of reflux in children with a history of urinary tract infections (UTIs) keeps evolving—it's hardly a settled issue. Regarding antibiotic prophylaxis in these children, said Saul P Greenfield, MD, FAAP, FACS, the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial reveals that it may be better to overtreat than undertreat.
Greenfield's presentation was "UTIs and vesicoureteral reflux (VUR): Current recommendations for evaluation and treatment: Impact of the RIVUR trial."
The RIVUR trial showed unquestionably that children with VUR (primarily low to intermediate grade) who go on antibiotics had half as many UTIs versus placebo.1
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Recurrent infection, by itself, is a worthwhile morbidity to prevent or reduce, even absent kidney damage. Some might say that versus kidney damage, a UTI is medically inconsequential. However, more than one-third of the RIVUR children who had infections that required medical attention visited an emergency department. When a baby has a high fever and infection, with or without a kidney issue, or if a child has burning on urination, these are real morbidities that can be prevented by daily antibiotic therapy.
Furthermore, initial RIVUR demographic data reveal that, presently, it is impossible to accurately diagnose reflux noninvasively.2 Some experts, and recent American Academy of Pediatrics guidelines, say that kidney ultrasound effectively reveals severe reflux, but that is untrue, said Greenfield. Approximately 90% of children in the RIVUR trial had normal renal ultrasounds.
What the RIVUR trial did not show—that observers perhaps hoped for—was that staying on antibiotics reduces kidney scarring. However, a clinical trial is hardly a real-world setting. RIVUR's stringent protocols enforced a degree of hypervigilance against UTIs, and, overall, the incidence of scarring is such that achieving statistical significance would require following thousands of patients over several years, an unrealistic goal. RIVUR, with 600 subjects, is the world's largest study of this disorder and likely will remain so.
The approach to VUR represents a paradigm for medicine itself. The pendulum constantly swings one way or another. Greenfield acknowledged that diagnosing and treating everyone with reflux overtreats a large number of people, but at present there is no reliable way to distinguish the higher-risk patients. The trial did show, however, that older toilet-trained children who had bowel and bladder dysfunction were more likely to have UTIs, even while on antibiotic prophylaxis.
REFERENCES
1. RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014;370(25):2367-2376.
2. Carpenter MA, Hoberman A, Mattoo TK, et al; RIVUR Trial Investigators. The RIVUR trial: profile and baseline clinical associations of children with vesicoureteral reflux. Pediatrics. 2013;132(1):e34-e45.
COMMENTARY
Dr Greenfield presents an excellent summary of a very important trial in pediatrics and pediatric urology. To put the RIVUR trial in context, clinicians have been inundated with suboptimal trials that showed that prophylactic antibiotics may not prevent infections in children with VUR. These data called into question the value of even diagnosing reflux: If the principal treatment for VUR, prophylactic antibiotics, did not help, why even bother diagnosing VUR? Many studies have shown that the number of voiding cystourethrograms (VCUGs) being performed has been steadily decreasing, and many pediatricians may have falsely assumed that this diagnosis is almost never important.
Given this background, this very well done study does indeed show that prophylactic antibiotics are effective in reducing the rate of UTIs in children with VUR. This is very important information for pediatricians. As Dr. Greenfield points out, the antibiotics may not have reduced renal scarring in this small, heavily scrutinized population, but just preventing clinical infections is in and of itself important in reducing morbidity, by reducing emergent and urgent visits and time off work for parents. Further, Dr. Greenfield correctly identifies for practicing pediatricians that ultrasound alone is an inadequate test for discovering VUR, and in a high-risk population, VCUG is still the gold standard for diagnosing VUR.
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Although I agree with most of Dr Greenfield’s points, I do differ in that I do not like to believe that overtreatment is better than undertreatment. It is important that we make every effort to hit the "sweet spot" wherein clinicians use predictive models and risk calculators (for example, taking bowel and bladder dysfunction into account) to better determine which patients need to be diagnosed and treated.
