The management of urinary tract infection and vesicoureteric reflux in children

Elisabeth Hodson
Centre for Kidney Research, The Children's Hospital at Westmead

Introduction: Reflux (VUR) of infected urine has been considered the most important risk factor for permanent renal damage in children. In the past 30 years emphasis has been placed on the diagnosis of VUR in children presenting with urinary tract infection (UTI), whether the child had acute pyelonephritis or lower tract infection. Children with VUR received long-term antibiotic prophylaxis or underwent ureteric reimplantation aiming at preventing further UTI and renal damage. Children without VUR were thought not to be at risk of renal damage and were not routinely given antibiotics. However 99mtechnetium dimercaptosuccinic acid (DMSA) scanning has shown that some children with acute or chronic renal damage after acute pyelonephritis do not have VUR. Also some babies, investigated following antenatal diagnosis of hydronephrosis, have symmetrically small kidneys on DMSA scan with dilating VUR (grades 3-5 on the international classification) before UTI occurs consistent with pre-existing renal dysplasia. These data challenge the contribution of VUR to the development of UTI and renal scarring and have led to a reassessment of the evidence supporting current management strategies for UTI and VUR.

(RCTs) to determine whether antibiotic prophylaxis prevents further UTI. Two recent systematic reviews identified only two RCTs comparing antibiotic prophylaxis with placebo or no treatment to prevent further UTI. Outcomes were reported in 63 children; all were aged over 2 years and only one child had VUR. Although both trials showed that prophylaxis reduced the number of further UTI (both symptomatic and asymptomatic), the small size, limited population studied and methodological problems of the studies casts doubt on the applicability of the results to children with VUR.

Ureteric reimplantation to prevent UTI and scarring: A systematic review identified six RCTs comparing ureteric reimplantation and long-term antibiotic prophylaxis for 6 months or more with antibiotic prophylaxis alone in children with dilating VUR. After two and five years of follow up, there was no significant difference in the occurrence of new scars or progressive renal scarring between surgically and medically treated groups. Though there was no difference in the total number of UTIs between surgically and medically treated groups, combined treatment resulted in a 60% reduction in febrile UTI over 5 years.

Antibiotic prophylaxis to prevent UTI in infants with VUR detected through antenatal or sibling screening: Around 15-20% children with antenatally detected hydronephrosis have isolated VUR. It is widely recommended that such children receive antibiotic prophylaxis to prevent UTI and renal damage. Forty-six infants with VUR but no UTI were randomised to receive antibiotic prophylaxis or placebo and were followed for 3 years. Dilating VUR was present in 30 babies (40 renal units) and 13 (15 renal units) had renal damage on DMSA at entry. Two children on placebo and none on prophylaxis (p=0.2) developed UTI and no child developed new renal damage. Thus screening for VUR and treating children with VUR is unlikely to be of clinical benefit.

Other interventions for children with UTI and VUR: Cohort studies have demonstrated a significantly lower risk of UTI in circumcised boys. A study of babies presenting with UTI showed a reduction in episodes of asymptomatic bacteriuria following circumcision compared with uncircumcised babies. While studies are required to confirm a significant reduction in symptomatic UTI following circumcision, it seems reasonable to consider circumcision in boys with recurrent UTI. Recurrent UTIs are commonly associated with voiding dysfunction and constipation. In uncontrolled studies, children with voiding dysfunction and VUR have rates of break through UTI while on antibiotic prophylaxis that are 2-3 times higher than in children without voiding dysfunction. High rates of new scarring are reported in children with UTI, VUR and voiding dysfunction. Though no RCTs have examined the effects of treating voiding dysfunction on UTI and renal damage, it is recommended that voiding dysfunction and constipation be corrected to reduce the likelihood of further UTI.

Conclusion: There are limited data to support the current management strategies of UTI and VUR. An RCT comparing antibiotics with placebo in children with UTI with or without VUR is in progress in Australia to determine if antibiotics are effective in preventing UTI. Information is still required on whether any therapy to prevent UTI is effective in preventing new or progressive renal damage.

Invited lecture at the Australian and New Zealand Society of Nephrology (ANZSN) Postgraduate Course in Nephrology, Sydney, 31st August and 1st September 2002.