title: The Swedish infant high-grade reflux trial: UTI and renal damage.
abstract: BACKGROUND
  High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4-5 can reduce the risk of UTI recurrence and renal scarring.
  
  
  METHODS
  This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants, <8 months of age with VUR grade 4-5 (Table) randomized to CAP (n = 39) or ET (with prophylaxis until resolution) (n = 38). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year. Parenchymal defects were seen in 67 (87%) children at entry, 39 (34 boys, 5 girls) of them characterized as generalized. At follow-up, renal deterioration (new scars or progress in old damaged area) and symptomatic UTIs were reported.
  
  
  RESULTS
  There were 27 recurrent febrile UTIs in 6 (16%) children in the ET group and in 10 (26%) in the CAP group (p = 0.43), in eight (36%) girls and eight (15%) boys (p = 0.039). Successful VUR outcome (VUR 0-2) was seen in 22 (59%) in the ET and eight (21%) in the CAP group (p = 0.0014). Multiple recurrences were only seen in patients with persistent dilating reflux at follow-up (p = 0.019). Deterioration on scintigraphy was seen in eight children (9 kidneys) with no difference between treatment groups (p = 0.48) or sex (p = 0.17). Renal deterioration was associated with high bladder capacity (BC) and large residual volume (PVR) at 1 year (p = 0.0092 and p = 0.041). Six of the eight children with renal deterioration had a recurrent UTI (p = 0.0032). Seven of nine renal units with deterioration were seen in children with persistent VUR 3-5 at follow-up. Univariable logistic regression identified female sex and high PVR as positive predictors for recurrent UTI (p = 0.039 and 0.034) and high PVR tended to predict renal deterioration (p = 0.053).
  
  
  CONCLUSIONS
  No differences between the treatment groups regarding recurrent UTI and renal deterioration could be found. Increased PVR and female sex were positive predictors for UTI recurrences. VUR grade at follow-up was correlated to UTI recurrence and renal deterioration.
  
  
  CONCLUSIONS
  This study did not show any difference between ET and CAP in reducing the risk of UTI recurrence or renal deterioration. The rate of VUR resolution was higher in the ET group and VUR grade at follow-up correlated with both UTI recurrence and renal deterioration.
authors.affiliation: Department of Paediatric Surgery, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: josefin.nordenstrom@vgregion.se.
authors.forename: Josefin
authors.initials: J
authors.lastname: Nordenström
authors.affiliation: Department of Paediatric Surgery, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Sjöström
authors.affiliation: Department of Paediatric Surgery, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Sillén
authors.affiliation: Department of Paediatric Clinical Physiology, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Rune
authors.initials: R
authors.lastname: Sixt
authors.affiliation: Department of Paediatrics, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Brandström
mesh_terms: D000367:Age Factors; D019072:Antibiotic Prophylaxis / Q000379:methods*; D002675:Child, Preschool; D003558:Cystoscopy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D013548:Sweden; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy*; D014563:Urodynamics; D014567:Urography / Q000379:methods; D014718:Vesico-Ureteral Reflux / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: High-grade VUR; Infant; Prophylaxis; Randomized controlled trial; Renal damage; Urinary tract infection