title: The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral reflux outcome.
abstract: BACKGROUND
  High-grade vesicoureteral reflux (VUR) in infants is associated with congenital renal abnormalities, recurrent UTI, and bladder dysfunction. Endoscopic treatment (ET) is a well-established method in children with low to moderate reflux grades, but there is a lack of randomised controlled trials regarding the use of ET versus continuous antibiotic prophylaxis in infants with high-grade VUR.
  
  
  OBJECTIVE
  This study aimed to determine whether high-grade VUR in infants can be treated with endoscopic injection and whether ET is superior to antibiotic prophylaxis in the treatment of VUR.
  
  
  METHODS
  This prospective, randomised, controlled, multicentre, 1-year follow-up trial comprised 77 infants (55 boys, 22 girls) <8 months of age with VUR grade 4-5 (n = 30/n = 47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free voiding observation were performed at study entry and after 1 year to evaluate VUR grade, and renal and bladder function.
  
  
  RESULTS
  VUR grade ≤2 was seen in 22 (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at follow-up (p = 0.0014). The success rate in the endoscopy group was 100% in unilateral grade 4, falling to 31% in bilateral grade 5 (p = 0.0094). Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to 0% in bilateral grade 5 (p = 0.037) (Table). Logistic regression analyses identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as positive predictors of VUR down-grading to ≤2 (area under ROC curve 0.88). In four patients with reflux resolution after one injection, dilating reflux recurred at the 1-year follow-up. One patient had a UTI possibly related to ET. In our material four patients required re-implantation, of whom one was obstructive after injection.
  
  
  CONCLUSIONS
  The opportunity to offer even small infants with high-grade VUR an alternative, minimally invasive treatment option is a great advance in paediatric urology. In this high-risk group, bilateral VUR grade 5 stands out with its poor bladder function and low chance of resolution. The recurrence rate of dilating VUR after successful ET is consistent with previous studies. The limitations are the relatively small number of patients and the short follow-up.
  
  
  CONCLUSIONS
  High-grade VUR in infants can be treated with injection therapy and the resolution rate is higher than that of prophylaxis treatment. The complication rate is low and VUR grade 4, unilaterality, and low residual urine are favourable for the resolution and down-grading of VUR.
authors.affiliation: Department of Paediatric Surgery, Paediatric Uronephrologic Centre, 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, Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Gundela
authors.initials: G
authors.lastname: Holmdahl
authors.affiliation: Department of Paediatrics, Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Brandström
authors.affiliation: Department of Paediatric Clinical Physiology, Paediatric Uronephrologic Centre, 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 Paediatric Radiology at the Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Eira
authors.initials: E
authors.lastname: Stokland
authors.affiliation: Department of Paediatric Surgery, Paediatric Uronephrologic Centre, 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 Surgery, Paediatric Uronephrologic Centre, Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Sjöström
mesh_terms: D019072:Antibiotic Prophylaxis / Q000379:methods*; D000070621:Cystography / Q000379:methods; D003558:Cystoscopy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013548:Sweden; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler / Q000379:methods; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D014563:Urodynamics; D014718:Vesico-Ureteral Reflux / Q000150:complications* / Q000000981:diagnostic imaging* / Q000628:therapy
keywords: Antibiotic prophylaxis; Endoscopic treatment; High-grade vesicoureteral reflux; Infant; Randomised