since the approval of dextranomer / hyaluronic acid ( dx / ha ) by the u.s . food and drug administration in 2001 , injection therapy for vesicoureteral reflux ( vur ) using dx / ha has become increasingly popular in many parts of the world . an increased probability of resolution of vur with the hydrodilatation implantation technique has been reported ( 1 ) , and several authors have reported high success rates with injection therapy that are comparable to those of open ureteroneocystostomy ( 1 , 2 ) . however , it should be remembered that these excellent results were attained by expert surgeons and that universally , there is a certain period of time required to overcome the high learning curve necessary to perform these procedures ( 3 , 4 ) . the average success rates of injection therapy for primary vur in children according to the reflux grade have been reported to be 79% for grade ii vur , 72% for grade iii , 63% for grade iv , and 51% for grade v by meta - analysis ( 5 ) . it should , therefore , be recognized that every child who undergoes dx / ha injection for primary vur is at risk of persistent reflux after the procedure . thus , it is important to elucidate the clinical meaning of persistent post - injection reflux in the process of applying injection therapy for vur in children . moreover , since the primary goals of managing vur are the prevention of acute pyelonephritis and renal damage , it is important that the probabilities of febrile urinary tract infection ( uti ) that may cause renal damage be evaluated . in this study , we sought to investigate the clinical value of persistent but downgraded vur after dx / ha injection by analyzing the incidence of pre- and post - operative febrile uti . also , we tried to investigate the surgical results of an additional single dx / ha injection in children with persistent post - injection reflux . the medical records of children who underwent dx / ha injection for primary vur performed by a single surgeon from november 2004 to january 2009 were retrospectively reviewed . preoperative patient characteristics , such as age , gender , laterality , and preoperative vur grade , were reviewed . lower urinary tract function was investigated in toilet trained children ( n = 110 ) . concerning the voiding symptoms and bowel movement , we used a structured questionnaire of ' the dysfunctional voiding scoring system ' ( 6 ) . the presence of bladder and bowel dysfunction ( bbd ) was determined from voiding symptoms focusing on frequency , urgency , incontinence , characteristics of urine stream , and bowel movement . subjects with other urologic anomalies , such as ureteropelvic junction obstruction , ureteral duplication , ureterocele , cystic kidney disease , or neuropathic bladder , were excluded . three months postoperatively , vur grade was assessed in all patients using vcug . the vur grade was determined according to the international reflux study classification ( 7 ) . if the persistent vur was bilateral , the higher of the two vur grades was used . the episodes of pre- and post - operative febrile utis ( episodes per year ) were compared in patients with or without persistent vur on voiding cystourethrography ( vcug ) 3 months postoperatively . febrile uti was defined as documented urine cultures of 100,000 colony - forming units ( cfus ) per milliliter or greater on a clean urine specimen with fever ( 38 or higher ) that necessitated hospital admission and administration of intravenous antibiotics ( 8) . the postoperative follow - up period for children with postoperative persistent reflux was defined as the period of time from the day of the first operation to the day of the second operation . continuous antibiotic prophylaxis was not routinely performed postoperatively , however low - dose prophylactic antibiotics ( trimethoprim 2 mg / sulfamethoxazole 10 mg per kg , once a day ) were administrated in selected cases . these were in children with persistent high grade vur ( higher than grade iv ) on vcug 3 months postoperatively , with a clinical history of frequent preoperative febrile uti episodes . also , the surgical outcome after an additional single injection was also investigated in patients who underwent more than one dx / ha injection treatment . statistical analysis was performed using spss 17.0 for windows ( spss for windows , spss inc , chicago , il , usa ) . a paired t - test was used to compare the pre- and post - operative vur grades or febrile uti episodes . a p value less than 0.05 was considered to be statistically significant . the study protocol was approved by the institutional review board of seoul national university hospital ( irb number : 0807 - 078 - 251 ) . under the board 's approval , the study protocol was approved by the institutional review board of seoul national university hospital ( irb number : 0807 - 078 - 251 ) . under the board 's approval , our study population comprised of 128 children ( 72 boys and 56 girls ) who underwent initial dx / ha injection for primary vur , with a mean age of 61.7  42.0 months . bilateral vur was present in 67 patients ( 53.9% ) , and was unilateral in 61 patients , in a total of 195 ureters . preoperative reflux grades were i in 12 ureters ( 6.2% ) , ii in 49 ( 25.1% ) , iii in 82 ( 42.1% ) , iv in 45 ( 23.1% ) , and v in 7 ( 3.6% ) . of the 110 toilet trained children , 42 ( 38.1% ) had bbd and the remained 68 ( 61.9% ) had not bbd . three months postoperatively , among the 195 ureters that were treated with dx / ha injection , vcug demonstrated that reflux resolved completely in 100 ureters , was persistent in 95 ureters ( 75 patients ) , and was newly developed in 2 ureters ( the vur grade was i in one ureter and ii in another ureter ) that had no preoperative reflux . among the 97 ureters that had persistent or newly developed reflux , 44 were treated with an additional dx / ha injection and 2 ( both grade v ) underwent open ureteroneocystostomy using cohen 's method . the mean duration of postoperative follow - up was 16.2  10.1 months . postoperative reflux grades of the 195 ureters were 0 in 100 ureters ( 51.3% ) , i in 21 ureters ( 10.8% ) , ii in 41 ( 21.0% ) , iii in 22 ( 11.3% ) , iv in 9 ( 4.6% ) , and v in 2 ( 1.0% ) . table 1 lists the subjects ' demographic characteristics and the pre- and post - operative vur grade data . when ureters with persistent or newly developed reflux were analyzed ( n = 97 ) , preoperative reflux grades were 0 in 2 ureter ( 2.1% ) , i in 4 ( 4.1% ) , ii in 15 ( 15.5% ) , iii in 36 ( 37.1% ) , iv in 34 ( 35.1% ) , and v in 6 ( 6.2% ) , and postoperative reflux grades were i in 22 ureters ( 22.7% ) , ii in 42 ( 43.3% ) , iii in 22 ( 22.7% ) , iv in 9 ( 9.3% ) , and v in 2 ( 2.1% ) ( fig . after dx / ha injection , 4 patients ( 3 patients with grade iv and 1 patient with grade v ) received continuous antibiotics prophylaxis . the success rate in the presence and absence of bbd was 38.1% ( 16 of 42 ) and 54.4% ( 37 of 68 ) , respectively ( p = 0.87 , two - sided fisher 's exact test ) . febrile utis occurred in 3 ( 5.7% ) of the 53 subjects who had no reflux on vcug 3 months postoperatively . the incidence of febrile uti was 0.35  0.39 per year before injection , and decreased significantly to 0.07  0.32 per year after injection in all the 53 children without reflux on vcug 3 months postoperatively ( p < 0.001 ) . in all of the three patients with febrile utis who underwent vcugs during the follow - up period , vur was detected in one patient and there was no vur in the two others . febrile utis occurred in 12 ( 16% ) of the 75 subjects who had persistent reflux . the incidence of febrile uti was 0.76  1.18 per year before injection , decreasing significantly to 0.20  0.61 per year after injection in the children with persistent reflux ( p < 0.001 ) ( fig . the postoperative vur grade distribution of those who experienced postoperative febrile utis was as follows : i in one ureter ( 8.3% ) , ii in four ( 33.3% ) , iii in five ( 41.7% ) , iv in one ( 8.3% ) , and v in one ( 8.3% ) . all patients had experienced preoperative febrile utis , and 11 had experienced more than 2 . the preoperative vur grade of the 44 ureters ( 32 children ) that were treated with a single additional dx / ha injection were i in 5 ureters ( 11.4% ) , ii in 21 ( 47.7% ) , iii in 12 ( 27.3% ) , iv in 6 ( 13.6% ) , and postoperative reflux grades were 0 in 29 ureter ( 65.9% ) , i in 7 ( 15.9% ) , ii in 4 ( 9.1% ) , iii in 4 ( 9.1% ) ( fig . our data demonstrated that even if a child has persistent reflux after dx / ha injection , the probability of febrile uti is markedly decreased . the decrement in the rate of post - injection febrile uti may be mainly a result of the decrease in the vur grade , and also due to the functional improvement of the bladder as children grow . it is well known that one of the most important risk factors for febrile uti in children with vur is the grade of the reflux ( 9 ) . therefore , the clinical significance of downgraded reflux after dx / ha injection is valuable in light that the primary goal of treatment for vur in children is to prevent renal damage associated with recurrent febrile utis . in our study , 164 ( 83.1% ) of the 197 ureters showed a vur lower than grade ii after single dx / ha injection . most of the cases showing persistent high - grade reflux postoperatively were downgraded to grade i or ii following a single additional dx / ha injection . the incidence of febrile uti after open ureteral reimplantation has been reported to be 8%-24% in previous studies ( 10 - 12 ) and the incidence of febrile uti after injection therapy for vur in children has been reported to be approximately 5% ( 8 , 11 , 13 , 14 ) . the lower risk for febrile uti after injection therapy compared to that of open surgery may be due to minimal changes in the bladder dynamics and/or a less favorable environment for bacterial adherence with injection . the proportion of the total 128 patients experiencing a febrile uti after dx / ha injection in our study was 11.7% ( 15 patients ) , which was slightly higher than those of previous reports ( 8 , 11 , 13 , 14 ) . this result may be due to the fact that our study population included a higher proportion of bilateral cases compared with previous studies . one notable finding is that most of the children who experienced postoperative febrile uti in our study had frequent preoperative febrile uti episodes , implying that children with a history of frequent preoperative febrile utis may be more susceptible to postoperative febrile uti and should be followed - up carefully . there were two cases ( 3.3% ) of newly developed contralateral reflux , but these were low grade . generally , the incidence of concomitant development of contralateral reflux when one side is corrected has been reported to be 5%-18% after open ureteroneocystostomy ( 15 , 16 ) and 8.3%-13.5% after injection therapy ( 17 - 19 ) . it has been suggested that the development of contralateral de novo reflux may be due to the elimination of a pop - off mechanism , surgical distortion of the trigone , or missed reflux on initial vcug . we defined febrile uti using a strict definition , which was culture - positive pyuria with fever of 38 or higher that necessitated hospital admission for intravenous antibiotics ; all of the children were followed - up postoperatively at our hospital ; and the postoperative follow - up protocol was standardized and applied to every patient . in our country , a child with a febrile uti is almost always admitted to a hospital . we applied the same criteria ( hospital admission ) for recording pre- and post - injection febrile uti . thus , differences between the counted and actual numbers of episodes of pre- and post - injection febrile utis were unlikely . in this study , a meta - analysis by aua vesicoureteral reflux guideline update committee demonstrated the relationship among bbd , vur , and febrile uti as follow ; 1 ) the risk of febrile uti in children with vur is greater in those with than without bbd , 2 ) the rate of cure following injection therapy is less in children with than without bbd , 3 ) the rate of postoperative uti is greater in children with than without bbd . therefore , when a child has an evidence of bbd , treatment of bbd should be indicated . there are insufficient data to recommend a specific treatment regimen for bbd , but possible treatment options include behavioral therapy , biofeedback , anticholinergic medications , or treatment of constipation ( 20 ) . we decided to administer low - dose prophylactic antibiotics to patients who had postoperative high grade persistent reflux with a clinical history of many preoperative uti episodes ; therefore , the antibiotics group was mixed with the non - antibiotics group during the postoperative follow - up period . however , among the 75 patients who had postoperative persistent vur , we prescribed prophylactic antibiotics to only 4 patients . it can be logically concluded that if antibiotics prophylaxis was not administrated to any children in the postoperative follow - up period , then the risk of febrile uti may have been slightly higher compared to that observed in the present results . although such prophylaxis is generally recommended in children with vur to prevent febrile utis and subsequent renal damage , there is not sufficient evidence to show that antibiotic prophylaxis has a real and consistent beneficial effect in this regard . a recent and well - designed study ( 21 ) revealed that low - dose prophylaxis may reduce the absolute risk of symptomatic utis in children with predisposing factors , such as vur , by approximately 7% . we think that our study data can reflect ' real - life ' clinical practice and the protocol for our study does not negatively affect its applicability to a population of children with vur because most clinicians generally would administer low - dose antibiotics to children with high grade reflux or those who are thought to be susceptible to uti . conclusively , in children with persistent vur , the number of febrile uti episodes may be decreased after dx / ha injection . after children who need a single additional injection receive the injection , the vur grade may decrease significantly .
we aimed to investigate the clinical value of persistent but downgraded vesicoureteral reflux ( vur ) after dextranomer / hyaluronic acid ( dx / ha ) injection in children . 
 the medical records of 128 children ( 195 ureters ) who underwent dx / ha injections for vur were reviewed . 
 the incidences of pre- and post - operative febrile urinary tract infections ( utis ) were analyzed in children with or without persistent vur on voiding cystourethrography ( vcug ) 3 months postoperatively . 
 the surgical results of vur persistent children who underwent a single additional injection were assessed . 
 the vur resolved completely in 100 ureters ( 51.3% ) , was persistent in 95 ureters , and newly developed in 2 ureters . 
 the incidence of pre / post - operative febrile utis were 0.35  0.39 per year and 0.07  0.32 per year in vur resolved children ( p < 0.001 ) , and 0.76  1.18 per year and 0.20  0.61 per year in vur persistent children ( p < 0.001 ) . 
 a single additional dx / ha injection ( 44 ureters ) resolved vur in 29 ureters ( 65.9% ) , and also reduced the vur to grade i in 7 ureters ( 15.9% ) , ii in 4 ( 9.1% ) , and iii in 4 ( 9.1% ) . even in children with persistent vur 
 after dx / ha injection , the incidence of febrile utis decreased markedly . 
 the vur grade significantly decreases after single additional dx / ha injection .