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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 1  |  Page : 57-68
Evaluating kidney damage from vesico-ureteral reflux in children


1 Department of Mother-Child and Biology-Genetics, University of Verona, Italy
2 Hymmonohematology and Transfusion Service, University of Parma, ParmaTransfusion Service, Verona Hospital, Verona, Italy
3 Department of Pediatrics and Clinical Medicine, Section of Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy

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   Abstract 

To review the most relevant clinical studies that evaluate kidney damage in children with primary vesico-ureteral reflux (VUR), we reviewed and compared randomized controlled trials and clinical trials from scientific literature. In these studies, vesico-ureteral reflux was diagnosed by voiding cystourethrogram and kidney damage was assessed by either DMSA scan or urography. Relative risk with 95% confidence intervals was calculated using Review Manager Software (The Cochrane Collaboration, 2000). The overall relative risk of kidney damage shown by DMSA scan and urography was statistically higher in children with vesico-ureteral reflux of various degrees than in controls (3.7 times and 2.8 times, respectively). However, in high-grade VUR, the relative risk of congenital kidney damage was 5.6 times that of controls. We conclude that severe VUR is frequently associated with early kidney damage, perhaps with prenatal onset. Progression of kidney damage may depend on the severity of VUR and untreated urinary tract infections. Prevention of congenital kidney damage from severe VUR is possible when there is early intervention, even during fetal growth.

Keywords: Meta-analysis, Primary vesico-ureteral reflux, Congenital kidney damage, Children

How to cite this article:
Zaffanello M, Franchini M, Brugnara M, Fanos V. Evaluating kidney damage from vesico-ureteral reflux in children. Saudi J Kidney Dis Transpl 2009;20:57-68

How to cite this URL:
Zaffanello M, Franchini M, Brugnara M, Fanos V. Evaluating kidney damage from vesico-ureteral reflux in children. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2019 Nov 22];20:57-68. Available from: http://www.sjkdt.org/text.asp?2009/20/1/57/44707

   Introduction Top


Vesico-ureteral reflux (VUR) occurs when urine flows backward from the bladder up through ureteric junction, and may reach the kidneys in the severe forms of the disease. Children with urinary tract infections (UTI) may have VUR, which must be classified according to severity before it can be treated. Voiding cystourethro­gram (VCUG) is the imaging technique most frequently used to diagnose and the ureter if there is incontinence of the vesico-classify VUR. The International Study Classification has established levels of severity from I to V, [1] which are still generally accepted.

Chronic severe VUR plays a role in the development of chronic kidney damage (KD) such as kidney growth failure and reflux nephro­pathy (RN). Because the pressure in the bladder is generally greater than that in the kidneys, the reflux of urine exposes the kidneys to unusually high pressure. This increased pressure can da­mage the kidneys and cause persistent paren­chymal abnormalities.

Furthermore, VUR predisposes to pyeloneph­ritis and renal parenchymal abnormalities or "renal scars". Although sterile VUR can cause renal scarring, most studies indicate that the appearance or extent of established renal scars indicates UTI. [2],[3] The use of antibiotics in mild­moderate VUR does not decrease the incidence of UTIs or reduce renal parenchymal damage any more than in controls; [4] however, the oppo­site seems true for high-grade VUR. [5],[6] More than 20 years ago, a high-grade form of VUR carried 4 to 6 times the risk of KD than low­grade VUR and 8 to 10 times the risk than non­refluxing kidneys. [7] Accordingly, children with low-grade VUR had almost 4 times the risk of developing permanent KD than children with non-refluxing units.

In light of the current management of recu­rrent UTIs, the level of severity of VUR might play the greatest role in the development of per­manent KD in children. Therefore, we have re­viewed the correlation between the severity of VUR and permanent KD.


   Methods Top


Related studies were purchased from the follo­wing electronic sources: MEDLINE, EMBASE, and reference lists of relevant articles. Rando­mized controlled trials (RCTs) and clinical trials (CTs), both retrospective and prospective, which evaluated the prevalence or incidence of KD in children with VUR, were included. Limits were set for children of both sexes, with and without UTIs. Those with VUR were iden­tified during an investigation for pelvic dila­tion, routine fetal ultrasound, and post-natal clinical follow-up after a UTI. The VCUG was the standard technique to diagnose and grade VUR. Children with all grades of VUR were included in the study. However, children with urinary tract abnormalities different from VUR, even if associated with it, were excluded from the study.

Antibiotics and monitoring for UTIs through periodic microbiological tests were included in the follow-up visits of these children. There were no restrictions between children on anti­biotics (even of various duration), whether they underwent periodical urinalysis or not. Renal units (RUs) with VUR of different grades of severity were investigated for prevalence of KD. As controls, KD was studied in RUs without VUR. Appropriate imaging techniques, such as DMSA scintigraphy and urography, allowed physicians to determine KD.

The studies were divided into three subsets. The "included studies" subset included those children who were suitable for statistical ana­lysis. Articles taken from this section were in­cluded in two other categories. The "excluded studies" included studies that did not make a comparison between KD associated with VUR and controls. Finally, the "other informative studies" group included only descriptive clini­cal investigations.

Subset 1: Included studies

An average of thirteen studies [4],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] published between 1992 and 2006 [Table 1] were inclu­ded in the meta-analyses. In particular, one study was an RCT multi-center study; [4] two were CT studies; [15],[16] seven were retrospective [9],[12],[13],[14],[17],[18],[19] and three were prospective. [8],[10],[11]

Statistical analyses were categorized accor­ding to the particular clinical pattern (i.e., chro­nic or acute KD and all grades or high-grade VUR) and different imaging techniques (DMSA scan or urography). The first analysis [Figure 1] evaluated persistent KD from all grades of VUR, of which subcategory 1 was chronic KD detected by DMSA scan and subcategory 2 was chronic KD detected by urography. [8],[10] Fur­thermore, the 2nd analysis [Figure 2] included acute KD detected by DMSA scan from all grades of VUR. Results 2b [Figure 2] was chronic KD only in high-grade VUR.

Excluded studies

Nineteen studies published between 1992-2006 were excluded from the statistical analysis. [5],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37] [Table 2] summarizes 15 retrospective and 3 prospective studies, and 1 clinical trial inclu­ding more than 3,300 children with VUR. Fi­nally, [Table 3] describes additional 8 descriptive studies published between 1992-2006. [38],[39],[40],[41],[42],[43],[44],[45] These data concern 4 retrospective, 2 prospective, and 2 clinical trials including more than 1,500 chil­dren with VUR.


   Statistical analysis Top


The overall risks of KD in refluxing and non­refluxing RUs were compared by univariate statistical analysis. The result was the propor­tion of patients with or without VUR who had KD. The relative risk (RR) was used as a mea­sure of summary effect. The dichotomous out­come showed a RR with 95% confidence inter­vals (CI) calculated using Review Manager Software (RevMan 4.1 for Windows, Oxford, UK, The Cochrane Collaboration, 2000). Sum­mary statistics were calculated using the ran­dom effect model, which takes into account "between study variability" as well as "within study variability". The heterogeneity between studies was analyzed using Cochran's Q statis­tic with an "α" of 0.05 used for statistical signi­ficance


   Results Top


Included studies

[Figure 1] and [Figure 2]a-b show the statistical results of our meta-analyses. Ten studies [4],[9],[11],[12],[14],[15],[16],[17],[18],[19] were included in the section "permanent KD detec­ted by DMSA scan" [Figure 1], (subcate-gory 1). For example, Bonnin et al studied KD in asymptomatic siblings of children with known VUR. Only a few siblings with VUR had KD. [11] Other studies showed a comparable risk of KD among categories. In particular, Garin et al de­monstrated that the risk of permanent KD after UTIs was the same for children with mild­moderate VUR as for those with no VUR. [4] Again, Orellana et al did not show a statistical difference of permanent KD. [16] However, after 2 years of follow-up, Taskinen et al showed that both serious UTIs and KD were complications frequently associated with VUR. [17] Furthermore, six additional studies showed that KD was more frequent in patients with VUR. [9],[12],[14],[15],[18],[19]

Finally, these studies showed an overall RR of permanent KD by DMSA scintigraphy 3.7 times higher in patients with VUR than in controls. In addition, the section including chronic KD measured by urography (subcate­gory 2) included two other studies [8],[10] showing a RR of KD 2.4 times higher in children with VUR. Including all data, the overall RR of persistent KD was 3.4 times higher with VUR. In conlusion, the risk of persistent KD mea­sured by urography was lower than that mea­sured by DMSA scan, but always significantly higher than in controls.

[Figure 2a] shows two studies on acute KD after UTIs. [13],[15] Abnormal DMSA scans were not different between children with and without VUR. In conclusion, the overall RR of acute KD in children with VUR was about 2 times higher than, but not statistically different from, controls.

[Figure 2b] shows four studies on permanent KD associated with high grades of VUR. [12],[14],[15],[19] The results were statistically significant and showed a RR of persistent KD 5.6 times higher in children with severe VUR than in unaffected children.

Excluded studies

[Table 2] shows nineteen studies carried out between 1992 and 2006. [5],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37] The method most frequently used to investigate KD was by DMSA scan. About 26% of children with VUR deve­loped kidney damage, particularly if associated with high grade VUR. [24],[25],[27],[30] Interestingly, KD was also observed in asymptomatic siblings of children with VUR, [20],[21],[35] which suggests a con­genital condition. [22],[28],[33] There were more male children with high grade VUR and KD, [22],[26] which worsened after UTIs. [28],[31] Sometimes, a voiding dysfunction could be associated with the above conditions.23 KD from UTIs was more common before 5 years of life. Still, with close supervision and prompt treatment of recurrent UTIs, children can progress well with either medical or surgical intervention. [5],[29],[34],[36] VUR diagnosed before the age of 3 years leaves less scarring than when diagnosed at later ages. [37]

Another eight studies are shown in [Table 3]. [38],[39],[40],[41],[42],[43],[44],[45] KD was associated with high grade VUR, [39] while its correlation with UTIs was not clearly proven. [32] Furthermore, RN was frequently con­genital [38] and its progression was not predicta­ble. [40] The choice method to detect KD was DMSA scan. [32],[38],[39],[42],[44] The VCUG was the common method to diagnose VUR, [41],[43],[45] whereas magnetic resonance voiding cystography was less sensitive. [45] In addition, ultrasound (US) detection of pelvic fluctuation facilitated the prediction of VUR grading. [42]


   Discussion Top


VUR, either alone or complicated by UTIs, is a risk for permanent kidney damage in small children. In particular, the more serious VUR is the greater the possibility for it to cause chronic KD. [39] Nevertheless, KD is frequently already evident at birth as a congenital condition that is not easily preventable; [11],[18],[33],[40] it tends to wor­sen during the first two years of life [46] perhaps due to complicated urinary tract infections. [28],[31] It is more frequent in males. [10] DMSA scinti­graphy is the method of choice to detect KD related to VUR and UTIs [12],[14],[16],[18] and is more sensitive than urography. [47]

The relative risk of children with VUR of de­veloping chronic KD is 3.7 times greater when measured by DMSA scan and 2.4 times greater when urography is used, ultimately underesti­mating the potential for KD. [8],[10],[46] Taken as a whole, our study gave 3.4 times the RR of KD. This must be taken as a mean value because it includes all grades of VUR. A recent investiga­ion showed comparable renal scarring in mild­moderate VUR compared with controls [4] and a high risk of permanent KD with high-grade VUR [30],[39] - 5.6 times that of controls (present data). Moreover, KD may coexist early with high-grade VUR, 11, 17 even during fetal life. On the contrary, the overall RR of acute KD in children with VUR was comparable to con­trols. [13],[15] ,present data

To sum up, according to most modern approa­ches, both UTIs and mild-grade VUR do not cause permanent kidney damage. However, the more severe the reflux, the greater the risk of new or progressive renal scarring, RN, and kidney growth failure. Severity of VUR, pa­tient's age, and presence of KD dictate how and when this condition should be treated.

Options of therapy include surgery and long­term chemoprophylaxis, which we have been using for several decades. Therapeutic approa­ches to VUR can be clinical in less severe cases or surgical in more serious conditions. The main objectives of treatment are prevention of onset and delay of progression of KD. Unfor­tunately, a long-term study covering many years showed that neither medical nor surgical therapy was the better choice. [46] Moreover, mo­dern management of VUR seems to still have conflicting results. On the one hand, neither treatment was able to protect against the prog­ression of chronic KD, [22],[48] and on the other hand, preservation of renal parenchyma from repeated injuries by means of early surgical and medical treatment has been reported. [5] Today, the controversy continues as to the suitable approach to VUR aimed at protecting renal function. [49]

Before resorting to surgery, treatment with antibiotics along with laboratory follow-up can help to prevent KD from recurring UTIs. [2] However, antimicrobials did not seem to have better results than surgery in reducing the risks of permanent KD. [49] Still, the inappropriateness of antibiotics has been suggested in mild-grade forms, [4] but it is recommended for severe cases of VUR, [6] especially while awaiting surgery. Finally, the only real benefit of surgery and antibiotics is to limit febrile UTIs, but both are insufficient in avoiding permanent KD in children with VUR. [48],[50],[51] This implies that mo­dern treatment of severe VUR does not confer a substantial clinical benefit in children. Perhaps this is because the same etiological conditions of severe VUR might contribute to chronic KD. [52] Again, permanent KD could have a close connection with severe VUR, whereas UTIs are additional contributors. The main target of mo­dern therapy remains the prevention of renal parenchyma injury instead of simply curing VUR. [50]

Finally, it is almost certain that severe VUR may lead to RN even during fetal life, but this is very improbable in mild forms. A cause and effect relationship between experimental VUR and KD has been reported in the fetus of animals. [53] The mechanical action of refluxing urine seems to be sufficient to cause RN, even in animals. On the contrary, it is emerging that the combination of severe VUR and congenital RN may derive from a common mechanism such as the result of a dysfunction in normal embryological evolution. [54]


   Conclusions Top


UTIs, if treated in time, will unlikely cause long-term kidney morbidity. KD is unexpected in mild forms of VUR, as opposed to high­grade forms despite existing antimicrobial the­rapies and surgical procedures. This is in line with the question of whether severe VUR or KD starts first, but it is likely that both begin and progress together. KD could possibly be primarily explained by congenital factors not uncontrolled UTIs. Consequently, prevention of long-term kidney morbidity is not possible until interventions start immediately after birth.

Current postnatal treatment offers few advan­tages in treating a problem that starts and progresses during fetal life. Severe VUR could be a malignant condition because it is asso­ciated with parenchymal damage, which occurs also in the absence of UTIs. Actually, physi­cians may only attempt an early diagnosis, continue monitoring for UTIs and surgical treatment to delay but unlikely avoid the wor­sening of KD from severe VUR.

We need an up-to-date pathogenesis of KD to understand why there is a high risk of KD in high-grade forms of VUR but not in mild forms, and we need to adequately utilize surgical, preventive, and state-of-the-art treatment for re­current UTIs. The situation today requires new preventive strategies and innovative treatment procedures to avoid congenital KD in primary severe VUR. This implies, for example, that the possible goal of new therapies should be early prevention of renal parenchyma injury starting from the uterus.

 
   References Top

1.Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Mobius TE. International system of radiographic grading of vesicoureteric reflux: International Reflux Study in Children. Pediatr Radiol 1985;15:105-9.  Back to cited text no. 1    
2.Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103:843-52.  Back to cited text no. 2    
3.Gordon I, Barkovics M, Pindoria S, Cole TJ, Woolf AS. Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta­analysis. J Am Soc Nephrol 2003;14: 739-44.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Garin EH, Olavarria F, Garcia Nieto V, Valen­ciano B, Campos A, Young L. Clinical signi­ficance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelo­nephritis: a multicenter, randomized, controlled study. Pediatrics 2006;117:626-32.  Back to cited text no. 4    
5.Sweeney B, Cascio S, Velayudham M, Puri P. Reflux nephropathy in infancy: a comparison of infants presenting with and without urinary tract infection. J Urol 2001;166:648-50.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Wald ER. Vesicoureteral reflux: The role of antibiotic prophylaxis. Pediatrics 2006;117:919-­22.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.McKerrow W, Davidson-Lamb N, Jones PF. Urinary tract infection in children. Br Med J (Clin Res Ed) 1984;289:299-303.  Back to cited text no. 7    
8.Berg UB. Long-term follow-up of renal mor­phology and function in children with recurrent pyelonephritis. J Urol 1992;148:1715-20.  Back to cited text no. 8  [PUBMED]  
9.Merrick MV, Notghi A, Chalmers N, Wilkinson AG, Uttley WS. Long-term follow up to deter­mine the prognostic value of imaging after urinary tract infections, Part 1: Reflux. Arch Dis Child 1995;72:388-92.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Pediatr 2000; 136:30-4.  Back to cited text no. 10    
11.Bonnin F, Lottmann H, Sauty L, et al. Scinti­graphic screening for renal damage in siblings of children with symptomatic primary vesico-ureteric reflux. Br J Urol Int 2001;87: 463-6.  Back to cited text no. 11    
12.Polito C, Rambaldi PF, Mansi L, Di Toro R, La Manna A. Unilateral vesicoureteric reflux: low prevalence of contralateral renal damage. J Pediatr 2001;138: 875-9.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Cascio S, Chertin B, Yoneda A, Rolle U, Kelleher J, Puri P. Acute renal damage in infants after first urinary tract infection. Pediatr Nephrol 2002; 17:503-5.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Caione P, Ciofetta G, Collura G, Morano S, Capozza N. Renal damage in vesico-ureteric reflux. BJU Int 2004;93:591-5.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Camacho V, Estorch M, Fraga G, et al. DMSA study performed during febrile urinary tract infection: a predictor of patient outcome? Eur J Nucl Med Mol Imaging 2004;31:862-6.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Orellana P, Baquedano P, et al. Relationship between acute pyelonephritis, renal scarring, and vesicoureteral reflux. Results of a coor-dinated research project. Pediatr Nephrol 2004; 19:1122-6.  Back to cited text no. 16    
17.Taskinen S, Ronnholm K. Post-pyelonephritic renal scars are not associated with vesico-ureteral reflux in children. J Urol 2005;173: 1345-8.  Back to cited text no. 17    
18.Tombesi M, Ferrari CM, Bertolotti JJ. Renal damage in refluxing and non-refluxing siblings of index children with vesicoureteral reflux. Pediatr Nephrol 2005;20:1201-2.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Temiz Y, Tarcan T, Onol FF, Alpay H, Simsek F. The efficacy of Tc99m dimercaptosuccinic acid (Tc-DMSA) scintigraphy and ultrasonography in detecting renal scars in children with primary vesicoureteral reflux (VUR). Int Urol Nephrol 2006;38:149-52.  Back to cited text no. 19    
20.Kenda RB, Fettich JJ. Vesicoureteric reflux and renal scars in asymptomatic siblings of children with reflux. Arch Dis Child 1992;67:506-8.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]
21.Buonomo C, Treves ST, Jones B, Summerville D, Bauer S, Retik A. Silent renal damage in symptom-free siblings of children with vesico­ureteral reflux: assessment with technetium Tc 99m dimercaptosuccinic acid scintigraphy. J Pediatr 1993;122:721-3.  Back to cited text no. 21  [PUBMED]  
22.Marra G, Barbieri G, Dell'Agnola CA, Caccamo ML, Castellani MR, Assael BM. Congenital renal damage associated with primary vesico-ureteral reflux detected prenatally in male infants. J Pediatr 1994;124:726-30.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Naseer SR, Steinhardt GF. New renal scars in children with urinary tract infections, vesico­ureteral reflux and voiding dysfunction: a pros­pective evaluation. J Urol 1997;158:566-8.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Connolly LP, Treves ST, Connolly SA, et al. Vesicoureteral reflux in children: incidence and severity in siblings. J Urol 1997;157:2287-90.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]
25.Puri P, Cascio S, Lakshmandass G, Colhoun E. Urinary tract infection and renal damage in sibling vesicoureteral reflux. J Urol 1998;160: 1028-30.  Back to cited text no. 25  [PUBMED]  
26.Hiraoka M, Hori C, Tsukahara H, et al. Vesico­ureteral reflux in male and female neonates as detected by voiding ultrasonography. Kidney Int 1999;55:1486-90.  Back to cited text no. 26  [PUBMED]  [FULLTEXT]
27.Goldman M, Bistritzer T, Horne T, Zoareft I, Aladjem M. The etiology of renal scars in infants with pyelonephritis and vesicoureteral reflux. Pediatr Nephrol 2000;14:385-8.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]
28.Lama G, Russo M, De Rosa E, et al. Primary vesicoureteric reflux and renal damage in the first year of life. Pediatr Nephrol 2000;15:205-10.  Back to cited text no. 28  [PUBMED]  [FULLTEXT]
29.Olbing H, Hirche H, Koskimies O, et al. Renal growth in children with severe vesicoureteral reflux: 10-year prospective study of medical and surgical treatment: the International Reflux Study in Children (European branch). Radiology 2000; 216:731-7.  Back to cited text no. 29  [PUBMED]  [FULLTEXT]
30.McIlroy PJ, Abbott GD, Anderson NG, Turner JG, Mogridge N, Wells JE. Outcome of primary vesicoureteric reflux detected following fetal renal pelvic dilatation. J Paediatr Child Health 2001; 36:569-73.  Back to cited text no. 30    
31.Yoneda A, Cascio S, Oue T, Chertin B, Puri P. Risk factors for the development of renal paren­chymal damage in familial vesicoureteral reflux. J Urol 2002;168:1704-7.  Back to cited text no. 31  [PUBMED]  
32.Cemerlic´-Zecevic´ E, Milicic´-Pokrajac D, Dzinovic´ A. Urinary tract infections and vesico­ureteral reflux as a cause of renal parenchymal damage. Med Arh 2002;56:14-6.  Back to cited text no. 32    
33.Nakai H, Kakizaki H, Konda R, et al. Prospective Study Committee of Reflux Nephropathy Forum, Japan: clinical characteristics of primary vesico­ureteral reflux in infants: Multicenter retros­pective study in Japan. J Urol 2003;163:309-12.  Back to cited text no. 33    
34.Ylinen E, Ala-Houhala M, Wikstrom S. Risk of renal scarring in vesicoureteral reflux detected either antenatally or during the neonatal period. Urology 2003;61:1238-43.  Back to cited text no. 34    
35.Ataei N, Madani A, Esfahani ST, et al. Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux. Pediatr Nephrol 2004;19:1127-31.  Back to cited text no. 35  [PUBMED]  [FULLTEXT]
36.Jodal U, Smellie JM, Lax H, Hoyer PF. Ten-year results of randomised treatment of children with severe vesicoureteral reflux: Final report of the International Reflux Study in Children. Pediatr Nephrol 2006;21:785-92.  Back to cited text no. 36  [PUBMED]  [FULLTEXT]
37.Pirker ME, Colhoun E, Puri P. Renal scarring in familial vesicoureteral reflux: Is prevention possible? J Urol 2006;176:1842-6.  Back to cited text no. 37  [PUBMED]  [FULLTEXT]
38.Polito C, La Manna A, Rambaldi PF, Nappi B, Mansi L, Di Toro R. High incidence of a generally small kidney and primary vesico-ureteral reflux. J Urol 2000;164:479-82.  Back to cited text no. 38  [PUBMED]  [FULLTEXT]
39.Silva JM, Diniz JS, Oliveira EA, et al. Features of primary vesicoureteral reflux and renal damage in children at a single institution in Brazil from 1969 to 1999. Int Urol Nephrol 2003;35:161-8.  Back to cited text no. 39  [PUBMED]  [FULLTEXT]
40.Marra G, Oppezzo C, Ardissino G, et al. Severe vesicoureteral reflux and chronic renal failure: A condition peculiar to male gender? Data from the ItalKid Project. J Pediatr 2004;144:677-81.  Back to cited text no. 40    
41.Hjalmas K, Lohr G, Tamminen-Mobius T, Seppanen J, Olbing H, Wikstrom S. Surgical results in the International Reflux Study in Children (Europe). J Urol 1992;148:1657-61.  Back to cited text no. 41    
42.Anderson NG, Allan RB, Abbott GD. Fluctua-ting fetal or neonatal renal pelvis: Marker of high­grade vesicoureteral reflux. Pediatr Nephrol 2004; 19:749-53.  Back to cited text no. 42  [PUBMED]  [FULLTEXT]
43.Rachmiel M, Aladjem M, Starinsky R, Strauss S, Villa Y, Goldman M. Symptomatic urinary tract infections following voiding cystourethrography. Pediatr Nephrol 2005;20:1449-52.  Back to cited text no. 43  [PUBMED]  [FULLTEXT]
44.Groshar D, Gorenberg V, Weissman I, Livne PM, Front D. Detection of permanent damage in kidneys with vesicoureteral reflux by quantitative single photon emission computerized tomography (SPECT) uptake of 99mtechnetium labeled dimmercaptosuccinic acid. J Urol 1996; 155:664-7.  Back to cited text no. 44  [PUBMED]  
45.Lee SK, Chang Y, Park NH, Kim YH, Woo S. Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: comparative study with voiding cystourethrography. J Magn Reson Imaging 2005;21:406-14.  Back to cited text no. 45  [PUBMED]  [FULLTEXT]
46.Birmingham Reflux Study Group. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: Five years' observation. Br Med J (Clin Res Ed) 1987;295: 237-41.  Back to cited text no. 46  [PUBMED]  [FULLTEXT]
47.Stokland E, Hellstrom M, Jacobsson B, Sixt R. Imaging of renal scarring. Acta Paediatr Suppl 1999;431:13-21.  Back to cited text no. 47    
48.Wheeler DM, Vimalachandra D, Hodson EM, Roy LP, Smith GH, Craig JC. Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev 2004;3:CD001532.  Back to cited text no. 48  [PUBMED]  [FULLTEXT]
49.Wheeler D, Vimalachandra D, Hodson EM, Roy LP, Smith G, Craig JC. Antibiotics and surgery for vesicoureteric reflux: a meta-analysis of ran­domised controlled trials. Arch Dis Child 2003; 88:688-94.  Back to cited text no. 49  [PUBMED]  [FULLTEXT]
50.Fanos V, Cataldi L. Antibiotics or surgery for vesicoureteric reflux in children. Lancet 2004; 364:1720-2.  Back to cited text no. 50  [PUBMED]  [FULLTEXT]
51.Williams GJ, Wei L, Lee A, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children. Cochrane Database Syst Rev 2006;3:CD001534.  Back to cited text no. 51  [PUBMED]  [FULLTEXT]
52.Hodson E, Wheeler D, Vimalchandra D, Smith G, Craig J. Interventions for primary vesicoureteric reflux. Cochrane Database Sysr Rev 2007;18: CD001532.  Back to cited text no. 52    
53.Gobet R, Cisek LJ, Chang B, Barnewolt CE, Retik AB, Peters CA. Experimental fetal vesicoureteral reflux induces renal tubular and glomerular damage, and is associated with persistent bladder instability. J Urol. 1999;162:1090-5.  Back to cited text no. 53    
54.Murer L, Benetti E, Artifoni L. Embryology and genetics of primary vesico-ureteric reflux and associated renal dysplasia. Pediatr Nephrol 2007;22:788-97.  Back to cited text no. 54  [PUBMED]  [FULLTEXT]

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Correspondence Address:
M Zaffanello
Department of Mother-Child and Biology-Genetics, University of Verona, Piazzale L. Scuro, 10 37134 Verona
Italy
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PMID: 19112220

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