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Gene Review

VUR  -  Vesicoureteral reflux

Homo sapiens

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Disease relevance of VUR


Psychiatry related information on VUR

  • The patients were children with VUR or normal genitourinary anatomy who presented with UTI or dysfunctional voiding and children screened for genitourinary problems such as hematuria, sibling reflux or bedwetting [6].
  • Although vesicoureteric reflux (VUR) is observed more commonly in infants than children with UTI, it is rare in uninfected patients at any age and should never be considered a normal finding during human development [7].
  • MATERIALS AND METHODS: We reviewed the records of 32 consecutive children with complicated enuresis who were referred for neurosurgical evaluation, including those with a history of refractory voiding dysfunction or incontinence associated with persistent vesicoureteral reflux, encopresis, or associated leg or back pain [8].
  • This includes improved evaluation of renal vasculature and parenchyma, assessment of vesicoureteral reflux in children, assessment of tubal patency in women, and evaluation of prostate diseases and erectile dysfunction in men [9].
  • Here we report on a boy with mild mental retardation, lobar HPE, epilepsy, mild pyramidal syndrome of the legs, ventricular septal defect, vesicoureteral reflux, preaxial polydactyly, and facial dysmorphisms [10].

High impact information on VUR


Chemical compound and disease context of VUR


Biological context of VUR

  • The TGF-beta1 gene polymorphism was determined, and we found significant over-representation of the TT genotype in primary VUR patients with CRI compared with normal renal function (P= 0.0035) [20].
  • Significantly higher K allele frequency was present in primary VUR with CRI children, as it was in the renal survival curve study [20].
  • Hence, VUR maps to a locus on chromosome 1 [1].
  • The VUR phenotype is associated with shortness of the submucosal segment of the ureter due to congenital lateral ectopia of the ureteric orifice [21].
  • Single strand conformational polymorphism (SSCP) analysis of 23 affected subjects in eight families with primary familial VUR showed no alterations in exons 2-5 of the PAX2 gene [2].

Anatomical context of VUR


Associations of VUR with chemical compounds

  • Renal ultrasonography and cystography were done on the newborn babies soon after delivery, and a dimercaptosuccinic acid (DMSA) radioisotope scan at 3 months was done on those with VUR [25].
  • 91 children (143 ureters) with primary vesicoureteric reflux (VUR) treated endoscopically by subureteric injection of 'Polytef' (polytetrafluoroethylene) paste were followed up for 2 to 5 1/2 years [26].
  • This study also suggests that VUR is almost certain to have occurred in a child who has bilateral abnormal 99mTc-DMSA images following UTI and is also commonly present in those with definite unilateral defects [27].
  • All patients underwent renal cortical scintigraphy (with technetium-99m dimercaptosuccinic acid or Tc-99m gluconate) and voiding cystourethrography (VCUG) to identify the presence of cortical defects and VUR, respectively [28].
  • MATERIALS AND METHODS: A total of 32 males and 81 females with a median age of 1 year (range 3 months to 10 years) underwent endoscopic correction of primary VUR with dextranomer/hyaluronic acid copolymer [29].

Regulatory relationships of VUR

  • Furthermore, 10 of 23 (44%) patients with VUR and seven of 19 (42%) controls carried the AT2 receptor gene variation [30].
  • RESULTS: The mean serum ICAM-1 level in the control group was 202 +/- 79 ng/mL (mean +/- 1 SD) compared with 347 +/- 96 ng/mL in children with VUR (P < 0.001) [31].
  • RESULTS: The mean serum ELAM-1 levels were 54.23 +/- 20.11 ng/ml in controls and 77.79 +/- 34.50 ng/ml in children with vesicoureteral reflux (p < 0.05) [32].

Other interactions of VUR

  • However, the frequency distribution of KLK1 promoter among VUR patients with or without CRI (A, 50.0% and 67.5%; B, 17.9% and 8.3%; H, 14.3% and 18.3%; K, 17.9% and 5.8%, respectively) was statistically different (P = 0.008) [20].
  • No significant linkage was found to 6p, where a renal and ureteric malformation locus has been reported, or to PAX2, mutations of which cause VUR in renal-coloboma syndrome [1].
  • There seems no doubt that VUR is linked to HLA whilst the case for PUJO is equivocal [33].
  • CONCLUSION: A prediction rule based on age, gender, family history, CRP and US results is useful in assessing the probability of VUR in the individual child with a first UTI and may help the physician to make decisions about performing additional imaging techniques [34].
  • The data showed that ACE gene polymorphisms were associated with progressive renal deterioration in Taiwanese children with VUR and might act synergistically with the -6 G allele of the AGT gene [35].

Analytical, diagnostic and therapeutic context of VUR

  • These included 69 patients with VUR, 110 with RN (determined by absence/presence of renal scarring on dimercaptosuccinc acid scan), 27 with chronic renal failure due to RN, and 40 patients (control group) with urinary tract infection and normal findings on renal ultrasonography and voiding cystoureterogram [5].
  • In this study, independent predictors obtained from patient history, physical examination and laboratory results for vesico-ureteric reflux (VUR) in children of 0-5 y with a first urinary tract infection (UTI) were assessed and the added value of renal ultrasound (US) investigated [34].
  • A systematic literature review and meta-analysis was performed to determine how effectively the finding of primary vesicoureteric reflux (VUR) on micturating cystography (MCU) in children hospitalized with UTI predicted renal parenchymal disease on (99m)Technetium-dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy [36].
  • MATERIALS AND METHODS: Three hundred two children younger than 11 years with urinary tract infection and grade III or IV VUR were randomly assigned to surgical (n = 149) or medical (n = 153) treatment and were followed up at serial intravenous urography for up to 5 years; 223, for up to 10 years (surgical, n = 110; medical, n = 113) [37].
  • MATERIALS AND METHODS: Two groups of children were examined prospectively: 124 with severe urinary tract infection, defined as patient hospitalization or a maximum temperature greater than 39.5 degrees C, and 135 with previously diagnosed VUR [38].


  1. Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1. Feather, S.A., Malcolm, S., Woolf, A.S., Wright, V., Blaydon, D., Reid, C.J., Flinter, F.A., Proesmans, W., Devriendt, K., Carter, J., Warwicker, P., Goodship, T.H., Goodship, J.A. Am. J. Hum. Genet. (2000) [Pubmed]
  2. Absence of PAX2 gene mutations in patients with primary familial vesicoureteric reflux. Choi, K.L., McNoe, L.A., French, M.C., Guilford, P.J., Eccles, M.R. J. Med. Genet. (1998) [Pubmed]
  3. Renal-coloboma syndrome: a multi-system developmental disorder caused by PAX2 mutations. Eccles, M.R., Schimmenti, L.A. Clin. Genet. (1999) [Pubmed]
  4. Vesicoureteral reflux increases the risk of renal scars: a study of unilateral reflux. Lee, J.H., Son, C.H., Lee, M.S., Park, Y.S. Pediatr. Nephrol. (2006) [Pubmed]
  5. Renin-angiotensin system polymorphisms and renal scarring. Pardo, R., Málaga, S., Coto, E., Navarro, M., Alvarez, V., Espinosa, L., Alvarez, R., Vallo, A., Loris, C., Braga, S. Pediatr. Nephrol. (2003) [Pubmed]
  6. A multivariate analysis of dysfunctional elimination syndrome, and its relationships with gender, urinary tract infection and vesicoureteral reflux in children. Chen, J.J., Mao, W., Homayoon, K., Steinhardt, G.F. J. Urol. (2004) [Pubmed]
  7. Vesicoureteric reflux and renal injury. Arant, B.S. Am. J. Kidney Dis. (1991) [Pubmed]
  8. Magnetic resonance imaging in children with voiding dysfunction: is it indicated? Pippi Salle, J.L., Capolicchio, G., Houle, A.M., Vernet, O., Jednak, R., O'Gorman, A.M., Montes, J.L., Farmer, J.P. J. Urol. (1998) [Pubmed]
  9. Ultrasound contrast agents and their use in urogenital radiology: status and prospects. Jakobsen, J.A., Correas, J.M. European radiology. (2001) [Pubmed]
  10. Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1. Koolen, D.A., Herbergs, J., Veltman, J.A., Pfundt, R., van Bokhoven, H., Stroink, H., Sistermans, E.A., Brunner, H.G., Geurts van Kessel, A., de Vries, B.B. J. Hum. Genet. (2006) [Pubmed]
  11. Mutation of the gene in a family with optic nerve colobomas, renal anomolies and vesicoureteral reflux. Sanyanusin, P., Schimmenti, L.A., McNoe, T.A., Ward, T.A., Pierpont, M.E., Sullivan, M.J., Dobyns, W.B., Eccles, M.R. Nat. Genet. (1996) [Pubmed]
  12. Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Sanyanusin, P., Schimmenti, L.A., McNoe, L.A., Ward, T.A., Pierpont, M.E., Sullivan, M.J., Dobyns, W.B., Eccles, M.R. Nat. Genet. (1995) [Pubmed]
  13. Correlation of P blood group, vesicoureteral reflux, and bacterial attachment in patients with recurrent pyelonephritis. Lomberg, H., Hanson, L.A., Jacobsson, B., Jodal, U., Leffler, H., Edén, C.S. N. Engl. J. Med. (1983) [Pubmed]
  14. Vesicoureteral reflux in children with uremia. Prognostic indicators for treatment and survival. Berger, R.E., Ansell, J.S., Shurtleff, D.B., Hickman, R.O. JAMA (1981) [Pubmed]
  15. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. Capozza, N., Caione, P. J. Pediatr. (2002) [Pubmed]
  16. Childhood urinary tract infection: a clinical analysis of 597 cases. Wu, C.Y., Chiu, P.C., Hsieh, K.S., Chiu, C.L., Shih, C.H., Chiou, Y.H. Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi. (2004) [Pubmed]
  17. Vesicoureteral reflux after intravesical instillation of bacillus Calmette-Guérin against carcinoma in situ of the bladder. Morita, T., Tokue, A. Urologia internationalis. (2004) [Pubmed]
  18. Delayed presentation of posterior urethral valves: a not so benign condition. Bomalaski, M.D., Anema, J.G., Coplen, D.E., Koo, H.P., Rozanski, T., Bloom, D.A. J. Urol. (1999) [Pubmed]
  19. Long-term efficacy of subureteral collagen injection for endoscopic treatment of vesicoureteral reflux in neurogenic bladder cases. Haferkamp, A., Möhring, K., Staehler, G., Gerner, H.J., Dörsam, J. J. Urol. (2000) [Pubmed]
  20. Significance of the tissue kallikrein promoter and transforming growth factor-beta1 polymorphisms with renal progression in children with vesicoureteral reflux. Lee-Chen, G.J., Liu, K.P., Lai, Y.C., Juang, H.S., Huang, S.Y., Lin, C.Y. Kidney Int. (2004) [Pubmed]
  21. Unravelling the genetics of vesicoureteric reflux: a common familial disorder. Eccles, M.R., Bailey, R.R., Abbott, G.D., Sullivan, M.J. Hum. Mol. Genet. (1996) [Pubmed]
  22. Relationship of asymptomatic bacteriuria and renal scarring in children with neuropathic bladders who are practicing clean intermittent catheterization. Ottolini, M.C., Shaer, C.M., Rushton, H.G., Majd, M., Gonzales, E.C., Patel, K.M. J. Pediatr. (1995) [Pubmed]
  23. Vesicoureteral reflux in boys with hypospadias. Shafir, R., Hertz, M., Boichis, H., Tsur, H., Aladjem, M., Jonas, P. Urology (1982) [Pubmed]
  24. Urothelial differentiation in vesicoureteric reflux and other urological disorders of childhood: a comparative study. Garthwaite, M.A., Thomas, D.F., Subramaniam, R., Stahlschmidt, J., Eardley, I., Southgate, J. Eur. Urol. (2006) [Pubmed]
  25. Screening of newborn babies for familial ureteric reflux. Scott, J.E., Swallow, V., Coulthard, M.G., Lambert, H.J., Lee, R.E. Lancet (1997) [Pubmed]
  26. Endoscopic correction of primary vesicoureteric reflux by subureteric injection of polytetrafluoroethylene. Puri, P. Lancet (1990) [Pubmed]
  27. Technetium-99m-DMSA studies in pediatric urinary infection. Clarke, S.E., Smellie, J.M., Prescod, N., Gurney, S., West, D.J. J. Nucl. Med. (1996) [Pubmed]
  28. Vesicoureteral reflux: an accurate predictor of acute pyelonephritis in childhood urinary tract infection? Ditchfield, M.R., De Campo, J.F., Cook, D.J., Nolan, T.M., Powell, H.R., Sloane, R., Grimwood, K., Cahill, S. Radiology. (1994) [Pubmed]
  29. Treatment of vesicoureteral reflux by endoscopic injection of dextranomer/hyaluronic Acid copolymer: preliminary results. Puri, P., Chertin, B., Velayudham, M., Dass, L., Colhoun, E. J. Urol. (2003) [Pubmed]
  30. Angiotensin II, type 2 receptor in the development of vesico-ureteric reflux. Hohenfellner, K., Hunley, T.E., Yerkes, E., Habermehl, P., Hohenfellner, R., Kon, V. BJU international. (1999) [Pubmed]
  31. Serum intercellular adhesion molecule (ICAM-1), a marker of renal scarring in infants with vesico-ureteric reflux. Miyakita, H., Puri, P., Surana, R., Kobayashi, H., Reen, D.J. British journal of urology. (1995) [Pubmed]
  32. Increased levels of circulating endothelial leukocyte adhesion molecule-1 (ELAM-1) in children with reflux nephropathy. Kobayashi, H., Wang, Y., Puri, P. Eur. Urol. (1997) [Pubmed]
  33. HLA linkage with familial vesicoureteral reflux and familial pelvi-ureteric junction obstruction. Mackintosh, P., Almarhoos, G., Heath, D.A. Tissue Antigens (1989) [Pubmed]
  34. Prediction of vesico-ureteric reflux in childhood urinary tract infection: a multivariate approach. Oostenbrink, R., van der Heijden, A.J., Moons, K.G., Moll, H.A. Acta Paediatr. (2000) [Pubmed]
  35. Renin-angiotensin system polymorphisms in Taiwanese primary vesicoureteral reflux. Liu, K.P., Lin, C.Y., Chen, H.J., Wei, C.F., Lee-Chen, G.J. Pediatr. Nephrol. (2004) [Pubmed]
  36. Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis. Gordon, I., Barkovics, M., Pindoria, S., Cole, T.J., Woolf, A.S. J. Am. Soc. Nephrol. (2003) [Pubmed]
  37. 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). Olbing, H., Hirche, H., Koskimies, O., Lax, H., Seppänen, U., Smellie, J.M., Tamminen-Möbius, T., Wikstad, I. Radiology. (2000) [Pubmed]
  38. Cyclic cystography: diagnostic yield in selected pediatric populations. Gelfand, M.J., Koch, B.L., Elgazzar, A.H., Gylys-Morin, V.M., Gartside, P.S., Torgerson, C.L. Radiology. (1999) [Pubmed]
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