今日の臨床サポート

膀胱尿管逆流

著者: 兼松明弘 兵庫医科大学病院 泌尿器科

監修: 松田公志 関西医科大学 泌尿器科学教室

著者校正/監修レビュー済:2020/09/10
患者向け説明資料

概要・推奨   

  1. 原発性VURの自然治癒予測因子として最も重視するものは、①国際分類グレード(VUR grade)であり、その他の主要なものとして②VUR診断年齢、③両側性か片側性か、④VUR出現時膀胱容量がある。
  1. 原発性VURの腎機能予後は、腎実質形成不全の有無で先天的に規定され、尿路感染による腎瘢痕形成の有無で後天的に影響される。
  1. 尿路感染症の制御の目的は腎機能のさらなる悪化の防止とともに、感染イベントそのものの患児や保護者の負担を軽減することにある。DMSA腎シンチグラフィでの実質異常所見は尿路感染発症リスクの予測因子である。
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。 閲 覧 にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご 契約が 必要となり ます。閲覧にはご契約が 必要となります。閲覧にはご契約が必要となります。閲覧 に はご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご 契約が必要とな ります。閲覧に はご契約が必要となります。閲覧にはご契約が必要となり ます。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
兼松明弘 : 特に申告事項無し[2021年]
監修:松田公志 : 講演料(アステラス製薬株式会社),奨学(奨励)寄付など(小野薬品工業株式会社)[2021年]

改訂のポイント:
  1. 前版は泌尿器科医対象AUAのGLと一般小児科医対象のAAPのGLを参考にしていた。その後本邦から診療手引きがだされた。これらの間には様々な相違点があり、それを明確に示すことでVURの診療を専門としない泌尿器科医・小児科医師が理解しやすいように配慮した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 膀胱尿管逆流(VUR)とは、膀胱尿管接合部の逆流防止機構の機能不全により、膀胱から上部尿路に尿が逆流することである。腎実質への細菌の侵入が容易になるため、有熱性尿路感染症(急性腎盂腎炎)を惹起することがある。
  1. 神経因性膀胱(機能的疾患)や後部尿道弁など(器質的疾患)に伴う下部尿路閉塞によって惹起される膀胱尿管逆流(VUR)は、続発性(二次性)VURであり、原疾患の診断と治療が優先されるので、通常の(原発性または一次性)VURとは区別される。
  1. VURは、尿路の先天性疾患のなかでも最も頻度が高いものの1つであり、健康な小児の1~3%、出生前超音波診断水腎症の10~20%、VUR小児の無症候性同胞の30%、尿路感染症(UTI)を発症した小児の30~40%に認められる[1]
  1. 乳幼児期に診断されるVURは、成長発達に伴う膀胱尿管移行部の成熟により、多くが自然改善する。
  1. 乳児期に有熱性尿路感染で診断されるVURは男児の方が多く、先天性の腎実質形成不全(低形成腎)が合併していることがある。高度包茎が増悪因子となっている可能性がある(C G)。
  1. 乳児期以後(排尿習慣が自立する年齢以後)に尿路感染で診断されるVURは女児の方が多く、排尿排便習慣異常(BBD)が増悪因子となっていることがある(M JG)
  1. 全年齢を通して、尿管拡張やDMSA腎シンチグラフィーでの異常が存在するか、排尿排便習慣異常(BBD)が併存している場合に、有熱性尿路感染を発症しやすい(C)。
  1. 急性腎盂腎炎の反復により腎実質が障害を受けることがあり腎瘢痕と呼ばれる。先天的な低形成腎と腎瘢痕の影響から、成長につれて高血圧や腎機能障害が発生することを逆流性腎症という。
問診・診察のポイント  
ポイント:
  1. 有熱性尿路感染febrile urinary tract infection, fUTIの原疾患としてVURの有無を検索すべきかどうか判断するポイントと、VURの存在がすでに診断されている状況での問診・診察のポイントがあり、以下は両者に関連する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: M A Sargent
雑誌名: Pediatr Radiol. 2000 Sep;30(9):587-93.
Abstract/Text BACKGROUND: The prevalence of vesicoureteral reflux in normal children has been estimated to be 0.4% to 1.8%. Based on epidemiological data, it can be estimated that 2.2% of girls and 0.6% of boys may be found to have reflux as a result of the investigation of urinary tract infection. This implies that most children with reflux will develop urinary tract infection. However, most children with reflux detected by screening do not develop infection. Hence the prevalence of vesicoureteral reflux in normal children may be higher than the previous estimates.
OBJECTIVE: To determine the prevalence of vesicoureteral reflux in groups of children with different clinical indications for cystogram.
MATERIALS AND METHODS: Over 250 articles from the literature were reviewed to determine the prevalence of vesicoureteral reflux in children undergoing cystogram. Means and 95% confidence limits were derived from the data in studies that met the inclusion criteria.
RESULTS: The prevalence of vesicoureteral reflux in children with urinary tract infection was 31.1% (95% CI: 29.9-32.8). The prevalence of vesicoureteral reflux varied between patient groups, but often approached or exceeded the prevalence in urinary tract infection. The prevalence in normal kidneys was 17.2% (95% CI: 14.4-20.1).
CONCLUSION: Vesicoureteral reflux is common in nearly all patient groups examined. The prevalence of vesicoureteral reflux in normal children is probably significantly higher than the traditional estimates.

PMID 11009294  Pediatr Radiol. 2000 Sep;30(9):587-93.
著者: W Farhat, D J Bägli, G Capolicchio, S O'Reilly, P A Merguerian, A Khoury, G A McLorie
雑誌名: J Urol. 2000 Sep;164(3 Pt 2):1011-5.
Abstract/Text PURPOSE: Academic research on pediatric nonneurogenic voiding dysfunction has long been hampered by the lack of a standardized reporting system for voiding symptoms. We evaluated the performance of a newly devised, objective instrument to quantify or grade the severity of abnormal voiding behaviors of children.
MATERIALS AND METHODS: There were 10 voiding dysfunction parameters that were assigned scores of 0 to 3 according to prevalence, and possible total scores ranged from 0 to 30. The Dysfunctional Voiding Symptom Score was completed by 2 groups of patients. Group 1 consisted of patients 3 to 10 years old presenting to the pediatric urology clinic with a history of diurnal urinary incontinence, urinary tract infections or abnormal voiding habits. Group 2 consisted of an age matched cohort with no history of urological complaints presenting to hospital clinics outside of urology. Patients diagnosed with organic or anatomical disease, such as posterior urethral valves or meningomyelocele, were excluded from our analysis.
RESULTS: Group 1 consisted of 104 patients (female-to-male ratio 4:1) with a median symptom score of 14 and group 2 consisted of 54 patients (female-to-male ratio 1.3:1) with a median score of 4. The dysfunctional voiding odds ratio was 2.93 for females compared to that of males. Using receiver operating characteristics the optimum cutoff score was 6.026 (sensitivity 92.77% and specificity 87.09%) for females and 9.02 (sensitivity of 80.95% and specificity of 91. 30%) for males. In addition, we found certain questions to be more reflective than others of dysfunctional voiding symptoms in our population.
CONCLUSIONS: The Dysfunctional Voiding Symptom Score appears to provide accurate and objective, that is, numerical, grading of voiding behaviors of children. Comparative research studies of dysfunctional voiding diagnosis and response to therapy as well as objective measurements of treatment efficacy and outcomes analysis should be aided greatly by this system.

PMID 10958730  J Urol. 2000 Sep;164(3 Pt 2):1011-5.
著者: RIVUR Trial Investigators, Alejandro Hoberman, Saul P Greenfield, Tej K Mattoo, Ron Keren, Ranjiv Mathews, Hans G Pohl, Bradley P Kropp, Steven J Skoog, Caleb P Nelson, Marva Moxey-Mims, Russell W Chesney, Myra A Carpenter
雑誌名: N Engl J Med. 2014 Jun 19;370(25):2367-76. doi: 10.1056/NEJMoa1401811. Epub 2014 May 4.
Abstract/Text BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial.
METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance.
RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group.
CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

PMID 24795142  N Engl J Med. 2014 Jun 19;370(25):2367-76. doi: 10.1056・・・
著者: Jyoti Upadhyay, Stéphane Bolduc, Darius J Bagli, Gordon A McLorie, Antonie E Khoury, Walid Farhat
雑誌名: J Urol. 2003 May;169(5):1842-6; discussion 1846; author reply 1846. doi: 10.1097/01.ju.0000058211.24641.66.
Abstract/Text PURPOSE: Dysfunctional voiding influences the presence and persistence of vesicoureteral reflux. We used a standardized published instrument, the dysfunctional voiding symptom score, to evaluate the association of dysfunctional voiding with vesicoureteral reflux. We report its use for monitoring improvement in and resolution of vesicoureteral reflux.
MATERIALS AND METHODS: In 1998, 114 patients with dysfunctional voiding were placed on behavioral modification. Of 58 patients (51%) who presented with urinary tract infection 27 (47%) had abnormal voiding cystourethrography, including 19 with reflux only. Baseline and followup dysfunctional voiding symptom score was determined in these 19 patients, who underwent prospective observational therapy and behavioral modification. We correlated the dysfunctional voiding symptom score with the evolution of vesicoureteral reflux.
RESULTS: Vesicoureteral reflux was present in 19 of the 58 patients (33%) with dysfunctional voiding and urinary tract infection. All affected patients were female with a mean age of 6.7 years and a mean followup of 24 months. Reflux grade in the 24 units was I to IV in 7, 9, 7 and 1, respectively. Mean dysfunctional voiding symptom score was 13.3 in patients with normal voiding cystourethrography and 11.7 in the vesicoureteral reflux group (p = 0.6). Reflux resolved in 3, 2 and 2 cases of grades I, II and III disease, respectively, while improvement (decrease of 2 or more grades) was noted in 4. Initial dysfunctional voiding symptom score in these 11 cases decreased from a mean of 9.6 (range 4 to 18) to 3.7 (range 0 to 12, p = 0.01). The 8 patients with persistent reflux had an initial dysfunctional voiding symptom score of 14.4 (range 4 to 21), which decreased to 11.1 (range 1 to 19, p = 0.18).
CONCLUSIONS: A significant decrease in the dysfunctional voiding symptom score appears to confirm compliance with behavioral modification and predicts ultimate reflux resolution. The dysfunctional voiding symptom score provides a noninvasive means of monitoring compliance with therapy during expectant treatment of patients with vesicoureteral reflux.

PMID 12686859  J Urol. 2003 May;169(5):1842-6; discussion 1846; author・・・
著者: Kazuyoshi Johnin, Kenichi Kobayashi, Teruhiko Tsuru, Tetsuya Yoshida, Susumu Kageyama, Akihiro Kawauchi
雑誌名: Int J Urol. 2019 Feb;26(2):160-171. doi: 10.1111/iju.13881. Epub 2018 Dec 19.
Abstract/Text Voiding cystourethrography is the most important fluoroscopic examination in pediatric urology for the investigation of lower urogenital tract diseases, such as vesicoureteral reflux or urethral stricture. However, this invasive procedure imposes a significant burden on children and their parents, and recently there has been a paradigm shift in the diagnosis and treatment of vesicoureteral reflux. In the 2011 revision, the American Academy of Pediatrics guidelines on urinary tract infection recommended abandoning routine voiding cystourethrography after the first febrile urinary tract infection. In 2014, the randomized intervention for children with vesicoureteral reflux study recommended discontinuation of routine continuous antibiotic prophylaxis for vesicoureteral reflux. The time is now ripe to radically reconsider indications for voiding cystourethrography and the procedure itself.

© 2018 The Japanese Urological Association.
PMID 30569659  Int J Urol. 2019 Feb;26(2):160-171. doi: 10.1111/iju.13・・・
著者: Carlos R Estrada, Carlo C Passerotti, Dionne A Graham, Craig A Peters, Stuart B Bauer, David A Diamond, Bartley G Cilento, Joseph G Borer, Marc Cendron, Caleb P Nelson, Richard S Lee, Jing Zhou, Alan B Retik, Hiep T Nguyen
雑誌名: J Urol. 2009 Oct;182(4):1535-41. doi: 10.1016/j.juro.2009.06.053. Epub 2009 Aug 15.
Abstract/Text PURPOSE: We determined the resolution rate of vesicoureteral reflux and the factors that influence it to formulate nomograms to predict the probability of annual resolution for individual cases of reflux.
MATERIALS AND METHODS: We studied 2,462 children with primary vesicoureteral reflux diagnosed between 1998 and 2006. Cox proportional hazards regression was used to model time to resolution as a function of statistically significant demographic and clinical variables. The resulting model was used to construct nomograms predicting the annual cumulative probability of reflux resolution.
RESULTS: Multivariate analysis showed that all cases of unilateral reflux resolved earlier than female bilateral reflux (HR 1.42, p <0.001). Additionally age less than 1 year at presentation (HR 1.31, p <0.001), lower reflux grade (2.96, p <0.001 for grade I; 2.28, p <0.001 for grade II; 1.63, p <0.001 for grade III), reflux diagnosed on postnatal evaluation for prenatal hydronephrosis or sibling screening (1.24, p = 0.002) and single ureter (1.55, p <0.001) were associated with significantly earlier resolution of reflux. Specific predicted cumulative probabilities of reflux resolution at annual intervals from diagnosis (1 to 5 years) were calculated for every possible combination of the significant variables.
CONCLUSIONS: Our analyses demonstrate that resolution of vesicoureteral reflux is dependent on age at presentation, gender, grade, laterality, mode of clinical presentation and ureteral anatomy. We constructed nomogram tables containing estimates of annual reflux resolution rate as a function of these variables. This information is valuable for clinical counseling and management decisions.

PMID 19683762  J Urol. 2009 Oct;182(4):1535-41. doi: 10.1016/j.juro.20・・・
著者: Zeb M McMillan, J Christopher Austin, Matthew J Knudson, Charles E Hawtrey, Christopher S Cooper
雑誌名: J Urol. 2006 Oct;176(4 Pt 2):1838-41. doi: 10.1016/S0022-5347(06)00619-7.
Abstract/Text PURPOSE: Reflux grade is the factor most commonly used to predict spontaneous reflux resolution. We evaluated other potential predictive factors aside from reflux grade relative to spontaneous resolution.
MATERIALS AND METHODS: We reviewed the records of 20 males and 98 females who were diagnosed with primary vesicoureteral reflux between ages 0 and 7 years between 1990 and 2000. Age, sex, height, weight, reflux grade, bladder volume at onset of reflux and laterality were recorded for the first, second and most recent voiding cystourethrogram or nuclear cystogram before spontaneous resolution or operative intervention.
RESULTS: Of 118 patients 75 (64%) had spontaneous resolution, 27 (23%) underwent corrective surgery and 16 (13%) are still being followed. Average age at diagnosis was 2.3 years (range 1 day to 7.7 years) and average followup was 4.3 years (range 0.2 to 14). Average time to spontaneous resolution was 2.2 years (range 0.5 to 10.3) vs a time to operative treatment of 3.6 years (range 0.2 to 11.2). There was a significantly higher spontaneous resolution rate for lower reflux grades (p = 0.0004). Reflux occurring at greater than 75% of predicted bladder capacity had a significantly higher resolution rate (p = 0.0005). The initial height and weight percentile was not significant for predicting spontaneous resolution. Breakthrough urinary tract infections were negative predictors of spontaneous resolution (p <0.0001).
CONCLUSIONS: In addition to grade, bladder volume relative to predicted bladder capacity at the onset of reflux appears to provide additional prognostic information regarding the likelihood of spontaneous resolution of primary vesicoureteral reflux.

PMID 16945667  J Urol. 2006 Oct;176(4 Pt 2):1838-41. doi: 10.1016/S002・・・
著者: Gerald C Mingin, Hiep T Nguyen, Laurence S Baskin, Susan Harlan
雑誌名: J Urol. 2004 Sep;172(3):1075-7; discussion 1077.
Abstract/Text PURPOSE: The management of high grade vesicoureteral reflux remains controversial, with breakthrough infections being an indication for surgical repair. We sought to determine if technetium dimercapto-succinic acid (DMSA) scan could help predict which children are at risk for breakthrough urinary tract infection.
MATERIALS AND METHODS: A retrospective review was performed on children presenting with a febrile urinary tract infection and prenatal hydronephrosis who were found to have vesicoureteral reflux and underwent a DMSA scan. Reflux was tabulated according to the highest grade. DMSA results were graded as 0-normal, no parenchymal or size defects, grade 1-focal parenchymal defects or less than a quarter of a renal unit involved, or grade 2-severe defects to include at least half of a renal unit, bilateral defects or unilateral atrophy.
RESULTS: A total of 120 consecutive patients were evaluated. An abnormal DMSA scan was documented in 57 (33 females and 24 males), and 35 with grade 1 and 22 with grade 2 defects. Of the patients 53 females and 10 males had a normal scan. Of the 57 children with an abnormal DMSA scan 6% presented with grades 1 and 2 vesicoureteral reflux, 24% with grade 3, 38% with grade 4 and 26% with grade 5. Of the children with grades 3 to 5 reflux 60% had a subsequent breakthrough infection. Of the 63 children with a normal DMSA scan 11% presented with grade 1 reflux, 28% with grade 2, 48% with grade 3, 11% with grade 4 and 2% with grade 5. Of these children 5 had a subsequent breakthrough infection.
CONCLUSIONS: An abnormality on DMSA scan in the presence of grade 3 to 5 reflux correlates with a greater chance of having a breakthrough infection (60%). We conclude that children with grade 3 to 5 vesicoureteral reflux and an abnormal DMSA scan are at increased risk for breakthrough urinary tract infection.

PMID 15311041  J Urol. 2004 Sep;172(3):1075-7; discussion 1077.
著者: Michiko Nakamura, Kimihiko Moriya, Takahiko Mitsui, Hiroshi Tanaka, Katsuya Nonomura
雑誌名: J Urol. 2009 Oct;182(4 Suppl):1694-7. doi: 10.1016/j.juro.2009.03.070. Epub 2009 Aug 18.
Abstract/Text PURPOSE: We investigated factors affecting the breakthrough urinary tract infection rate during prophylactic antibiotic treatment in children with primary vesicoureteral reflux.
MATERIALS AND METHODS: Medical charts were retrospectively reviewed in children with primary vesicoureteral reflux diagnosed at age 12 months or less who received prophylactic antibiotics and underwent (99m)Tc-dimercapto-succinic acid scan. Parameters assessed for their relation to breakthrough urinary tract infection were gender, presenting symptoms, age at presentation, prophylactic antibiotic type, reflux grade at presentation and scan findings.
RESULTS: Enrolled in the study were 52 boys and 6 girls with a mean age at presentation of 3.7 months and a mean followup of 42.5 months. Urinary tract infection was a presenting symptom in 46 children. Low reflux grade (1-3) was identified in 18 children and 40 had high grade reflux (4-5). Abnormal (99m)Tc-dimercapto-succinic acid scan was documented in 36 children (62%). During followup breakthrough vesicoureteral reflux developed in 12 children, including 11 of 36 (31%) with an abnormal scan but only 1 of 22 (5%) with a normal scan (p = 0.021). The breakthrough urinary tract infection-free rate during followup was significantly lower in children with an abnormal scan (p = 0.033). Other factors were not significantly associated with the breakthrough urinary tract infection rate.
CONCLUSIONS: Abnormal (99m)Tc-dimercapto-succinic acid scan may be a factor predicting breakthrough urinary tract infection in children with primary vesicoureteral reflux. Prophylactic antibiotics may have a limited treatment role in children with an abnormal scan.

PMID 19692059  J Urol. 2009 Oct;182(4 Suppl):1694-7. doi: 10.1016/j.ju・・・
著者: H Bouachrine, J L Lemelle, F Didier, M Schmitt
雑誌名: Br J Urol. 1996 Dec;78(6):936-9.
Abstract/Text OBJECTIVE: To describe the pre- and post-natal characteristics of primary vesico-ureteric reflux (VUR) in a retrospective study of babies presenting with VUR suspected from pre-natal ultrasonography.
PATIENTS AND METHODS: Between 1984 and 1994. 61 children (41 boys and 20 girls) with primary VUR were followed for 2 years after the pre-natal detection of urinary tract anomalies. Patients with VUR secondary to infravesical obstruction and duplex systems were excluded. The mean age at ante-natal diagnosis was 28.4 weeks of gestation; in 37 the reflux was bilateral and 98 refluxing units were reviewed.
RESULTS: According to the international classification of VUR, 8% were grade 1, 32% grade 2, 38% grade 3, 16% grade 4 and 6% grade 5. Twelve patients (22 refluxing units) underwent ureteric re-implantation. Six kidneys showed renal scars on isotope renography and two nephrectomies were carried out in patients < 2 years old: in 40 patients (64 renal units) the VUR resolved spontaneously. Of the latter, eight were grade 1, 20 grade 2, 27 grade 3 and nine grade 4: seven patients (10 refluxing units) are still being followed and awaiting a decision on treatment.
CONCLUSION: This study confirms the predominance of boys in those with ante-natally suspected VUR. The spontaneous resolution during the first 2 years of life was apparent in most cases, even in those with severe reflux (grade 3-5).

PMID 9014723  Br J Urol. 1996 Dec;78(6):936-9.
著者: C K Yeung, M L Godley, H K Dhillon, I Gordon, P G Duffy, P G Ransley
雑誌名: Br J Urol. 1997 Aug;80(2):319-27.
Abstract/Text OBJECTIVE: To examine the characteristics of primary vesico-ureteric reflux (VUR) in young infants following prenatal hydronephrosis.
PATIENTS AND METHODS: The study comprised 155 consecutive infants with VUR detected at a mean age of 8.7 weeks (SD 6.3). Reflux units (n = 236) were analysed for relationships between gender, severity of reflux, exposure to urinary tract infection (UTI) and the presence of focal and generalized types of kidney damage on imaging. Bladder wall thickness (from ultrasonography) was examined in comparison with a further group of 29 males without VUR.
RESULTS: Male infants predominated (117 of 155, 75%); bilateral VUR affected the same proportion (52%) of males and females. Most kidneys exposed to VUR (158 of 236. 67%) were normal and of the 78 abnormal kidneys (57 without UTI), 53 showed generalized damage (only eight exposed to UTI) and 71 (91%) were associated with severe (grades IV and V) reflux that predominantly affected males (P < 0.001). Grade V reflux was almost exclusively a male disorder. Most female units (45 of 58, 78%) compared with 46% (82/178) of male units had mild (grades I to III) reflux that was independently associated with normal kidneys. The mean bladder wall thickness was significantly greater for males with VUR than for females with VUR and for males without VUR.
CONCLUSIONS: Two distinct but not exclusive patterns of VUR were identified: (i) mild reflux associated with normal kidneys that affected most females and a proportion of males; (ii) severe reflux combined with kidney damage, most likely fetal in origin, that is almost exclusively a male disorder.

PMID 9284209  Br J Urol. 1997 Aug;80(2):319-27.
著者: J A Stock, D Wilson, M K Hanna
雑誌名: J Urol. 1998 Sep;160(3 Pt 2):1017-8.
Abstract/Text PURPOSE: When prenatal ultrasound reveals urinary tract dilatation, fetal reflux is suspected. Postnatal voiding cystourethrography confirms the diagnosis. The origin of reflux nephropathy is controversial, and the roles of urinary tract infection and pressure effects of sterile reflux on the developing kidneys are debatable. We evaluate the relationship between sterile reflux and renal scarring.
MATERIALS AND METHODS: We reviewed the records of 100 infants and children seen during a 15-year period in whom fetal reflux had been diagnosed, including 81 with bilateral and 19 with unilateral vesicoureteral reflux. In 12 of the 19 patients voiding cystourethrography revealed unilateral grade IV or V reflux, and they comprise the study group. Split renal function was measured in all 12 patients by radionuclide renal scan shortly after birth and before urinary tract infection developed.
RESULTS: Individual renal function was 0 to 40% in all refluxing renal units. Split renal function was less than 10% in 3 kidneys, 10 to 30% in 5 and 30 to 40% in 4. There were 2 nonfunctioning kidneys. In the remaining 10 kidneys isotope distribution on the nuclear scan indicated decreased renal length and mass. Subsequently 7 patients had breakthrough urinary tract infections while on antibiotic chemoprophylaxis. Nephrectomy, and nephroureterectomy and ureteral reimplantation with or without tapering were performed in 3 and 9 refluxing ureters, respectively. Pathological examination of the 3 nephrectomy specimens revealed severe renal dysplasia consisting of persistent primitive ducts and nests of metaplastic cartilage.
CONCLUSIONS: Our study supports the notion that renal impairment associated with severe fetal reflux is present at birth, and it is likely due to congenital dysplasia.

PMID 9719267  J Urol. 1998 Sep;160(3 Pt 2):1017-8.
著者: Hideo Nakai, Hidehiro Kakizaki, Ryuichiro Konda, Yutaro Hayashi, Shozo Hosokawa, Satoru Kawaguchi, Hirofumi Matsuoka, Katsuya Nonomura, Kenji Shimada, Takeshi Kawamura, Prospective Study Committee of Reflux Nephropathy Forum, Japan
雑誌名: J Urol. 2003 Jan;169(1):309-12. doi: 10.1097/01.ju.0000042766.09295.72.
Abstract/Text PURPOSE: We evaluate clinical characteristics of primary vesicoureteral reflux in infants in a multicenter study in Japan with special reference to the relation of renal parenchymal damage to urinary tract infection and gender.
MATERIALS AND METHODS: Infants younger than 1 year old with primary vesicoureteral reflux were recruited from 14 hospitals during the 3-year registration period beginning in January 1996 and ending in December 1998. Various clinical parameters as well as renal parenchymal lesion on dimercaptosuccinic acid scintigraphy were evaluated.
RESULTS: Of 356 infants enrolled 296 (83%) were male and 60 (17%) were female. In 85% of infants presenting symptom was febrile urinary tract infection. There were 204 bilateral (57%) and 152 unilateral (43%) cases. Reflux was bilateral in 56% of males versus 65% of females, and high grade (grades IV and V) in 58% of males versus 55% of females. Diffuse parenchymal lesion was similarly noted in infants with or without prior urinary tract infection (38% and 46%, respectively) and was more often noted in male than in female infants (42% versus 25%).
CONCLUSIONS: Despite the current use of screening prenatal ultrasound, many infants are still diagnosed as having vesicoureteral reflux only after the occurrence of urinary tract infection. The greater severity of renal parenchymal lesion in male infants combined with similar incidence of diffuse parenchymal lesion in those with or without prior infection suggests preexisting congenital abnormalities in the male refluxing kidney.

PMID 12478178  J Urol. 2003 Jan;169(1):309-12. doi: 10.1097/01.ju.0000・・・
著者: Per Brandström, Elisabeth Esbjörner, Maria Herthelius, Gundela Holmdahl, Göran Läckgren, Tryggve Nevéus, Ulla Sillén, Rune Sixt, Ingrid Sjöberg, Eira Stokland, Ulf Jodal, Sverker Hansson
雑誌名: J Urol. 2010 Jul;184(1):274-9. doi: 10.1016/j.juro.2010.01.055. Epub 2010 May 15.
Abstract/Text PURPOSE: We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection.
MATERIALS AND METHODS: Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle.
RESULTS: During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy.
CONCLUSIONS: Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20478580  J Urol. 2010 Jul;184(1):274-9. doi: 10.1016/j.juro.2010・・・
著者: Gundela Holmdahl, Per Brandström, Göran Läckgren, Ulla Sillén, Eira Stokland, Ulf Jodal, Sverker Hansson
雑誌名: J Urol. 2010 Jul;184(1):280-5. doi: 10.1016/j.juro.2010.01.059. Epub 2010 May 20.
Abstract/Text PURPOSE: We compared reflux status in children with dilating vesicoureteral reflux treated in 3 groups, including low dose antibiotic prophylaxis, endoscopic therapy and a surveillance group on antibiotic treatment only for febrile urinary tract infection.
MATERIALS AND METHODS: A total of 203 children 1 to younger than 2 years with grade III-IV reflux were recruited into this open, randomized, controlled trial. Endoscopic treatment was done with dextranomer/hyaluronic acid copolymer. The main end point was reflux status after 2 years. Data were analyzed by the intent to treat principle.
RESULTS: Reflux status improved in all 3 treatment arms. Of patients in the prophylaxis, endoscopic and surveillance groups 39%, 71% and 47%, respectively, had reflux resolution or downgrading to grade I-II after 2 years. This was significantly more common in the endoscopic than in the prophylaxis and surveillance groups (p = 0.0002 and 0.0030, respectively). After 1 or 2 injections 86% of patients in the endoscopic group had no or grade I-II reflux but recurrent dilating reflux was seen in 20% after 2 years.
CONCLUSIONS: Endoscopic treatment resulted in dilating reflux resolution or downgrading in most treated children. After 2 years endoscopic treatment results were significantly better than the spontaneous resolution rate or downgrading in the prophylaxis and surveillance groups. However, of concern is the common reappearance of dilating reflux after 2 years.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20488469  J Urol. 2010 Jul;184(1):280-5. doi: 10.1016/j.juro.2010・・・
著者: Per Brandström, Elisabeth Esbjörner, Maria Herthelius, Svante Swerkersson, Ulf Jodal, Sverker Hansson
雑誌名: J Urol. 2010 Jul;184(1):286-91. doi: 10.1016/j.juro.2010.01.061. Epub 2010 May 20.
Abstract/Text PURPOSE: We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux randomly allocated to 3 management alternatives, including antibiotic prophylaxis, endoscopic treatment or surveillance only as the control.
MATERIALS AND METHODS: At 23 centers a total of 203 children were included in the study, including 128 girls and 75 boys 1 to younger than 2 years. Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection (194) after prenatal screening (9). Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. The febrile urinary tract infection rate was analyzed by the intent to treat principle.
RESULTS: We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys (p = 0.0001). There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 (19%) on prophylaxis, 10 of 43 (23%) with endoscopic therapy and 24 of 42 (57%) on surveillance (p = 0.0002). In girls the recurrence rate was associated with persistent reflux after 2 years (p = 0.0095). However, reflux severity (grade III or IV) at study entry did not predict recurrence.
CONCLUSIONS: In this randomized, controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys. Antibiotic prophylaxis and endoscopic treatment decreased the infection rate.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20488494  J Urol. 2010 Jul;184(1):286-91. doi: 10.1016/j.juro.201・・・
著者: Per Brandström, Tryggve Nevéus, Rune Sixt, Eira Stokland, Ulf Jodal, Sverker Hansson
雑誌名: J Urol. 2010 Jul;184(1):292-7. doi: 10.1016/j.juro.2010.01.060. Epub 2010 May 23.
Abstract/Text PURPOSE: We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group.
MATERIALS AND METHODS: Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle.
RESULTS: New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001).
CONCLUSIONS: In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20494369  J Urol. 2010 Jul;184(1):292-7. doi: 10.1016/j.juro.2010・・・
著者: Ulla Sillén, Per Brandström, Ulf Jodal, Gundela Holmdahl, Anders Sandin, Ingrid Sjöberg, Sverker Hansson
雑誌名: J Urol. 2010 Jul;184(1):298-304. doi: 10.1016/j.juro.2010.03.063. Epub 2010 May 20.
Abstract/Text PURPOSE: We investigated the prevalence and types of lower urinary tract dysfunction in children with vesicoureteral reflux grades III and IV, and related improved dilating reflux, renal damage and recurrent urinary tract infection to dysfunction.
MATERIALS AND METHODS: A total of 203 children between ages 1 to less than 2 years with reflux grades III and IV were recruited into this open, randomized, controlled, multicenter study. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done at study entry and 2-year followup. Lower urinary tract function was investigated by noninvasive methods, at study entry with 4-hour voiding observation in 148 patients and at 2 years by structured questionnaire and post-void residual flow measurement in 161.
RESULTS: At study entry 20% of patients had lower urinary tract dysfunction, characterized by high bladder capacity and increased post-void residual urine. At 2 years there was dysfunction in 34% of patients. Subdivision into groups characteristic of children after toilet training revealed that 9% had isolated overactive bladder and 24% had voiding phase dysfunction. There was a negative correlation between dysfunction at 2 years and improved dilating reflux (p = 0.002). Renal damage at study entry and followup was associated with lower urinary tract dysfunction at 2 years (p = 0.001). Recurrent urinary tract infections were seen in 33% of children with and in 20% without dysfunction (p = 0.084).
CONCLUSIONS: After toilet training a third of these children with dilating reflux had lower urinary tract dysfunction, mainly voiding phase problems. Dysfunction was associated with persistent reflux and renal damage while dysfunction at study entry did not predict the 2-year outcome.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20488486  J Urol. 2010 Jul;184(1):298-304. doi: 10.1016/j.juro.20・・・
著者: Jose de Bessa, Flavia Cristina de Carvalho Mrad, Evilin Feitosa Mendes, Marcia Carvalho Bessa, Victor Pereira Paschoalin, Ricardo Brianezi Tiraboschi, Zein Mohamed Sammour, Cristiano Mendes Gomes, Luis H Braga, José Murillo Bastos Netto
雑誌名: J Urol. 2015 May;193(5 Suppl):1772-7. doi: 10.1016/j.juro.2014.10.092. Epub 2015 Mar 25.
Abstract/Text PURPOSE: The followup and treatment of children with vesicoureteral reflux has been debated for many years. Antibiotic prophylaxis has a role for preventing urinary tract infection in these children. Recent studies and guidelines suggested that prophylaxis has little or no role in preventing urinary tract infection in those children, especially those with low grades (I and II) of reflux.
MATERIALS AND METHODS: We analyzed all published randomized, controlled trials comparing antibiotic prophylaxis vs no prophylaxis or placebo in children with vesicoureteral reflux. The children were divided into those with nondilated (grades I and II) and dilated (grades III and IV) vesicoureteral reflux. After data were analyzed the RIVUR study was published and, therefore, it was added to the analyzed data.
RESULTS: After analyzing the first published studies we found that antibiotic prophylaxis would be beneficial only in children with high grade vesicoureteral reflux. With the addition of the data in the RIVUR study these results changed. The new pooled data support antibiotic prophylaxis in all children with vesicoureteral reflux.
CONCLUSIONS: Vesicoureteral reflux management is still controversial. In contrast to recently published studies and guidelines, this meta-analysis supports antibiotic prophylaxis in all children with vesicoureteral reflux regardless of reflux grade. More studies are needed to support this finding.

Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 25817142  J Urol. 2015 May;193(5 Suppl):1772-7. doi: 10.1016/j.ju・・・
著者: Pankaj Hari, Smriti Hari, Aditi Sinha, Rakesh Kumar, Arti Kapil, Ravindra Mohan Pandey, Arvind Bagga
雑誌名: Pediatr Nephrol. 2015 Mar;30(3):479-86. doi: 10.1007/s00467-014-2943-z. Epub 2014 Aug 31.
Abstract/Text BACKGROUND: The benefits of long-term low-dose antibiotics in preventing urinary tract infection (UTI) and renal damage in children with primary vesicoureteric reflux (VUR) are unclear.
METHODS: Children aged between 1 and 12 years with VUR grade I-IV and a microbiologically proven UTI were randomized into two groups to receive either antibiotic prophylaxis [2 mg/kg trimethoprim + sulfamethoxazole (TMP-SMX)] daily or placebo, respectively, for 12 months. Primary outcome was microbiologically confirmed symptomatic UTI. Intention-to-treat analysis using time-to-event data was performed.
RESULTS: A total of 93 children (66.7 % boys) with a median age of 4.6 years were enrolled in this study; VUR grade III-IV was present in 73.1 % of these children. At least one symptomatic UTI occurred in ten (21.3 %) patients receiving antibiotic prophylaxis and in three (6.5 %) patients receiving placebo [hazard ratio in antibiotic group 3.9; 95 % confidence interval (CI) 1- 14; log rank test P = 0.02). Compared to the group receiving placebo, the antibiotic group had a 14.8 % increased risk for developing UTI (95 % CI 1-28; P = 0.03). Of the total number of episodes of UTI, 58.3 % of those in the antibiotic group were caused by TMP-SMX-resistant bacteria compared to 20 % in the placebo group (P = 0.15). A renal scan at 12 months revealed that six of 37 (16.2 %) patients in the antibiotic group and seven of 43 (16.3 %) patients in the placebo group had new or worsening of pre-existing scar.
CONCLUSIONS: Long-term antibiotic prophylaxis with TMP-SMX is associated with increased risk of symptomatic UTI compared to placebo in children with grade I-IV VUR.

PMID 25173357  Pediatr Nephrol. 2015 Mar;30(3):479-86. doi: 10.1007/s0・・・
著者: Véronique Phan, Jeffrey Traubici, Brian Hershenfield, Derek Stephens, Norman D Rosenblum, Denis F Geary
雑誌名: Pediatr Nephrol. 2003 Dec;18(12):1224-8. doi: 10.1007/s00467-003-1287-x. Epub 2003 Oct 30.
Abstract/Text Standardized evaluation of all newborns with antenatally recognized hydronephrosis (ANH) at The Hospital for Sick Children (HSC) has included voiding cystourethrography (VCUG). This paper reviews this protocol to determine: (1) the prevalence of vesicoureteral reflux (VUR) in isolated ANH and (2) the value of performing VCUG in cases of mild hydronephrosis, defined as renal pelvis dilatation <10 mm on postnatal ultrasonography (US). A retrospective chart review was performed on infants referred with ANH. The inclusion criterion was isolated ANH. Exclusion criteria were (1) presence of additional genitourinary abnormalities and (2) no VCUG. Pelviectasis was categorized according to the anteroposterior diameter of the renal pelvis. There were 111 infants with isolated ANH. All except 3 underwent VCUG. There were 68 children (63%) with normal postnatal US or mild pelviectasis (<10 mm). VUR was detected in 16 patients, of whom 10 had mild or absent pelvic dilatation. There was no correlation between the degree of pelviectasis on postnatal US and the presence or severity of VUR ( P=0.567 and P=0.802). VUR was detected in 15% of children with isolated ANH, many of whom had normal postnatal US or mild postnatal pelviectasis. VCUG is the only reliable test for detecting postnatal VUR.

PMID 14586679  Pediatr Nephrol. 2003 Dec;18(12):1224-8. doi: 10.1007/s・・・
著者: A M van Eerde, M H Meutgeert, T P V M de Jong, J C Giltay
雑誌名: Ultrasound Obstet Gynecol. 2007 Apr;29(4):463-9. doi: 10.1002/uog.3975.
Abstract/Text OBJECTIVE: To investigate the value of prenatally detected hydronephrosis (PNH) as a prognostic factor for vesico-ureteral reflux (VUR).
METHODS: The MEDLINE database was searched for articles on PNH and VUR published between 1980 and 2004. A total of 18 studies were identified and reviewed for various aspects. Results were separated for primary and/or secondary VUR whenever possible, because of the different underlying pathogenic mechanisms.
RESULTS: There was considerable variation between the different studies with respect to methodology and study design. One of the main discrepancies was the way in which postnatal abnormalities were ascertained: by postnatal ultrasound, voiding cystourethrogram (VCUG) alone, or combined or sequential ultrasound and VCUG. Taking these limitations into account, the published data showed there to be a mean prevalence of 15% for postnatal primary VUR after PNH. Of all patients with PNH, 53% had no postnatal anomalies, whereas 29% had other anomalies, such as duplex collecting systems.
CONCLUSIONS: Of all infants with PNH, 15% had primary VUR proven postnatally and 53% had no other anomalies detected. We suggest a standardized protocol for future studies, to enable better comparison of follow-up protocols. Published by John Wiley & Sons, Ltd.

Copyright (c) 2007 ISUOG.
PMID 17390310  Ultrasound Obstet Gynecol. 2007 Apr;29(4):463-9. doi: 1・・・
著者: T E Wiswell, D W Geschke
雑誌名: Pediatrics. 1989 Jun;83(6):1011-5.
Abstract/Text The records of 136,086 boys born in US Army hospitals from 1980 to 1985 were reviewed for indexed complications related to circumcision status during the first month of life. For 100,157 circumcised boys, there were 193 complications (0.19%). These included 62 local infections, eight cases of bacteremia, 83 incidences of hemorrhage (31 requiring ligature and three requiring transfusion), 25 instances of surgical trauma, and 20 urinary tract infections. There were no deaths or reported losses of the glans or entire penis. By contrast, the complications in the 35,929 uncircumcised infants were all related to urinary tract infections. Of the 88 boys with such infections (0.24%), 32 had concomitant bacteremia, three had meningitis, two had renal failure, and two died. The frequencies of urinary tract infection (P less than .0001) and bacteremia (P less than .0002) were significantly higher in the uncircumcised boys. Serious complications from routine prepuce removal are rare and relatively minor. Circumcision may be beneficial in reducing the occurrence of urinary tract infections and their associated sequelae.

PMID 2562792  Pediatrics. 1989 Jun;83(6):1011-5.
著者: D Singh-Grewal, J Macdessi, J Craig
雑誌名: Arch Dis Child. 2005 Aug;90(8):853-8. doi: 10.1136/adc.2004.049353. Epub 2005 May 12.
Abstract/Text OBJECTIVE: To undertake a meta-analysis of published data on the effect of circumcision on the risk of urinary tract infection (UTI) in boys.
DATA SOURCES: Randomised controlled trials and observational studies comparing the frequency of UTI in circumcised and uncircumcised boys were identified from the Cochrane controlled trials register, MEDLINE, EMBASE, reference lists of retrieved articles, and contact with known investigators.
METHODS: Two of the authors independently assessed study quality using the guidelines provided by the MOOSE statement for quality of observational studies. A random effects model was used to estimate a summary odds ratio (OR) with 95% confidence intervals (CI).
RESULTS: Data on 402,908 children were identified from 12 studies (one randomised controlled trial, four cohort studies, and seven case-control studies). Circumcision was associated with a significantly reduced risk of UTI (OR = 0.13; 95% CI, 0.08 to 0.20; p<0.001) with the same odds ratio (0.13) for all three types of study design.
CONCLUSIONS: Circumcision reduces the risk of UTI. Given a risk in normal boys of about 1%, the number-needed-to-treat to prevent one UTI is 111. In boys with recurrent UTI or high grade vesicoureteric reflux, the risk of UTI recurrence is 10% and 30% and the numbers-needed-to-treat are 11 and 4, respectively. Haemorrhage and infection are the commonest complications of circumcision, occurring at rate of about 2%. Assuming equal utility of benefits and harms, net clinical benefit is likely only in boys at high risk of UTI.

PMID 15890696  Arch Dis Child. 2005 Aug;90(8):853-8. doi: 10.1136/adc.・・・
著者: J D van Gool, M A Vijverberg, T P de Jong
雑誌名: Scand J Urol Nephrol Suppl. 1992;141:58-69.
Abstract/Text Assessment of children with daytime wetting starts with the distinction between 'enuresis diurna' and 'functional incontinence', incontinence being defined as any form of wetting caused by bladder/sphincter dysfunction. Standard history-taking does not allow for a sharp enough distinction: pertinent questions have to be asked about daytime wetting, night-time wetting, micturition, and about urge and reactions to urge. By using urodynamics to expose the pathophysiology behind the patterns of bladder/sphincter dysfunction, these questions were formulated and validated in a series of 156 children, referred with persistent daytime wetting to a programme for cognitive bladder training. With history-taking organized into a simple questionnaire, complemented by urodynamics, four patterns of bladder/sphincter dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and lazy bladder syndrome. A strong correlation was found between recurrent urinary tract infections and non-neuropathic bladder/sphincter dysfunction, implying that detection and treatment of bladder/sphincter dysfunction is essential in every child with recurrent urinary tract infections, especially in the presence of vesico-ureteral reflux.

PMID 1609253  Scand J Urol Nephrol Suppl. 1992;141:58-69.
著者: S A Koff, T T Wagner, V R Jayanthi
雑誌名: J Urol. 1998 Sep;160(3 Pt 2):1019-22.
Abstract/Text PURPOSE: We determine whether functional bladder and/or bowel disorders influence the natural history or treatment of children with primary vesicoureteral reflux.
MATERIALS AND METHODS: We assessed 143 children with primary vesicoureteral reflux that stopped spontaneously or was surgically corrected for functional bowel and/or bladder disorders, including bladder instability, constipation and infrequent voiding, termed the dysfunctional elimination syndromes.
RESULTS: Dysfunctional elimination syndromes were present in 66 of 143 children (43%) thought to have primary vesicoureteral reflux. Of these 66 patients 54 (82%) had a breakthrough urinary tract infection and underwent reimplantation compared to only 18% without the syndromes. Of 70 children who had a breakthrough urinary tract infection dysfunctional elimination syndromes were present in 54 (77%) and absent in 16 (23%). Of the remaining 73 patients who did not have a breakthrough infection dysfunctional elimination syndromes were present in 12 (16%) and absent in 61 (84%). In children with dysfunctional elimination syndromes the resolution of reflux that was 1 grade less severe required an average of 1.6 years longer. After the disappearance of reflux, urinary tract infection developed in 18 children, including 14 (78%) with dysfunctional elimination syndromes. Unsuccessful surgical outcomes involving persistent, recurrent and contralateral reflux occurred only in children with dysfunctional elimination syndromes.
CONCLUSIONS: Dysfunctional elimination syndromes are common and are often unrecognized in children with primary reflux. These syndromes are associated with delayed reflux resolution and an increased rate of breakthrough urinary tract infection, which leads to reimplantation surgery. Dysfunctional elimination syndromes also adversely affect the results of reimplantation and represent a risk for recurrent urinary tract infection after reflux resolves. The evaluation and management of dysfunctional elimination syndromes should be an integral part of the treatment of every child with vesicoureteral reflux. Effective evaluation and treatment may be made cost-effective by decreasing the followup, the number of breakthrough urinary tract infections and the number of children requiring reimplantation.

PMID 9719268  J Urol. 1998 Sep;160(3 Pt 2):1019-22.
著者: Michael J Dawrant, Nochiparambil Mohanan, Prem Puri
雑誌名: J Urol. 2006 Oct;176(4 Pt 2):1847-50. doi: 10.1016/S0022-5347(06)00621-5.
Abstract/Text PURPOSE: Minimally invasive endoscopic treatment for vesicoureteral reflux has become an established alternative to long-term antibiotic prophylaxis and surgical intervention in children. We determined the long-term efficacy and safety of this treatment for high grade reflux in infants.
MATERIALS AND METHODS: We retrospectively reviewed the medical records of 411 consecutive infants who underwent endoscopic treatment of grade III to V vesicoureteral reflux between June 1985 and October 2004. A total of 29 patients (7%) were excluded from study because they were lost to followup or the medical records were incomplete. Of the remaining 382 infants, including 203 males, 274 had bilateral and 108 had unilateral vesicoureteral reflux. This represented 642 high grade refluxing units with grade III to V disease in 232, 339 and 71, respectively. A dimercapto-succinic acid scan performed in 312 infants revealed renal scarring in 88 (28%). The tissue augmenting substance used for endoscopic injection was polytetrafluoroethylene and dextranomer/hyaluronic acid copolymer in 432 and 210 ureters, respectively. Endoscopic treatment was done at a median age of 7 months (range 2 months to 1 year). Median followup in these patients was 7 years (range 6 months to 20 years).
RESULTS: Complete resolution of vesicoureteral reflux after a single injection occurred in 443 ureters (69%), including 73% with dextranomer/hyaluronic acid copolymer and 65% with polytetrafluoroethylene. Of the 642 ureters 127 (20%) required more than 1 injection to correct vesicoureteral reflux. In 60 ureters vesicoureteral reflux was downgraded to grade I or II and no further treatment was given, while 12 ureters that failed to respond to endoscopic treatment required open surgical intervention. Only 1 ureter required reimplantation to treat vesicoureteral obstruction.
CONCLUSIONS: Endoscopic correction is a safe, effective, minimally invasive outpatient procedure for high grade vesicoureteral reflux in infants. Early correction of vesicoureteral reflux may provide protection from reflux associated renal damage and prolonged antibiotic use.

PMID 16945670  J Urol. 2006 Oct;176(4 Pt 2):1847-50. doi: 10.1016/S002・・・
著者: Sumit Dave, Antoine E Khoury
雑誌名: Indian J Urol. 2007 Oct;23(4):403-13. doi: 10.4103/0970-1591.36714.
Abstract/Text Vesicoureteral reflux is a common clinical entity and is one of the keystones of the establishment of pediatric urology as a urological subspeciality. There has been continued evolution in the management of vesicoureteral reflux as new insights are gained on its role in renal damage. The optimal treatment algorithm remains controversial. This review aims to highlight the current literature on VUR and its association with urinary tract infections and renal damage. The protocol of management of a child with VUR followed at The Hospital for Sick Children, Toronto is described.

PMID 19718297  Indian J Urol. 2007 Oct;23(4):403-13. doi: 10.4103/0970・・・

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