Urogenital Infections and Inflammations

T.E. Bjerklund Johansen, F. M.E. Wagenlehner, Y.-H. Cho, T. Matsumoto, J. N. Krieger, D. Shoskes, K. Naber

Vesicoureteral reflux: surgery versus medical treatment

 Gundela Holmdahl 1
Sofia Sjöström 2


1 Pediatric surgery and urology, Queen Silvia Childrens Hospital, Sahlgrens Academy, Gothenburg, Sweden
2 Pediatric surgery and urology, Queen Silvia Childrens Hospital, Sahlgrens Academy, Göteborg, Sweden

Abstract

Vesicoureteral reflux is most often diagnosed after febrile urinary tract infection during childhood or at follow-up after a prenatal ultrasound showing dilated upper urinary tracts. The goal of any medical or surgical treatment is to prevent urinary tract infection, which can result in acquired renal damage and in the long run hypertension and chronic renal failure.

The condition is heterogeneous and is usually regarded as a congenital urinary abnormality, but may just as well occur due to a functional or neurogenic bladder dysfunction. The grade of reflux and the grade of congenital renal damage varies.

The treatment options are surveillance with prompt treatment of febrile urinary tract infection, low dosage antibiotic prophylaxis and different surgical methods to cure the reflux.

Despite grade of reflux the spontaneous resolution rate is high, which makes conservative treatment safe if no complications occur. Asymptomatic children with low-grade reflux need no further follow-up or treatment, but in grade 3–5 reflux, there is no consensus yet about which treatment is the best. The treatment should be designed individually for every patient depending on age, sex, grade of reflux, dilatation of the urinary tract, recurrent UTI and microbial resistance, compliance to treatment, bladder dysfunction and type of renal damage.


Summary of recommendations

Strategy of treatment depends on age of the child, sex, grade of reflux, co-existing obstruction, recurrent pyelonephritis, bladder dysfunction and renal damage.

The treatment aims to:

  • Prevent urinary tract infections
  • Prevent progressive renal damage
  • Minimize complications or harms from unnecessary treatment

Recommendations:

  1. Due to high spontaneous reflux resolution rate of all grades of reflux, most children should be treated conservatively, if no complications occurs (GoR A)
  2. Asymptomatic children with reflux grade 1–2 need no further follow-up or treatment (GoR A).
  3. Children with reflux grade 3–5 are recommended antibacterial prophylaxis, boys during the first year of life, girls until potty-trained (GoR A).
  4. When using antibacterial prophylaxis, side effects and development of bacterial resistance must be taken in consideration (GoR A).
  5. Diagnosis and treatment of urinary tract infection must be treated promptly and effectively taking into account that children with VUR more often have infection caused by non-E. coli than children with uncomplicated UTI’s (GoR B).
  6. Bladder and bowel dysfunction increases the risk of recurrent UTI and should probably be treated (GoR B).
  7. Circumcision can be considered in predisposed young boys (GoR C).
  8. Surgical correction of reflux with endoscopic treatment or open surgery including mini-invasive techniques could be used if recurrent UTI and/or progressive renal damage. It has been shown to reduce incidence of pyelonephritis and may have a modest beneficial effect on reducing the incidence of acquired renal scarring (GoR A).
  9. There is no surgical treatment that is superior to any others when it comes to prevention of recurrent UTI and progression of renal damage (GoR C).

Introduction

Vesicoureteral reflux (VUR) is the pathological retrograde backflow of urine through an incompetent vesicoureteric junction. Normally the oblique entrance of the ureter though the detrusor muscle and the mucosa of the bladder wall creates a valve-mechanism preventing retrograde flow of urine from the bladder to the upper urinary tract. This mechanism can be altered either by a congenital anomaly at the formation of the ureteric orifice or caused by functional or neurogenic bladder-dysfunction. The prevalence of VUR is about 1% in children and it is found in 25–30% investigated after urinary tract infection (UTI) [1], [2]. VUR is diagnosed through voiding cystourethrography (VCU) and is graded 1–5 depending on the severity of ureteral and renal pelvis dilatation [3].

VUR and UTI

VUR does no harm to the kidney per se if the urine is sterile, but it increases the risk of bacterial contamination to the renal pelvis, which could lead to pyelonephritis and renal scarring [4]. Recurrent pyelonephritis should be treated promptly to avoid progress of renal damage [5], [6], which can lead to impaired glomerular function, hypertension and in some cases even end stage chronic kidney disease (CKD) [7], [8], [9], [10]. The main goal in the treatment of VUR is to prevent repeated UTI’s and to minimize the risk of acquired renal damage. The risk of recurrent febrile UTI (fUTI) in VUR patients is multifactorial and variables increasing the risk are high-grade (dilated) VUR, bladder and bowel dysfunction, history of prior fUTI, renal damage, male sex during infancy and female sex after the first year of life [10], [11]. In some recent publications computerised models for predicting fUTI in children with primary VUR are presented using multiple variables of the above mentioned for risk grading in the individual patient with accuracy of about 75% [12], [13]. Children with congenital urinary abnormalities more often have infections with non-E.coli than other children with UTI [14], [15], which must be taken into considerations when choosing treatment.

VUR and renal damage

Besides the risk of renal scarring from pyelonephritis, most often seen as defects in the renal contour apically or caudally, high-grade VUR (4–5) is also associated with a congenital renal abnormality shown as a small kidney with generalised poor uptake and/or lowered differential renal function (DRF) seen in technetium DMSA scans [16], [17], [18]. This defect probably represents poor development during gestation (dysplasia or hypoplasia) rather than a consequence of UTI. The risk of renal damage, both acquired (focal) and congenital (generalised) increases with increasing grade of VUR [10].

VUR and lower urinary tract dysfunction (LUTD) 

Many children with high-grade VUR have lower urinary tract dysfunction with a large bladder capacity and increased post void residual (PVR) or overactive bladder (OAB) with symptoms of bladder instability and infrequent voiding and/or constipation [11], [19]. Lower urinary tract dysfunction and renal damage are both risk factors for recurrent UTI, especially in children with VUR [11], [20], [21]. Evaluation of bladder and bowel function through bowel and micturition diary, measurements of flow and post void residual (PVR) is therefore of great importance in the management of children with VUR. Lower urinary tract dysfunction in VUR patients is also associated with less probability of spontaneous resolution of reflux [17], [22], [23].

Special concerns regarding VUR in girls versus boys and younger versus older children 

Generally VUR is more common in girls than in boys with a ratio of 4:1 in children older than 1 year [24]. In infants diagnosed with VUR <1 year of age on the other hand, there is a clear predominance of males where high-grade VUR is often accompanied by congenital renal dysplasia [16], [25]. These infants with high-grade VUR often develop lower urinary tract dysfunction characterized by large capacity bladder with high post void residual (PVR). The risk of recurrent febrile UTI (FUTI) is highest during infancy, especially in boys with declining number of infections after the infant year [26]. Girls with VUR seem to have a continuous risk of new infections even after potty training [27], [28]. Prompt treatment of febrile UTI is considered especially warranted in infants, since the kidneys in children less than two years of age are more prone to renal scarring secondary to ascending infections [29], [30].

VUR and spontaneous resolution

Spontaneous resolution of VUR over time is seen in 30–50% of children with dilated reflux (grade 3–5) and the resolution rate in undilated reflux (grade 1–2) is up to 80% within 4–5 years of follow-up [31], [32]. Spontaneous resolution is also depending on age, sex (higher in boys during the infant year), uni or bilaterality of VUR, lower urinary tract dysfunction (LUTD), and prevalence of renal damage at diagnosis [17], [23], [31]. Therefore individualized risk evaluation must be made in each patient before choosing optimal treatment.

The optimal treatment of VUR in children is constantly re-evaluated in the dialogue between paediatricians and paediatric urologists. Even though the subject has been the topic of hundreds of publications during the last decades, still the grade of evidence for different treatment options of medical or surgical intervention with the overall am of making a difference in preserving renal function in a long-term perspective is surprisingly low.

Methods

A systematic literature search was performed, with end date March 2016, in PubMed and Cochrane databases with the following key words (VUR OR vesicoureteral reflux OR vesicoureteral reflux) AND (treatment OR therapy OR surgery) and the following limitations (filters) Randomized Controlled Trial; Systematic Reviews; Meta-Analysis, English abstract available, only peer reviewed.

A total of 264 publications were identified, which were screened by title and abstract. After exclusion of duplicates, irrelevant or to old publications a total of 43 were included into the review (analysis), supplemented by 2 studies known to the authors published after March 2016.

The studies were rated according to the level of evidence (LoE) and the grade of recommendation (GoR) using ICUD standards (for details see Preface).

Results

Conservative treatments

Antibiotic prophylaxis (CAP) or surveillance

For a long time antibiotic prophylaxis has been a standard initial management in children with all grades of VUR. This is questioned today, both because of that new studies have shown that the effectiveness of CAP is doubtful and because of fear of the raising antimicrobial resistance. The poor compliance to treatment, estimated to be only 40% will lower the effectiveness and that must also be taken into consideration [33].

For low grade or asymptomatic reflux there is low or no evidence today that CAP will prevent UTI or renal damage [34], [35], [36], [37], [38], [39], [40] (LoE 1a) but if the child presents with dilating reflux or a history of recurrent UTI’s there are studies that have shown that prophylaxis is superior to surveillance concerning prevention of UTI [34], [41], [42], [43] (LoE 1b). In contrast to this, the American RIVUR study showed that CAP reduced the risk for UTI regardless of reflux grade (grade 2–4) [44], which made authors of recent meta-analyses to recommend prophylaxis to children with all grades of reflux [45], [46]. It is shown that CAP increases the risk of infection due to antibiotic resistant bacteria [46], [47] (LoE 1a). In the Swedish reflux study, where 1 year old children with persisting grade 3–4 VUR were randomized to surveillance, CAP or endoscopic treatment and followed for 2 years there was a significant difference between girls and boys, with a higher risk of UTI for girls without prophylaxis. These results led to the recommendation to stop CAP at 1 year of age in boys and continued prophylactic treatment in girls until potty-trained [41].

The evidence for CAP to prevent renal scarring is minimal according to several Cochrane reports [47], [48], [49] (LoE 1a). A study that has been able to show a significant higher risk to develop renal scarring without treatment, was the Swedish reflux study [50]. Furthermore, in a Cochrane report from 2011 [47] it was stated that 33 children would need long-term antibiotic prophylaxis to prevent one more child developing kidney damage over the course of 2–3 years.

Randomised controlled studies evaluating antibiotic prophylaxis versus surveillance in VUR children is summarised in Table 1.

Table 1: Randomised controlled trials evaluating outcome of medical treatment versus surveillance of VUR in children
Author, year Study size (N=) Patient age (years) VUR grade Intervention and Objectives Results
Craig et al.,
2002 [40]
46 <3 months 1–5

Low dose antibiotic prophylaxis versus placebo in infants with VUR diagnosed after antenatal hydronephrosis or heredity

Primary objective reduction of UTI and prevention of new renal damage
Antibiotic prophylaxis to asymptomatic VUR infants did not significantly reduce the frequency of UTI or new renal damage during the first 3 years of life.
Garin et al.,
2006 [36]
236 (113 VUR patients) <18 0–3

Antibiotic prophylaxis versus surveillance in children diagnosed with acute pyelonephritis

Primary objectives to evaluate the role of VUR in the risk for UTI. Evaluating reduction of UTI and prevention of new renal damage with antibiotic prophylaxis

Mild/moderate VUR does not increase the risk for UTI, pyelonephritis or renal scarring in children after UTI.

Antibiotic prophylaxis does not reduce the risk for UTI, pyelonephritis or renal scarring after 1 year follow-up
Montini et al. (PREDICT),
2008 [37]
338 (128 VUR patients) <7 0–3

Antibiotic prophylaxis versus surveillance in children after a first febrile UTI

Primary objective reduction of UTI. Secondary objective reduction of new renal damage
Antibiotic prophylaxis does not reduce the rate of febrile urinary tract infections. No difference in renal outcome between treatment groups.
Pennesi et al., 2008 [39] 100 <3 2–4

Antibiotic prophylaxis versus surveillance in VUR children after a first acute pyelonephritis

Primary objectives reduction of UTI and prevention of new renal damage
No difference in pyelonephritic episodes or new renal damage between treatment groups after 2 years of follow-up
Rossey-Kesler et al., 2008 [35] 225 <3 1–3

Antibiotic prophylaxis versus surveillance in young children with low grade VUR

Primary objective reduction of UTI
No difference in occurrence of UTI between treatment groups overall, but antibiotic prophylaxis significantly reduced UTI in boys with grade 3 VUR after 18 months follow-up.
PRIVENT Craig et al., 2009 [42] 576 (243 VUR patients) <18 0–5

Low dose antibiotic prophylaxis versus surveillance in predisposed children

Primary objective reduction of UTI
Low dose antibiotic treatment decreases the number of UTI in predisposed children
The Swedish reflux trial in children, Brandström et al., 2010 [41], [50] 203 1–2 3–4

Three armed study evaluating surveillance versus antibiotic prophylaxis versus endoscopic treatment in young children with VUR

Primary objectives reduction of UTI , prevention of new renal damage (and resolution of VUR)

Antibiotic prophylaxis and endoscopic treatment both reduced the number of UTI in girls compared to surveillance and prophylaxis reduced the frequency of new renal damage in girls.

No difference between active treatment and surveillance in boys.
Hari et al.,
2014 [38]
93 1–12 1–2, 3–4

Antibiotic prophylaxis versus placebo in children with VUR and UTI

Primary objectives reduction of UTI and prevention of new renal damage

Long-term antibiotic prophylaxis is associated with increased risk of UTI and increased risk of infections with resistant bacteria’s

No difference in new renal damage after 1 year follow-up.
RIVUR, Hoberman et al., 2014 [44] 697 0.5–3 1–2, 3–4

Antibiotic prophylaxis versus placebo in children with VUR after first UTI.

Primary objectives prevention of UTI and prevention of new renal damage
Antibiotic prophylaxis reduces the risk of UTI but no difference between treatment groups in new renal damage.

Probiotics

The use of probiotics has been suggested to reduce the number of UTI in children with VUR, but in a RCT where probiotics was compared to CAP no treatment was superior to the other [51] (LoE 1b).

Bladder/bowel dysfunction (BBD)

Treatment of BBD is considered to be an import factor in the care of children with VUR. Even though identified as a risk factor for persistent reflux and recurrent UTI in several observational studies, there are few RCT and meta analyses that has been able to show a general or specific urotherapeutic treatment that reduces the risk for UTI and renal scars [34] in a pediatric VUR population (LoE 1b). Sillén initiated clean intermittent catheterization (CIC) in a small cohort of VUR patients with recurrent fUTI and bladder dysfunction and found no effect on spontaneous resolution of VUR [52]. In two studies evaluating treatment of bladder dysfunction in VUR patients they found no evidence of advantages of anticholinergic therapy on UTI recurrences [21] or reflux resolution [53]. In one study treatment with alfa blockers in children with BBD resulted in reflux down-grading, but effect on UTI and renal scars were not shown [54].

Circumcision

To reduce number of UTI in children with VUR, circumcision in infant boys is an option, even if there is scarce with evidence (LoE 3). In a study from Turkey it was shown that circumcision decreases colonization of periurethral bacterial pathogenic flora and circumcision plus CAP reduces risk of UTI in boys with low-grade VUR [55].

Surgical treatments

Open surgery

If reflux resolution is the main goal, it is well known that open surgical procedure with reimplantation of the ureter have good results with abolishing of reflux grade 1–4 in >97% and in grade 5 in >80% [56], [57], [58], [59], [60], [61]. This is to be compared with spontaneous disappearance of the reflux with resolution rates of 30–50% (LoE 1a). In the International Reflux study it was shown that surgery was superior to medical treatment concerning recurrent pyelonephritis but there was no difference in renal outcome, even in long-term follow up of 10 years [29], [62], [63], [64], [65]. The same results were found in another study comparing open surgery to CAP in VUR children [66]. This was shown to be true even in severe bilateral disease [67]. Still it must be considered that open surgery needs a long hospital stay and is a stressful event for the child and family.

Endoscopic treatments (ET)

Endoscopic treatment is today a well established method and meta analyses has shown that ET abolish or down grade the reflux on average in 77% of ureters injected [68] (LoE 1a). This seems to be independently of type of bulking material [69], [70], [71] and perhaps the results could be improved by the injection technique used [72]. The results also depend on the grade of reflux, with lower efficiency in grade 5 and bilateral reflux [60], [73], [74]. This is shown in the Swedish infant high-grade reflux study with 100% success rate in unilateral grade 4 to 30% in bilateral grade 5 [75]. The study shows that it is also doable with ET in infants. In infants, it must be taken into consideration that high grade reflux is often a complex malformation with bladder dysfunction and/or vesicoureteral obstruction, making ET less suitable and patient selection important. ET is more efficient than surveillance and prophylaxis in reflux resolution but a concern is the recurrence rate of about 20% after 2 year follow-up [76], [77].

Looking at the effect on frequency of UTI and renal damage the ET results are comparable to open surgery.

Minimal invasive methods

Minimal invasive anti-reflux techniques including laparoscopic and robotic assisted surgery are increasing in popularity but there are no randomized studies available supporting the superiority versus other surgical methods (LoE 4). We found one case control study comparing miniureteroneocystostomy to ET presenting greater success of this minimal invasive technique in VUR outcome [78].

Randomised controlled trials comparing surgical intervention with antibiotic prophylaxis are summarized in Table 2.

Table 2: Randomised controlled trials evaluating outcome of medical versus surgical treatment of VUR in children
Author, year Study size (N=) Patient age (years) VUR grade Intervention and Objectives Results
Birmingham reflux study group, 1983 [56], 1987 [57] 161 0–15 1–5*
(*all grades)

Open surgery versus non operative management

Primary objectives differences in UTI, renal damage and renal function

No difference between treatment groups in breakthrough UTI, renal function or renal damage

VUR resolved in 98% of surgical and 50% of medical treated.
The International Reflux Study in Children, European branch, 1992 [59], [62], 1998 [29], 2003 [64], 2006 [63]

306 (5-years follow-up)

252 (10-years follow-up)
<11 3–4

Open surgery versus antibiotic prophylaxis

Primary objectives differences in UTI, renal damage and renal function

Higher incidence of febrile UTI in medical group at 5 years

No difference between treatment groups in renal damage or renal function at 5 years

Higher incidence of febrile UTI in medical group but no difference in renal outcome at 10 years
The International Reflux Study in Children, American branch, 1992 [65], [79] 132 <11 3–4 Open surgery versus antibiotic prophylaxis

Higher incidence of febrile UTI in medical group

No differences in renal damage or renal function at 5 years
Smellie et al., 2001 [67] 52 1–12 3–5 bilateral VUR and nephropathy

Open surgery versus antibiotic prophylaxis

Primary objective change in renal function (GFR)
No difference between treatment groups in renal function (GFR ) after 10 years
Capozza et al., 2002 [73] 61 2–4 >1, mean 4

Endoscopic treatment versus antibiotic prophylaxis

Primary objective differences in VUR resolution

Differences in UTI or renal damage not evaluated

ET superior to antibiotic prophylaxis in VUR resolution
The Swedish reflux trial in children, Brandström et al., 2010 [41], [50], [76] 203 1–2 3–4

Endoscopic treatment versus antibiotic prophylaxis versus surveillance

Primary objectives differences in UTI, Renal damage and VUR resolution.

Antibiotic prophylaxis and endoscopic treatment both reduce UTI in girls compared to surveillance and antibiotic treatment reduce new renal damage in girls. No difference between active treatment and surveillance in boys.

ET superior to medical treatment or surveillance in VUR resolution
The Swedish Infant High-Grade Reflux Trial, Nordenström et al., 2017 [75], [80] 77 <8 months 4–5

Endoscopic treatment versus antibiotic prophylaxis

Primary objectives differences in UTI, renal damage, VUR resolution and bladder function.

No differences in UTI or renal damage in total study population

ET superior to antibiotic prophylaxis in VUR resolution

Conclusion

Vesicoureteral reflux is a complex topic, and a risk-oriented therapy should account for this complexity. Symptomatic high-grade reflux with recurrent UTI needs therapy, but there is no difference in outcome concerning number of pyelonephritis and acquired renal scars if the child is put on antibiotic prophylaxis or endoscopic treatment or open surgery. In the decision making you must take into account the drawbacks with CAP with compliance to treatment, side effects of the medicine and antimicrobial resistance. On the other hand all operative management needs anestethia and expensive hospital care. ET is a simpler method but the result concerning reflux resolution is inferior to open surgery.

Conservative treatment also includes treatment of bowel and bladder dysfunction. It is known that BBD is a risk factor for UTI and renal cortical scaring. Reflux resolution and endoscopic surgical success rate is also dependent on BBD. Still, it is hard to prove that general or specific treatments of the dysfunction will change renal outcome or frequency of UTI.

There is minimal evidence in the literature that any treatment of low-grade reflux will reduce number of UTI and renal damage.

Both in Europe and in America guidelines on vesicoureteral reflux are established. In 2012 the EAU guidelines on Vesicoureteral reflux was published [81]. AUA organised in 2005 the Vesicoureteral Reflux Guideline Update Committee and a summary of the work was published in 2010 [34]. The guidelines have in common that the management is based on the goals of minimizing the risk of acute infection and renal injury, while minimizing the morbidity of investigations and management and avoid overtreatment. In the guidelines the management is dependent on age, sex, BBD, UTI and reflux grade and is summarised by Routh et al. in a publication from 2012 (Table 3) [60].

Table 3: Summary of the EAU/ESPU and AUA guidelines of VUR treatment in children summarised by Routh et al. [60]
Organization Patient age, year BBD Febrile UTI VUR grade Initial management Indication for surgery
EAU/ESPU <1 N/A No I–III Observation
<1 N/A No IV–V CAP Breakthrough UTI
<1 N/A Yes All CAP Breakthrough UTI
1–5 No Either All CAP Persistent VUR, breakthrough UTI
1–5 Yes Yes I–III Treat BBD, CAP Persistent VUR, breakthrough UTI
1–5 Yes Yes IV–V Treat BBD, CAP vs surgery Persistent VUR, breakthrough UTI
>5 No No All CAP Persistent VUR, breakthrough UTI
>5 Either Yes All Treat BBD if present, CAP vs surgery Persistent VUR, breakthrough UTI
AUA <1 N/A No I–II Observation or CAP, consider circumcision in boys Breakthrough UTI
<1 N/A No III–V CAP, consider circumcision in boys Breakthrough UTI
<1 N/A Yes All CAP, consider circumcision in boys Initial vs after breakthrough UTI
>1 Yes Both All Treat BBD, CAP Initial vs after breakthrough UTI
>1 No Both All Consider CAP (if renal scar, recurrent UTI)

Further research

Generally when it comes to management of VUR there are few randomised controlled trials comparing different treatment strategies. In recent years there are numerous publications comparing the outcome of VUR resolution with different endoscopic techniques or bulking agents but there are very few with the aim of identifying risk patients for progressive renal damage or interventions that actually means a difference in long-time renal outcome.

Moreover both RCT and observational studies merge cohorts with different ages, different grades of reflux and other risk factors such as LUTD and renal damage. Conclusions about the optimal individualized treatment for each patient can therefore seldom be made. Bladder dysfunction increases the risk of UTI, renal damage and persistence of VUR but very few controlled studies evaluate the role of targeted treatment towards LUTD in VUR patients.

We call for randomised controlled studies with patient stratification that takes into account more risk factors than the primary VUR and with a primary objective significantly reducing the risk of UTI or even more specific saving renal function.


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[26] Zorc JJ, Levine DA, Platt SL, Dayan PS, Macias CG, Krief W, Schor J, Bank D, Shaw KN, Kuppermann N; Multicenter RSV-SBI Study Group of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Clinical and demographic factors associated with urinary tract infection in young febrile infants. Pediatrics. 2005 Sep;116(3):644-8. DOI: 10.1542/peds.2004-1825
[27] Hellström A, Hanson E, Hansson S, Hjälmås K, Jodal U. Association between urinary symptoms at 7 years old and previous urinary tract infection. Arch Dis Child. 1991 Feb;66(2):232-4. DOI: 10.1136/adc.66.2.232
[28] Coulthard MG, Lambert HJ, Keir MJ. Occurrence of renal scars in children after their first referral for urinary tract infection. BMJ. 1997 Oct;315(7113):918-9. DOI: 10.1136/bmj.315.7113.918
[29] Piepsz A, Tamminen-Möbius T, Reiners C, Heikkilä J, Kivisaari A, Nilsson NJ, Sixt R, Risdon RA, Smellie JM, Söderborg B. Five-year study of medical or surgical treatment in children with severe vesico-ureteral reflux dimercaptosuccinic acid findings. International Reflux Study Group in Europe. Eur J Pediatr. 1998 Sep;157(9):753-8.
[30] Benador D, Benador N, Slosman D, Mermillod B, Girardin E. Are younger children at highest risk of renal sequelae after pyelonephritis? Lancet. 1997 Jan 4;349(9044):17-9. DOI: 10.1016/S0140-6736(96)06126-0
[31] Estrada CR Jr, Passerotti CC, Graham DA, Peters CA, Bauer SB, Diamond DA, Cilento BG Jr, Borer JG, Cendron M, Nelson CP, Lee RS, Zhou J, Retik AB, Nguyen HT. Nomograms for predicting annual resolution rate of primary vesicoureteral reflux: results from 2,462 children. J Urol. 2009 Oct;182(4):1535-41. DOI: 10.1016/j.juro.2009.06.053
[32] Elder JS, Peters CA, Arant BS Jr, Ewalt DH, Hawtrey CE, Hurwitz RS, Parrott TS, Snyder HM 3rd, Weiss RA, Woolf SH, Hasselblad V. Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children. J Urol. 1997 May;157(5):1846-51. DOI: 10.1097/00005392-199705000-00093
[33] Copp HL, Nelson CP, Shortliffe LD, Lai J, Saigal CS, Kennedy WA; Urologic Diseases in America Project. Compliance with antibiotic prophylaxis in children with vesicoureteral reflux: results from a national pharmacy claims database. J Urol. 2010 May;183(5):1994-9. DOI: 10.1016/j.juro.2010.01.036
[34] Peters CA, Skoog SJ, Arant BS Jr, Copp HL, Elder JS, Hudson RG, Khoury AE, Lorenzo AJ, Pohl HG, Shapiro E, Snodgrass WT, Diaz M. Summary of the AUA Guideline on Management of Primary Vesicoureteral Reflux in Children. J Urol. 2010 Sep;184(3):1134-44. DOI: 10.1016/j.juro.2010.05.065
[35] Roussey-Kesler G, Gadjos V, Idres N, Horen B, Ichay L, Leclair MD, Raymond F, Grellier A, Hazart I, de Parscau L, Salomon R, Champion G, Leroy V, Guigonis V, Siret D, Palcoux JB, Taque S, Lemoigne A, Nguyen JM, Guyot C. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol. 2008 Feb;179(2):674-9; discussion 679. DOI: 10.1016/j.juro.2007.09.090
[36] 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 Mar;117(3):626-32. DOI: 10.1542/peds.2005-1362
[37] Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, Cecchin D, Pavanello L, Molinari PP, Maschio F, Zanchetta S, Cassar W, Casadio L, Crivellaro C, Fortunati P, Corsini A, Calderan A, Comacchio S, Tommasi L, Hewitt IK, Da Dalt L, Zacchello G, Dall'Amico R; IRIS Group. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics. 2008 Nov;122(5):1064-71. DOI: 10.1542/peds.2007-3770
[38] Hari P, Hari S, Sinha A, Kumar R, Kapil A, Pandey RM, Bagga A. Antibiotic prophylaxis in the management of vesicoureteric reflux: a randomized double-blind placebo-controlled trial. Pediatr Nephrol. 2015 Mar;30(3):479-86. DOI: 10.1007/s00467-014-2943-z
[39] Pennesi M, Travan L, Peratoner L, Bordugo A, Cattaneo A, Ronfani L, Minisini S, Ventura A; North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics. 2008 Jun;121(6):e1489-94. DOI: 10.1542/peds.2007-2652
[40] Craig J, Roy LP, Sureshkumar P, Burke J, Powell H, Hodson E. (2002). Long-term antibiotics to prevent urinary tract infection in children with isolated vesicoureteric reflux: A placebo-controlled randomized trial. Nephrology, suppl. 2002;13.
[41] Brandström P, Esbjörner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol. 2010 Jul;184(1):286-91. DOI: 10.1016/j.juro.2010.01.061
[42] Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds GJ, McTaggart SJ, et al. Antibiotic Prophylaxis and Recurrent Urinary Tract Infection in Children. New England Journal of Medicine. 2009 Oct 29;361(18):1748–59. DOI: 10.1056/NEJMoa0902295
[43] Leslie B, Moore K, Salle JL, Khoury AE, Cook A, Braga LH, Bägli DJ, Lorenzo AJ. Outcome of antibiotic prophylaxis discontinuation in patients with persistent vesicoureteral reflux initially presenting with febrile urinary tract infection: time to event analysis. J Urol. 2010 Sep;184(3):1093-8. DOI: 10.1016/j.juro.2010.05.013
[44] RIVUR Trial Investigators, Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014 Jun 19;370(25):2367-76. DOI: 10.1056/NEJMoa1401811
[45] de Bessa J Jr, de Carvalho Mrad FC, Mendes EF, Bessa MC, Paschoalin VP, Tiraboschi RB, Sammour ZM, Gomes CM, Braga LH, Bastos Netto JM. Antibiotic prophylaxis for prevention of febrile urinary tract infections in children with vesicoureteral reflux: a meta-analysis of randomized, controlled trials comparing dilated to nondilated vesicoureteral reflux. J Urol. 2015 May;193(5 Suppl):1772-7. DOI: 10.1016/j.juro.2014.10.092
[46] Wang HH, Gbadegesin RA, Foreman JW, Nagaraj SK, Wigfall DR, Wiener JS, Routh JC. Efficacy of antibiotic prophylaxis in children with vesicoureteral reflux: systematic review and meta-analysis. J Urol. 2015 Mar;193(3):963-9. DOI: 10.1016/j.juro.2014.08.112
[47] Nagler EV, Williams G, Hodson EM, Craig JC. Interventions for primary vesicoureteric reflux. Hodson EM, editor. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2011. DOI: 10.1002/14651858.CD001532.pub4
[48] Wheeler D, Vimalachandra D, Hodson E, Smith G, Craig J. Interventions for primary vesicoureteric reflux. Hodson E, editor. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2004. DOI: 10.1002/14651858.CD001532.pub2
[49] Hodson EM, Wheeler DM, Smith GH, Craig JC, Vimalachandra D. Interventions for primary vesicoureteric reflux. Hodson EM, editor. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2007. DOI: 10.1002/14651858.CD001532.pub3
[50] Brandström P, Nevéus T, Sixt R, Stokland E, Jodal U, Hansson S. The Swedish Reflux Trial in Children: IV. Renal Damage. The Journal of Urology. 2010 Jul;184(1):292–7. DOI: 10.1016/j.juro.2010.01.060
[51] Lee SJ, Shim YH, Cho SJ, Lee JW. Probiotics prophylaxis in children with persistent primary vesicoureteral reflux. Pediatr Nephrol. 2007 Sep;22(9):1315-20. DOI: 10.1007/s00467-007-0507-1
[52] Sillén U, Holmdahl G, Hellström AL, Sjöström S, Sölsnes E. Treatment of bladder dysfunction and high grade vesicoureteral reflux does not influence the spontaneous resolution rate. J Urol. 2007 Jan;177(1):325-9; discussion 329-30. DOI: 10.1016/j.juro.2006.09.009
[53] Ahn SH, Shim SY, Lee JW, Cho SJ, Lee SJ. The Effect of an Anticholinergic Agent(Oxybutynin) on Spontaneous Resolution of Primary Vesicoureteral Reflux. Journal of the Korean Society of Pediatric Nephrology. 2003;7(2):174-80.
[54] Kajbafzadeh A-M, Baradaran N, Sadeghi Z, Tourchi A, Saeedi P, Madani A, et al. Vesicoureteral Reflux and Primary Bladder Neck Dysfunction in Children: Urodynamic Evaluation and Randomized, Double-Blind, Clinical Trial on Effect of α-Blocker Therapy. The Journal of Urology. 2010 Nov;184(5):2128–33. DOI: 10.1016/j.juro.2010.06.132
[55] Gücük A, Burgu B, Gökçe İ, Mermerkaya M, Soygür T. Do antibiotic prophylaxis and/or circumcision change periurethral uropathogen colonization and urinary tract infection rates in boys with VUR? Journal of Pediatric Urology. 2013 Dec;9(6):1131–6. DOI: 10.1016/j.jpurol.2013.04.014
[56] Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux: two years’ observation in 96 children. BMJ. 1983 Jul 16;287(6386):171–4. DOI: 10.1136/bmj.287.6386.171
[57] Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years’ observation. Birmingham Reflux Study Group. BMJ. 1987 Jul 25;295(6592):237–41. DOI: 10.1136/bmj.295.6592.237
[58] Garcia-Aparicio L, Rovira J, Blazquez-Gomez E, García-García L, Giménez-Llort A, Rodo J, et al. Randomized clinical trial comparing endoscopic treatment with dextranomer hyaluronic acid copolymer and Cohen’s ureteral reimplantation for vesicoureteral reflux: Long-term results. Journal of Pediatric Urology. 2013 Aug;9(4):483–7. DOI: 10.1016/j.jpurol.2013.03.003
[59] Hjälmås K, Löhr G, Tamminen-Möbius T, Seppänen J, Olbing H, Wikström S. Surgical Results in the International Reflux Study in Children (Europe). The Journal of Urology. 1992 Nov;148(5):1657–61. DOI: 10.1016/S0022-5347(17)36996-3
[60] Routh JC, Bogaert GA, Kaefer M, Manzoni G, Park JM, Retik AB, Rushton HG, Snodgrass WT, Wilcox DT. Vesicoureteral reflux: current trends in diagnosis, screening, and treatment. Eur Urol. 2012 Apr;61(4):773-82. DOI: 10.1016/j.eururo.2012.01.002
[61] Venhola M, Huttunen NP, Uhari M. Meta-analysis of vesicoureteral reflux and urinary tract infection in children. Scand J Urol Nephrol. 2006;40(2):98-102. DOI: 10.1080/00365590500499529
[62] Jodal U, Koskimies O, Hanson E, Löhr G, Olbing H, Smellie J, et al. Infection Pattern in Children with Vesicoureteral Reflux Randomly Allocated to Operation or Long-Term Antibacterial Prophylaxis. The Journal of Urology. 1992 Nov;148(5):1650–2. DOI: 10.1016/S0022-5347(17)36994-X
[63] Jodal U, Smellie JM, Lax H, Hoyer PF. Ten-year results of randomized treatment of children with severe vesicoureteral reflux. Final report of the International Reflux Study in Children. Pediatric Nephrology. 2006 Mar 25;21(6):785–92. DOI: 10.1007/s00467-006-0063-0
[64] Olbing H, Smellie JM, Jodal U, Lax H. New renal scars in children with severe VUR: a 10-year study of randomized treatment. Pediatric Nephrology. 2003 Nov 1;18(11):1128–31. DOI: 10.1007/s00467-003-1256-4
[65] Weiss R, Duckett J, Spitzer A. Results of A Randomized Clinical Trial of Medical Versus Surgical Management of Infants and Children with Grades III and IV Primary Vesicoureteral Reflux (United States). The Journal of Urology. 1992 Nov;148(5):1667–73. DOI: 10.1016/S0022-5347(17)36998-7
[66] Elo J, Tallgren LG, Alfthan O, Sarna S. Character of Urinary Tract Infections and Pyelonephritic Renal Scarring After Antireflux Surgery. The Journal of Urology. 1983 Feb;129(2):343–6. DOI: 10.1016/S0022-5347(17)52089-3
[67] Smellie JM, Barratt TM, Chantler C, Gordon I, Prescod NP, Ransley PG, Woolf AS. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial. The Lancet. 2001 Apr;357(9265):1329–33. DOI: 10.1016/S0140-6736(00)04520-7
[68] Routh JC, Inman BA, Reinberg Y. Dextranomer/hyaluronic acid for pediatric vesicoureteral reflux: systematic review. Pediatrics. 2010 May;125(5):1010-9. DOI: 10.1542/peds.2009-2225
[69] Habeeb Abid M. 504 Comparative study between the use of dextranomer hyaluronic acid copolymer (Dexel) versus polyacrylate polyalcohol copolymer (Vantris) in the endoscopic treatment of vesicoureteral reflux (VUR) in children. European Urology Supplements. 2015 Apr;14(2):e504. DOI: 10.1016/S1569-9056(15)60497-3
[70] Moore K, Bolduc S. Prospective Study of Polydimethylsiloxane vs Dextranomer/Hyaluronic Acid Injection for Treatment of Vesicoureteral Reflux. The Journal of Urology. 2014 Dec;192(6):1794–800. DOI: 10.1016/j.juro.2014.05.116
[71] Oswald J, Riccabona M, Lusuardi L, Bartsch G, Radmayr C. Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Urology. 2002 Nov;60(5):894–7. DOI: 10.1016/S0090-4295(02)01903-9
[72] Akin M, Erginel B, Karadag CA, Yildiz A, Özçelik GS, Sever N, et al. A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux. International Urology and Nephrology. 2014 Jun 26;46(11):2057–61. DOI: 10.1007/s11255-014-0771-5
[73] Capozza N, Caione P. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: A randomized comparison with antibiotic prophylaxis. The Journal of Pediatrics. 2002 Feb;140(2):230–4. DOI: 10.1067/mpd.2002.121380
[74] Elder JS, Diaz M, Caldamone AA, Cendron M, Greenfield S, Hurwitz R, et al. Endoscopic Therapy for Vesicoureteral Reflux: A Meta-Analysis. I. Reflux Resolution and Urinary Tract Infection. The Journal of Urology. 2006 Feb;175(2):716–22. DOI: 10.1016/S0022-5347(05)00210-7
[75] Nordenström J, Holmdahl G, Brandström P, Sixt R, Stokland E, Sillén U, Sjöström S. The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral reflux outcome. J Pediatr Urol. 2017 Apr;13(2):130-138. DOI: 10.1016/j.jpurol.2016.08.026
[76] Holmdahl G, Brandström P, Läckgren G, Sillén U, Stokland E, Jodal U, et al. The Swedish Reflux Trial in Children: II. Vesicoureteral Reflux Outcome. The Journal of Urology. 2010 Jul;184(1):280–5. DOI: 10.1016/j.juro.2010.01.059
[77] Lee EK, Gatti JM, Demarco RT, Murphy JP. Long-term followup of dextranomer/hyaluronic acid injection for vesicoureteral reflux: late failure warrants continued followup. J Urol. 2009 Apr;181(4):1869-74; discussion 1874-5. DOI: 10.1016/j.juro.2008.12.005
[78] Ashley R, Vandersteen D. Outcome analysis of mini-ureteroneocystostomy versus dextranomer/hyaluronic acid copolymer injection for unilateral vesicoureteral reflux. J Urol. 2008 Oct;180(4 Suppl):1611-3; discussion 1614. DOI: 10.1016/j.juro.2008.04.084
[79] Duckett JW, Dixon walker R, Weiss R. Surgical Results: International Reflux Study in Children—United States Branch. The Journal of Urology. 1992 Nov;148(5):1674–5. DOI: 10.1016/S0022-5347(17)36999-9
[80] Nordenström J, Sjöström S, Sillén U, Sixt R, Brandström P. The Swedish infant high-grade reflux trial: UTI and renal damage. Journal of Pediatric Urology. 2017 Feb;13(2):146-154. DOI: 10.1016/j.jpurol.2016.12.023
[81] Tekgül S, Riedmiller H, Hoebeke P, Kočvara R, Nijman RJ, Radmayr C, Stein R, Dogan HS; European Association of Urology. EAU guidelines on vesicoureteral reflux in children. Eur Urol. 2012 Sep;62(3):534-42. DOI: 10.1016/j.eururo.2012.05.059

The ZB MED – Information Center for Life Sciences, Germany, together with the European Association of Urology (EAU) provided the opportunity to publish a “Living Textbook” on “Urogenital Infections and Inflammations” in an open access form. This “Living Textbook” represents also an update of the Textbook on Urogenital Infections published 2010 by the International Consultation on Urological Infections and the EAU: http://www.icud.info/urogenitalinfections.html.

The “Living Textbook” will cover infections and inflammations of the kidney, the urinary tract, as well as the male and female genital tract considering pathogenesis, diagnostics, treatment, prophylaxis and future aspects. The “Living Textbook” will be structured into about 26 Sections each with two section co-chairs responsible for peer review of the chapters of each section. Each chapter should reflect the background to the topic and highlight all of the critical evidence relating to the subject. The intention is to provide an up to date, concise synthesis of the literature on that topic, and for clinical topics also recommendations based on levels of evidence for contemporary clinical practice, as well as suggested research recommendations.

The editors hope that this “Living Textbook” may become a useful instrument for physicians of different specialties taking care about patients suffering from these diseases.

Truls E. Bjerklund Johansen (Norway),

Florian ME Wagenlehner (Germany),

Yong-Hyun Cho (South Korea),

Tetsuro Matsumoto (Japan),

John N Krieger (USA),

Daniel Shoskes (USA),

Kurt G. Naber (Germany).

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General

The textbook will be structured in sections with two co-chairs each. Each section will start with an introductory chapter written by the two respective co-chairs presented like an editorial commentary in regard to the following chapters (see proposed contents of the book). The two co-chairs of each section will also peer review all chapters in their section and stimulate a consensus discussion within their section together with the authors and the main editors if needed.

Chapters

Each chapter should reflect the background to the topic and highlight all of the critical evidence relating to the subject. The intention is to provide an up to date, concise synthesis of the literature on that topic, and for clinical topics also recommendations based on levels of evidence for contemporary clinical practice, as well as suggested research recommendations.

Manuscript

Each manuscript should have up to approximately 3,000 words (excluding abstract, tables/figures and references). The abstract should count about 300 words.

Structure

The outline of each chapter should be structured as follows (similar as in the edition 2010, which can be downloaded for free: http://www.icud.info/urogenitalinfections.html):

  1. Abstract
  2. Summary of recommendations*/key notes*
    (*which ever term is more appropriate)
  3. Introduction
  4. Methods
  5. Results
  6. Further research
  7. Conclusions
  8. Acknowledgement
  9. Conflict of interest of each author
  10. References

Citation style

As a citation style, the Vancouver style is preferred.

Please mark your references in the text with square brackets ([1], [2], ...).

Summary of recommendations

We would like to have the Summary of recommendations at the beginning after the abstract (as in the edition 2010). However, we do not expect as in the edition 2010, that each recommendation is also specified according to Level of Evidence and Grade of Recommendation, because such a claim would not only need a systematic literature search (see below), but also a structured discussion in a defined group of experts.

Systematic literature search

A systematic literature search should be performed, at least of PUBMED/MEDLINE but ideally of several relevant databases in addition (like Cochrane CENTRAL) to find recent, high quality systematic reviews and/or primary research studies. It is not expected to perform for all chapters a de novo systematic review, if such reviews are already published recently, but it still may be indicated for some items. For questions relating therapy, it should be focused on evidence from (systematic reviews of) randomized controlled trials if available.

The method of the systematic literature search needs to be fully described in the section “Methods”, e.g.:

“A systematic literature search was performed for the last ... (usually 10) years in MEDLINE, Cochrane etc. with the following key words ... and the following limitations: e.g. UTI, age (adult?), ... clinical studies ... English ... abstract available ... only peer reviewed ...

A total of ... publications were identified, which were screened by title and abstract ... After exclusion of duplicates ... a total of ... were included into the review (analysis), supplemented by citations or known to the authors ... ”.

Clinical topics

Clinical topics should be focused on the importance to clinical practice according to the up to date scientific knowledge as presented in the literature. It should relate to questions/complaints/symptoms of patient/population concerning definition, diagnosis, therapy/prevention, intervention, and outcome in comparison, if different approaches are feasible. Please choose patient-important outcomes and focus on those, which you deem critical for decision-making.

Level of evidence and grade of recommendations

Any recommendation should be based on the level of evidence and the grade of recommendation. For this purpose the following system, modified from the Oxford Centre for Evidence-based Medicine should be used (EAU guidelines 2015):

Level of evidence (LE)

Level Type of evidence
1a Evidence obtained from meta-analysis of randomised trials
1b Evidence obtained from at least one randomised trial
2a Evidence obtained from one well-designed controlled study without randomization
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports.
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities.

Grade of Recommendations (GoR)

Grade Nature of recommendations
A Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
B Based on well-conducted clinical studies, but without randomised clinical trials
C Made despite the absence of directly applicable clinical studies of good quality

Comments (EAU guidelines 2015)

The aim of assigning a LE and grading recommendations is to provide transparency between the underlying evidence and the recommendation given.

It should be noted that when recommendations are graded, the link between the level of evidence and grade of recommendation is not directly linear. Availability of randomized controlled trials may not necessarily translate into a grade “A” recommendation where there are methodological limitations or disparity in published results.

Alternatively, absence of high level evidence does not necessarily preclude a grade A recommendation, if there is overwhelming clinical experience and consensus. In addition, there may be exceptional situations where corroborating studies cannot be performed, perhaps for ethical or other reasons and in this case unequivocal recommendations are considered helpful for the reader. The quality of the underlying scientific evidence - although a very important factor – has to be balanced against benefits and burdens, values and preferences and costs when a grade is assigned.

Since the same rating system should be used in all chapters, for the sake of brevity the same sentence could be used in “Methods” for all manuscripts, because the rating system will be described in details in the Preface of the book:

“The studies were rated according to the level of evidence and the strength of recommendations graded according to a system used in the EAU guidelines modified from the Oxford Centre for Evidence-based Medicine [1].”

References

[1] European Association of Urology. Guidelines. Methodology section. 2015 ed. Arnhem: European Association of Urology; 2015. p. 3. ISBN/EAN: 978-90-79754-80-9. Available from: http://uroweb.org/wp-content/uploads/EAU-Extended-Guidelines-2015-Edn..pdf

The Living Handbook of Urogenital Infections and Inflammations is issued by:

European Association of Urology
att. Maurice Schlief, EAU executive manager business affairs

P.O.Box 30016
NL-6803 AA Arnhem, The Netherlands

Phone: 0031-26-38.90.680
E-mail: m.schlief@uroweb.org

Editor in Chief

responsible for the contents according to § 5 TMG and § 55 Abs. 2 RStV (Germany):

Kurt G. Naber, MD, PhD
Assoc. Professor of Urology

Technical University of Munich
Karl-Bickleder-Str. 44c
94315 Straubing, Germany

E-mail: kurt.naber@nabers.de

John N. Krieger MD, PhD

University of Washington Section of Urology

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Daniel Shoskes MD, PhD

Cleveland Clinic Glickman Urological and Kidney Institute

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Yong-Hyun Cho MD, PhD

St. Mary's Hospital, The Catholic University of Korea Department of Urology

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Tetsuro Matsumoto MD, PhD

University of Occupational and Environmental Health Department of Urology

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Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen Clinic of Urology and Andrology

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Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital Urology Department

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Kurt G. Naber MD, PhD

Technical University of Munich

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Riccardo Bartoletti

University of Pisa
Department of Translational Research and New Technologies

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Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital
Urology Department

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PD Dr. med. Gernot Bonkat

University Basel
alta uro AG, Merian Iselin Klinik, Center of Biomechanics & Calorimetry (COB)

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Prof. Tommaso Cai MD

Santa Chiara Regional Hospital
Dept. of Urology

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Dr Leyland Chuang

Ng Teng Fong Hospital, National University Health System
Department of Medicine

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Prof. Milan Cizman

University Medical Centre
Department of Infectious Diseases

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Alison Crawford MSc

Queen's University
Department of Psychology

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Pfofessor Svetlana Dubrovina MD, PhD

Rostov Medical State University
Obstetrics and Gynaecology

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Dr Valerie Huei Li Gan MBBS (S'pore), MRCS (Edin), MMed (Surg), FAMS (Urology)

Singapore General Hospital
Department of Urology

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Philip Hanno

University of Pennsylvania

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Ass prof MD Gundela Holmdahl

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology

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Udo B. Hoyme

HELIOS Hospital Erfurt Ltd.
Department of Gynecology and Obstetrics

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David Hunstad

Washington University School of Medicine
Pediatrics / Molecular Microbiology

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Gitte M. Hvistendahl

Aarhus University Hospital

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Prof. Michael KOGAN M.D., PhD

Rostov State Medical University
Department of Urology

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Dr Akihiro Kanematsu

Hyogo College of Medicine
Department of Urology

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Frieder Keller

University Hospital Ulm
Department Internal Medicine 1, Nephrology

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Professor Katarzyna Kilis-Pstrusinska PhD, MD

Wroclaw Medical University
Department of Pediatric Nephrology

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MD, PhD Tae-Hyoung Kim

Chung-Ang University
Urology

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John N. Krieger MD, PhD

University of Washington
Section of Urology

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Prof Ekaterina Kulchavenya

Novosibirsk Research TB Institute, Novosibirsk State Medical University

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Dr Christina Kåbjörn Gustafsson

Ryhov Hospital Jönköping
Pathology

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Dr. Bela Köves

South Pest Teaching Hospital
Department of Urology

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Dr. med. Giuseppe Magistro

Ludwig-Maximilians-University of Munich
Department of Urology

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Vittorio Magri

ASST-North
Urologic Clinic

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András Magyar

South-Pest Hospital
Department of Urology

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Professor Emeritus Brian Morris

University of Sydney
School of Medical Sciences

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Baerbel Muendner-Hensen

ICA-Deutschland e.V.

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Stephen F. Murphy

Feinberg School of Medicine, Northwestern University
Department of Urology

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Kurt G. Naber MD, PhD

Technical University of Munich

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Prof. Yulia Naboka

Rostov State Medical University
Department of Microbiology

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Dr. J. Curtis Nickel MD

Queen's University
Department of Urology

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Professor Ralph Peeker MD PhD

University of Gothenburg
Department of Urology

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Tamara Perepanova

N.A. Lopatkin Research Institute of Urology and Interventional Radiology

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Prof. Gianpaolo Perletti M. Clin. Pharmacol.

University of Insubria
Department of Biotechnology and Life Sciences

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Felice Petraglia

Department of Biomedical, Experimental and Clinical Sciences, University of Florence
Obstetrics and Gynecology

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Dr. Jörgen Quaghebeur PhD. Med. Sci.

University Hospital Antwerp and University Antwerp
Department of Urology

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Yazan F. Rawashdeh

Aarhus University Hospital
Paediatric Urology Section, Department of Urology

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Professor Claus Riedl MD

-
Urology

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Matthew Roberts

The University of Queensland
Faculty of Medicine

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PD Dr. med Guido Schmiemann MPH

Institut für Public Health und Pflegeforschung, Universität Bremen
Abteilung Versorgungsforschung

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Caroline Schneeberger MD PhD

Academic Medical Center (AMC)

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Prof. Dr. med. Peter Schneede

Klinikum Memmingen
Department of Urology

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Aaron C. Shoskes

Des Moines University Medical College of Ostheopathic Medicine

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Daniel Shoskes MD, PhD

Cleveland Clinic
Glickman Urological and Kidney Institute

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Prof. Dr. Roswitha Siener

University of Bonn
University Stone Centre, Department of Urology

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Sofia Sjöström

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology

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Mathew Sorensen

University of Washington School of Medicine
Department of Urology

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Prof. Dr. Dr. Walter Ludwig Strohmaier FEBU

Regiomed-Klinikum Coburg. Medical School Regiomed
Urology and Paediatric Urology

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Satoshi Takahashi

Sapporo Medical University School of Medicine
Department of Infection Control and Laboratory Medicine

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Professor Paul Anantharajah Tambyah

Yong Loo Lin School of Medicine, National University Hospital
Department of Medicine

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Peter Tenke

South-Pest Hospital
Department of Urology

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Praveen Thumbikat


Department of Urology

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Dr. Jose Tiran Saucedo

IMIGO / Universidad de Monterrey
Obstetrics and Gynaecology

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Dominic Tran-Nguyen

Des Moines University

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Dean Tripp

Queen's University
Psychology, Anesthesia & Urology

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Prof. SEONGHEON WIE

The Catholic University of Korea, St. Vincent's Hospital
Division of Infectious Diseases, Department of Internal Medicine

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Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen
Clinic of Urology and Andrology

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Assoc. Prof. Christian Wejse

Aarhus University, Aarhus University Hospital
Department of Infectious Diseases/Center for Global Health, Dept of Public Health

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Prof. Dr. Mete Çek

Trakya University, School of Medicine
Urology

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