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\begin{document}

\title{Clinical management of vesicoureteral reflux with respect to EAU
Guidelines: A multicenter study}



\author[1]{Eda Tokat}%
\author[2]{Serhat Gurocak}%
\author[2]{Seçil Özkan}%
\author[3]{Hasan Serkan Dogan}%
\author[4]{Burak Citamak}%
\author[5]{Nihat Satar}%
\author[6]{Volkan Izol}%
\author[6]{Mutlu Deger}%
\author[7]{Şaban Sarıkaya}%
\author[8]{Yakup Bostancı}%
\author[7]{Murat Gülşen}%
\author[9]{Bülent Önal}%
\author[10]{Elif Altınay Kırlı}%
\author[11]{Berk Burgu}%
\author[11]{Tarkan Soygür}%
\author[12]{Koray Ağras}%
\author[13]{Bilge Karabulut}%
\author[14]{Cem Akbal}%
\author[15]{Çağrı Akın Şekerci}%
\author[16]{Deniz Demirci}%
\author[17]{Numan Baydilli}%
\author[4]{Serdar Tekgul}%
\author[2]{Mustafa Özgür Tan}%
\affil[1]{Sağlık Bakanlığı Ankara Eğitim ve Araştırma Hastanesi}%
\affil[2]{Gazi University Faculty of Medicine}%
\affil[3]{Hacettepe University Faculty of Medicine}%
\affil[4]{Hacettepe University}%
\affil[5]{Çukurova Üniversitesi Tıp Fakültesi}%
\affil[6]{Cukurova University Faculty of Medicine}%
\affil[7]{Ondokuz Mayis University Faculty of Medicine}%
\affil[8]{Ondokuz Mayis Universitesi Tip Fakultesi}%
\affil[9]{İstanbul Üniversitesi-Cerrahpaşa Cerrahpaşa Tıp Fakültesi}%
\affil[10]{İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi}%
\affil[11]{Ankara University Faculty of Medicine}%
\affil[12]{Affiliation not available}%
\affil[13]{Ankara Child Health Diseases Hematology Oncology Training And Research Hospital}%
\affil[14]{Acibadem Universitesi Tip Fakultesi}%
\affil[15]{Marmara University School of Medicine}%
\affil[16]{Erciyes Universitesi Tip Fakultesi}%
\affil[17]{Erciyes University}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Purpose: We designed a multicenter, retrospective study to investigate
the current trends in initial management of reflux with respect to EAU
guidelines in Urology clinics of our country. Materials and Methods: The
study group consisted of 1988 renal units (RU) of 1345 patients treated
surgically due to VUR between years 2003-2017 in 9 different
institutions. Patients were divided into 2 groups according to time of
initial treatment and also grouped according to risk factors by ``EAU
guidelines on VUR''. Results: 1426 RUs were treated initially
conservatively and 562 RUs were initially treated with surgery. In
initially surgically treated group, success rates of surgery decreased
significantly in low and moderate risk groups after 2013 (p=0.046,
p=0.0001, respectively), while success rates were not significantly
different in high risk group (p=0.46). While 26.6\% of patients in low
risk group were initially surgically treated before 2013, this rate has
increased to 34.6\% after 2013, but the difference was not statistically
significant (p=0.096). However, performing surgery as the initial
treatment approach increased significantly in both moderate and high
risk groups (p=0.000 and p=0.0001, respectively) after 2013. Overall
success rates of endoscopic and UNC operations were 65\% and 92.9\%
before 2013, 60\% and 78.5\% after 2013, respectively. Thus the overall
success rate for surgery was 72.6\%. There was significant difference
between success rates of UNC operations before and after 2013(p=0.000),
while the difference was not significant in the STING group (p=0.076).
Conclusion: Current trends in management of reflux in our country do not
yet follow the EAU guidelines on VUR in low and moderate risk groups.%
\end{abstract}%



\sloppy


\textbf{Title: Clinical management of vesicoureteral reflux with respect
to EAU Guidelines:}

\textbf{A multicenter study}

\textbf{Short title: Effect of EAU Guidelines on VUR management}

\textbf{Authors:} Eda Tokat \textsuperscript{1} ,Serhat
Gurocak\textsuperscript{2} , Secil Ozkan\textsuperscript{3}, Hasan
Serkan Dogan~\textsuperscript{4} , Burak Citamak \textsuperscript{4} ,
Nihat Satar \textsuperscript{5}, Volkan Izol \textsuperscript{5}, Mutlu
Deger\textsuperscript{5} , Saban Sarikaya~\textsuperscript{6}, Yakup
Bostanci~\textsuperscript{6} , Murat Gulsen~\textsuperscript{6} , Bulent
Onal~\textsuperscript{7} , Elif Altinay Kirli~\textsuperscript{7} , Berk
Burgu \textsuperscript{8} , Tarkan Soygur \textsuperscript{8} , Perviz
Haciyev~\textsuperscript{8} , Koray Agras~\textsuperscript{2} , Bilge
Karabulut~\textsuperscript{9} , Cem Akbal~\textsuperscript{10}, Cagri
Akin Sekerci \textsuperscript{11}, Deniz Demirci~\textsuperscript{12} ,
Numan Baydilli~\textsuperscript{12} , Serdar Tekgul~\textsuperscript{4},
Mustafa Ozgur Tan~\textsuperscript{2}

\textbf{The authors' institutional affiliations:}

\textsuperscript{1} Department of Urology, University of Health
Sciences, Ankara Training and Research Hospital, Ankara, TURKEY

\textsuperscript{2} Department of Pediatric Urology, Gazi University
School of Medicine, Ankara, TURKEY

\textsuperscript{3} Department of Public Health, Gazi University School
of Medicine, Ankara, TURKEY

\textsuperscript{4} Department of Pediatric Urology, Hacettepe
University School of Medicine, Ankara, TURKEY

\textsuperscript{5} Department of Urology, Cukurova University School of
Medicine, Adana, TURKEY

\textsuperscript{6} Department of Urology, Samsun Ondokuz May\selectlanguage{polish}ı\selectlanguage{english}s
University School of Medicine, Samsun, TURKEY

\textsuperscript{7} Department of Pediatric Urology, Istanbul University
Cerrahpasa School of Medicine, Istanbul, TURKEY

\textsuperscript{8} Department of Pediatric Urology, Ankara University
School of Medicine, Ankara, TURKEY

\textsuperscript{9} Department of Pediatric Urology, University of
Health Sciences, Ankara Child Health and Diseases Hematology Oncology
Trainig and Research Hospital, Ankara, TURKEY

\textsuperscript{10} Department of Urology, Ac\selectlanguage{polish}ı\selectlanguage{english}badem University School
of Medicine, Istanbul, TURKEY

\textsuperscript{11} Department of Urology, Marmara University School of
Medicine, Istanbul, TURKEY

\textsuperscript{12} Department of Urology, Erciyes University School of
Medicine, Kayseri, TURKEY

\textbf{Corresponding Author :} Eda Tokat (
https://orcid.org/0000-0001-6528-9149)

\textbf{Address :} Department of Urology, University of Health Sciences,
Ankara Training and Research Hospital, Ulucanlar caddesi No:89,
Alt\selectlanguage{polish}ı\selectlanguage{english}nda\selectlanguage{polish}ğ/\selectlanguage{english}Ankara, 06230, Turkey

\textbf{Tel :+9} 05556748379 \textbf{E-mail :}edatokat@gmail.com

\textbf{Acknowledgements:}

This multicenter study is carried out under the leadership of `Society
of Turkish Paediatric Urology' and data is supplied from the member
clinics of the society. This research did not receive any specific grant
from funding agencies in the public, commercial, or not-for-profit
sectors.

\textbf{Clinical practice in vesicoureteral reflux with respect to EAU
Guidelines: A multicenter study}

\textbf{Abstract}

\textbf{Purpose:} We designed a multicenter, retrospective study to
investigate the current trends in initial management of reflux with
respect to EAU guidelines in Urology clinics of our country.

\textbf{Materials and Methods:} The study group consisted of 1988 renal
units (RU) of 1345 patients treated surgically due to VUR between years
2003-2017 in 9 different institutions. Patients were divided into 2
groups according to time of initial treatment and also grouped according
to risk factors by ``EAU guidelines on VUR''.

\textbf{Results:} 1426 RUs were treated initially conservatively and 562
RUs were initially treated with surgery. In initially surgically treated
group, success rates of surgery decreased significantly in low and
moderate risk groups after 2013 (p=0.046, p=0.0001, respectively), while
success rates were not significantly different in high risk group
(p=0.46). While 26.6\% of patients in low risk group were initially
surgically treated before 2013, this rate has increased to 34.6\% after
2013, but the difference was not statistically significant (p=0.096).
However, performing surgery as the initial treatment approach increased
significantly in both moderate and high risk groups (p=0.000 and
p=0.0001, respectively) after 2013. Overall success rates of endoscopic
and UNC operations were 65\% and 92.9\% before 2013, 60\% and 78.5\%
after 2013, respectively\textbf{.} Thus the overall success rate for
surgery was 72.6\%. There was significant difference between success
rates of UNC operations before and after 2013(p=0.000), while the
difference was not significant in the STING group (p=0.076).

\textbf{Conclusion:} Current trends in management of reflux in our
country do not yet follow the EAU guidelines on VUR in low and moderate
risk groups.

\textbf{Keywords:} Vesicoureteral reflux; reflux risk grouping; reflux
treatment management; EAU/ESPU guidelines on vesicoureteral reflux;
pediatric urology

\textbf{Main Text}

\textbf{Introduction}

Vesicoureteral reflux(VUR) is the non-physiologic retrograde flow of
urine from the bladder to the kidneys in children which can lead to
pyelonephritis and secondary renal injury due to renal scarring {[}1{]}.
Though it is a common urogenital abnormality in children with the
prevalence of 0.4-1.8\%, every stage of management of VUR is still under
debate {[}2{]}. The clinical management of reflux includes
observational, medical and surgical therapies. The surgical correction
of reflux has been the mainstay approach in high grade reflux but
generally it is not the sole objective of management considering the
aims of treatment: to avoid the occurrence of urinary tract infections
(UTI) and to avoid development of new renal scars {[}3{]}. Also the
benefit and necessity of antibiotic prophylaxis in low grade reflux are
under debate. Thus, management should be individualized and based on
each patient's age, gender, grade of reflux, presence of renal scar,
clinical course, bilaterality, ipsilateral renal function, bladder
dysfunction (related lower urinary tract symptoms (LUTS) such as
urgency, urge incontinence, weak stream, hesitancy, frequency) and
parental preference {[}4{]}. Patients who have both VUR and lower
urinary tract dysfunction (LUTD) may have elevated risk of kidney damage
and worse outcome after treatment {[}5{]}. If LUTD is detected in a
reflux patient, it should be treated initially regardless choice of
treatment method.

The ``European Association of Urology (EAU) Guidelines on Vesicoureteral
Reflux in Children (September 2012)'' created a modified risk
classification by analyzing and defining risk factors such as age, sex,
reflux grade, LUTD, anatomic abnormalities, and kidney status for each
patient. They grouped patients into three groups according to the risk
classification and made recommendations for each group based on early
risk assessment. The authors aimed to identify cases requiring immediate
intervention or to avoid overtreatment in the spontaneous resolution
expected patients or only requiring conservative therapy {[}6{]}. We
hypothesized that the publication of guidelines altered the initial
management approach to patients with VUR. Therefore, we designed a
multicenter retrospective study to investigate the current trends in
initial management of reflux with respect to EAU guidelines and their
effect on results of treatments in our country. As a secondary outcome,
this study tried to highlight the preoperative determinants of
postoperative success rates of VUR correction techniques; either
endoscopic treatment or open reimplantation.

\textbf{Material and Methods}

The study group consisted of 1988 renal units (RU) of 1345 consecutive
patients who were referred to 9 different urology clinics in all across
our country and treated surgically due to VUR between years 2003-2017.
The institutions that agreed to send their data for this study are
composed of mostly members of European Society for Pediatric Urology
(ESPU) and also members of Turkish Pediatric Urology Society and are in
collaboration with each other and reference centers for treatment of
pediatric urology patients in our country. Accordingly, the protocols
for initial evaluation, treatment decisions and follow up were basically
the same. The study was based on clinical registry and a data extraction
form (Appendix 1) including parameters agreed by the board of Turkish
Pediatric Urology Society was sent to all centers included in this study
and gathered back for analysis. Thus all of the consecutive cases with
available data and follow up were included. The main intention of the
study was whether we followed the new guidelines for reflux and how did
it affect our success.

Among all the referred 1345 consecutive patients 1426 (71.7\%) RUs were
treated initially conservatively and 562 (28.2\%) RUs were initially
treated with surgery. Mean time elapsed between initial treatment and
operation was 16.67 months (1-192).

Diagnostic evaluation included medical history (age, sex, history of
urinary tract infection, presence of LUTS), physical examination, urine
culture, renal ultrasonography (USG) and voiding cystourethrography
(VCUG). Demarcaptosuccinic acid scanning (DMSA) was used to affirm the
parenchymal changes detected by USG or in patients with high grade
reflux or history of acute pyelonephritis. Patients were treated
regarding the institutional preference and categorized retrospectively
according to the risk classification of EAU guidelines on VUR. Surgical
indications were presence of additional ureteral anomaly, high grade
reflux, gender, age beyond resolution-persistent reflux, breakthrough
infections, renal scarring and noncompliance with medical management
(especially for rural patients). Conservative treatment consisted of
continuous antibiotic prophylaxis (CAP) and/or anticholinergic drugs.
Dosages of antibiotics were 50-100 mg/kg/day for Ampicillin
(\textless{}2 months old patients) and 2 mg/kg/day for
Trimethoprim-Sulfamethoxazole (\textgreater{}2 months). All the patients
beyond toilet training age were evaluated for LUTS and treated if needed
prior to the choice of treatment method. LUTS of patients were treated
with urotherapy (timed voiding, dietary manipulation for fluid intake
and constipation and anticholinergics (mainly oxybutynin hydrochloride).
In all patients endoscopic subureteric transurethral injection and/or
open ureteral reimplantation were carried out to correct the reflux.
Patients were divided into two groups according to time of initial
treatment being before or after 2013 and also grouped according to risk
factors under guidance of ``EAU guidelines on Vesicoureteral Reflux in
Children''. Preoperative and postoperative data of patients with VUR
were retrospectively reviewed. Preoperative clinical parameters such as
age and gender of the patient, grade and laterality of reflux, presence
of renal scar and lower urinary tract symptoms, initial and follow-up
treatments and durations, outcomes of medical treatment and surgical
procedures and postoperative data of patients were analyzed
retrospectively. After treatment modalities patients were followed
clinically by presence of symptoms, regular urine culture, USG and DMSA
scan. Breakthrough infections, new renal scars on DMSA, reflux on VCUG
(if performed) or additional complications like increase in
hydronephrosis were accepted as surgical treatment failure.
Postoperative VCUG was not routinely performed in all patients. The main
indications for postoperative VCUG were new renal scar formation on DMSA
scan and having breakthrough urinary tract infection. Statistical
analysis was performed by SPSS ver. 15.0 (SPSS Inc., Chicago, IL, USA).
Categorical variables were compared using the chi-square test and
regression analysis was carried out. Statistical significance was
considered as p[?]0.05.

\textbf{Results}

The mean follow-up duration of the 1345 patients (1988 RUs) with the
mean age of 5.18 \selectlanguage{ngerman}±3.6 (0-18) years, was 32 (1-184) months. 70\% (941)
percentage of patients was female and 30\% (404) were male. 118 (8.8\%)
patients were known to have anatomic abnormalities like ureterocele,
solitary kidney, ectopic ureter, Hutch or paraureteral diverticulum and
most commonly duplications (3.7\%). 35.8\% (482) of patients were
treated due to LUTD prior to the treatment of reflux. Renal scar was
detected on preoperative DMSA scintigraphy in 64.2\% (864) percentage of
patients (defining at least a moderate risk according to guidelines.)
The percentages of patients with right, left sided and bilateral reflux
were 18.7\%, 33.4\% and 47.8\% respectively. 54.1 \% of the renal units
were presented with low grade reflux (grade 1-3), while 45.9\% were high
(grade 4-5). 811 (60.3\%) patients initially referred with breakthrough
urinary tract infection (Table 1).

Among the preoperative parameters, only the presence of renal scar on
DMSA and treating lower urinary tract symptoms were found to determine
the postoperative success rates significantly (p:0.002, p:0.000); while
age, sex, grade of reflux, risk groups had no effect. (regression
analysis results)

65 (3.3\%) RUs were excluded in analysis of surgical treatment success
due to lost to follow-up or insufficient data. Accordingly, 1238
(\%62.3) RUs were treated with subureteric injection (STING) (533
unilateral; 705 bilateral) and 685(34.4\%) RUs with Cohen type
ureteroneocystostomy (UNC) (199 unilateral; 486 bilateral). The
percentages of both endoscopic and open reimplantations were 63.1\%,
36.1\% before 2013 and 61.2\%, 32.3\% after 2013, respectively. 353
(17.7\%) children had urinary tract infection and 275 (13.8\%) children
had new renal scar formation on DMSA postoperatively. Also 83 children
with new renal scar had postoperative urinary tract infection
additionally. 67 (3.4\%) patients had increasing hydronephrosis while
persistent reflux was detected in 541 (27.2\%) patients among ones who
had postoperative VCUG. Success rates of endoscopic and UNC operations
were 65\% and 92.9\% before 2013, 60\% and 78.5\% after 2013,
respectively\textbf{.} Thus the overall success rate for surgery was
72.6\%. There was significant difference between success rates of UNC
operations before and after 2013(p=0.000), while the difference was not
significant in the STING group (p=0.076).

Then, the patients were grouped into three risk groups according to EAU
VUR risk classification and percentages of the low, moderate and high
risk groups were 18.9\%, 52.6\% and 28.5\% respectively. The data were
analyzed due to risk groups, time of diagnosis and initial treatment
modalities. As stated before among all the referred 1345 consecutive
patients 1426(71.7\%) RUs were treated initially conservatively prior to
surgery and 562(28.2\%) RUs were initially treated with surgery on
referral. Mean time elapsed between initial treatment and operation was
16.67 months (1-192). In initially surgically treated group, success
rates of surgery decreased significantly in low and moderate risk groups
after 2013 (p=0.046, p=0.0001, respectively), while success rates were
not significantly different in high risk group (p=0.46) (Table 2). The
overall success rate in initially surgically treated group before 2013
was 80.9\%. That was decreased to 70.5\% after 2013 (p=0.004).

While 26.6\% of patients in low risk group were surgically treated
before 2013, this rate has increased to 34.6\% after 2013, but the
difference was not statistically significant (p=0.096). However,
performing surgery as the initial treatment approach increased
significantly in both moderate and high risk groups (p=0.000 and
p=0.0001, respectively) after 2013. Thus, we can say that there was
increased preference for surgical treatment initially in moderate and
high risk groups after 2013 (Table 3).

Among the patients with low grade 1-2 reflux (Grade 1-2), only one
patient had UNC and 71 patients had subureteric injection initially.
During follow up, the total number of patients who had subureteric
injection had risen to 206 while 20 patients had UNC. The mean time
between the initial treatment and surgical intervention was 14.2 months
and the mean follow-up duration of this group was 24.8 months. 69.5 \%
percentage of these low grade VURs had successful clinical outcomes
after surgery.

\textbf{Discussion}

Despite the optimal management of reflux has been discussed over more
than thirty years several times in the literature, it is still
contradictory which type of treatment, medical or surgical is superior
{[}1{]}. The main two aims of treating reflux is to avoid the
development of new renal scars and to avoid the urinary tract infections
in attempt to preserve kidney function {[}3{]}. From past to present
treatment management has been based on age, sex, presence of renal scar,
grade of reflux, laterality of reflux, presence of bladder dysfunction
and toilet training. Starting from this contradiction about treatment of
reflux, EAU published guidelines on VUR in second half of 2012 {[}6{]}.
In the guidelines patients are grouped into three groups, according to
being symptomatic/asymptomatic, gender, before or after toilet training
(age), grade of reflux, presence of LUTD and kidney status. As well,
initial and follow up treatment methods are suggested for each group.

According to EAU guidelines the hallmarks of low risk disease are normal
kidneys, low grade reflux (grade 1-3) and absence of LUTD. In the low
risk group, there are two options of initial treatment: either no
treatment or CAP, similar to the AUA guidelines {[}6, 7{]}. In the
classical and new guidelines, surgery is not offered to patients with
grades 1-2 reflux, in the absence of breakthrough infections or new
renal scars. With a minor difference in classical view, grade 3 reflux
was not accepted as low grade and surgery was an option if persistent
after 5 years of age {[}8{]}. Although it is not recommended to do
surgery initially in low risk group, use of CAP in every reflux patient
or observational management in primary reflux is still controversial.
There are several studies declaring the efficacy of CAP, such as the
well- known randomized studies; the PRIVENT study, the RIVUR study and
Swedish Reflux Trial {[}9-14{]}. Nevertheless, a large number of studies
supporting the insignificant difference between CAP and observational
management in VUR were also carried out {[}15-18{]}. In our study, CAP
was preferred in the initially conservatively treated group rather than
no treatment. However, despite the guidelines there might be increased
tendency to surgical interventions in the low risk group after 2013 but
not significant.

In the moderate risk group, CAP is the offered initial treatment method
and intervention may be considered in case of breakthrough infections
and persistent reflux. Also LUTD treatment should be given if needed. In
all groups treatment for LUTD was given initially and it was seen to be
effective on clinical success of reflux treatment. In our study,
performing surgery as initial treatment approach increased significantly
in the moderate group after 2013 that might be partially related to the
parental incompliance.

Increased surgical preference (UNC/endoscopic) as an initial treatment
method in low (it was not significant though) and moderate risk groups
might seem controversial but considered to reflect our cultural attitude
towards definitive treatment. Initial preference of surgical treatments
in these low grade refluxes (72 patients) representing incompatibility
with the EAU guidelines, could be attributed to parental preference and
patients coming from rural areas because of difficult follow up. The
centers included in the study are referral centers and the patients
usually come from distant regions. Thus the follow up could be
problematic. The increase could also be attributed to increased surgical
expertise and confidence in pediatric urology practice over the years in
our country. In addition, our study has a retrospective design and nine
clinics were included from different parts of the country. Due to the
fact that pediatric urologists from different centers might have
different treatment tendencies for the patient with similar clinical
variables, this could be another reasonable explanation for the
increased preference for surgical treatment modalities. In the study by
Prisca et al. parental incompliance was a negative predictive factor in
VUR resolution and these patients had a worsening tendency because of
being un-followed. The authors proposed that parental compliance should
be considered in EAU guidelines application{[}19{]}.

The high risk disease is defined as high grade reflux (grade 4-5) and
abnormal kidneys and the initial treatment is mostly suggested surgical
in the EAU guidelines (greater possibility or may be considered) and
definitely surgical in classical management strategies. In the high risk
groups, the priority of open surgery, after the treatment of LUTD if
needed (in symptomatic cases after toilet training with high grade
reflux and abnormal kidney) {[}6{]}. In our study we determined
increased preference of surgical treatments as initial method in the
high risk group after 2013. This is usual and in concordance with the
guidelines. The result was in compliance with the recommendations of the
guidelines. Consequently, there was preference of surgical methods in
all groups after 2013. Before 2013 we were classically treating patients
surgically according to age (being \textless{}1, 1-5 or
\textgreater{}5), gender (female), grade of reflux, presence of
additional ureteral anomaly and renal functions-renal scar on DMSA scan
{[}8{]}. In the meantime, we accepted persistent reflux-hydronephrosis
and new renal scar formation or breakthrough infections while the
patient is under antibiotic prophylaxis as surgical indications in
low-moderate risk groups.

Success rates of treatment in high risk group were not different after
2013, because of the same attitude towards the more successful UNC
before and after 2013. In low and moderate risk groups guidelines prefer
conservative methods first and if necessary surgery as the next step.
However, performing surgery as the initial treatment approach increased
in all groups after 2013 as patients were increasingly referred from
rural areas (risk of lost to follow up and parental preference). The
decreased success rate after 2013 in initially surgically treated group
could be attributed to multiple factors. Pediatric urology is still
evolving in our country within time and all the institutions included in
this study are training centers. Thus there is increasing variability
and divergence in treatment attitudes among regions effecting success
rates throughout the country. There is surely increasing population and
immigration in our country and easy transportation facilities have been
causing increased referral. This decrease in success rate should alert
us about more serious consideration and concordance with the new EAU
guidelines on VUR. These factors might be also related to our overall
surgical success rate for reflux surgery (both endoscopic and UNC) that
was 72.6\%. Success rates of endoscopic and UNC operations were 65\% and
92.9\% before 2013, 60\% and 78.5\% after 2013, respectively. Thus the
overall success rate for surgery was 72.6\%. There was significant
difference between success rates of UNC operations before and after
2013(p=0.000), while the difference was not significant in the STING
group (p=0.076).This could be partly due to increased preference of
surgical treatments as initial method in the high risk group after 2013.
The high risk disease is high grade reflux (grade 4-5) that is usually
treated with UNC and more technically demanding compared to UNC's done
for lower grades of reflux. Also the centers included in the study were
referral (complicated cases) and teaching institutions.

The main limitations of the study are being retrospective and
multi-central. Thus, institutional preferences and success achievements
could be variable. However, the study represents large number of
patients and a wide and scattered spectrum of treatment attitude towards
reflux treatment in our country. All the centers included known to be
experienced in pediatric urology in our country and patients were
accepted from pediatric nephrologists when the medical treatment fails
thus the study reflects a selection bias for surgery. Pediatric
nephrologists follow-up successful patients with medical therapy and
refers urologists unsuccessful patients for the surgical option so this
results in uneven distribution of the sample.

\textbf{Conclusions}

As a conclusion current trends in management of reflux in our country do
not yet follow the EAU guidelines on VUR in low and moderate risk
groups. This might be due to several factors including parental
preference, cultural attitudes, surgical expertise and approach of
different pediatric urology clinics. As expected there is an increased
tendency for initial surgical treatment in high risk groups in
accordance with the EAU guidelines. The overall success rate could be
low due to variability between clinics and reference of complex cases to
the tertiary centers as well as inclusion of endoscopic surgery and
increased preference of surgical treatments as initial method in the
high risk group after 2013 as high risk disease is high grade reflux
(grade 4-5) that is usually treated with UNC and more technically
demanding compared to UNC's done for lower grades of reflux.

\textbf{Conflicts of Interest:}

All authors disclose any potential conflict of interest.

\textbf{Funding Sources:}

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.

\textbf{Authorship}

Conception and Design: Eda Tokat, Serhat Gurocak, Mustafa Ozgur Tan

Acquisition of Data: Eda Tokat, Burak Citamak, Mutlu Deger, Murat
Gulsen, Elif Altinay Kirli, Perviz Haciyev , Koray Agras, Cagri Akin
Sekerci, Numan Baydilli

Analysis and interpretion of Data: Eda Tokat, Secil Ozkan, Serhat
Gurocak, Mustafa Ozgur Tan

Drafting and revising critically: Eda Tokat, Serhat Gurocak , Hasan
Serkan Dogan~ ,Nihat Satar, Volkan Izol , Saban Sarikaya, Yakup Bostanci
, Bulent Onal, Berk Burgu , Tarkan Soygur, Cem Akbal, Deniz Demirci ,
Serdar Tekgul, Mustafa Ozgur Tan

All the authors have given the approval of the final version to be
published and agreed to be accountable for all aspects of the work.

\textbf{Availability of data and materials:} All the data supporting our
fndings is contained in the manuscript. The datasets used and/or
analysed in the current study is available from the corresponding author
on reasonable request

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