Paediatrica Indonesiana

VOLUME 50 September ‡ NUMBER 5

Review Article

The management of vesicoureteral reflux in children

Nurul Akbar, Arry Rodjani

Epidemiology

Vesicoureteral reflux (VUR) is defined as retrograde flow of urine from the bladder to the ureter. It is usually asymptomatic but commonly found in children with urinary tract infection (UTI). The prevalence is about LQJHQHUDOSHGLDWULFSRSXODWLRQ  However, the prevalence in children with UTI is much higher, UHDFKLQJ  6LPLODUSUHYDOHQFH  LV also reported in CiptoMangunkusumo Hospital.(3)

Etiology

Primary vesicoureteral reflux

Primary VUR is a congenital lesion not associated Figure 1. Vesicoureteral junction in normal state and with any underlying obstructive or neuromuscular TGƀWZ6) phenomenon. It is suggested to be related to the failure of antireflux mechanism at the vesicoureteral junction (VUJ) resulting in regurgitation. This regurgitation Secondary vesicoureteral reflux can cause spread of infection from the bladder to the ureter and kidney. Once the infection has reached the Secondary reflux is not a congenital primary pelviocalyceal system of the kidney, microorganism disorder. It is caused by anatomical or functional can invade the parenchyma through intrarenal reflux obstruction, bladder inflammation, or direct injury (IRR).(3) Primary VUR is usually detected during to orifice which is previously intact. It is suggested radiologic evaluation of children with UTI. It can also found prenatally by the finding of hydronephrosis.(5) Congenital primary VUR is characterized by short From The Department of Urology Medical School University of Indonesia intramural ureter length relative to its diameter. The – Cipto Mangunkusumo Hospital, Jakarta, Indonesia QRUPDOUDWLRLV(6) however in some conditions, the ratio is less causing dysfunction of normal antireflux Reprint request to: Nurul Akbar, MD, Department of Urology Medical School University of Indonesia – Cipto Mangunkusumo Hospital, Jakarta, mechanism (Figure 1). Indonesia

Paediatr Indones, Vol. 50, No. 5, September 2010‡259 Nurul Akbar et al: The management of vesicoureteral reflux in children

WKDWWKHPDMRULW\RIORZJUDGHUHIOX[ JUDGH,,,, LV VHJPHQWDOLVFKHPLDZKLFKLQWXUQDFWLYDWHVWKHUHQLQ a secondary reflux which may improve with bladder angiotensin system. The activation of this system, maturation.  along with the abnormality of sodium transport due One of the commonest cause of secondary VUR to reduced area containing the Na/K ATPase pumps is voiding dysfunction, which is abnormality of one or and renal artery stenosis found in neuromuscular more phase of voiding cycle. In a normal cycle, the dysplasia, can result in hypertension.  bladder dilates as the urine fills in before contracts +\SHUWHQVLRQRFFXUVLQXSWRDGXOW normally at voiding or emptying. During the filling SRSXODWLRQLQZHVWHUQFRXQWULHVRIZKLFKLV phase, there should be no contraction or premature idiopathic. Renal abnormality comprises a significant increase of pressure, while in the voiding phase, proportion in the etiology of hypertension in adult. external urethral sphincter should completely relax %DUDLHWDOUHSRUWHGWKDW985LVIRXQGLQ so that urine will flow continuously until the bladder of adult population accidentally diagnosed to have is emptied. Interrupted urine flow or incomplete hypertension without any obvious renal parencyma or emptying is a sign of voiding dysfunction.(8) vascular abnormality. This prevalence is tenth times In children with voiding dysfunction, secondary of that was previously reported in children.  VUR is usually resulted from the high bladder pressure. The high pressure can also cause the development of diverticulum which is a local outpouching of bladder Classification wall due to muscular weakness. It also cause bladder dysfunction responsible for frequency or incontinentia ,QWKH,QWHUQDWLRQDO5HIOX[6WXG\&RPPLWWHH symptoms.(8) established a reflux classification system. VUR is classified into five degree of severity based ureter and renal pelvicalyceal morphology seen in VCUG. The Patophysiology classification is useful for standardized description of reflux severity which is particularly important Vesicoureteral reflux occurs due to increase of in clinical management, subject classification intrabladder pressure causing pathogen organism in research, clinical course documentation, and to be transmitted to the ureter and pelvis, or in quantification of association between reflux and other severe cases, to the collecting duct and papillary clinical parameters that might affect the resolution tubules, a phenomenon called intrarenal reflux of reflux.  (IRR). Intrarenal reflux usually occurs in polar The classification of VUR severity is described area. On voiding cystourethrogram (VCUG), it is as follows: grade I, backflow of urine into the ureter characterized by the presence of contrast material in without any sign of dilatation; grade II, backflow renal parenchyma, both in the collecting duct and of urine into the ureter and pelvicalyceal system nephron. Intrarenal reflux can result in formation without any sign of dilatation; grade III, mild to of renal scar.(3, 6, 9) moderate dilatation of ureter dan renal pelvicalyces Initial studies about IRR were conducted by with minimal blunting of fornices; grade IV, moderate 5ROOHVWRQLQDQG5RVHLQZKRREVHUYHG dilatation of pelvicalyceal system with turtuous ureter; reflux in neonates and infants. The studies revealed grade V, severe dilatation of ureter and pelvicalyceal that renal scar is always formed in parenchyma system, blunted round calyces, and severely dilated VHJPHQWH[SRVHGWR,555DQVOH\DQG5LVGRQLQ turtuous ureter (Figure 2). also reported that scar is only formed in exposed area, either to infected urine or IRR.(6) Not all VUR result in renal scar. Low or moderate grade VUR do not The characteristics of VUR increase the incidence of renal scar or UTI,  while WKHKLJKJUDGHRQH JUDGH,99 KDVWKHKLJKHUULVN The main symptom of VUR is recurrent UTI which  is often accompanied by fever. Other symptoms could Renal scar will cause arterial disruption and be day or night incontinence; irritable symptoms

260‡Paediatr Indones, Vol. 50, No. 5, September 2010 Nurul Akbar et al: The management of vesicoureteral reflux in children

(KIWTG874FGITGGQHUGXGTKV[DCUGFQP+PVGTPCVKQPCN4GƀWZ5VWF[ such as frequency, urgency, and/or painful urination; The association between VUR, obstructive symptoms such as hesitance, dribbling, voiding dysfunction, and UTI intermittent and/or straining at urination; back, loin, or abdominal pain, and/or hematuria.(8) Proteinuria, Urinary tract infection can result in reflux. Inflammation nephrolithiasis, or hematuria during pregnancy can occuring at the vesicoureteral junction and bladder also be found.  Radiological examination shows wall can cause edema and loss of junction flexibility. XQLODWHUDORUELODWHUDOUHIOX[LQRIFDVHV Moreover endotoxin also can disrupt ureter peristaltic VUR can also be suspected by the presence which results in incompetent vesicoureteral junction. of its complications, such as hypertension, voding (3) On the other hand, VUR is also a risk factor for dysfunction,(8) impaired renal growth, or chronic renal recurrent UTI. Controversies exist regarding the failure. Undiagnosed reflux can cause the formation effectivity of VUR surgical repair to overcome recurrent of renal scar and reflux nephropathy (RN).  Those 87,VLQFHPRUHWKDQRISDWLHQWVVWLOOH[SHULHQFH complications often occur in VUR patients with recurrency after surgery. UTI.(5) Vesicoureteral reflux also can result from high Reflux nephropathy is defined as focal renal intrabladder pressure due to voiding dysfunction.(8, scar in one or both kidneys due to primary VUR and  $SUHYLRXVVWXG\UHYHDOHGWKDWRISDWLHQWV UTI.  It is the most common etiology of childhood with voiding dysfunction experience VUR. Voiding hypertension.  In an England survey, the dysfunction mainly occurred in female children SUHYDOHQFHRI51LVHVWLPDWHGWREHLQFKLOGUHQ with UTI. Indeed, it underlies the development of and adults.(4),Q&LSWR0DQJXQNXVXPRKRVSLWDO infection.  Many studies reported that the frequency of UTI children with VUR have already had reflux of recurrent UTI is higher in children with voiding QHSKURSDWK\DQGKDGH[SHULHQFHGFKURQLF dysfunction compared to those without.  The renal failure.(3) In other studies, the prevalence of improvement of voiding dysfunction decreases the UHIOX[QHSKURSDWK\YDULHGEHWZHHQ  The incidence of UTI and enhances VUR resolution.  prevalence of hypertension in reflux nephropathy is parallel to the severity of renal impairment and decreased function.  Management of VUR However, VUR can resolve spontaneously in RIFDVHV  In fact, the rate of spontaneous Several treatment choices are available, which are FORVXUHFDQEHDVKLJKDVDVWKHFKLOGUHQJURZ observation guarded by prophylactic antibiotic, older.  Hutch proposed the theory of intramural endoscopy using dextranomer hyaluronic acid ureter maturation to explain the spontaneous FRSRO\PHU '[+$ DQGVXUJLFDOFRUUHFWLRQ resolution of reflux. As children grow older, the length Ureteroneocystostomy is the gold standard therapy of intramural ureter will also increase so that antireflux IRU985ZLWKVXFFHVVUDWHRIDQGIRUJUDGH mechanism will function more properly.(3)

Paediatr Indones, Vol. 50, No. 5, September 2010‡261 Nurul Akbar et al: The management of vesicoureteral reflux in children

,,9DQGJUDGH9UHIOX[UHVSHFWLYHO\  or chronic renal failure. Various outcomes have been In Cipto Mangunkusumo Hospital, the reported in mild VUR, but in severe VUR, prophylactic management is determined according to the grade antibiotics are recommended, especially for those of reflux. Grade I and III is managed by conservative waiting for surgery schedule.  +RZHYHUORQJWHUP WUHDWPHQW&KLOGUHQZLWKJUDGH,99985LVPDQDJHG study found that neither medical treatment nor surgery by surgical repair. Ureteroneocystostomy is reserved for is superior to each other. Moreover, contradictive FKLOGUHQDJHGPRUHWKDQ\HDUVROGZKRGRQRWVKRZ results were reported in both treatment approaches. signs of intrabladder obstruction, recurrent intractable No treatment was proven to be effective for preventing 87,DQRPDO\RIXUHWHURVWLXP KRUVHVKRHRUJROIKROH the progression of chronic renal failure, but one study like), or decreased renal function.(3) showed that early medical or surgical treatment can prevent recurrent injury to renal parenchyma.  The true benefit of surgery or antibiotic treatment might Prophylactic antibiotics lay on its role in preventing UTI, but they are probably not adequately effective in preventing permanent Prophylactic antibiotic is basically given as an chronic renal failure. Thus, the main goal of therapy is effort to keep the urine sterile while waiting for to prevent the renal parenchymal injury, no to cure the spontaneous resolution to occur. The rationale is that reflux.  Considering the possibility of spontaneous antibiotic can reduce bacterial colonization (especially resolution of reflux, long term antibiotic prophylaxis Enterobacteriaceae) in urethral orifice to prevent the is the main treatment to prevent recurrent UTI which occurrence of ascending infection. To achieve this, can involve renal parenchyma (pyelonephritis) and ideally antibiotics should be broad spectrum and cause permanent renal damage. However, it should be have high concentration in the urine with minimal UHPHPEHUHGWKDWROGHUFKLOGUHQDQGKLJKJUDGHUHIOX[ influence on normal gut flora.(9) Common antibiotics have lower possibility of spontaneous resolution.  for UTI eradication and prevention are listed on the A study in Paris comparing the use of long (8 days) following table. and short duration (3 days) ceftriaxone for children Prophylactic antibiotics may prevent chronic with acute pyelonephritis found that the incidence of renal failure due to recurrent UTI.  0HWDDQDO\VLV renal scar is not different.  The comparison of oral showed that prophylaxis antibiotics have comparable to intravenous cephalosporin also did not result in outcome to surgery in reducing the risk of permanent GLIIHUHQWRXWFRPHV1HXKDXVUHSRUWHGWKDWRUDOVLQJOH GRVHFHIWLEXWHQIRUGD\VFRPSDUHGWRLQWUDYHQRXV Table 1. Antibiotic dosage for treatment and prevention of UTI in children(3) ceftriaxone or ceftibuten had comparable outcomes Prophy- LQFKLOGUHQDJHG\HDUVZLWKDFXWHS\HORQHSKULWLV Dose mg/ Type of drugs Frequency (Age) NCZKU diagnosed based on DMSA.  kg/day mg/kg** Another alternative treatment is the use of Parenteral prophylactic probiotic in children with primary VUR. Ampicillin 100 Every 12h (<1 wk old) Every 6-8h (>1 wk old) Lee et al reported that it has comparable effectiveness %GHQVCZKOG 100 Every 8h compared to antibiotic.(30) Gentamicin 5 Every 12h (<1 wk old) A randomized controlled trial in Italia evaluated 7.5 Every 8h (>1 wk old) 1TCN ſTUVNKPG  WKHHIIHFWLYHQHVVRI\HDUFRXUVHRISURSK\ODFWLF #OQZKEKNNKP 20-40 Every 8h WULPHWKRSULPVXOSKDPHWKR[D]ROHLQSDWLHQWV Ampicillin 50-100 Every 6h ZLWKJUDGH,,,,985,WUHYHDOHGWKDWWKHRFFXUUHQFH %GRJCNGZKPG 50 Every 6-8h Nitrofurantoin* 5-7 Every 6 1-2 RIS\HORQHSKULWLVRUUHQDOVFDUDWWKHHQGRI\HDU 5WNſUQZC\QN 120-150 Every 6-8h 50 follow up was not different between the antibiotic Trimethoprim* 6-12 Every 12h 2 and placebo group.  Another study also reported 5WNHCOGVQZC\QN 30-50 Every 12h 10 0CNKFKZKECEKF 50 Every 12h 20 that the use of prophylactic antibiotics did not reduce the recurrency of UTI after first episode, either in 0QVTGEQOOGPFGFHQTPGYDQTPUQTTGPCNKPUWHſEKGPE[RCVKGPVU  (QTRTQRJ[NCZKUUKPINGFQUGCVPKIJV VQCEJKGXGJKIJGTEQPEGPVTCVKQPKP children with or without primary VUR. A French urine) study also found that prophylaxis antibiotics could

262‡Paediatr Indones, Vol. 50, No. 5, September 2010 Nurul Akbar et al: The management of vesicoureteral reflux in children not reduce the incidence of UTI in children with risk of morbidity.(34) ORZJUDGH985(33) Chung et al suggested the use of Deflux injection Cotrimoxazole or nitrofurantoin can be given as the first treatment of choice for VUR in children. in single dose. Cotrimoxazole is often given as initial 'HIOX[ZKLFKZDVILUVWLQWURGXFHGLQLVDEXONLQJ drug. Trimethoprim itself is reported to be as effective agent injected into ureter orifice or bladder subtrigonal DVWULPHWKRSULPVXOSKDPHWR[D]ROH7ULPHWKRSULP area using endoscopy. It works by creating solid buffer is excreted slowly through the prostate or vaginal behind intrabladder ureter and lengthening the secretion thus preventing periurethral contamination intramural ureter (Figure 3 and 4).  Deflux is the while nitrofurantoin is excreted rapidly through most frequent agent studied. Other agents include urine and its antibactrial effect will disappear after teflon, silicone, bovine collagen, and polyacrylate KRXUV6RPHFHQWHUVSUHIHUWRXVHFHSKDOH[LQLQ polyalcohol copolymer. Most centers reported the children with G6PD deficiency. Amoxicllin, nalidixic VXFFHVVUDWHRI'HIOX[LQMHFWLRQLVPRUHWKDQZKLOH acid, and quinolones are not recommended to be used ORQJWHUPIDLOXUHUDWHYDULHVEHWZHHQ6XFFHV as prophylactic antibiotics since resistance of gut flora WKHUDS\LVPRUHFRPPRQLQORZJUDGHUHIOX[  might develop.(9) 7KHXVHRIGH[WUDQRPHUK\DOXURQLFDFLGFR SRO\PHU '[+$ LVYHU\UHFRPPHQGHGIRUJUDGH,,, VUR. Its usage has also been reported in complex Endoscopy VUR with duplex ureter or paraureteral diverticulum ZLWKVXFFHVVUDWHRIDQGUHVSHFWLYHO\ (QGRVFRS\KDVEHHQUHSRUWHGDVWKHILUVWOLQH Since the introduction of DxHA, endoscopy is often WUHDWPHQWIRU985(QGRVFRS\JXLGHGK\DOXURQLF preferred over open surgical ureter reimplantation to acid/dextranomer injection into ureter orifice is treat VUR. The complication of DxHA injection is increasingly used as antireflux treatment as medical the formation of mound calcification at ureter orifice treatment with prophylactic antibiotics results in which can obscure the diagnosis of distal ureter stone. bacterial resistance while open surgery poses greater 

(KIWTG7TGVGTQTKſEGCUUJQYPD[ŎTKIKFE[UVQU- Figure 4. Injection was stopped after volcano-like copy’ during injection of periureter area appearance obtained

Paediatr Indones, Vol. 50, No. 5, September 2010‡263 Nurul Akbar et al: The management of vesicoureteral reflux in children

Another method of treatment is to reimplant 7KHPDLQFRPSOLFDWLRQRIH[WUDEODGGHUUHLP WKHWUDQVWULJRQDOLQWUDEODGGHUXUHWHUXVLQJ&2 plantation is voiding dysfunction. Recurrent UTI, pneumobladder laparoscopy. The procedure uses progressive renal scar, hypertension, and gestational three trochars which are introduced into suprapubic hypertension are long term complications that may area. After ureter is taken out from the bladder, the occur.(35, 44) submucosa is incised, then ureter is reimplanted Simforoosh et al reported their success in using absorbable 5/0 or 6/0 thread. Bladder drain is performing trigonoplasty laparascopy using technique NHSWXQWLOSRVWRSHUDWLYHGD\7KHVXFFHVVRIWKH VLPLODUWR*LO9HUQHWRSHQSURFHGXUH7KHVXFFHVV procedure is evaluated by USG and/or VCUG. Success UDWHDFKLHYHGLQJUDGH,,,9985,Q*LO9HUQHW UDWHRIKDVEHHQUHSRUWHG  technique, distal ureter orifice is minimally dissected and approximated into the midline.(35) Open surgery Intractable VUR may be managed by open surgery. Extrabladder ureteroneocystostomy is a safe Children with recurrent ISK and progressive renal and effective procedure for this condition. Indeed, impairment, especially those with severe VUR, some authors reported that ureteroneocystostomy are recommended to undergo surgical correction FDQEHSHUIRUPHGE\PLQLPDOLQFLVLRQ FPOHQJWK  besides receiving antibiotic prophylaxis.  Somogyi DWWKHLQJXLQDODUHD PLQLXUHWHURQHRF\VWRVWRP\  et al classified surgical procedure into temporary or ZLWKVXFFHVVUDWH,QKLJKJUDGH ,,,,9 985 permanent. Temporary interventions (cutaneous this procedure has higher success rate compared to ureterostomy, percutaneous transrenal drainage) aim to '[+$ YVS  (45, 46)3VRDV+LWFK reduce obstructive symptoms and VUR until definite technique is performed in patients with persistent reflux procedure can be performed in optimal condition. or obstruction whose previous ureteroneocystostomy Permanent surgical procedure is done by reimplanting failed to correct the disorder.  ureter and excision of narrowed distal ureter segment XVLQJ3ROLWDQR/HDGEHWWHURU&RKHQWHFKQLTXH  Problems Ureter implantation is the treatment of choice IRU985%RWKH[WUDDQGLQWUDEODGGHUUHLPSODQWDWLRQ Children suffering from VUR who are not treated FDQEHSHUIRUPHGE\VXUJHU\RUODSDURVFRS\/LFK GHYHORSUHQDOVFDUDQGDWOHDVWRIWKHPKDG Gregoir technique is more easy to perform and require hypertension.(48) Hypertension can enhance the VKRUWHUWLPHWKDQ3ROLWDQR/HDGEHWWHUPRUHRYHUE\ SURJUHVVLRQRIFKURQLFUHQDOIDLOXUHFDXVLQJ this technique gross hematuria can be avoided. This of children have to undergo renal transplantion. This H[WUDEODGGHUDSSURDFKDOVRUHGXFHSRVWRSHUDWLYH problem requires an effective and feasible guidelines pain and bladder spasm resulting in lower morbidity, for VUR management.(9) PDNLQJWKH/LFK*UHJRLUWHFKQLTXHEHFRPHWKH Treatment modalities for VUR in children consist procedure of choice for unilateral VUR.(43) In bilateral of long term antibiotic prophylaxis and/or laparascopic UHIOX[WZRVWDJH3VRDV+LWFKWHFKQLTXHLVSHUIRUPHG or open surgical procedure. Conservative treatment to avoid bladder dysfunction.  with prophylactic antibiotics can preserve renal

Table 2. The rate of UTI according to treatment modalities

Publication 5VWF[ Intervention UTI (%) Authors 5GVVKPI N P year duration AB No AB Jodal Germany 2006 10 year AB vs. surgery 306 25.2 13.6 <0.03 5QWVJ Lee 2007 6 month AB vs. probiotic 120 21.6 18.3 0.926 Korea Pennesi Italy 2007 2 month AB vs. no treatment 100 18 16 0.71 Montini Italy 2008 12 month AB vs. no treatment 338 7.1 9.5 >0.05 Roussey-Kesler French 2008 18 month AB vs. no treatment 225 17 26 0.2 0QVG#$ RTQRJ[NCZKUCPVKDKQVKE

264‡Paediatr Indones, Vol. 50, No. 5, September 2010 Nurul Akbar et al: The management of vesicoureteral reflux in children

Table 3. Renal scar formation according to treatment modalities 5ECTHQTOCVKQP Publication Authors 5GVVKPI Duration 4CPFQOK\CVKQP N (%) P year AB No AB Jodal Germany 2006 10 years Antibiotic vs. surgery 306 48.8 49.6 >0.05 5QWVJ Lee 2007 6 months Antibiotic vs. probiotic 120 15.4 9.1 0.596 Korea Antibiotic vs. no Pennesi Italy 2007 2 months 100 40 36 0.4 treatment Antibiotic vs. no Montini Italy 2008 12 months 338 1,1 1,9 >0.05 treatment Long vs. short-term Bouissou French 2007 9 months 386 17 13 >0.05 antibiotic Intravenous vs. oral Neuhaus 5YKV\GTNCPF 2007 6 months 365 45.8 26.3 0.2 antibiotic

Table 4. Outcomes of endoscopy technique Publication 5VWF[ 5WEEGUUTCVG Mean length of Name 5GVVKPI Methods N year Duration (%) stay (days) Nelson 75# 2009 1 years Endoscopy vs. open surgery 9.496 - 2.0 Chung Hong Kong 2009 3 months &GƀWZKPLGEVKQP 42 85.9 3.4 Polyacrylate polyalcohol Ormaechea $TC\KN 2010 1 years 83 83.6 - (PPC) &GZVTCPQOGTJ[CNWTQPKECEKF Molitierno 75# 2008 3 months 52 85 - EQRQN[OGT &Z*# Dave Canada 2008 3 months &Z*# 126 50 - Lee 75# 2009 1 years &Z*# 219 46.1 - 24 Cohen transvesicoscopic Valla French 2009 72 92 2.8 months ureter reimplantation

6CDNG5WEEGUUTCVGQHQRGPUWTIGT[VGEJPKSWG Publication 7TGVGTTGƀWZ Mean 5WEEGUUTCVG Name 5GVVKPI Technique N Male Female year (Unit) age (%) 5KOHQTQQUJ Iran 2008 Trigonoplasty 65 56 9 103 5,68 94.1 Ashley 75# 2008 Mini- 57 48 9 57 4,0 100 Politano-Leadbetter and Glenn- Mor Israel 2003 100 21 79 146 6,0 51 Anderson advancement Lich-Gregoir vs 5EJYGPVPGT Austria 2006 44 29 15 44 5,5 98 Politano-Leadbetter function by keeping the urine sterile and preventing Follow Up recurrency of infection. This treatment goal also can be achieved by surgical procedure, however whether All VUR patients must have regular examination medical or surgical management is superior to each during therapy, and whenever required, imaging other still become a continuing debate.(49, 50) The evaluation should be done. The role of imaging is to ULVNRIDQWLPLFURELDOUHVLVWDQFHSRVHGE\ORQJWHUP detect spontaneous resolution, monitor the formation prophylactic antibiotics makes surgical correction of new renal scar, detect abnormal kidney growth, and become the treatment of choice, and since antireflux monitor renal function.(3) LPSODQWZDVLQWURGXFHGLQODSDURVFRSLFVXUJHU\ It is recommended to VCUG evaluation is preferred over open procedure.  PRQWKVDIWHUVXUJHU\ZKLFKFDQEHUHSHDWHG

Paediatr Indones, Vol. 50, No. 5, September 2010‡265 Nurul Akbar et al: The management of vesicoureteral reflux in children weeks afterward or if obstructive symptoms recur. Primary Vesicoureteric Reflux as a Predictor of Renal Damage Initial screening is done with ultrasonography to in Children Hospitalized with Urinary Tract Infection: A assess the progression or hydronephrosis and grossly 6\VWHPDWLF5HYLHZDQG0HWD$QDO\VLV-$P6RF1HSKURO evaluate the renal parenchyma/cortex, blood pressure  examination, urinalysis, urine culture, as well as serum 5. Sharbaf FG, Fallahzadeh MH, Modarresi AR, Esmaeili M. ureum and creatinine. It is recommended to perform Primary Vesicoureteral Reflux in Iranian Children. Indian those examinations every 3 months. Patients with 3HGLDWULFV renal scar are recommended to have renal scintigraphy 6. Roehrborn CG, McConnell JD. Reflux and Megaureter. HYDOXDWLRQDWPRQWKVDIWHUVWDUWLQJWKHUDS\DQG ,Q:HLQ$-HGLWRU&DPSEHOO8URORJ\HG3KLODGHOSKLD have routine blood pressure monitoring.(6) (OVHYLHU  6DQWRVR$7DUPRQR6DQWRVD$5RGMDQL$6DIULDGL) Refluks. In: Guidelines Pediatrik Urologi. Jakarta: Ikatan Conclusions $KOL8URORJL,QGRQHVLDS 8. Nemett DR, Fivush BA, Mathews R, Camirand N, Eldridge Vesicoureteral reflux is defined as retrograde flow MA, Finney K, et al. A randomized controlled trial of the of urine from baldder to ureter. The prevalence in HIIHFWLYHQHVVRIRVWHRSDWK\EDVHGPDQXDOSK\VLFDOWKHUDS\LQ FKLOGUHQLVDERXW,WLVXVXDOO\DV\PSWRPDWLFEXW treating pediatric dysfunctional voiding. Journal of Pediatric commonly found in children showing UTI symptoms 8URORJ\   ZLWKDSUHYDOHQFHRI8QWUHDWHGFKLOGUHQPD\ 9. Bagga A, Hari P. Vesicoureteric Reflux and Reflux develop renal scar, reflux nephropathy, hypertension, Nephropathy. In: Bagga A, editor. New Delhi: Indian voiding dysfunction, retarded kidney growth, and 3HGLDWULFV chronic renal failure.  *DULQ(+2ODYDUULD)1LHWR9*9DOHQFLDQR%&DPSRV The management include observation A, Young L. Clinical Significance of Primary Vesicoureteral guarded by prophylactic antibiotic, endoscopy using Reflux and Urinary Antibiotic Prophylaxis After Acute GH[WUDQRPHUK\DOXURQLFDFLGFRSRO\PHU '[+$  Pyelonephritis: A Multicenter, Randomized, Controlled and open surgical correction. Prophylactic antibiotics 6WXG\3HGLDWULFV can not reduce the prevalence of renal scar formation.  .HUHQ5&DUSHQWHU0$+REHUPDQ$6KDLNK10DWRR Early surgical correction may prevent UTI. Endoscopy 7.&KHVQH\5:HWDO5DWLRQDOHDQG'HVLJQ,VVXHVRIWKH is now preferred for surgery considering its lower 5DQGRPL]HG,QWHUYHQWLRQIRU&KLOGUHQ:LWK9HVLFRXUHWHUDO morbidity compared to open procedure and high 5HIOX[ 5,985 6WXG\3HGLDWULFV66 VXFFHVVUDWH  +RZHYHURSHQVXUJHU\VWLOOKDV  *RRQDVHNHUD&'$'LOORQ0-+\SHUWHQVLRQLQUHIOX[ WKHKLJKHVWVXFFHVVUDWHZKLFKFDQUHDFK QHSKURSDWK\%-8,QWHUQDWLRQDO    %DUDL6%DQGRSDGKD\D\D*3%KRZPLN'3DWHO&'0DOKRWUD A, Agarwal P, et al. Prevalence of Vesicoureteral Reflux In References 3DWLHQWV:LWK,QFLGHQWDOO\'LDJQRVHG$GXOW+\SHUWHQVLRQ 8URORJ\    %XWOHU/'6\PRQV%.+HQGHUVRQ6/6KRUWOLIIH/'6SLHJHO  .RKOHU-7HQFHU-7K\VHOO+)RUVEHUJ/9HVLFRXUHWHUDO D. Hypnosis reduces distress and duration of an invasive reflux diagnosed in adulthood. Incidence of urinary tract PHGLFDOSURFHGXUHIRUFKLOGUHQ3HGLDWULFV  H infections, hypertension, proteinuria, back pain and renal e85. FDOFXOL1HSKURO'LDO7UDQVSODQW  .KRXU\$%DJOL'-5HIOX[DQG0HJDXUHWHU,Q:HLQ$-  *RRQDVHNHUD&'$'LOORQ0-5HIOX[QHSKURSDWK\DQG .DYRXVVL/51RYLFN$&3DUWLQ$:3HWHUV&$HGLWRUV K\SHUWHQVLRQ-RXUQDORI+XPDQ+\SHUWHQVLRQ &DPSEHOO:DOVK8URORJ\WKHG3KLODGHOSKLD(OVHYLHU 504. S  .|KOHU-57HQFHU-7K\VHOO+)RUVEHUJ/+HOOVWU|P 3. Sihombing R. Refluks Vesikoureter Dengan Dan Tanpa 0/RQJ7HUP(IIHFWVRI5HIOX[1HSKURSDWK\RQ%ORRG Nefropati Refluks Pada Anak Dengan Infeksi Saluran Kemih. Pressure and Renal Function in Adults. Nephron Clin Pract -DNDUWD8QLYHUVLWDV,QGRQHVLD FF  *RUGRQ,%DUNRYLFV03LQGRULD6&ROH7-:RROI$6  6LOYD$&6H6LOYD-03'LQL]-663LQKHLUR69%/LPD(0

266‡Paediatr Indones, Vol. 50, No. 5, September 2010 Nurul Akbar et al: The management of vesicoureteral reflux in children

Vasconcelos MA, et al. Risk of hypertension in primary children with persistent primary vesicoureteral reflux. Pediatr YHVLFRXUHWHUDOUHIOX[3HGLDWU1HSKURO 1HSKURO²  6LOYD-032OLYHLUD($'LQL]-66%RX]DGD0&)9HUJDUD  3HQQHVL07UDYDQ/3HUDWRQHU/%RUGXJR$&DWWDQHR$ RM, Souza BC. Clinical course of prenatally detected primary Ronfani L, et al. Is antibiotic prophylaxis in children with YHVLFRXUHWHUDOUHIOX[3HGLDWU1HSKURO vesicoureteral reflux effective in preventing pyelonephritis  6LOYD-03'LQL]-660DULQR963/LPD(0&DUGRVR/6% and renal scars? A randomized, controlled trial. Pediatrics 9DVFRQFHORV0$HWDO&OLQLFDOFRXUVHRIFKLOGUHQDQG   HH adolescents with primary  0RQWLQL*5LJRQ/=XFFKHWWD3)UHJRQHVH)7RIIROR$ YHVLFRXUHWHUDOUHIOX[3HGLDWU1HSKURO Gobber D, et al. Prophylaxis After First Febrile Urinary  1DVHHU656WHLQKDUGW*)1HZ5HQDO6FDUV,Q&KLOGUHQ:LWK Tract Infection in Children? A Multicenter, Randomized, Urinary Tract Infections, Vesicoureteral Reflux And Voiding &RQWUROOHG1RQLQIHULRULW\7ULDO3HGLDWULFV Dysfunction: A Prospective Evaluation. Journal of Urology    5RXVVH\.HVOHU*9*DGMRV1,+RUHQ%,FKD\//HFODLU  6QRGJUDVV:5HODWLRQVKLS2I9RLGLQJ'\VIXQFWLRQ7R MD, Raymond F, et al. Antibiotic Prophylaxis for the Urinary Tract Infection And Vesicoureteral Reflux In Prevention of Recurrent Urinary Tract Infection in Children &KLOGUHQ3HGLDWULF8URORJ\   :LWK/RZ*UDGH9HVLFRXUHWHUDO5HIOX[5HVXOWV)URP  6LOOHQ8%ODGGHU'\VIXQFWLRQDQG9HVLFRXUHWHUDO5HIOX[ a Prospective Randomized Study. THE JOURNAL OF $GYDQFHVLQ8URORJ\ 852/2*<  &KDPLH.&KL$+X%.HHJDQ.$.XU]URFN($ 34. Nelson CP, Copp HL, Lai J, Saigal CS. Is Availability of &RQWHPSRUDU\2SHQ8UHWHUDO5HLPSODQWDWLRQ:LWKRXW Endoscopy Changing Initial Management of Vesicoureteral Morphine: Assessment of Pain and Outcomes. Journal of 5HIOX["-RXUQDORI8URORJ\ 8URORJ\ 35. Simforoosh N, Hariri H. Management of vesicoureteral reflux  -RGDO86PHOOLH-0/D[++R\HU3)7HQ\HDUUHVXOWVRI without indwelling catheter and drain, using trigonoplasty randomized treatment of children with severe vesicoureteral WHFKQLTXH-RXUQDORI3HGLDWULF8URORJ\ reflux. Final report of the International Reflux Study in 36. Ormaechea M, Ruiz E, Denes E, Gimenez F, F T Dénes, &KLOGUHQ3HGLDWULF1HSKURORJ\   Moldes J, et al. New Tissue Bulking Agent (Polyacrylate  )DQRV9&DWDOGL/$QWLELRWLFVRUVXUJHU\IRUYHVLFRXUHWHULF Polyalcohol) for Treating Vesicoureteral Reflux: Preliminary UHIOX[LQFKLOGUHQ/DQFHW 5HVXOWVLQ&KLOGUHQ-RXUQDORI8URORJ\  =DIIDQHOOR0)UDQFKLQL0%UXJQDUD0)DQRV9(YDOXDWLQJ  0ROLWLHUQR-$6FKHU]+&.LUVFK$-(QGRVFRSLFLQMHFWLRQ .LGQH\'DPDJHIURP9HVLFR8UHWHUDO5HIOX[LQ&KLOGUHQ of dextranomer hyaluronic acid copolymer for the treatment Saudi Journal of Kidney Diseases and Transplantation of vesicoureteral reflux in duplex ureters. Journal of Pediatric    8URORJ\  &KXQJ3+</DQ/&/:RQJ..<7DP3.+'HIOX[ 38. Dave S, Lorenzo AJ, Khoury AE, Braga LHP, Skeldon SJ, Injection for the Treatment of Vesicoureteric Reflux in Suoub M, et al. Learning From the Learning Curve: Factors Children—A Single Centre’s Experience. Asian J Surg $VVRFLDWHG:LWK6XFFHVVIXO(QGRVFRSLF&RUUHFWLRQRI    Vesicoureteral Reflux Using Dextranomer/Hyaluronic Acid  %RXLVVRX)0XQ]HU&'HFUDPHU65RXVVHO%1RYR5 &RSRO\PHU-RXUQDORI8URORJ\ Morin D, et al. Prospective, Randomized Trial Comparing  /HH (. *DWWL-0'H0DUFR570XUSK\-3/RQJ7HUP Short and Long Intravenous Antibiotic Treatment of Followup of Dextranomer/Hyaluronic Acid Injection for Acute Pyelonephritis in Children: Dimercaptosuccinic 9HVLFRXUHWHUDO5HIOX[/DWH)DLOXUH:DUUDQWV&RQWLQXHG Acid Scintigraphic Evaluation at 9 Months. Pediatrics )ROORZXS-RXUQDORI8URORJ\ HH 40. Gargollo PC, Paltiel HJ, Rosoklija I, Diamond DA. Mound  1HXKDXV7-%HUJHU&%XHFKQHU.3DUYH[3%LVFKRII Calcification After Endoscopic Treatment of Vesicoureteral G, Goetschel P, et al. Randomised trial of oral versus 5HIOX[:LWK$XWRORJRXV&KRQGURF\WHV³$1RUPDO9DULDQW sequential intravenous/oral cephalosporins in children RI0RXQG$SSHDUDQFH"-RXUQDORI8URORJ\ with pyelonephritis. European Journal of Pediatrics      9DOOD-66WH\DHUW+*ULIILQ6-/DXURQ-)UDJRVR$&$UQDXG  /HH6-6KLP<+&KR6-/HH-:3URELRWLFVSURSK\OD[LVLQ P, et al. Transvesicoscopic Cohen ureteric reimplantation

Paediatr Indones, Vol. 50, No. 5, September 2010‡267 Nurul Akbar et al: The management of vesicoureteral reflux in children

IRUYHVLFRXUHWHUDOUHIOX[LQFKLOGUHQ$VLQJOHFHQWUH\HDU  H[SHULHQFH-RXUQDORI3HGLDWULF8URORJ\  $VKOH\59DQGHUVWHHQ'2XWFRPH$QDO\VLVRI0LQL  6RPRJ\L52EHUULWWHU=-XKDV]=9DMGD33LQWHU$% Ureteroneocystostomy Versus Dextranomer/Hyaluronic Acid Combination of vesicoureteric reflux and vesicoureteric Copolymer Injection for Unilateral Vesicoureteral Reflux. junction obstruction. Scandinavian Journal of Urology and -RXUQDORI8URORJ\ 1HSKURORJ\  +LQPDQ)8UHWHUDO5HFRQVWUXFWLRQDQG([FLVLRQ,Q$WODV 43. Schwentner C, Oswald J, Lunacek A, Deibl M, Koerner I, RI8URORJLF6XUJHU\HG3KLODGHOSKLD:%6DXQGHUV %DUWVFK*HWDO/LFK*UHJRLU5HLPSODQWDWLRQ&DXVHV/HVV &RPSDQ\S 'LVFRPIRUWWKDQ3ROLWDQR/HDGEHWWHU7HFKQLTXH5HVXOWVRI 48. Lama G, Tedesco MA, Graziano L, Calabrese E, Grassia D3URVSHFWLYH5DQGRPL]HG3DLQ6FDOH2ULHQWHG6WXG\LQD C, Natale F, et al. Reflux nephropathy and hypertension: 3HGLDWULF3RSXODWLRQ(XURSHDQ8URORJ\ correlation with the progression of renal damage. Pediatr  0RU</HLERYLWFK,=DOWV5/RWDQ'-RQDV35DPRQ- 1HSKURO $QDO\VLVRIWKHORQJWHUPRXWFRPHRIVXUJLFDOO\FRUUHFWHG 49. Nielsen JB, Frékiár J, Rehling M, Jérgensen TM, Djurhuus YHVLFRXUHWHULFUHIOX[%-8,QWHUQDWLRQDO -&$\HDUIROORZXSRIFRQVHUYDWLYHWUHDWPHQWIRUYHVLFR  $VKOH\59DQGHUVWHHQ'0LQL8UHWHURQHRF\VWRVWRP\ XUHWHULFUHIOX[%-8,QWHUQDWLRQDO A Safe and Effective Outpatient Treatment for Unilateral  )DXVW:&3RKO+*5ROHRISURSK\OD[LVLQYHVLFRXUHWHUDO 9HVLFRXUHWHUDO5HIOX[-RXUQDORI8URORJ\ UHIOX[&XUU2SLQ8URO

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