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Journal of Indian Association of Pediatric Surgeons
     Journal of Indian Association of Pediatric Surgeons
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Table of Contents   
REVIEW ARTICLE
Year : 2019  |  Volume : 24  |  Issue : 1  |  Page : 4-14
 

Consensus on the management of posterior urethral valves from antenatal period to puberty


1 Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
2 Consultant Pediatric Surgeon, Department of Pediatric Surgery, King Saud Hospital, Uneyzha City, Kingdom of Saudi Arabia
3 Department of Pediatric Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
4 Department of Pediatric Surgery, SMS Medical College, Jaipur, Rajasthan, India
5 Department of Pediatric Surgery, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
6 Department of Pediatric Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
7 Department of Pediatric Surgery, Maulana Azad Medical College, Delhi, India
8 Department of Paediatric Surgery, Paediatric Surgery Centre and PG Institute, Sangli, Maharashtra, India
9 Department of Paediatric Surgery, Deccan College of Medical Sciences, Hyderabad, India
10 Department of Paediatric Surgery, Gauhati Medical College, Guwahati, Assam, India
11 Consultant Pediatric Surgeon, Institute of Child Health, Kolkata, West Bengal, India

Date of Web Publication19-Dec-2018

Correspondence Address:
Shilpa Sharma
Room No. 4001, Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.JIAPS_148_18

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   Abstract 


The need for successful management of posterior urethral valves always captivates the minds of pediatric surgeons. Its success, however, depends on several factors ranging from prenatal preservation of upper tracts to postoperative pharmacological compliance. Regardless of measures available, some cases do not respond and progress to end stage. The management depends on several issues ranging from age and severity at presentation to long-term follow-up and prevention of secondary renal damage and managing valve bladder syndrome. This article is based on a consensus to the set of questionnaires, prepared by research section of Indian Association of Paediatric Surgeons and discussed by experienced pediatric surgeons based in different institutions in the country. Standard operating procedures for conducting a voiding cystourethrogram and cystoscopy were formulated. Age-wise contrast dosage was calculated for ready reference. Current evidence from literature was also reviewed and included to complete the topic.


Keywords: Antenatal obstructive uropathy, chronic kidney disease, posterior urethral valves, renal dysplasia, valve bladder


How to cite this article:
Sharma S, Joshi M, Gupta DK, Abraham M, Mathur P, Mahajan J K, Gangopadhyay A N, Rattan SK, Vora R, Prasad G R, Bhattacharya N C, Samuj R, N. Rao K L, Basu A K. Consensus on the management of posterior urethral valves from antenatal period to puberty. J Indian Assoc Pediatr Surg 2019;24:4-14

How to cite this URL:
Sharma S, Joshi M, Gupta DK, Abraham M, Mathur P, Mahajan J K, Gangopadhyay A N, Rattan SK, Vora R, Prasad G R, Bhattacharya N C, Samuj R, N. Rao K L, Basu A K. Consensus on the management of posterior urethral valves from antenatal period to puberty. J Indian Assoc Pediatr Surg [serial online] 2019 [cited 2019 Jan 18];24:4-14. Available from: http://www.jiaps.com/text.asp?2019/24/1/4/247899





   Introduction Top


Posterior urethral valves (PUV) are a common anomaly that presents to a pediatric surgeon or pediatric urologist for management. They are the most common cause of chronic kidney disease due to urinary tract obstruction in children. The antenatal cases are far more than those that actually reach term and are delivered live. The prognosis can be improved if the anomaly is tackled soon after diagnosis. Morbidity in terms of recurrent urinary tract infection (UTI), deteriorating renal functions, and growth failure may be reduced by timely and aggressive interventions, which involves surgery, pharmacology, and clean intermittent catheterization (CIC). The long-term outcome, however, remains poor if there is associated renal dysplasia. Due to inherited spectrum of this disease, the management and outcome often differ in the hands of different surgeons and different institutes. This topic and the surrounding controversies were prepared on the basis of questionnaires for a panel discussion. The responses were subsequently compiled and supplemented with a thorough literature review in an effort to formulate uniform guidelines and depth in understanding.


   Antenatal Diagnosis Top


The antenatal sonographic findings in PUV include overdistended bladder (megacystis) and thickened bladder wall (normally <2 mm, pathologic >3 mm), bilateral or unilateral hydroureteronephrosis, oligohydramnios, and poor bladder emptying over a 30 min scan. Other findings include hyperechoic kidneys (renal dysplasia, renal cortical cyst), oligohydramnios, urinoma, or fetal ascites. The sonographic finding of an enlarged fetal bladder may simply be a transitory normal variant. However, it may also be secondary to reflux, obstructive, neurogenic, or myopathic causes. Repeated sonographic monitoring for persistence of findings, for changes in bladder enlargement, and for changes in the volume of amniotic fluid is required as these signs may be the indicators of abnormalities of renal function and risk factors for a poor prognosis.[1]

After exclusion of transient physiological dilatation, a careful examination of the fetal spine should be performed. The presence of hydronephrosis in association with enlarged bladder is indicative of obstructive uropathy or serious malformation and its absence is likely indicative of normal variation in size. The sensitivity and specificity of the antenatal diagnosis of PUV have been reported as 94% and 43%, respectively.[2] Increased bladder wall thickness and bladder dilatation were strongly associated with the diagnosis of PUV (P < 0.001).[2] On the contrary, a thick-walled bladder was observed in 39% and a dilated bladder in 48% of the infants, with a postnatal diagnosis other than PUV.[2]

The keyhole appearance due to a distended posterior urethra is suggestive of obstructive uropathy. The most common cause is PUV. Other causes include vesicoureteral reflux, bilateral junction stenosis, Prune–Belly syndrome, primary megaureter, and ectopic obstructive ureteral implantation.[2] In females, the most common cause is urethral atresia. Other causes of fetal lower urinary tract obstruction include but are not limited to obstructive ureterocele, urethral stricture or agenesis, persistent cloaca, and megalourethra. The ultrasound findings of many of these conditions are similar, and it is often difficult to differentiate the cause of the urinary obstruction until after delivery. The presence of the keyhole sign alone was not found to be predictive of a diagnosis of PUV (P = 0.27).[2] A “keyhole” bladder was more likely to be associated with urethral atresia (54.5%) than PUVs (40.9%).[3] A neurogenic bladder may also have a keyhole appearance. The reason for this discrepancy is that the hypotonic bladder neck may give the sonological picture of a keyhole.


   Poor Prognostic Markers Top


These include oligohydramnios (low amniotic fluid volume defined as the maximum vertical pocket ≤2.0 cm), urinary ascites, perinephric urinoma (maybe pop off), increased renal echogenicity, and cortical cysts. Diagnosis of PUV up to the second trimester is associated with high perinatal mortality and risk of end-stage renal disease (ESRD), particularly if there is severe bilateral hydronephrosis with oligohydramnios, and findings suggestive of renal dysplasia.[4],[5],[6] When oligohydramnios is detected in the second trimester, the mortality may be as high as 90%–95%.[4]


   Counseling and Intervention Top


Even in the era of antenatal diagnosis and early intervention, the long-term prognosis of PUV is far from satisfactory. At follow-up after 18 years of age, chronic renal failure was detected in 54%, hypertension in 37.5% with ESRD developing in 21%, and presence of lower urinary tract symptoms in 29%.[7] The diagnosis is based on sonological findings which should be repeated by two different observers, one of which should be a trained radiologist in Level 2 antenatal sonography. In India, medicolegal termination in view of bad prognosis for a fetal condition is permitted as per law. Furthermore, the sex determination is prohibited and a punishable offense. Accordingly, if an obstructive uropathy is diagnosed before 20 weeks, the prognosis of the anomaly is explained to the parents. Most young parents with an insignificant obstetric history, in consultation with a gynecologist, after counseling from a pediatric surgeon and a radiologist opt for medical termination of pregnancy. Few parents with bad obstetric history, following in vitro fertilization, late conception, precious baby, Muslim religion prefer to continue pregnancy with a guarded prognosis.

In cases diagnosed between 20 and 24 weeks, with oligohydramnios, echogenic kidneys, bladder urine tap showing poor prognosis, a guarded medical termination or watchful attitude for intrauterine demise may be adopted. The outcome of pregnancy and long-term prognosis in cases of PUV diagnosed antenatally at <24 weeks are extremely poor primarily due to the prolonged oligohydramnios and the damage to the fetal kidneys due to the involvement of the upper tracts. In cases diagnosed between 20 and 24 weeks, without any poor prognostic factors, the pregnancy may be continued until term with a repeat ultrasonography (USG) at monthly intervals for any signs of poor prognosis.

When the pregnancy is between 24 and 34 weeks, fetal intervention may be offered if indicated and available. However, it has been realized that antenatal resection of valve has high complication and does not improve prognosis. In patients with severe oligohydramnios, amnioinfusion may be considered to continue pregnancy till fetal lung maturity and prevent any mishap.

Beyond 34 weeks, intensive 2 weekly monitoring is required for amniotic fluid content. If oligohydramnios or other signs of poor prognosis appear, induced delivery or cesarean section in case of failure may be offered based on fetal indication. If the amniotic fluid is adequate, the pregnancy may be continued till term.


   Indications and Role of Fetal Intervention Top


  1. Diagnosis of obstructive uropathy confirmed on two separate scans by two experts individually
  2. Oligohydramnios
  3. Gestation <34 weeks
  4. Unilateral or bilateral hydroureteronephrosis without abnormal karyotyping
  5. Detailed USG showing no evidence of renal dysplasia
  6. Absence of ruptured membranes, chorioamnionitis, placental abruption, or active labor
  7. Cordocentesis: If the serum beta-2-microglobulin level drawn from the fetal umbilical cord blood is <5.6 mg/L, then fetal therapy may be offered
  8. Fetal vesicocentesis: The fetal bladder is tapped, and the urine is analyzed for biochemistry and fetal electrolyte levels. [Table 1] depicts the parameters showing that the kidney is salvageable and fetal intervention can be planned.
Table 1: Threshold values of fetal urine parameters that predict good renal function

Click here to view


The prenatal USG may not be highly reliable in differentiating fetuses with obstruction and those without obstruction.[8] Hence, fetal intervention based on USG should be done with caution. An initial study on fetal urine biochemistry had suggested a beta-2-microglobulin >2 mg/L as an indicator of poor renal function.[9] The threshold was increased to 4 mg/L, and now, it is 10 mg/L. In case some parameters are deranged, a repeat bladder tap can be performed after an interval of 48 h. If the fetal urine becomes progressively hypoosmolar as indicated by better biochemical analysis results, intervention may be planned.

Besides termination of pregnancy, the options for intervention include vesicoamniotic shunting and fetal endoscopic ablation of valves. The first case of prenatal surgery to relieve obstructive uropathy was performed in 1981.[10] Surgical fetal intervention primarily in the form of vesicoamniotic shunt placement was based upon the rationale that restoring amniotic fluid to normal levels by shunting fetal urine from the obstructed urinary system to the amniotic space would prevent lung hypoplasia and thus improve neonatal survival. However, over the past three decades since the introduction of fetal intervention for obstructive uropathy, data on outcome of fetal surgery for PUV suggest that it is associated with an increased risk of fetal and maternal morbidity without proven benefit for long-term renal outcome.

Fetal endoscopic ablation is a relatively newer interventional modality first reported in 1995 by Quintero et al.[11] Most of the available outcome data relate to vesicoamniotic shunting. It has been seen that vesicoamniotic shunting in PUV does correct the existing oligohydramnios, although the perinatal mortality and long-term survival after this procedure remain poor.[12],[13] This fact is important as the parents need to be counseled that the incidence of renal failure in childhood, even after vesicoamniotic shunting, could be as high as 50%.[14] Moreover, the procedure has a 45% complication rate which includes shunt blockage, preterm delivery, and urinary ascites. Thus, while shunting improves the pulmonary outcome and not renal outcome, fetoscopic valve ablation may improve both.

Currently, fetal surgery for PUV should be considered only for fetuses who have a high risk of in utero or neonatal death due to midtrimester severe oligohydramnios and who have both a normal karyotype and evidence of good renal function based upon fetal urinary evaluation.


   Need for Early Referral Top


There is a dire need for good collaboration between the pediatric surgeon with the triad of gynecologist, radiologist, and perinatologist or pediatrician for diagnosis and timely referral. There should be joint meetings, case discussions, participation in postgraduate teaching, and creation of awareness about the possible treatment options available from the pediatric surgeon perspectives. The parents should be informed in detail about the various situations and the protocols to be followed. They are the best ones to convey the plans of the different specialists to each other.


   Postnatal Management Top


If the baby after birth is unstable, in metabolic acidosis and uremia, urinary catheterization is done immediately. Once drainage is established, the patient may have large urinary water and solute losses because of tubular dysfunction, resulting in an inability to concentrate the urine or normally absorb solutes (sodium and potassium). In addition, some patients with PUV due to urinary obstruction may have type IV renal tubular acidosis. As a result, careful monitoring of serum electrolyte including serum bicarbonate and fluid status is required with timely replacement of fluid and electrolytes as needed. One may have to put two intravenous lines for chasing the output and supplementing bicarbonate. Diversion is to be considered if there is persistent elevation of serum creatinine. Primary ablation is the preferred mode of management with urinary catheter drainage for at least 72 h.


   Postnatal Diagnosis Top


The various common modes of presentation according to age are given in [Table 2].
Table 2: Varied nonurological and urological presentations in posterior urethral valves

Click here to view



   Investigations Top


  1. USG of the kidneys, ureters, bladder (KUB), and posterior urethra
  2. Renal function tests and serum electrolytes
  3. Blood gas analysis if baby is sick
  4. Voiding cystourethrogram (VCUG)
  5. Renal dynamic scan to assess renal function after the baby is 1 month of age. The scan should be done with a catheter in situ in cases with hydroureteronephrosis
  6. Dimercaptosuccinic acid (DMSA) scan to assess scarring in the presence of reflux
  7. Diagnostic cystoscopy may be done in cases who are already diagnosed during antenatal scans. Nakai et al. described a top-down approach where they picked up some patients with mild concomitant PUV among patients with primary vesicoureteral reflux (VUR).[15]



   Age-Wise Standard Operating Procedures For Conducting a Proper Voiding Cystourethrogram Top


Ideally, a pediatric surgeon and a radiologist should perform the procedure in conjunction. Once the protocol of the investigation has been established as a routine and workforce is trained, the responsibility may be taken over by the radiologist. Following are the guidelines for conducting the procedure. Preprocedure antibiotics should be given 1–2 days prior and 2–3 days after the procedure. Older children are instructed to clear their bowel before the investigation. If urosepsis is present, it should be treated with intravenous antibiotics, and the urine should be sterile before the procedure. All equipment should be laid out on a sterile trolley by a nurse/technician. The suite should be warmed for babies and infants.


   Important Information of the Contrast Agent Top


  • Urografin 30% contains 40 mg of sodium diatrizoate and 260 mg of meglumine diatrizoate per mL[16]
  • Urografin 76% contains 100 mg of sodium diatrizoate and 660 mg of meglumine diatrizoate per mL.[16]


The inactive ingredients include sodium calcium edentate and water for injection.

The child with renal dysfunction, diabetes, repeated studies, and hypertension should be properly hydrated before and after the study. Contrast media which are warmed to body temperature before administration are better tolerated and can be injected more easily because of reduced viscosity. Using an incubator, only the calculated number of bottles needed for the same examination day should be warmed up to 37°C. Pretesting sensitivity testing using a small test dose of contrast medium is not recommended as it has no predictive value. Furthermore, sensitivity testing itself has occasionally led to serious and even fatal hypersensitivity reactions.

Side effects may present in the form of nausea, vomiting, sensation of pain, a general feeling of warmth, mild swelling of the face, lips, tongue, or throat, conjunctivitis, coughing, itching, running nose, sneezing, hives, headache, disturbance in breathing, difficulty in breathing, and skin redness. Allergic reaction may occur rarely in the form of allergic rash, other kinds of skin rash, cramp, and whitening eyes. Severe reactions requiring emergency treatment can occur in the form of a circulatory reaction accompanied by blood vessel dilation and subsequent low blood pressure, increase in heart rate, difficulty in breathing, agitation, confusion, and “turning blue,” possibly leading to unconsciousness. Allergic reactions occur more frequently in patients with an allergic disposition. These reactions can be aggravated in patients taking beta--blockers for maintenance of blood pressure. Temporary renal failure may occur in rare cases. Preventive measure against acute renal failure following contrast medium administration includes ensuring adequate hydration.

Fluid and electrolyte balance must be corrected before the examination. Newborns and infants are susceptible to electrolyte imbalance. Care should be taken regarding the dose of contrast medium to be given [Table 3] and [Table 4], the technical performance of the radiological procedure, and the patient status. Anxiety and pain may increase the risk of side effects or intensify contrast medium-related reactions.
Table 3: The age-wise maximum dose of the contrast agent that can be used and the formulae for calculating the maximum expected bladder capacity

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Table 4: The weight-wise maximum dose of the contrast agent that can be used and the suggested dilution to attain a volume near the maximum expected bladder capacity

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   Newborn to 3 Months Age or Up to 5 kg Top


  1. Two attendants should hold the newborn in the supine position. A plain skiagram covering the kidneys, ureters and bladder region and the lumbosacral spine is taken in anterior-posterior and lateral position to assess the spine and bowel gases
  2. The genitalia should be cleaned with betadine scrub and dried
  3. A 1–2 ml syringe should be used to instill 1 ml of xylocaine jelly in the urethra or layered over an infant feeding tube no. 5/6 French (Fr). The feeding tube should be inserted gradually till it reaches the bladder, 4 cm proximal to the black mark
  4. The position of the baby is made in such a manner that the pelvis is covered in an oblique manner with one leg extended and the other abducted and knee flexed. The direction of the urethra should all clear of the pubic rami and in line with the bladder
  5. The contrast is prepared in a dilution of 1:1 initially. This is so as in cases of PUV, the bladder is usually distended and may contain a postvoid residue. Further, in the presence of reflux, the urine may dilute the contrast. The dilution may be increased to up to 1:3 if there is minimal urine in the bladder and the presence of high-grade reflux requires more volume of contrast preparation. Higher concentration may mask lesions such as diverticula and ureteroceles
  6. About 10 ml of diluted contrast is slowly injected to outline the bladder and assess its size. The contrast may also be given as a slow infusion. An AP film may be taken in the filling phase
  7. Another 10 ml is then slowly injected/infused till the bladder is full. Right oblique and left oblique views are taken
  8. Another 5–10 ml is slowly injected/infused to assess the presence of reflux. In case higher grade reflux is present, more contrast can be injected till both the kidneys are visualized
  9. The catheter is then slowly removed and a container is placed below the baby to collect the urine. The baby is encouraged to pass urine, and the voiding fill is captured in the right or left oblique manner
  10. During the whole procedure, intermittent still shots are captured as instructed to the radiographer on the machine. Relevant fluoroscopic videos may also be obtained taking care not to expose the baby to unnecessary radiation exposure.


The baby is cleaned with clean water, wiped, and dried after the procedure. The parents are encouraged to give excessive fluids.


   Infants Top


The procedure is same as above. The infant feeding tube may be of size 7/8 Fr. The expected maximum bladder capacity of 7 mL/kg should be kept in mind while injecting contrast preparation. The volume may be higher in the presence of reflux.


   Toddlers Top


These are most difficult to manage and may require video games of smartphones to keep them occupied during the procedure. The infant feeding tube may be of size 9/10 Fr. Koffman formula for the expected maximum bladder capacity of (age + 2) × 30 ml should be kept in mind while injecting contrast preparation. The volume may be higher in the presence of reflux.


   Boys More Than 3 Years Top


The preputial skin should be clean and retractable before subjecting them to VCUG. The procedure should be explained to them. The parents may be asked to bring an extra pair of clothing of the child. If the child is uncomfortable to void in a supine or semireclining position, the machine may be adjusted so that he can stand and void. The lateral oblique films enable us to pick up the diverticulae if any. In the presence of higher grade reflux in older boys, the dilution may be up to 1:4–5. The child is encouraged to drink excessive fluids and triple void postprocedure.


   Standard Operating Procedure Guidelines For Cystoscopy For Posterior Urethral Valve Top


Zero/Six degree 6.5 Fr panendoscope is good for cystoscopy in neonates <3 kg weight. An 8/9 Fr miniature pediatric cystourethroscope with a 4/5 Fr working channel may allow insertion of a Bugbee electrode to fulgurate the valves under vision. Zero/thirty degree 8.5/9.5 Fr cystourethroscope/resectoscope may be used for diagnosis in babies over 3.5 kg. The 8/10/11 Fr resectoscope with 0° telescope is preferred for visualization and fulguration/incision of the valves. The sickle-shaped cold knife is preferred by most surgeons. Others may use the cutting loop, hook with or without ball-tip electrode, sharp-angled electrode, or blunt-angled electrode. For infusion, warm normal saline may be used. Some prefer 1.5% glycine for fulguration. The neodymium-doped yttrium-aluminum-garnet laser may be used for fulgurating the PUV in smaller caliber urethra as this can be performed with the smaller available cystoscope that has a side channel, admitting the laser fiber.[17] The appropriate instruments are chosen and lined up on the sterile instrument tray in chronological order. An antibiotic dose of co-amoxiclav at 30 mg/kg intravenous is given at the time of induction.

After induction under general anesthesia and caudal analgesia, the baby is put in lithotomy position with feet supported in stirrups. The genital area is cleansed with an antiseptic solution taking care to retract the prepuce while cleaning and pulling it back and draped. Xylocaine (lidocaine monohydrochloride) jelly 2% is instilled in the urethra with a 5 ml syringe in the maximum dose of 4.5 mg/kg/dose or maximum 300 mg/dose. Each ml of 2% lidocaine contains 20 mg of lidocaine HCl. An infant may require 3–5 mL (60–100 mg of lidocaine HCl). The endoscope is well lubricated and inserted into the urethra to the bladder, and the urine sample is collected for analysis and culture and sensitivity if required. The ureteric orifices are seen for size and position. The bladder wall is inspected for trabeculations, sacculations, and diverticulae. The scope is gradually withdrawn along the posterior bladder wall, bladder neck into the posterior urethra till the verumontanum bulge is appreciated on the PUV. The configuration of the bladder neck is noted. The posterior urethra should be carefully inspected, and the valve configuration is noted as it appears just distal to the verumontanum. The resectoscope is assembled with either the cold/sickle blade or Bugbee electrode. The resectoscope sheath is advanced into the bladder. The video camera is connected for better visibility of all on the screen. The mobility and direction of the cold knife/electrode are examined in the bladder. The electrode/knife is withdrawn and the resectoscope is brought into the posterior urethra. The knife/electrode is again advanced and brought to hook against the valve at 5 o' clock position. The procedure is repeated for the other two positions at 7 and 12 o'clock positions. The resectoscope is gradually removed from the urethra, and the stream of urine is visualized by gentle Crede's maneuver. A check scopy may be done for assessing the effectiveness of the procedure. The urinary catheter is left for 72 h or till the diuresis has subsided whichever is later.


   Alternatives to Primary Fulguration Top


If the smallest size scope is not available for preemie, one should put in a catheter and drain the bladder. The parents are counseled. One option is to wait and reassess after 2–4 weeks, and if still not feasible, a vesicostomy may be done. The other option is to refer to a center with availability. Valvotomy with indigenous valvulotomes (Chooramani or Abraham) is a blind procedure but safe in selected experienced hands. However, with recent developments, most centers have appropriate-sized instruments. The use of a Fogarty catheter to disrupt valve in low birth weight babies is not recommended.


   Indications For Diversion Top


If primary ablation cannot be done due to nonavailability of appropriate instruments or due to technical reasons, the next preferred procedure is vesicostomy particularly in very preterm infants in whom visualization or ablation of the valve is not possible.

Higher diversion is not indicated if the renal parameters have become normal and the upper tracts are not tortuous as it does not improve outcome as compared to vesicostomy. It may affect bladder cycling and may have an impact on bladder function. However, if the baby is in urosepsis and the upper tracts are dilated and tortuous with deranged renal parameters despite 1 week of catheterization, higher diversion in the form of ureterostomy is indicated. It may be done on the one side to allow the bladder to grow with urine from the other kidney and also allowing the distal ureterostomy to act as a pop-off mechanism for reflux. In severe cases, bilateral ureterostomy may prove to be life-saving.


   Vesicoureteral Reflux in Posterior Urethral Valves Top


VUR is present in about ⅓ to ½ of the patients of PUV.[18] Half of these will have unilateral reflux and the other half would have bilateral. VUR will resolve in at least one-third of the patients with relief of obstruction. The remaining two-thirds would require deflux injection or surgery. Resolution of reflux has also been seen with addition of alpha-blockers. High-grade reflux with dysplasia leading to a nonfunctioning kidney may require nephrectomy. It is unclear whether VUR in PUV independently affects long-term functions. The incidence of ESRD before 16 years was highest in a patient with bilateral VUR up to 25% followed by 7% with unilateral VUR. Serum creatinine level was persistently elevated in patients with VUR at diagnosis, after 6 months, and after 12 months.[19]


   Bladder Dysfunction in Posterior Urethral Valves Top


Approximately one-third of the patients have persistent bladder dysfunction after PUV ablation, and these require pharmacological therapy and CIC. In one case series, severe bladder dysfunction requiring CIC was predictive of ESRD.[18],[20] A high incidence of patients up to 50%–70% have high postvoid residue due to bladder neck hypertrophy. Radiological indicators of bladder dysfunction include persistent upper tract dilatation, posterior urethral dilatation, VUR, trabeculation and diverticula in bladder, and significant postvoid residual urine.


   Renal Dysplasia, Chronic Kidney Disease, and End-Stage Renal Disease in Posterior Urethral Valves Top


Prenatal renal parenchymal changes consistent with renal dysplasia are seen in about 60% of infants in prenatally diagnosed PUV patients.[21] A study on the histology of kidney specimens from children with PUV who underwent nephrectomy reported that approximately 80% of the specimens showed primary dysplastic malformations (mesenchymal or fetal cartilage tissue or dysplastic glomeruli and tubuli) in the presence of well-developed renal parenchyma and all specimens showed secondary pathologies such as renal-cortical atrophy, interstitial fibrosis, and interstitial-nephritis atrophy.[22] Organogenesis of the kidney is terminated at the 12th gestational week and secondary renal damage is irreversible at the 20th gestational week, but prenatal urinary diversion of the upper urinary tract is feasible in the 20th gestational week at the earliest. These facts must be taken into account when considering intrauterine urinary diversion. About 15%–20% cases of PUV progress to ESRD.[18],[21] Recurrent infection with scarring is thought to be a risk factor for ESRD in the long term. However, in one study of 119 patients, recurrent infection was present in almost half patients group and was not associated with increased risk of ESRD.[21]


   Follow-Up Top


The protocols may vary from center to center and among different surgeons/nephrologists with the main aims remaining universal.

The principles of follow-up for PUV are to:

  1. Maximize renal function
  2. Minimize urinary infections
  3. Minimize renal scarring
  4. Assess voiding dysfunction
  5. Attaining urinary continence
  6. Assess bladder growth
  7. Assess need for renal replacement therapy and renal transplant.


    • Postfulguration: 3 months, 6 months, 9 months, 1 year, annually up to 15 years of age: Urea, creatinine, complete blood count, electrolytes, midstream urine for analysis, USG with postvoid residue measurement, examination of urine stream/uroflowmetry were noted. More than 10% of the prevoid volume is abnormal and described as significant postvoid residue
    • Check cystoscopy/VCUG at 3 months postfulguration: If symptoms persist/routine (optional). Morphological normalization of the posterior urethra after fulguration on VCUG has been described as a significant factor in prognosis[23]
    • Corrected glomerular filtration rate (GFR) – 1, 3, 5, 10, 13, 15 years
    • Renal scan (diethylenetriaminepentaacetic acid/) Technetium-99m ethylene dicysteine (EC)/ 99mTc-mercaptoacetyltriglycine (MAG3) – 3 months and 1, 3, 5, 8, 11, 13, 15 years
    • DMSA – If Hydroureteronephrosis/VUR are present, then at 3 months and 1, 3, 5, 10, 15 years
    • If HDUN/VUR present, then voiding diary for 1 week at 1, 3, 5, 10, and 15 years
    • If dribbling/reflux present, urodynamic study at 3, 5, 10, and 15 years.



   Indications For Repeat Voiding Cystourethrogram During Follow-Up Top


  1. At 3 months postfulguration: If symptoms persist/routine (optional). Check VCUG should be mandatory before labeling the patient as valve bladder or any other sequelae[23]
  2. If HDUN present postfulguration on USG, repeat VCUG at 2, 5, and 10 years
  3. To assess structural anomalies such as diverticuli, obstructive lesions – residual valves, and strictures
  4. To assess if VUR is present during bladder filling, voiding, or both
  5. If deflux/ureteral reimplantation planned
  6. To study the bladder anatomy before bladder augmentation or renal transplant.



   Urodynamic Study Top


Urodynamic studies are helpful in with radiological signs of persistent bladder dysfunction, significant postvoid residue, persistent VUR on anticholinergics and CIC. The other indications for urodynamic study are as follows:[24]

  1. Persistent daytime urinary incontinence beyond the age of 5 years
  2. Deterioration in renal function (rising creatinine or drop in GFR) with no obvious cause such as growth spurt
  3. Increase in upper tract dilatation in the absence of ongoing outflow obstruction
  4. Before renal transplantation to ensure a safe, compliant low-pressure urinary tract
  5. To assess the efficacy of treatment or intervention
  6. As a research tool to study the evolution or natural history of developing bladder function in boys with successfully treated PUV
  7. Functional problems – detrusor-sphincter discoordination or suspected dyssynergia
  8. Bladder emptying, true and false residuals.



   Drug Treatment Top


A variety of agents have been used to treat bladder overactivity.

Anticholinergics

Anticholinergic agents are commonly used to treat reduced bladder compliance and the overactivity during bladder filling. The most common side effect of the anticholinergics is dryness of mouth. During the initial treatment period, there is more symptomatic improvement when anticholinergics are combined with bladder training as against each modality alone. Agents such as imipramine, oxybutynin chloride, and tolterodine tartrate have been found to be effective for noncompliant or overactive bladder.[25] The safe dose in children is oxybutynin 0.2 mg/kg/day in 2–4 divided doses and imipramine 0.7–1.2 mg/kg/dose, 2–3 doses per day. Pro-Banthine may be given in a dose of 0.5 mg/kg/dose twice a day although it is not popular among pediatric surgeons.

Oxybutynin inhibits stretch-induced bladder smooth muscle cell proliferation in vitro studies.[26] A protective effect of oxybutynin on bladder function and structureless collagen infiltration in the detrusor with fewer glycogen granules on the hypertrophic and ischemic bladder changes is an argument for an early start of oxybutynin treatment in children with urethral valves.[26]

Oral tolterodine may be preferred over oxybutynin by some because of the reduced risk of dry mouth. It has been seen in adults that extended-release preparations of oxybutynin or tolterodine are preferred to immediate-release preparations because there is less risk of dry mouth.[27]

The use of two anticholinergic medications simultaneously (oxybutynin, tolterodine, and/or solifenacin) could optimize the medical therapy for children in whom single-agent anticholinergic therapy has failed.[28]

Inappropriate use of anticholinergic medications may induce iatrogenic myogenic failure. Therefore, they should be used only with urodynamic monitoring.[29] Fortunately, this drug-induced myogenic failure is reversible on stopping treatment.[30]

Alpha-adrenergic blockers

Terazosin in doses ranging from 0.25 to 2 mg has proved to be safe and results in significant improvement in bladder emptying in PUV. There was a reduction of 85% in the pretreatment postvoid residual urine volume.[31] Hypotension was not a common side effect in children.

Chemoprophylaxis

Night-time uroprophylaxis is prescribed in cases with associated VUR. The cyclical chemoprophylaxis of 3 weekly cephalexin, septra, and amoxicillin is usually prescribed


   Role Of Nephrologist Top


The nephrologist should be involved earlier in cases of deranged renal parameter. They take care of timely institution of renal replacement therapy including Vitamin D, soda bicarbonate, calcium, erythropoietin, and manage renal tubular acidosis. Proteinuria depicts early renal damage. Measuring plasma renin level and screening for microalbuminuria are not a routine practice.


   Refluxing Loop Ureterostomy Top


The valve bladder in the initial 1–2 years following valve ablation has a reduced capacity with detrusor overactivity and high voiding pressures. In the presence of gross reflux and impaired renal function, a low refluxing ureterostomy, proposed by Philip Ransley, helps to neutralize the abnormal bladder dynamics and at the same time maintains bladder cycling.[24] The ureterostomy can be closed at a later date; alternatively if associated with a poorly functioning kidney, it can proceed to a nephrectomy.


   Timed Voiding Top


The patients and the parents should be counseled about bladder functioning, need for adequate fluid intake, recognizing the urge sensation, need for regular bladder emptying, and eradication of urine holding maneuvers.[25] The children with dilated upper tracts should be encouraged to do double or triple voiding. Constipation should be avoided. Adequate bladder emptying can be achieved by timed voiding both during the waking time and during the sleeping time in older children. In cases where the postvoid residue is significant, CIC should be taught. The frequency of CIC depends on the severity of bladder dysfunction.


   Clean Intermittent Catheterization Top


The bladder may not be able to empty completely due to inherent ineffective detrusor contractions or as a side effect of the anticholinergic medications, necessitating the use of catheters to empty the bladder. CIC should be initiated at an early age when indicated. It improves the bladder instability and also the renal function with an increase in the median differential GFR.[32] It was interesting to note that in this study, there was functional renal deterioration in those patients who stopped CIC. The sensate perineum and the dilated posterior urethra may make doing CIC difficult in a child, leading to noncompliance and deterioration of upper tracts. An abdominal catheterizing channel may be a viable alternative to keep the bladder empty.[33]


   Nocturnal Bladder Management Top


This involves timed emptying of the bladder or continuous drainage as an adjunct to the treatment of bladder dysfunction. The valve bladder syndrome is associated with a persistent bladder dysfunction characterized by chronic overdistention of the urinary bladder, which is exacerbated by associated polyuria. There is a long period of full bladder in the night during sleep leading to increased pressures that will impair the upper tract drainage with further deterioration of renal function. Nocturnal bladder drainage reduces the frequency of UTIs, improves upper tract dilatation, and improves continence. Overnight drainage in conjunction with daytime CIC can be appropriate management in children with poorly compliant bladders, especially in the early stages of renal compromise.[34],[35]


   Biofeedback Therapy and Pelvic Floor Exercises Top


Children with urodynamically proved lower urinary tract dysfunction after successful valve ablation could be managed by biofeedback therapy and home pelvic floor exercises, with an overall consistent good response in 70%.[36] This could possibly avoid or reduce anticholinergic drugs and avoid CIC.


   Bladder Neck Ablation Top


Secondary bladder neck obstruction has been over diagnosed in patients with PUV. Earlier, endoscopic bladder neck incision or open bladder neck repairs used to be made with poor clinical outcome. There are few reports of reduced detrusor overactivity, reduced need for anticholinergic medications, and better bladder urodynamics following simultaneous bladder neck incision and valve ablation.[37] The practice has not been adopted universally as long-term results are awaited.


   Bladder Augmentation Top


Augmentation of the bladder may be required in PUV patients with valve bladder when medical management fails to prevent the deterioration of renal function or the bladder is very small with thickened wall and renal transplant has been planned. The parents should be aware of the associated metabolic consequences and long-term complications such as metabolic acidosis and malignancy. Enterocystoplasty achieves a better storage function outcome while ureterocystoplasty has shown a durable functional and urodynamic improvement in valve bladder patients.[38]


   Renal Transplantation Top


As up to 50% of PUV patients can end in ESRD, renal transplantation may be required. Preoperative bladder management and continued monitoring of bladder and kidney function postoperatively are of paramount importance in the preservation of allograft function. This may require bladder augmentation to increase the bladder capacity. Reconstruction of the lower urinary tract followed by renal transplantation is a safe and efficient approach restoring the lower urinary tract before immunosuppressive therapy and supplying the best possible reservoir for a transplanted kidney.[39] However, renal transplantation can be performed safely without preemptive bladder augmentation as no difference was seen in renal outcome and bladder capacity. Thus, the decision about the need for bladder augmentation can be made after normal diuresis is restored.[40]


   Outcome Top


Poor prognostic factors include prenatal detection at <24 weeks gestation, respiratory distress at birth, urinary sepsis, dyselectrolytemia, nadir serum creatinine >0.8 mg/dL, bilateral VUR, hyperechoic kidneys, and absence of pop-off mechanism. It is speculated but it is unclear that later presentations have better outcome. A serum creatinine of 0.3–0.7 mg/dL for children under age 3 and 0.5–1.0 mg/dL for children ages 3–18 years is considered safe. Persistently elevated serum creatinine after procedure is a risk factor for ESRD. A serum creatinine of 1 mg/dL or above at 1 year of is poor prognosis.


   Conclusion Top


The management of PUV is from the antenatal period to puberty. Early fulguration of the valves after stabilization is the first step in management. It is a famous aphorism that the management of PUV actually begins after valve fulguration. A department dealing with neonatal urological problems should have good antenatal support system and endourological instrumentation for timely intervention. It is vital to identify the bladder dysfunction and manage it appropriately to prevent any deleterious effects on the upper tracts. A judicious mix of timed voiding, anticholinergics, and bladder drainage is important. Postfulguration, a close watch on upper urinary tract functions and renal tubular acidosis by regular serum creatinine and soda bicarbonate levels along with postvoid residue is imperative. Those showing evidence of noncompliant bladder in spite of medical management may become candidate for augmentation. Deterioration of upper function with persistent high creatinine suggests ESRD and need for renal replacement. Long-term follow-up till adolescence is therefore a key in management. Appropriate timely management improves the long-term survival.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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    Abstract
   Introduction
   Antenatal Diagnosis
    Poor Prognostic ...
    Counseling and I...
    Indications and ...
    Need for Early R...
   Postnatal Management
   Postnatal Diagnosis
   Investigations
    Age-Wise Standar...
    Important Inform...
    Newborn to 3 Mon...
   Infants
   Toddlers
    Boys More Than 3...
    Standard Operati...
    Alternatives to ...
    Indications For ...
    Vesicoureteral R...
    Bladder Dysfunct...
    Renal Dysplasia,...
   Follow-Up
    Indications For ...
   Urodynamic Study
   Drug Treatment
   Role Of Nephrologist
    Refluxing Loop U...
   Timed Voiding
    Clean Intermitte...
    Nocturnal Bladde...
    Biofeedback Ther...
    Bladder Neck Abl...
   Bladder Augmentation
    Renal Transplant...
   Outcome
   Conclusion
    References
    Article Tables

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  2005 - Journal of Indian Association of Pediatric Surgeons | Published by Wolters Kluwer - Medknow 

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