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ORIGINAL ARTICLE
Year : 2014  |  Volume : 19  |  Issue : 3  |  Page : 133-137
 

Posterior urethral valve: Prognostic factors and renal outcome


Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication9-Jul-2014

Correspondence Address:
Minu Bajpai
Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9261.136459

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   Abstract 

Objective: The aim was to study the outcome of posterior urethral valve (PUV) cases treated by stepladder protocol and the prognostic factors affecting the outcome. Materials and Methods: Hospital records of all PUV patients treated by stepladder protocol between January 1992 and December 2013 were reviewed. The studied parameters were: Age at presentation, serum creatinine, types of surgical intervention, vesicoureteral reflux (VUR) on initial voiding cystourethrogram (VCUG), renal cortical scars, plasma renin activity (PRA), and glomerular filtration rate (GFR). Results: Of 396 PUV patients treated during the study period, 152 satisfied study criteria. The age at presentation ranged from 2 days to 15 years (mean 31.3 months). The mean follow-up period was 5 years (range: 2-18 years). Primary endoscopic valve ablation was the most common initial procedure. Chronic renal failure was seen in 42.7% patients at the last follow-up. Serum creatinine at presentation, initial PRA levels, initial GFR, and PRA levels at last follow-up were significant predictors of final renal outcome. Age at presentation (<1 vs. >1 year), presence/absence of VUR on initial VCUG and renal cortical scars had no significant correlation with ultimate renal function. Conclusion: Our study confirms the high prognostic significance of initial serum creatinine, PRA levels and GFR in cases with PUV. PRA also holds promise in long-term follow-up of these patients as a marker of progressive renal damage.


Keywords: Plasma renin activity, posterior urethral valve, stepladder protocol, valve ablation


How to cite this article:
Bhadoo D, Bajpai M, Panda SS. Posterior urethral valve: Prognostic factors and renal outcome. J Indian Assoc Pediatr Surg 2014;19:133-7

How to cite this URL:
Bhadoo D, Bajpai M, Panda SS. Posterior urethral valve: Prognostic factors and renal outcome. J Indian Assoc Pediatr Surg [serial online] 2014 [cited 2019 Nov 12];19:133-7. Available from: http://www.jiaps.com/text.asp?2014/19/3/133/136459



   Introduction Top


Posterior urethral valve (PUV) is the most common cause of lower urinary tract obstruction in male children with a broad spectrum of clinical presentation, disease severity and associated sequelae. [1],[2] Progressive renal deterioration is common and 25-40% of PUV patients develop renal failure at varying ages. [2],[3],[4]

Several studies have been done to identify possible prognostic factors which affect the long-term renal outcome in these cases, but the data is conflicting. [2],[3],[4],[5] These prognostic factors can help in planning management and serve as a guide in parental counseling. The aim of this study was to report the long-term renal outcome and determine the prognostic significance of various factors in PUV cases.


   Materials and methods Top


The study consisted of patients registered and followed-up at our Pediatric Urology Clinic for management of PUV between January 1992 and December 2013. The hospital records of all the patients were carefully reviewed for age at presentation, preoperative evaluation, surgical intervention, and postoperative follow-up.

Patients with history of prior surgical intervention, incomplete data or history of antihypertensive drug use were excluded.

A total of 396 patients with PUV were treated during aforementioned period. Out of these, 152 fulfilled the study criteria and were included in the analysis. All these patients were managed by stepladder protocol [Figure 1], [6] which involved primary valve ablation in stable cases and catheterization in unstable ones. Patients stabilizing with catheterization also underwent valve ablation, while those showing no improvement after catheterization were subjected to high urinary diversion in form of bilateral ureterostomy. Vesicostomy was performed only when small sized cystoscopes were not available. All patients underwent voiding cystourethrogram (VCUG) for detection of vesicoureteral reflux (VUR) while Tc-99m dimercaptosuccinic acid (DMSA) scan was performed for renal scar detection. Glomerular filtration rate (GFR) was measured by diethylenetriaminepentaacetic acid scans using multiple sampling method (venous blood samples drawn at 60, 90, 150 and 180 min). Plasma renin activity (PRA) was measured by radio-immunoassay using commercially available kit (SB REN-2, DiaSorin, Stillwater, Minnesota, USA) pre- and postoperatively.
Figure 1: The "step ladder" protocol. USPCN*: Ultrasound guided percutaneous nephrostomy

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The records of all patients were reviewed regarding age at presentation, type of surgical intervention, VUR on initial VCUG, presence/absence of renal cortical scarring. Furthermore, serum creatinine, GFR, and PRA values at presentation and last follow-up were studied. Patients were classified as those with chronic renal failure (CRF) and those without it at the last follow-up. Analysis was done with IBM ® statistical package for the social sciences (SPSS ® ) Statistics 20 (IBM, Armonk, New York, United States). Values are reported as the mean ± standard deviation unless otherwise reported. Associations between categorical variables were examined by Yates corrected Chi-square test. Statistical comparisons between group means were done by the unpaired Student's t-test. P <0.05 was considered as significant.


   Results Top


Total number of patients who met the study criteria was 152. The age at presentation ranged from 2 days to 15 years (mean 31.3 months) with 49% (74 patients) presenting within 1 year of age and 51% (78 patients) beyond 1 year of age. The mean follow-up period was 5 years (range: 2-18 years). Primary endoscopic valve ablation was the most common initial procedure, which was carried out in 128 (84.2%) cases [Table 1]. Vesicostomy was performed in 18 (11.8%) cases, while only 6 (3.9%) underwent high ureterostomy. CRF was seen in 42.7% (65 of 152) patients at the last follow-up.
Table 1: Types of primary procedures performed

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In patients presenting within 1 year of age CRF developed in 47.3% (35 of 74) and in those presenting beyond 1 year of age it was seen in 38.4% (30 of 78). The difference was statistically insignificant (P = 0.326). Renal failure developed in 43.7% (56 of 128) patients who underwent primary valve ablation. Five of 18 (27.7%) undergoing vesicostomy and 4 of 6 patients who underwent ureterostomy had CRF at the last follow-up.

When initial serum creatinine was ≤1 mg/dl before valve ablation, CRF developed in 21 of 91 (23%) while it developed in 44 of 61 (72%) who presented with creatinine above 1 mg/dl (P < 0.05). The mean GFR at presentation was 39.55 ± 19.97 ml/min/1.73 m 2 in patients who developed CRF when compared to 70.39 ± 24.03 in patients who did not develop CRF. This was statistically significant (P < 0.05).

Vesicoureteral reflux at initial VCUG was present in 93 (61.2%) patients. It was bilateral in 60 (39.5%), right sided in 19 (12.55) and left sided in 14 (9.2%) patients. CRF was seen at the last follow-up in 46.2% (43 of 93) and 37.3% (22 of 59) patients with and without VUR, respectively. However, this was not statistically significant (P = 0.315). Renal cortical scarring on DMSA scan was seen in 56.6% (86 out of 152) patients. CRF developed in 48.8% (42 patients) with renal scars and in 34.8% (23 of 69) without renal scars. However, this did not reach statistical significance (P = 0.099).

The mean PRA at presentation was 11.2 ± 8.30 ng/ml/h in patients who developed CRF, while the corresponding value in cases without CRF was 6.02 ± 5.31. The difference was statistically significant (P < 0.05). The mean PRA value at last follow-up in patients with CRF was 9.59 ± 4.86 ng/ml/h compared with a value of 4.86 ± 3.71 in patients who did not develop CRF. This difference was also statistically significant (P < 0.05).


   Discussion Top


Posterior urethral valve is one of the most serious congenital urinary tract anomalies that can lead to deleterious effect on future bladder and renal function. [2] Despite improve in survival of these patients as many as 25-60% may have significant impairment in renal function in long-term follow-up. [2],[3],[4],[5],[7] Ultimate renal function in PUV patients depends on a number of well-known factors. Renal function deterioration has been linked to age at presentation, GFR, prenatal diagnosis, renal dysplasia, VUR, renal scarring, nadir creatinine during 1 st year of life, upper tract obstruction, bladder dysfunction, and urinary tract infection (UTI).

In the recent decades, primary endoscopic valve ablation has become the mainstay of treatment in PUV cases. [4] In our study it was the most common initial procedure which was performed in 128 (84.2%) patients. This consisted of 72 cold knife incisions, 51 laser fulgurations and 5 Bugbee fulgurations. Cold knife incision is safe in all neonates and children and is superior to diathermy in relieving PUV obstruction in a single attempt. [8] Vesicostomy was done in 18 (11.8%) cases because of unavailability of small sized cystoscopes. Only 6 (3.9%) patients underwent high ureterostomy as they failed to improve after 48 h period of bladder catheterization.

Age at presentation has been suggested as a predictor of renal function in children with PUV. [3],[9] However, the data on this issue are conflicting. Prenatal diagnosis was initially thought to improve the outcome, but earlier studies failed to show that the long-term outcome in prenatally detected PUV cases is better than symptomatic cases detected postnatally. [3],[4] In our study, the renal function outcome was worse in patients presenting within 1 year of age compared with those presenting after 1 year of age but the difference was not statistically significant (P > 0.05). Our findings were similar to those reported by Parkhouse et al. [2]

Many groups have found serum creatinine as a useful prognostic indicator. [3],[5],[10],[11] Sarhan et al. have reported that initial serum creatinine was significantly higher in boys with a poor renal outcome than in those with a favourable outcome (P < 0.05). [12] In our study, serum creatinine at presentation was an important prognostic factor for final renal outcome. When initial serum creatinine was ≤1 mg/dl the incidence of CRF was 23%, while if it was above 1 mg/dl, the incidence increased to 72% and the difference was statistically significant (P < 0.05). These results were similar to those reported by earlier studies. [10],[12]

Serum creatinine at age 1 year has greater predictive value than the level at diagnosis. [6],[7],[10] Serum creatinine <0.8 mg/dl at age 1 year is associated with practically normal final renal function. [11] In our study, <50% of total patients were diagnosed at an age ≤1 year. Thus, we could not measure the values at 1 year of age or study its effect.

Mean GFR in patients who ultimately developed renal failure, was significantly lower than those without renal failure (P < 0.05). [13] Similarly, we found that the mean GFR at presentation in patients who did not develop CRF was 70.39 ± 24.03 ml/min/1.73 m 2 compared to 39.55 ± 19.97 in patients who ultimately developed CRF. This difference was statistically significant (P < 0.05). Our findings were supported by a study done by Sarhan et al. [12]

The role of VUR in PUV is still controversial. VUR is the major cause of postnatal renal damage in cases with PUV and persistent VUR is associated with a poor outcome. [2] Some groups consider that high grade bilateral VUR significantly correlates with prognosis while others have not found any such correlation. [5],[7],[11] In our study, the presence or absence of VUR did not significantly correlate with the final renal outcome, confirming the results of most published series. Most VUR disappear once bladder is stabilized with anticholinergics and posttreatment persistent upper tract dilatation should be investigated for vesicoureteral junction obstruction and detrusor dysfunction by a complete urodynamic evaluation. [11] Endoscopic hyaluronic acid/dextranomer injection can be used safely in PUV patients with persistent various grades of VUR after valve ablation. [14] CRF developed more often in cases with VUR (46.2%) than without it (37.3%) but the difference was not statistically significant.

Bladder dysfunction has been recognized as one of the most important factors for the long-term outcome in these cases. [15] Children with PUV develop detrusor fibrosis results in decreased compliance and instability leading to poor emptying and recurrent UTI. [16] This bladder dysfunction contributes to the long-term morbidity despite adequate relief of obstruction due to the valves. Some authors recommend early aggressive anticholinergic therapy and timed voiding for management of bladder dysfunction in children with PUV. [17] Anticholinergic therapy effectively eliminates bladder instability. However, it may increase bladder capacity and decreases voiding detrusor pressure, which can lead to myogenic failure. Recently, α-1 blockers have gained wide attention because of its ability to decrease intravesical pressure and outlet resistance thereby improving voiding dysfunction and upper tract dilatation. [18] Sarin and Sinha studied the efficacy of simultaneous endoscopic bladder neck incision and primary endoscopic valve incision in patients with PUV and failed to demonstrate any significant difference. [19]

Chronic renal failure developed in 48.8% patients with renal cortical scars compared to 34.8% in patients without renal scars. However, the difference was statistically insignificant (P = 0.099). This finding is similar to previously published studies. [20] The treatment of end-stage renal disease in children with PUV is challenging. In PUV patients, renal transplantation can be performed safely and effectively including those who have undergone previous proximal urinary tract diversion. [21] In a low capacity, poorly compliant bladder in children with PUVs who do not respond to medical management, early intervention may prevent deterioration in renal function and augmentation cystoplasty is a safe and effective method to achieve continence. [22]

There is tubulointerstitial damage in congenital uropathiesand activation of renin angiotensin system, of which PRA is one such manifestation. [23] The decline in renal function after valve ablation is accompanied by activation of RAS reflected in a gradual rise in PRA. Therapy with angiotensin converting enzyme-inhibitors stabilizes and then improves renal function, thereby, retarding the pace of renal damage. [24] In this study, the mean PRA at presentation was higher in patients who developed CRF than who did not. This difference was statistically significant (P < 0.05). Furthermore, the mean PRA at last follow-up in patients with CRF was significantly higher than those with without CRF (P < 0.05). These observations were consistent with findings of earlier studies. [20],[23],[24]

Early identification of detrimental factors causing long-term renal deterioration is required in patients with PUV in counseling patients as well as in guiding future therapy. Urinary transforming growth factor-beta 1, tumor necrosis factor-alpha and microalbumin levels were high in patients with PUV and can be used as biomarkers for the early recognition of ongoing renal damage in patients with PUV. [25]


   Conclusion Top


Our study confirms the high prognostic significance of initial serum creatinine and GFR values in cases with PUV. Furthermore, initial PRA is an important significant factor in predicting long-term renal outcome. PRA also holds promise in long-term follow-up of these patients as a marker of progressive renal damage.

 
   References Top

1.Dinneen MD, Duffy PG. Posterior urethral valves. Br J Urol 1996;78:275-81.  Back to cited text no. 1
    
2.Parkhouse HF, Barratt TM, Dillon MJ, Duffy PG, Fay J, Ransley PG, et al. Long-term outcome of boys with posterior urethral valves. Br J Urol 1988;62:59-62.  Back to cited text no. 2
    
3.Reinberg Y, de Castano I, Gonzalez R. Prognosis for patients with prenatally diagnosed posterior urethral valves. J Urol 1992;148:125-6.  Back to cited text no. 3
    
4.El-Ghoneimi A, Desgrippes A, Luton D, Macher MA, Guibourdenche J, Garel C, et al. Outcome of posterior urethral valves: To what extent is it improved by prenatal diagnosis? J Urol 1999;162:849-53.  Back to cited text no. 4
    
5.Lopez Pereira P, Espinosa L, Martinez Urrutina MJ, Lobato R, Navarro M, Jaureguizar E. Posterior urethral valves: Prognostic factors. BJU Int 2003;91:687-90.  Back to cited text no. 5
    
6.Bajpai M, Dave S, Gupta DK. Factors affecting outcome in the management of posterior urethral valves. Pediatr Surg Int 2001;17:11-5.  Back to cited text no. 6
    
7.Lal R, Bhatnagar V, Mitra DK. Long-term prognosis of renal function in boys treated for posterior urethral valves. Eur J Pediatr Surg 1999;9:307-11.  Back to cited text no. 7
    
8.Babu R, Kumar R. Early outcome following diathermy versus cold knife ablation of posterior urethral valves. J Pediatr Urol 2013;9:7-10.  Back to cited text no. 8
    
9.El-Sherbiny MT, Hafez AT, Shokeir AA. Posterior urethral valves: Does young age at diagnosis correlate with poor renal function? Urology 2002;60:335-8.  Back to cited text no. 9
    
10.Sarhan O, El-Dahshan K, Sarhan M. Prognostic value of serum creatinine levels in children with posterior urethral valves treated by primary valve ablation. J Pediatr Urol 2010;6:11-4.  Back to cited text no. 10
    
11.Ansari MS, Gulia A, Srivastava A, Kapoor R. Risk factors for progression to end-stage renal disease in children with posterior urethral valves. J Pediatr Urol 2010;6:261-4.  Back to cited text no. 11
    
12.Sarhan OM, El-Ghoneimi AA, Helmy TE, Dawaba MS, Ghali AM, Ibrahiem el-HI. Posterior urethral valves: Multivariate analysis of factors affecting the final renal outcome. J Urol 2011;185:2491-5.  Back to cited text no. 12
    
13.Bajpai M, Singh A. Plasma renin activity: An early marker of progressive renal disease in posterior urethral valves. J Indian Assoc Pediatr Surg 2013;18:143-6.  Back to cited text no. 13
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14.Bajpai M, Verma A, Panda SS. Endoscopic treatment of vesico-ureteral reflux: Experience of 99 ureteric moieties. J Indian Assoc Pediatr Surg 2013;18:133-5.  Back to cited text no. 14
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15.Puri A, Bhatnagar V, Grover VP, Agarwala S, Mitra DK. Urodynamics-based evidence for the beneficial effect of imipramine on valve bladders in children. Eur J Pediatr Surg 2005;15:347-53.  Back to cited text no. 15
    
16.Aitken KJ, Bägli DJ. The bladder extracellular matrix. Part I: Architecture, development and disease. Nat Rev Urol 2009;6:596-611.  Back to cited text no. 16
    
17.De Gennaro M, Capitanucci ML, Capozza N, Caione P, Mosiello G, Silveri M. Detrusor hypocontractility in children with posterior urethral valves arises before puberty. Br J Urol 1998;81 Suppl 3:81-5.  Back to cited text no. 17
    
18.McGuire EJ, Weiss RM. Secondary bladder neck obstruction in patients with urethral valves: Treatment with phenoxybenzamine. Urology 1975;5:756-8.  Back to cited text no. 18
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19.Sarin YK, Sinha S. Efficacy of bladder neck incision on urodynamic abnormalities in patients with posterior urethral valves. Pediatr Surg Int 2013;29:387-92.  Back to cited text no. 19
    
20.Bajpai M, Pratap A, Tripathi M, Bal CS. Posterior urethral valves: Preliminary observations on the significance of plasma Renin activity as a prognostic marker. J Urol 2005;173:592-4.  Back to cited text no. 20
    
21.DeFoor W, Tackett L, Minevich E, McEnery P, Kitchens D, Reeves D, et al. Successful renal transplantation in children with posterior urethral valves. J Urol 2003;170:2402-4.  Back to cited text no. 21
    
22.Kajbafzadeh AM, Quinn FM, Duffy PG, Ransley PG. Augmentation cystoplasty in boys with posterior urethral valves. J Urol 1995;154:874-7.  Back to cited text no. 22
    
23.Goonasekera CD, Dillon MJ. Reflux nephropathy and hypertension. J Hum Hypertens 1998;12:497-504.  Back to cited text no. 23
    
24.Bajpai M, Chaturvedi PK, Bal CS, Sharma MC, Kalaivani M. Posterior urethral valves: Persistent renin angiotensin system activation after valve ablation and role of pre-emptive therapy with angiotensin converting enzyme-inhibitors on renal recovery. J Indian Assoc Pediatr Surg 2013;18:74-8.  Back to cited text no. 24
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25.Mandelia A, Bajpai M, Agarwala S, Gupta AK, Kumar R, Ali A. The role of urinary TGF-β1 , TNF-α, IL-6 and microalbuminuria for monitoring therapy in posterior urethral valves. Pediatr Nephrol 2013;28:1991-2001.  Back to cited text no. 25
    


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