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BACKGROUND: Posterior urethral valves (PUV) may cause subtle to severe obstruction of the urethra, resulting in a broad clinical spectrum. PUV are the most common cause of chronic renal disease in boys. Our purpose was to report the incidences of kidney and bladder dysfunction in boys treated with endoscopic valve resection for PUV. METHODOLOGY: We...
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Citations
... There is a lot to reflect upon and learn. It strikes a chord across our specialties since most clinicians dealing with these children and their families believe that more needs to be done and these ambitions have been repeated often in the literature [2,3]. These reviews and reflections bring out much more than the weakness of "silo care"; they point not only to a need for better co-ordinated care but also better understanding and high-end translational research to reduce long-term morbidity in this cohort. ...
... Tilstanden kraever livslang nefro-urologisk opfølgning, da ca. 60% enten vil have påvirket nyre eller blaerefunktion[18,19].Hypospadi er en medfødt tilstand, hvor urinrøret munder ud på ventralsiden af penis (Figur 2Figur 2) med spaltet forhud og peniskrumning. Scrotale misdannelser kan evt. ...
Paediatric urology is a subspeciality of urology, with close links to paediatric surgery. This review concludes that a holistic life-long approach to management in highly specialised treatment centres is essential for many of the rare congenital conditions - in Denmark, paediatric urology is centralised to two institutions: Rigshospitalet in Copenhagen and Aarhus University Hospital in Aarhus. Other than performing basic urology in paediatric patients, both centres specialise in complex and rare urological conditions and thus have been accredited by the European Reference Network on rare diseases through the eUrogen collaboration. Patient populations have covered span from prenatal to childhood, transition and for some anomalies, even into adulthood.
... The estimated incidence of PUVs is 1/4000 -1/5000 births, with approximately 35% being diagnosed antenatally and 55% being diagnosed postnatally. 1 This condition implies a high morbidity as up to 60% of children diagnosed with PUVs will develop chronic kidney disease (CKD) and up to 25% of them will develop end stage renal disease (ESRD) requiring dialysis or kidney transplantation. 2 This occurs because early obstruction in utero causes renal damage secondary to obstructive uropathy and renal dysplasia to varying degrees. 3 Known factors associated with an increased risk of developing CKD include early diagnosis before birth and early evidence of poor kidney and bladder function. 1-2 Early diagnosis often means more severe renal dysplasia and bladder dysfunction, which can further damage the kidneys. ...
... These elevated pressures lead to structural changes seen both in the ureters and kidneys. 3 Bladder dysfunction including daytime incontinence is a significant sequela of PUVs, with incontinence rates ranging from 4-35%. 4 Long term, children may develop valve bladder syndrome with poor emptying and high bladder pressures. Small case studies in Europe have shown that early intervention with a bladder regimen and early toilet training, in addition to teaching families about clean intermittent catheterization (CIC) can help preserve renal function and improve bladder function over time. ...
... 7 It is currently estimated that 55% of patients with PUVs will have underlying bladder dysfunction. 3,9 In our practice, PUV patients who continue to have incontinence or recurrent UTIs beyond toilet-trained age will undergo urodynamics to assess if there are any concerning findings including decreased compliance, hypercontractility, or urinary retention. Additionally, video urodynamics can identify any vesicoureteral reflux or residual valves causing bladder dysfunction. ...
Introduction:
Posterior urethral valves (PUVs) is a congenital condition in which an obstruction in the urethra prevents drainage of urine from the bladder in males, with up to 60% of children diagnosed developing chronic kidney disease (CKD). The primary aim of this study was to identify novel factors that may predict development of CKD and end-stage real disease (ESRD) in children with PUVs to potentially address modifiable factors and delay progression. The secondary aim was to compare rates of catheterization and incontinence between our patients and other case series to provide information to parents about long-term bladder outcomes.
Methods:
A single-center, retrospective cohort study was performed of all children referred to our multidisciplinary clinic for PUV diagnosis between 2005 and 2019. Univariable associations of different variables with the composite outcome CKD or ESRD were evaluated.
Results:
Thirty of 46 patients (65%) developed CKD, with the majority (40%) being stage 2 CKD (n=12). Seven of 30 patients (23%) developed ESRD requiring renal replacement therapy. Fourteen of 26 (30%) required clean intermittent catheterization (CIC) initiation with a median CIC initiation age of 4.3 years. Creatinine nadir post-valve ablation, oligohydramnios, and initiation of CIC are significant predictors in developing CKD.
Conclusions:
This review reiterates that children born with PUVs have a high morbidity rate, with a high proportion developing CKD. Using a multidisciplinary approach to PUV patient care allows for better family education, early intervention of bladder dysfunction, and possibly better long-term preservation of renal function.
... The imaging follow-up includes repeated sonographic evaluation of the urinary tract and biological markers in cases of renal insufficiency. A multidisciplinary team is required to monitor and manage the different aspects of the pathology, i.e. the evolution of renal function [41], the urodynamic function of the bladder [42] and the possibility of recurring infections associated with the reflux. Children with a poorer prognosis regarding renal function are those with an early diagnosis (antenatal) and abnormal renal parenchyma (cystic obstructive dysplasia or reflux nephropathy). ...
Congenital uropathies are the most common fetal anomalies. They include a wide spectrum of anomalies ranging from mild pelvis dilation to complex urinary tract malformations. Prenatal imaging not only allows for their diagnosis but, in experienced hands, it can differentiate obstructive from refluxing or malformative uropathies. Such precise prenatal information allows for intervention before birth in select cases or for adapting the postnatal workup to provide a better long-term outcome. For the different types of congenital uropathies, we describe their prenatal presentations on US and the complementary role of fetal MRI where indicated. We correlate these findings with postnatal workup and summarize the updated neonatal diagnostic and clinical/surgical management.
... Duckett used the term 'full blown valve bladder syndrome' and implicated upper tract diversions as a an essential cause [5]. Mitchell [6,7] and Podesta [8] proposed that primary valve fulguration is the key in reducing the incidence of valve bladder, although around 30-40% of patients who undergo primary PUV ablation also develop valve bladder [9][10][11]. ...
... Schober et al. [19] reported that patients with normal imaging of the urinary tract presented with night time incontinence and frequency. Hennus et al. [11] in a systematic review reported that incidence of renal and bladder dysfunction in patients with PUV varied widely due to a lack of standardised quantification of obstruction and its severity. In addition the timing of urodynamic study, they felt was important in finding overactivity as patients developed decompensation and low pressures as they went through puberty. ...
Background/aims
Prompt and early treatment of valve bladder is known to improve renal outcome in patients with PUV. We hypothesized that bladder height width ratio (HWR) measurement on voiding cystourethrogram (VCUG) could predict development of valve bladder.
Methods
All patients who underwent primary PUV ablation and evaluated later with urodynamics were included. Valve bladder was suspected when there were daytime wetting, persistent hydroureteronephrosis, and elevated detrusor pressures on urodynamics. VCUGs were analysed for HWR: maximum height/width of bladder. ROC curve analysis was performed to identify HWR that could predict development of urodynamic abnormality.
Results
Between 2012 and 2017, 102 patients were studied: median age at valve ablation 25 days (3–125 days); follow-up 5 years (3–7 years). The ROC curve comparing post-ablation HWR with occurrence of valve bladder showed a cut-off of 1.45 (AUC 0.93). HWR cut-off of 1.45 had a sensitivity of 89% and specificity of 84% in predicting future valve bladder. Detrusor overactivity was noticed on urodynamics in 41/55 (74%) of those with HWR > 1.45 compared 5/47 (11%) in those with HWR < 1.45 (p = 0.001).
Conclusion
Bladder height width ratio on VCUG is a useful parameter to predict development of future valve bladder in children with PUV.
... PUV is the commonest cause of lower urinary tract obstruction in male children (13). Even after successful PVA, the majority of patients will suffer bladder dysfunction. ...
Objective:
To assess the effect of bladder neck morphology and its incision (BNI) in patients with posterior urethral valve (PUV) on early reintervention rate.
Patients and methods:
Infants undergoing PUV ablation (PVA) before 24 months of age and had at least 18 months of follow-up, were categorized into three groups according to the bladder neck appearance on baseline radiological and endoscopic examination: group 1; normal bladder neck underwent PVA, group 2; high bladder neck underwent PVA plus BNI, group 3; high bladder neck underwent PVA only. Early reintervention was defined as the need for check cystoscopy because of persistent renal function deterioration, worsening hydronephrosis and/or unsatisfactory VCUG improvement during the 1st six months post primary PVA.
Results:
Between 2000 and 2017, a total of 114 patients underwent PVA and met the study criteria with a median follow-up of 58 (18-230) months. For group 1, 16 (22.9%) patients needed readmission. Check cystoscopy was free and no further intervention was performed in 5(7.5%) and re-ablation was performed in 11(15.7%) patients. For group 2, 3(14.3%) patients needed reintervention. Re-ablation and re-ablation plus BNI were performed in 1(4.8%) and 2(9.5%), respectively. For group 3, cystoscopy was free in 1(4.3%), re-ablation and re-ablation plus BNI were performed 2(8.7%) and 1(4.3%), respectively. There were no significant differences in the re-admission and re-intervention rates among the three study groups (p=0.65 and p=0.50, respectively).
Conclusion:
In morphologically high bladder neck associated PUV, concomitant BNI with PVA doesn't reduce early re-intervention rate.
... Urine is then transported to the bladder through the ureter(s) and expelled out of the body through the urethra. Apart from the endocrine functions of the kidney, a functioning urinary system is vital to the human body; and a total blockage of the filtration or micturition mechanisms is not compatible with life (Hennus et al. 2012). With the aim of providing a viable, yet socially functional urinary system, the bladder must sustain the continuous cycle of filling and micturating with organized and synchronized sphincter activity (Andersson and Arner 2004;Fry and McCloskey 2019). ...
The human bladder maintains a cycle of filling, storing, and micturating throughout an individual’s lifespan. The cycle relies on the ability of the bladder to expand without increasing the intravesical pressure, which is only possible with the controlled relaxation of well-complaint muscles and the congruously organized construction of the bladder wall. A competent bladder outlet, which functions in a synchronous fashion with the bladder, is also necessary for this cycle to be completed successfully without deterioration. In this paper, we aimed to review the contemporary physiological findings on bladder physiology and examine the effects of amino acids on clinical conditions affecting the bladder, with special emphasis on the available therapeutic evidence and possible future roles of the amino acids in the treatment of the bladder-related disorders.
... Even after successful PUV ablation, persistent BD (a.k.a. valve bladder syndrome) is seen in 70-80% of patients [1,27,28]. Most infants and young children with PUV have reduced capacity, hypocompliant bladders with or without detrusor overactivity (DO). ...
Introduction
Posterior urethral valve (PUV) is the leading etiology of lower urinary tract obstruction (LUTO) in boys and is an important cause of end-stage renal disease (ESRD) in children. The aim of this article is to review the current status on antenatal intervention for PUV as well as postnatal medical and surgical management.
Main body
MEDLINE, EMBASE, Pubmed and Google Scholar search was conducted throughout December 2020 using the keywords: posterior urethral valves, congenital urinary obstruction, antenatal, valve bladder syndrome, medical, anticholinergics, alpha blocker, antibiotics, biofeedback, diversion, augmentation cystoplasty and renal transplantation. Only papers written in English were included. The relevant literature was summarized. Despite advances in antenatal intervention for fetal LUTO, it remains associated with considerable fetal and maternal morbidity. Patient selection criteria for antenatal intervention are greatly debated. Fetal intervention has resulted in improved perinatal survival in properly selected cases, with a questionable benefit to postnatal renal function. There is decent evidence supporting the use of anticholinergics in infants and young children following valve ablation, with less robust evidence advocating alpha blockers, overnight catheter drainage and biofeedback. The role of urinary diversion remains contentious. Optimizing bladder dynamics is crucial for successful renal transplantation outcomes.
Conclusion
While antenatal intervention has failed to improve renal function outcomes of PUV, patient-centered medical and sometimes surgical interventions can help delay the progression of chronic kidney disease. Lifelong monitoring and management of the associated bladder dysfunction is indispensable even after successful renal transplantation.
... Obstruction initiates mechanical, hypoxic stimuli and ECM remodelling which induce signaling and downstream gene expression changes leading to production of ECM enzymes and release of growth factors [19][20][21][22] . A sequence of inflammation, hypertrophy and hyperplasia leads to an almost intractable state which persists despite adequate treatment of the initial obstruction 3,9,[23][24][25] . During obstruction, this state is exacerbated by the epigenetic drug, decitabine (DAC) 26 . ...
... The inciting obstruction can be anatomical or neuronal, and appears in all sexes and ages, though its most common cause is prostate hypertrophy in older males. The societal cost is huge as COBD decreases quality of life, and can lead to incontinence, overactivity, UTI, renal scarring and kidney failure [2][3][4][5][6][7] . The COBD bladder in vivo shows many stable changes, including de-differentiation and hypertrophy of SMC, as well as Figure 1. ...
Partial bladder outlet obstruction due to prostate hyperplasia or posterior urethral valves, is a widespread cause of urinary dysfunction, patient discomfort and also responsible for immense health care costs. Even after removal or relief of obstruction, the functional and pathologic aspects of obstruction remain as a chronic obstructive bladder disease (COBD). Epigenetic changes, such as DNA methylation, contribute to the persistent character of many chronic diseases, and may be altered in COBD. We tested whether candidate genes and pathways and the pathophysiology of COBD were affected by a hypomethylating agent, decitabine (DAC). COBD was created in female Sprague-Dawley rats by surgical ligation of the urethra for 6 weeks, followed by removal of the suture. Sham ligations were performed by passing the suture behind the urethra. After removal of the obstruction or sham removal, animals were randomized to DAC treatment (1 mg/kg/3-times/week intraperitoneally) or vehicle (normal saline). Bladder function was non-invasively tested using metabolic cages, both one day prior to de-obstruction at 6 weeks and prior to sacrifice at 10 weeks. Residual volume and bladder mass were measured for each bladder. Bladders were examined by immunostaining as well as qPCR. The effects of DNA methyltransferase (DNMT)-3A knockout or overexpression on smooth muscle cell (SMC) function and phenotype were also examined in bladder SMC and ex vivo culture. Residual volumes of the DAC treated group were not significantly different from the NS group. Compared to COBD NS, COBD DAC treatment helped preserve micturition volume with a significant recovery of the voiding efficiency (ratio of the maximum voided volume/maximum bladder capacity) by one third (Fig. 1, p > 0.05). Brain-derived neurotrophic factor (BDNF) variants 1 and 5 were upregulated by COBD and significantly reduced by DAC treatment. Deposition of collagen in the COBD bladder was reduced by DAC, but gross hypertrophy remained. In bladder SMC, DNMT3A overexpression led to a loss of contractile function and phenotype. In bladders, persistently altered by COBD, inhibition of DNA-methylation enhances functional recovery, unlike treatment during partial obstruction, which exacerbates obstructive pathology. The underlying mechanisms may relate to the gene expression changes in BDNF and their effects on signaling in the bladder.
... [20] A systematic review has noted a wide variation in the cumulative incidence of renal and bladder dysfunction in affected patients after endoscopic valve resection. [21] Nevertheless, some authors suggest that prenatal and postnatal comorbidities, such as renal dysplasia and urinary tract infection respectively, rather than postnatal interventions, determine the future renal outcomes. [22] More recently, another study has proposed that the bladder contractility index (BCI) from a well-performed urodynamic study could be a useful tool for prognostication in PUV patients. ...
... [19,39] A similar systematic review reported an average of 22% (0%-32%) as CKD prevalence rate and 11% (0%-20%) as ESKD prevalence rate. [21] However, wide disparities in CKD prevalence from 20% to 65% and ESKD prevalence from 8% to 21% have also been documented in other studies. [40,41] From some of the reviewed studies, we identified several factors that could represent predictors of future renal outcomes. ...
... [4,26,27,29,34] Some of these factors are in tandem with those identified by Neyas et al., [42] such as baseline eGFR, bladder dysfunction, and VUR. More importantly, nadir serum creatine has been identified as the most reliable predictor of future renal dysfunction, [21] which agrees with the finding of the present systemic review. ...
Background and Objectives: Several studies show that most infants with posterior urethral valve (PUV) do
not fully recover their renal function, despite postnatal interventions to obviate the consequences of lower urinary
tract obstruction. This systematic review assesses the future risks of chronic kidney disease (CKD) and end‑stage
kidney disease (ESKD) in infants with postnatally‑repaired PUV. Methods: We electronically searched PubMed,
Medline, Embase, and Google Scholar databases for articles published between 2000 and 2020 (Date of the last
search: September 12, 2020) using appropriate descriptors. We selected the studies based on adopted eligibility
and exclusion criteria. We independently retrieved relevant data from the selected studies using a preconceived
data‑extraction form. We analyzed the aggregate data among the selected studies that signified future CKD and
ESKD after the postnatal intervention and computed their mean prevalence rates. We also calculated the average
point estimate of CKD and ESKD relative risks (RR) as the effect estimate at a 95% confidence interval. Results:
Eleven studies were selected and reviewed, in which a total of 1362 patients were managed and followed up for
variable periods. The aggregate data on ESKD prevalence from seven studies showed that a total of 112 patients
developed ESKD out of a total patient population of 446, giving a calculated mean ESKD prevalence of 24%. The
CKD prevalence data in nine studies showed that 210 patients had CKD, out of 741 patients that were followed
up, with a calculated mean CKD prevalence of 28%. The pooled RR of ESKD in seven studies and RR of CKD in
nine studies was 0.5 (−0.48, 1.48) and 0.57 (−0.41, 1.55), respectively. Conclusions: Future risks of CKD and
ESKD is still high in patients with postnatally‑repaired PUV. We advocate a management approach that involves
a synergy between pediatric nephrologists and urologists to ensure prompt renoprotective strategies and timely
surgical intervention.
Keywords: Chronic kidney disease, end‑stage kidney disease, glomerular dysfunction, posterior urethral valve,
postnatal interventions, renal outcome
