A consensus process to identify research priorities in paediatric urology in the United Kingdom.

INTRODUCTION: Paediatric urologists manage a spectrum of conditions, much of the evidence for relevant treatment pathways is of low quality. For many conditions treatment varies according to location and surgeon; children with the same condition might have surgery in one unit but watchful waiting in another. Underlying this variation are differences in opinion, and insufficient high-level evidence with few prospective randomized studies. Such studies may be challenging to design, fund and recruit into, and are more likely to succeed if there is a collaborative approach. Research prioritization is a tool to identify the research of most value. Delphi methodology is an interpretive technique aiming to gain the consensus view of interested parties. The British Association of Paediatric Urologists (BAPU) set out to ascertain consensus on what paediatric urologists, working in the UK, consider to be areas of priority for research. This paper describes the process used, and the resulting list of research questions. METHODS: A scoping survey of paediatric urologists in the UK was undertaken to identify an initial set of research questions. These were refined by the BAPU research committee (BAPU RC), then prioritized using a modified Delphi process. During Stage 1a multiple new research questions were submitted leading to Stage 1b, an interim process. All UK paediatric urologists were invited to take part in Stage 2 of the prioritization process. RESULTS: Sixty-five questions were submitted to the scoping survey by 24 paediatric urologists. The BAPU RC refined these to 60 questions, which were submitted to Stage 1a of the modified Delphi process. Sixty-seven people completed Stage 1a, at the same time submitting 224 additional research questions. The BAPU RC revised the entire question set, ensuring the key subject of the original question was not altered and novel questions were retained. The BAPU RC undertook interim scoring of the resultant 79 questions, the top scoring 25 questions plus 5 lower scoring 'wild card' questions (to ensure the breadth of the specialty was represented) were put forward to Stage 2. A total of 65 people completed Stage 2, including a lay representative. A list of 30 priority research questions was generated; the top 10 includes management of neuropathic bladder, posterior urethral valves, antibiotic prophylaxis, DSD & CAH, continence, male external genitalia, VUR and transition care (Table). CONCLUSION: This process has provided BAPU, paediatric urologists in the UK, and funders with areas of research considered a priority in the specialty.

Posterior Urethral Valves, Unilateral Vesicoureteral Reflux, and Renal Dysplasia (VURD) Syndrome: Long-Term Longitudinal Evaluation of the Kidney Function.

The presence of unilateral vesicoureteral reflux (VUR), and renal dysplasia associated with posterior urethral valves (PUV) (VURD syndrome) was believed to represent a pressure-released pop-off mechanism protecting kidney function. We aimed to investigate its role with respect to long-term kidney function in a cross-sectional and longitudinal analysis. We compared the iohexol glomerular filtration rate (GFR) measured at 5 (GFR5) and 10 (GFR10) years of age in children with (Group A) and without (Group B) VURD syndrome, who underwent PUV resection under 2 years of age. VURD syndrome was diagnosed in cases of unilateral loss of kidney function (<15% on nuclear medicine test) associated with ipsilateral grade IV-V VUR. VURD syndrome was diagnosed in 16 (12.8%) out of 125 patients who met the inclusion criteria. While the median GFR5 was similar in the 2 groups [Group A: 87.3 (74.7-101.2) mL/min/1.73 m2 vs. Group B: 99.6 (77-113) mL/min/1.73 m2, p-value: 0.181], the median GFR10 values were significantly lower in children with VURD syndrome [Group A: 75.7 (71.2-85.9) mL/min/1.73 m2 vs. Group B: 95.1 (81.2-114.2) mL/min/1.73 m2, p-value: 0.009]. Similar results were obtained in a longitudinal analysis of the children with GFR measurement available both at 5 and 10 years of age [GFR5 in Group A: 93.1 (76.9-103.5) mL/min/1.73 m2 vs. Group B: 97.5 (80-113) mL/min/1.73 m2, p-value: 0.460; GFR10: Group A: 71.9 (71.9-85.9) mL/min/1.73 m2 vs. Group B: 94.8 (81.5-110.6) mL/min/1.73 m2, p-value: 0.024]. In conclusion, VURD syndrome does not show a protective role in kidney function preservation. On the contrary, it seems to be associated with a deterioration of the kidney function on a long-term follow-up.

Morbidity following suprapubic line insertion for videourodynamics in children.

INTRODUCTION: Previously in our unit, urodynamics were delayed after insertion of suprapubic (SP) lines. We postulated that performing urodynamics on the same day as SP line insertion would not result in increased morbidity. We retrospectively compared complications in those having urodynamics on the same day against those who had delayed urodynamics. PATIENTS AND METHODS: Notes were reviewed for patients undergoing urodynamics via SP lines from May 2009 until December 2018. In 2014 we modified our practice to allow urodynamics on the same day as SP line insertion in some patients. Patients undergoing videourodynamics would have two 5 Fr (mini Paed) SP lines inserted under general anaesthesia. Patients were divided into two groups: those that had urodynamics on the same day as SP line insertion and those that had urodynamics after an interval of more than one day. The outcome measure was the number of problems affecting those in each group. The two groups were compared using Mann-Whitney U tests and Fisher's Exact tests. RESULTS: There were a total of 211 patients with a median age of 6.5 years (range three months to 15.9 years). Urodynamics were performed on the same day in 86. Delayed Urodynamics were performed at an interval of more than one day in 125. Adverse events included pain or difficulty with voiding, increased urinary frequency, urinary incontinence, leak from catheter site, extravasation, extension of in-patient stay, visible haematuria, urethral catheterisation, and urinary tract infection. Problems affected 43 (20.4%) children. In the same day group, 11 (13.3%) patients had problems, in the delayed group 32 (25.6%) had problems; this was statistically significant (p = 0.03). The difference in combined incidence of important problems (requiring urethral catheterisation, extended admission or abandonment of urodynamics) was not statistically significant between the two groups. CONCLUSION: When using suprapubic catheters for urodynamics there is no additional morbidity when catheters are inserted on the same day as the urodynamics study compared to when urodynamic are delayed.

Posterior urethral valves and urachal cyst: an unusual combination.

Combination of posterior urethral valves and urachus remnants has been described as rare occurrence. We report a case of a baby boy with normal antenatal scans, in whom the presence of large urachal cyst and posterior urethral valves causing high pressure bladder and chronic kidney disease was found. The patient underwent ablation of posterior urethral valves at 23 days of life and urachal cyst removal at age of 4 and a half months.

Spontaneous bladder rupture secondary to posterior urethral valves in a boy with Down syndrome.

We describe a case of a 3-year-old boy with Down syndrome who developed a bladder rupture as a consequence of an undiagnosed posterior urethral valve (PUV). He had a history of urinary tract infections and constipation and was acutely admitted in poor condition and underwent laparotomy that revealed peritoneal sepsis secondary to bladder perforation. Bladder was drained using a suprapubic catheter and the condition of the boy gradually improved. Once stable, a cystourethroscopy confirmed the presence of PUV. Video-urodynamic studies performed at the check cystoscopy showed the bladder to be of reduced compliance (end fill pressure at 100 mL fill 30 cmH2O) with raised voiding pressures (76-100 cmH2O) and significant incomplete bladder emptying. Currently, the patient is doing very well, serum creatinine has normalised, he is infection-free and thriving; his bladder is managed with a vesicostomy.

Native nephrectomy in the management of hypertension in children with kidney disease: a tool to improve blood pressure control.

AIM: Hypertension in children with abnormal kidneys often requires multiple antihypertensive agents (complex), or could present with complications (e.g. hypertensive encephalopathy). Our objective in this report is to evaluate blood pressure control following unilateral or bilateral laparoscopic native nephrectomy in children with renal hypertension. MATERIALS AND METHODS: Single-centre retrospective review of all children who underwent nephrectomy for management of hypertension over a recent study period (2008-2017) with post-operative follow-up of at least 3 years. We describe the association of age, primary kidney disease and blood pressure and its management including time to resolution following unilateral or bilateral nephrectomy. RESULTS: During the 9-year study period, 21 of 215 (9.8%) children underwent nephrectomy for management of hypertension. We included 19 children [6 with unilateral native nephrectomy (UNN) and 13 with bilateral native nephrectomy (BNN)] in this study as they continued with their follow-up at our centre. Out of the 19 children, 15 had laparoscopic retroperitoneoscopic nephrectomies and 4 had laparoscopic transperitoneal nephrectomies. Six children had unilateral nephrectomy and 13 children had bilateral nephrectomies [7 were pre-transplant (haemodialysis-6, peritoneal dialysis-1) and 6 were post-kidney transplant]. Fifteen of 19 children (79%) had complete resolution [5 UNN and 10 BNN] and 3 (16%) partial resolution [1 UNN and 2 BNN]. One patient with BNN was observed to have no change in blood pressure control. CONCLUSION: Our data demonstrate improved management of hypertension in 95% of the children. Nephrectomy could offer a reasonable treatment option for selected group of complex and complicated renal hypertension.

Urodynamic Outcomes in Children after Single and Multiple Injections for Overactive and Low Compliance Neurogenic Bladder Treated with Abobotulinum Toxin A.

PURPOSE: Intradetrusor botulinum toxin is an established part of the treatment pathway for pediatric patients with neurogenic bladder. We determined the urodynamic effect of single and multiple administrations of abobotulinum toxin A in pediatric patients with neurogenic bladder, and determined the urodynamic efficacy of abobotulinum toxin A in low compliance vs overactive bladders. MATERIALS AND METHODS: We conducted a single center retrospective review of all pediatric patients with neurogenic bladder treated with abobotulinum toxin A. Videourodynamic data on cystometric capacity, maximum neurogenic detrusor overactivity pressure and compliance were gathered before and after the first abobotulinum toxin A administration and after the last administration. Patients were divided into low compliance and overactive bladder groups depending on initial videourodynamics findings. Paired t-test was used to compare videourodynamic outcomes before vs after abobotulinum toxin A injection. The Mann-Whitney U test was used to compare bladder groups. RESULTS: A total of 30 patients were included in the study. Of these patients 15 (50%) received multiple abobotulinum toxin A injections. There were 16 patients (53%) with overactive bladder. Abobotulinum toxin A administration significantly improved cystometric capacity (p <0.0001) and maximum neurogenic detrusor overactivity (p=0.0001). Overall, compliance did not change significantly (p=0.25). There was no significant difference in urodynamic parameters between first and last abobotulinum toxin A injections. Improvement in cystometric capacity (p=0.05) and maximum neurogenic detrusor overactivity (p=0.25) was similar between the low compliance and overactive bladder groups. Compliance significantly improved in the low compliance group vs the overactive bladder group (p=0.016). CONCLUSIONS: Intradetrusor abobotulinum toxin A improves cystometric capacity and maximum neurogenic detrusor overactivity in pediatric patients with neurogenic bladder. This effect is maintained over multiple injections. Compliance is significantly improved in patients with low compliance bladder vs overactive bladder.

Nephrotic syndrome in infancy can spontaneously resolve.

Nephrotic syndrome in the first year of life (NSFL) is a heterogeneous group of disorders, the management of which is supportive, as most patients do not respond to immunosuppression. Prognosis is guarded, as the syndrome tends to lead to end-stage renal failure. We describe four cases, all of which went into spontaneous remission. These patients had severe nephrosis that began postnatally at ages 15 days to 7 months and had preceding symptoms of viral infections. One infant had proven pertussis and required ventilation for respiratory failure. Renal biopsies showed varying degrees of mesangial expansion and increased cellularity. Two biopsies showed mild mesangial sclerosis and the other two only scattered globally sclerosed glomeruli. Supportive treatment was started with 20% albumin infusions, diuretics, penicillin, and thyroxine. Angiotensin-converting enzyme (ACE) inhibitors were used to reduce proteinuria in all infants, and one was also treated with indomethacin. The nephrosis gradually resolved, and protein-lowering medications were successfully weaned completely 5-30 months after presentation. The patients were protein free with normal renal function at last follow-up. Investigations including viral studies and autoimmune profiles were negative. Genetic studies for NPHS1, NPHS2, WT1, and LAM-ß were negative. We therefore describe a subgroup of NSFL with good prognosis associated with infectious prodromes. This is also the first-described case of pertussis causing nephrotic syndrome.

Collapsing glomerulopathy in a girl with systemic lupus erythematosus.

Collapsing glomerulopathy has increasingly been recognised in patients with conditions other than HIV. The non-HIV form of collapsing glomerulopathy generally shows little response to standard therapies. We describe a 12-year-old girl with a pre-existing diagnosis of systemic lupus erythematosus presenting with renal failure. A renal biopsy gave the histological diagnosis of collapsing glomerulopathy with evidence of "full-house" immunostaining. We propose collapsing glomerulopathy in her case, as no other cause was found was secondary to systemic lupus erythematosus. The immunophenotype of her podocytes suggested a partial de-differentiation that might have been important in her partial response to immunosuppression.