Lower urinary tract dysfunction in pediatrics progress to kidney disease in adolescents: Toward precision medicine in treatment

Table 1 Management of neurogenic bladder dysfunction to prevent upper tract deterioration

Management of neurogenic bladder dysfunction in children
Ref.	Mode of action and advantages	Limitations
CIC[8-11]	Enable complete bladder emptying and prevent high bladder pressure and urinary tract infection	Required proper education and compliance, pediatrics and some children are not able to perform CIC
Oral oxybutynin[12]	Antimuscarinic, suppress detrusor hyper-reflexia, prevent high pressure	Dry mouth, abdominal pain that leads to discontinuation of treatment. Limited availability of liquid oxibutynin for children. Risk to develop dementia
Intravesical oxybutynin[13-21]	Intravesical oxybutynin chloride combined with hydroxypropyl cellulose leads to mucosal adhesion and minimal side effects	Administered with urethral catheter twice daily
Solifenacin succinate[22-31]	Works against muscarine receptors in detrusor muscles, relaxes it and decreases intravesical pressure. It is a competitive muscarinic receptor antagonist. Available as one daily oral suspension and is used in pediatric population	Minimal adverse effects
Tolterodine[32]	Antimuscarinic and calcium channel modulating properties. Available for children as a solution or as tablet. Oral solution is available for children from 5-16 yr	Low incidence of adverse effects (1.5%)
Propiverine hydrochlorid[33,34]	Antimuscarinic and calcium channel modulating properties. Low incidence of adverse events. Superior tolerability over oxybutynin	Minimal adverse effects
Trospium chloride[35,36]	Antimuscarinic and calcium channel modulating properties. Dosage 10-45 mg administered three times per day. Is tolerated by children	Minimal adverse effects
Mirabegron	β3-adrenoceptor agonist, demonstrated to be effective in adults with overactive bladder	Still not approved for children
Onabotulinum toxin A (Botox—BTX-A)[45-48]	Is injected in the detrusor muscle, leading to fits relaxation. The dose should not exceed 6 U/kg, ranging from 50, 100 and 200 U. 200 U are a well-tolerated and effective treatment for children aged 5–17 yr with NBD. Patients may be considered for reinjection when the clinical effect of the previous injection diminishes (median 6-12 mo in most children)	Repeated injections are safe and effective in children
Neural stimulations[49-54]	Sensory fibers in the pudendal nerve (afferents) innervates the urethra sensation of urine flow. This will lead to reflex generation of positive feedback to enhance bladder contraction in amplitude and duration and inhibit contraction of the external urethral sphincter. Electrical activation of pudendal nerve afferents provides a new approach to restore efficient bladder emptying. Long-term outcome in children showed good results maintained for 2 yr	Maintenance treatment was necessary in 29% of children. Cost-effective as a primary treatment
Vesicostomy[55-62]	Patients with impaired renal function before kidney transplantation would improve or stabilize kidney function after vesicostomy. The long-term outcomes of vesicostomy in NBD patients are effective in reversing the deleterious consequences when conservative treatment fails	Vesicostomy is an incontinent abdominal stoma. The child will have a social embarrassment
Renal transplantations[63-65]	Children with renal insufficiency due to NBD can receive a renal allograft and achieve good long-term results. Correction of structural urogenital abnormalities and optimization of emptying and storage functions of the bladder has to be achieved before renal transplantation	There is no one technique for the urinary drainage of the lower urinary tract, it should be individualized for each case

CIC: Clean intermittent catheterization; NBD: Neurogenic bladder dysfunction.