Causes and management of urinary system problems in children on long-term home invasive mechanical ventilation
Abstract
Many ventilator-dependent children have comorbid conditions including urinary tract disorders. We aimed to present a focused review of the literature describing the causes and management of urinary system problems in children with long-term home mechanical ventilation. We performed a literature search in PubMed/MEDLINE, Scopus, and Web of Science with keywords “children,” “home mechanical ventilation,” “urinary system,” “urinary tract,” “neurogenic bladder,” “clean intermittent catheterization,” “urinary tract infection,” “urolithiasis,” and “acute kidney injury.” We included original articles, reviews, guidelines, and case reports published in English. Ventilator-dependent children may have neurogenic bladder/bowel dysfunction which renders them prone to urinary tract infection, high bladder pressure, vesicoureteral reflux, hydronephrosis, and renal dysfunction. These children require bladder catheterization, medications affecting parasympathetic/sympathetic nervous systems, or surgical procedures to prevent urinary infections, and to maintain continence and renal functions. However, bladder catheterization or surgical procedures like augmentation cystoplasty may also be complicated with urinary infections, urolithiasis, or urethral strictures. Urolithiasis frequency is also increased due to immobilization-related hypercalciuria, hypocitraturia caused by antiepileptic drugs, urinary stasis, and urinary infections. On the other hand, mechanical ventilation can impair renal function by reduction of cardiac output, redistribution of intrarenal blood flow and stimulation of sympathetic and hormonal pathways. Children requiring long-term invasive home mechanical ventilation may have other comorbid conditions, including urinary system diseases, which become manifest as these patients are being kept alive due to the advances in ventilation strategies. These children must be carefully observed for urological complications and managed accordingly to prevent kidney injury.
1 INTRODUCTION
In the past few decades, increasing number of children have received noninvasive or invasive home mechanical ventilation (HMV).1 Children requiring invasive ventilation constitute a diverse group of patients, including congenital airway malformations, upper airway obstruction, advanced pulmonary disease, neuromotor disease, or defects in respiratory drive (Table 1).2-4
| Central respiratory control disorders | Congenital central hypoventilation Brain tumors |
| Neuromuscular diseases | Muscular dystrophies Spinal muscular atrophy Congenital myopathy Spinal cord injury |
| Chest wall deformity | Kyphoscoliosis |
| Airway diseases | Tracheomalacia, tracheal stenosis Craniofacial malformations Obstructive sleep apnea |
| Lung diseases | Chronic lung disease of prematurity Cystic fibrosis |
| Mixed disorders | Cerebral palsy Mucopolysaccharidosis |
Many ventilator-dependent children also have other comorbid conditions with their own set of intensive health care needs involving dependence on non-respiratory technologies (e.g., dialysis, bladder catheterization, ventriculoperitoneal shunt, gastrostomy tube) and different subspecialists like nephrology, gastroenterology, and neurology.2 Thus, these children have complex healthcare needs resulting in medical fragility and functional limitations. It is the longevity of the diseases and malformations in those patients that cumulatively produce the problems, whom are now being kept alive due to the advances in ventilation strategies, including HMV.1
2 URINARY SYSTEM PROBLEMS IN CHILDREN WITH HMV
Many ventilator-dependent children are immobile, constipated, and need bladder catheterization due to neurogenic bladder (NB). These children are at risk for urolithiasis, urinary tract infection (UTI), vesicoureteral reflux (VUR), or upper tract deterioration leading to chronic kidney disease (CKD) (Table 2). We aimed to describe the causes and management of urinary system problems in children with HMV and to present a focused review of the literature on this subject.
Search strategy
We performed a literature search in PubMed/MEDLINE, Scopus, and Web of Science with keywords “children,” “home mechanical ventilation,” “urinary system,” “urinary tract,” “neurogenic bladder,” “clean intermittent catheterization,” “urinary tract infection,” “nephrolithiasis,” “urolithiasis,” and “kidney injury.” We included original articles, reviews, guidelines, and case reports published in English.
| Problem | Etiology |
|---|---|
| Urine incontinence | Neurogenic bladder dysfunction |
| Urinary tract infection | Neurogenic bladder dysfunction Constipation Bladder catheterization (indwelling/clean intermittent) |
| Urinary stone disease | Immobilization related hypercalciuria Medications Gastrostomy feeding Urinary tract infection Augmentation cystoplasty |
| Acute kidney injury | Mechanical ventilation related |
| Chronic kidney disease | Obstructive uropathy due to neurogenic bladder/urolithiasis Vesicoureteral reflux due to neurogenic bladder Urinary tract infection |
2.1 Neurogenic bladder
Many children requiring HMV also had neurological disorders leading to bladder dysfunction. The most common cause of NB in children is neurospinal dysraphism. Among other causes are spinal cord injuries, and central nervous system abnormalities including cerebral palsy.5
Children with NB can present with detrusor-sphincter dyssynergia characterized by the inability to empty the bladder, incontinence, UTIs, and VUR. Patients who do not receive proper management develop severe complications in the upper urinary tract leading to renal failure requiring dialysis and/or transplantation.5-7
- 1.
Recurrent febrile UTIs where previously identified or newly diagnosed VUR may indicate a deteriorating bladder.
- 2.
Abnormal bladder contour suggesting a neurogenic cause in an otherwise neurologically intact child.
- 3.
Development of hydroureteronephrosis.
- 4.
Change in continence.
- 5.
Suspicion of progressive spinal cord tethering.
- 6.
Evaluating the response to therapy.8
The main goals of treatment are preservation/improvement of renal function, prevention of UTIs, and urinary tract deterioration. Clean intermittent catheterization (CIC) is the preferred method of management in urinary retention. Anticholinergics are the first-line drugs for treating detrusor overactivity. When these fail, surgical interventions are considered.9, 10
2.1.1 Clean intermittent catheterization
CIC provides a method of emptying the bladder at regular intervals. There are a variety of catheters ranging from standard polyvinylchloride and latex catheters, to hydrophilic or antimicrobial-coated catheters.11 CIC reduces bladder pressure, eliminates post-voiding volume, preserves renal function, and improves urinary incontinence.6 Delay in starting CIC is associated with recurrent febrile UTIs.10 CIC itself, on the other hand, is associated with several complications like UTI, trauma, meatal stenosis, urethral stricture, and even bladder perforation reducing patient compliance.12 Among 28 boys and young adult males with NB, macroscopic hematuria, major urethral lesions, and epididymitis were reported in 19, 5, and 1 patients, respectively.13 Recently, 41 of 141 patients with NB including children were reported to have febrile genitourinary infections: 32 pyelonephritis, 10 epididymitis, and 1 prostatitis.10 However, CIC-related UTI risk is less compared with indwelling catheterization. Thus, CIC should be considered as an alternative to short-term or long-term indwelling urethral catheterization.14
Performing CIC only three times/day is associated with a fivefold increased UTI risk compared with six times/day due to high residual bladder urine. Thus, CIC should be performed no less than four times to sufficiently reduce residual urine volume.14 CIC four to six times/day is recommended for children with NB to empty the bladder regularly.10
A Cochrane review shows that UTI incidence is neither affected by the use of sterile or clean technique; coated or uncoated catheters; single or multiple-use of catheters; the individual performing CIC (child/guardian); or by any other strategy.15 There is a trend to reduce potentially pathogenic bacteria by hydrophilic catheters.16 However, based on the current data, no statement can be made, that one catheter type, technique, or strategy is better than the other.9
Complications of CIC, like UTI and urinary tract trauma, usually occur in the early stages due to poor technique by the caregiver reducing the patients' compliance with CIC. Therefore, caregiver education is essential to establish appropriate CIC technique, to minimize complications, and to improve compliance with CIC.9
2.1.2 Indwelling catheter
Some children may require an indwelling catheter due to limited assistance from a caregiver or being clinically unstable. The complication rate is higher in indwelling catheters than in other methods of bladder management. Bladder capacity and compliance decrease over time due to constant decompression, and catheter-related infections leading to bladder wall fibrosis.17
2.1.3 Anticholinergic medication
Detrusor overactivity causes a high-pressure bladder, which is dangerous for the upper urinary tract. Antimuscarinic/anticholinergic drugs reduce detrusor overactivity, lower the intravesical pressure and the rate of renal deterioration.18 Therefore, anticholinergics should be started if detrusor overactivity is demonstrated in the urodynamic study.9, 19 Oxybutynin is the most frequently used anticholinergic in children with >90% success rate. It binds to M1-M2-M3 muscarinic receptors within the bladder. It can be given by oral, transdermal, or intravesical routes. However, its use is limited by dose-dependent side effects (mouth dryness, flushing, blurred vision, heat intolerance, constipation, impaired cognitive function, etc.) in up to 76% of the patients.20 The dosage is 0.1–0.4 mg/kg/day in three doses. Intravesical administration (0.1-0.8 mg/kg/day in three doses) avoids the first-pass hepatic effect causing higher bioavailability, less metabolites, and less side effects.20 Tolterodine, solifenacin, trospium chloride, and propiverine are the other anticholinergic drugs that have been used safely in children. However, all antimuscarinics are still off-label use in neonates and young children.9 Tolterodine was developed as a nonselective antagonist of muscarinic receptors to treat overactive bladder. It displays functional selectivity for the urinary bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity.21 Extended-release capsules are effective in children with NB. Solifenacin is an M3 selective antimuscarinic and is well tolerated even in long-term treatment.17
ß3 agonists like mirabegron may be an alternative agent in patients with NB.22-24 It has been approved by FDA for the treatment of neurogenic detrusor overactivity in children >3 years of age in 2021. Mirabegron has similar efficacy, but lower rates of side effects compared to antimuscarinic agents.17
2.1.4 Drugs decreasing bladder outlet resistance
Selective and nonselective alpha-blockers like doxazosin (0.5–1.0 mg) or tamsulosin hydrochloride (0.4–0.8 mg) have been used to treat detrusor-sphincter dyssynergia and to lower bladder pressure during voiding with variable efficacy. These drugs facilitate bladder emptying causing a low-pressure bladder and creating a safer situation for the kidneys.9, 17, 25
2.1.5 Surgical management of NB
- o
Incontinent procedures for preserving renal function
| Procedure | Indications | Complications |
|---|---|---|
| I. Incontinent procedures for preserving renal function | ||
| Cutaneous vesicostomy | In young children, when CIC and anticholinergics are ineffective | Requires diaper, skin irritation, negative social implication |
| Suprapubic cystostomy | When a long-term indwelling catheter is needed | Adverse effects on bladder epithelium, bladder cancer |
| Ileovesicostomy | As cutaneous vesicostomy | High residual urine with predisposition to UTIs |
| Incontinent intestinal diversions | Hydronephrosis with renal deterioration | Ureteroileal stenosis, stoma stenosis, excessive conduit length |
| Procedures to decrease external sphincter resistance (sphincterotomy/botulinum toxin injection) | Continuous bladder drainage | Skin breakdown, ulceration, infection |
| II. Continent procedures that achieve continence and low bladder pressure | ||
| Botulinum toxin injection to the detrusor | Detrusor overactivity with poor response to anticholinergics and noncompliance with CIC | Temporary; insufficient to ensure upper tract protection |
| Bladder augmentation | When conservative measures, including botulinum toxin, fail to keep a low-pressure bladder with good capacity and compliance | Urinary calculi, metabolic acidosis, bladder perforation, febrile UTIs, nutritional deficiencies, tumors |
| Continent catheterizable channel (Mitrofanoff appendicovesicostomy) | When self-catheterization is not feasible | |
| III. Procedures to increase bladder outlet resistance | ||
| Injection of bulking agents, periurethral slings, artificial urinary sphincters, bladder neck reconstruction, bladder neck closure, urethral lengthening | Lower-level spinal cord injury leading to intermittent or constant incontinence | High failure rate especially in urethral bulking agents |
- Abbreviations: CIC, clean intermittent catheterization; UTI, urinary tract infection.
Cutaneous vesicostomy
Cutaneous vesicostomy protects the kidneys in infants and young children with NB when CIC and anticholinergics are ineffective or not feasible.17 However, it requires diapers, and is associated with skin irritation and negative social implications. Thus, it is only a temporary measure.
Suprapubic cystostomy
Long-term use of indwelling catheters increases the risk of bladder cancer. They are used rarely after the introduction of CIC. In these rare situations, suprapubic cystostomy is an alternative to urethral catheter, providing a theoretical advantage of the avoidance of genital lesions caused by prolonged urethral catheterization. However, there is no evidence of the superiority of suprapubic cystostomy over urethral catheterization.17
Ileovesicostomy
Ileovesicostomy, interposition of an ileal segment between the bladder and the skin, has the advantage of placing the stoma in the lower abdomen, where it can be fitted with a collection bag. The main disadvantage is high residual urine with the potential for UTIs. It is a viable approach in children who are physically/socially unable to handle catheterization.26
Incontinent intestinal diversions
The indications for an ileal or colon conduit include hydronephrosis with decreasing renal function and inability for effective bladder catheterization. Complications include deterioration of renal functions caused by ureteroileal stenosis, stoma stenosis, and excessive conduit length.17
Urinary diversion through intestinal segments also causes some metabolic complications (Table 4). Reduction of intestinal absorptive surface may cause diarrhea, dehydration, and acidosis. Terminal ileum is not routinely used due to bile-salt and vitamin-B12 malabsorption leading to deficiency of fat-soluble vitamins and vitamin-B12. Exposure of bowel to urinary solutes causes acidosis and electrolyte abnormalities. The most common metabolic change is hyperchloremic metabolic acidosis due to reabsorption of ammonium and secretion of bicarbonate through the intestinal epithelium. Other abnormalities include hypokalemia, hyperchloremia, hypocalcemia, hyperammonemia, and elevated serum creatinine. The use of stomach may lead to hypokalemia, hypochloremia, and metabolic alkalosis, especially in the presence of baseline renal dysfunction. Bone metabolism is also altered due to malabsorption of calcium and vitamin D; mobilization of calcium, carbonate, and sodium to buffer chronic metabolic acidosis; and impaired renal activation of vitamin D due to acidosis. Bone demineralization is most important in growing children. Urolithiasis risk is also increased in these patients because of dehydration, urine stasis, intestinal mucus secretion, hypercalciuria due to bone dissolution, and hyperoxaluria due to fat malabsorption.27, 28
| Metabolic complications |
|---|
| Diarrhea |
| Malabsorption |
| Hyperchloremic metabolic acidosis |
| Electrolyte abnormalities |
| Bone demineralization |
| Stone formation |
| Renal and hepatic function |
| Impaired drug metabolism |
Procedures to decrease bladder outlet resistance
- o
Continent procedures that achieve continence and low bladder pressure
Injection of botulinum toxin
Children with detrusor overactivity and poor compliance for CIC or unresponsive to anticholinergics are treated with intravesical botulinum-toxin A injection to reduce intravesical pressure and provide continence. There are several botulinum-toxin A formulations possessing individual potencies and different, although sometimes overlapping, indications like cervical dystonia, laryngeal dystonia, primary axillary hyperhidrosis, sialorrhea, blepharospasm, chronic migraine, upper-limb spasticity and neurogenic detrusor overactivity: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®) and incobotulinumtoxinA (Xeomin®). Dose ratio is 2–3:1:1 for Dysport®, Botox®, and Xeomin®, respectively. There are no significant differences in safety and efficacy among them. Xeomin®, free of complexing proteins, was suggested to have greater efficacy with reduced sensitization risk. However, its clinical significance has not been determined.29-31
The best pharmacological result is achieved when the neurotoxin reaches all the nerve terminals innervating the target muscle(s). Thus, botulinum-toxin-induced paralysis develops after 2–3 days from injection and reaches its maximum within 1–2 weeks. Paralysis maintains this level for a variable period depending on the anatomic site. Its effect gradually declines to the original level within 3–4 months for skeletal nerves and about 1 year for autonomic ones. The gradual recovery of neuronal activity is attributed to two phenomena: First, growth factor secreted by denervated muscle causes the development of axonal sprout producing temporary reinnervation (early recovery phase). Second, vesicular neurotransmitter release returns to the original nerve terminal (late recovery phase). However, repeat treatments may yield sustained efficacy.29, 30
OnabotulinumtoxinA is more effective in overactive bladders than in noncompliant bladders without contractions. Initially, improved capacity and compliance with reduced detrusor pressure for up to 10 months were reported. Recent studies report a 33%–45% increase in capacity with a similar decrease in detrusor pressure which is insufficient to ensure upper tract protection in significant bladder dysfunction.17, 32
Other indications of botulinum-toxin in children with HMV include sialorrhea, dystonia, and spasticity.30 Adverse effects of botulinum-toxin in children with cerebral palsy include procedural/focal adverse effects, flu-like symptoms, and asthenia. However, respiratory symptoms and respiratory tract infections are the most frequent adverse events.33
Bladder augmentation
Enterocystoplasty using ileal or sigmoid segments increases bladder capacity and compliance. Prerequest for this procedure is the acceptance and ability to perform CIC by parents. Although enterocystoplasty is urodynamically effective, it has many complications, including urolithiasis, metabolic acidosis, bladder perforation, febrile UTIs, nutritional deficiencies, and development of tumors.17, 34
Continent catheterizable channel
- o
Procedures to increase bladder outlet resistance
Children with lower-level spinal cord injury may demonstrate normal bladder volumes but reduced bladder outlet resistance leading to incontinence. No available medical treatment like α-adrenergics has been validated to increase bladder outlet resistance. Procedures to increase outlet resistance include injection of bulking agents into bladder neck or proximal urethra, periurethral slings, and artificial urinary sphincters.17 Bladder neck reconstructive operations like Young-Dees-Leadbetter technique, bladder neck closure, and urethral lengthening procedures (Pippi-Salle or Kropp) have also been used for neurogenic incontinence.35-37 Bladder neck procedures may necessitate bladder augmentation and a continent catheterizable stoma to prevent upper tract damage.25
2.2 Constipation
Children with NB usually also have neurogenic bowel dysfunction leading to chronic constipation with stool incontinence which has an even greater impact on quality of life. Constipation is also associated with UTI due to improper filling and voiding caused by pressure on the bladder. Diet with small-portioned fiber food and adequate fluid intake is advocated.25 Regular bowel emptying is important. The bowel regimen includes mild laxatives (mineral oil) combined with retrograde enemas. Rectal suppositories and digital stimulation by caregivers can also be used. Retrograde transanal irrigation reduces the risk of fecal incontinence.9 If transanal-irrigation becomes difficult or impossible due to anatomic/social circumstances, antegrade-irrigation using a MACE-stoma (Malone Antegrade Continence Enema), which can be placed in the left abdomen is an option. MACE-stoma provided successful bowel management in 70% of the patients. However, it is a time-consuming procedure taking at least 20–60 min. In addition, stomal complications (infection, leakage, stenosis) develop in two thirds of the patients and surgical revision is needed in one third.25
2.3 Urinary tract infections
In children with NB, catheter-associated UTIs are the most frequent complication with a prevalence of 40–60% and incidence of 1–10 UTIs/year.38 These children are subjected to multiple procedures, hospital admissions and non-urinary infectious complications leading to the acquisition of nosocomial strains and the development of resistant strains through antibiotic treatments.39
There is no consensus for prevention, diagnosis, and treatment of UTIs in these patients. CIC increases the possibility of bacteriuria by introducing microorganisms into the bladder.7 The catheter colonization increases by 3-10%/day after insertion.40 Asymptomatic bacteriuria, seen in >50% of children on CIC, does not require treatment.9, 41 Febrile UTI, on the other hand, is a risk factor for kidney damage. This risk increases with each new febrile UTI: 2.8%, 25.7%, and 28.6% after the first, second, and ≥3 infections, respectively.40, 42 Therefore, the risk of febrile UTIs must be minimized. Continuous antibiotic prophylaxis (CAP) has been reported to lower UTI recurrence in children with high-grade primary VUR.43 However, in children with NB, CAP did not prevent symptomatic UTIs and new renal scarring, but increased the risk of bacterial resistance.44 CAP might even increase the rate of symptomatic UTI.7 However, in the presence of recurrent febrile UTIs and VUR, CAP should be started.44 Cranberry capsules might also reduce the rate of bacteriuria and UTI.9
Because of the high prevalence of asymptomatic bacteriuria, the diagnosis of UTI in children with NB requiring CIC should rely on not only the growth of bacteria in the urine, but also the clinical signs, such as cloudy urine, abdominal or flank pain, and vomiting, as well as exclusion of other sources of infection which are common in this fragile population.7
2.4 Vesicoureteral reflux
Persistent functional obstruction with high bladder pressure can disrupt the ureterovesical junction resulting in the development of VUR which, in association with CIC-related bacteriuria, allows the bacteria to reach the kidney leading to pyelonephritis.7 Therefore, the treatment is primarily related to bladder dysfunction. CIC and medical therapy resolve VUR in 30%–50% of patients and may also reverse the bladder remodeling caused by elevated bladder pressure.45 However, ureteral reimplantation should be considered in the presence of low-pressure high-grade reflux. Endoscopic treatment has a failure rate of up to 75% after a median follow-up of 4.5 years. Open surgical ureteroneocystostomy techniques have a higher success rate but increase the risk of ureterovesical obstruction.9
2.5 Upper urinary tract injury
Patients requiring mechanical ventilation have increased risk of kidney injury both due to the underlying neurogenic disease-associated lower urinary tract dysfunction and to mechanical ventilation itself.
2.5.1 Kidney injury due to lower urinary tract dysfunction
High intravesical pressure and hydronephrosis can cause renal failure in NB.46 The incidence of this complication is significantly lower in patients performing proper CIC compared with those using other bladder emptying methods.47 Another cause of renal failure is high-pressure VUR. Prevention of high intravesical pressure, residual urine volume, and febrile UTIs by CIC, anticholinergics, CAP or surgical correction of high-grade VUR may decrease the incidence of upper tract deterioration.9
2.5.2 Kidney injury due to mechanical ventilation
Mechanical ventilation can alter renal function by several mechanisms including reduction of cardiac output, redistribution of intrarenal blood flow, and stimulation of sympathetic/hormonal pathways.48
Cardiovascular changes
Positive intrathoracic pressure inhibits venous return to the heart decreasing the effective circulating volume (preload) and increasing the inferior venacaval pressure with resultant renal congestion. Compression of pulmonary and mediastinal vasculature, on the other hand, results in increased right ventricular afterload. These alterations decrease cardiac output and renal perfusion.49
Intrarenal changes
Positive-pressure ventilation causes the release of vasoactive mediators resulting in redistribution of intrarenal blood flow from cortical to juxtamedullary nephrons. This, in turn, leads to reduction in glomerular filtration and increased sodium reabsorption which requires high oxygen utilization.49
Hormonal changes
Shift of blood from the intrathoracic vessels to the abdomen decreases atrial pressure activating stretch receptors and release of antidiuretic hormone which mainly acts as a vasopressor in response to decreased blood pressure. Decreased distal sodium delivery and increased β-sympathetic stimulation increase renin release which in turn stimulates aldosterone secretion and sodium retention in ventilated patients. Decreased atrial pressure also inhibits atrial natriuretic peptide secretion contributing to reduced natriuresis and urine volume. Altered metabolism of endothelin and nitric oxide also contributes to directing intrarenal blood flow from cortex to medulla. However, the specific roles of these hormones and peptides remain uncertain.49
Urine biomarkers like tissue inhibitor of metalloproteinase 2, insulin-like growth factor binding protein-7, mitochondrial DNA, and ATP synthase subunit-β have been investigated for early detection of ventilator-associated kidney injury and help in selecting patient-specific mechanical ventilation.50 Noninvasive ventilation reduces cardiovascular risk by improving endothelial function.48
2.6 Urinary stone disease
Immobilization due to fractures, paralysis, or motor disability causes resorption of the skeleton resulting in hypercalcemia and hypercalciuria.51 Immobilization-related bone loss is more severe in children due to the increased bone metabolism in growing organisms. Immobile children are 10 times more likely to develop recurrent urolithiasis.52 Thus, calcium metabolism in immobile children should be followed up routinely. In addition, these patients are prone to UTIs that can cause alkaline urine with predisposition to struvite or calcium-phosphate calculi.53 Immobility and UTIs in children with spinal injury increase the stone risk from 1.9% to 9.4% after 5 and 20 years, respectively.17
Many children with HMV also require gastrostomy for proper feeding. These children do not have a typical pediatric diet and do not self-regulate their water intake according to thirst. In one study, gastrostomy-fed children had higher urine pH and 64% of them formed calcium phosphate calculi.54 With frequent co-morbid neurological conditions, Gastrostomy-fed children may also be prescribed lithogenic drugs like the antiseizure medications topiramate or zonisamide that inhibit carbonic anhydrase activity leading to hypocitraturia, metabolic acidosis, alkaline urine, and an increase in the formation of calcium phosphate stones.55
Surgical treatment of the NB by augmentation cystoplasty using certain bowel segments further increases the rate of bladder calculi development to about 50%. Recurrence rates are also quite high, with 50% of patients experiencing a recurrent stone within 5 years.56
2.6.1 Treatment
Medical treatment
Hydration and diet
Hydration should be encouraged in all patients to decrease urinary supersaturation. A low sodium diet (<2–3 mEq/kg/d for young children and <2.4 g in adolescents) should be instituted because it decreases urinary calcium levels. Calcium intake must not be restricted in growing children. Besides, high-calcium diet was shown to decrease stone formation in adults. In adults, animal protein restriction decreases calcium oxalate production, but protein should not be restricted in children during periods of growth.57
Hypocitraturia
Citrate inhibits stone formation via various mechanisms. It forms complexes with calcium increasing its solubility. Hypocitraturia is one of the most common metabolic abnormalities along with hypercalciuria in stone-forming children, occurring in 20% to 60%.58, 59 Hypocitraturia is associated with acid–base disorders (renal tubular acidosis, diarrhea, malabsorption), hypokalemia, diet (animal protein, high sodium, ketogenic diet), genetic influence (vitamin D receptor polymorphisms), and medications (ACE inhibitors, acetazolamide, land ithium).59 Hypocitraturia and renal tubular acidosis are also seen in children treated with antiepileptic drugs inhibiting carbonic anhydrase enzyme.55, 59 Hypocitraturia is treated with potassium-citrate supplementation.60
Hypercalciuria
Immobilization-associated hypercalciuria constitutes an important risk factor of calcium-oxalate and calcium-phosphate stone development. Since the urine is hypersaturated, the use of indwelling catheters for long periods should be avoided in these patients. Potassium-citrate therapy may further reduce stone formation in hypercalciuric patients. The use of bisphosphonates like alendronate for preventing hypercalciuria was reported as a supportive/complementary measure for calcium nephrolithiasis in immobile patients.61
Surgical treatment
Expectant management is the initial approach in children with small asymptomatic stones (<4–5 mm) with the possibility of spontaneous passage. Medical expulsive therapy using α-blockers (tamsulosin and doxazosin) increases the rate of spontaneous ureteral stone passage with a low rate of adverse events in children aged 2–15 years with a distal ureteral stone of <10 mm. The dosage was 0.03 mg/kg/day for 3 weeks for doxazosin and 0.2–0.4 mg/day for 4–6 weeks for tamsulosin.62 One randomized controlled study in children aged 6–14 years showed higher efficacy of silodosin compared to tamsulosin.63 On the other hand, EAU and ESPU Guidelines state that the experience with medical expulsive therapy in children is limited showing different results.25 Nonsteroidal anti-inflammatory drugs, the first choice for pain relief in renal colic, have beneficial effects on the expulsion of urinary calculi.64
Currently, most pediatric stones can be managed by shock wave lithotripsy (SWL). Endoscopic treatment is used for ureter/bladder stones. Percutaneous removal or retrograde intrarenal surgery is also possible for kidney stones in children. Only a small proportion of children will require open surgery (Table 5). All stones should be removed if possible, since postoperative residual fragments pass spontaneously in only 20–25% of cases. If present, any obstructive uropathy should be managed together with stone removal therapy to prevent recurrence.62
| Stone size/location | Primary treatment | Secondary treatment |
|---|---|---|
| Staghorn | PCNL | Open surgery, SWL |
| Pelvis, <10 mm | SWL | RIRS, PCNL, micro-PCNL |
| Pelvis, 10–20 mm | SWL | PCNL, RIRS, micro-PCNL, open surgery |
| Pelvis, >20 mm | PCNL | SWL, open surgery |
| Lower pole calyx, <10 mm | SWL | RIRS, PCNL, micro-PCNL |
| Lower pole calyx, >10 mm | PCNL | SWL, micro-PCNL |
| Upper ureter | SWL | PCNL, URS, open surgery |
| Lower ureter | URS | SWL, open surgery |
| Bladder | Endoscopy |
- Abbreviations: PCNL, percutaneous nephrolithotomy; RIRS, retrograde intrarenal surgery; SWL, shockwave lithotripsy; URS, ureteroscopy (reference44).
3 CONCLUSION
Many ventilator-dependent children also have other major comorbid conditions that become manifest as these patients are being kept alive due to the advances in ventilation strategies, including HMV. Many children requiring invasive home ventilation are also immobile and have neurogenic bladder/bowel dysfunction. In addition, some of these patients might have seizures requiring antiepileptic drugs with predisposition to urolithiasis. All these accompanying abnormalities predispose these children to UTIs, urolithiasis, and upper urinary tract disorders that could result in CKD. Thus, these patients must be carefully observed for complications and managed accordingly to prevent kidney injury. Recommendations for children with bladder/bowel dysfunction are summarized in Box 1.
Box 1. Conclusions
-
Immobilization and bladder/bowel dysfunction can lead to urinary tract infections, urolithiasis, and upper urinary system deterioration.
-
Urodynamic studies should be performed to ensure low-pressure urine storage.
-
Low-pressure urinary storage may be provided by clean intermittent catheterization, medications, or surgery.
-
Adequate urinary drainage is needed to minimize urinary tract infections, urolithiasis, and upper urinary system deterioration.
AUTHOR CONTRIBUTIONS
Alper Soylu: Investigation; writing—original draft; methodology; writing—review and editing; Salih Kavukçu: Conceptualization; investigation; supervision; writing—original draft; writing—review and editing; methodology.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
All data relevant to the study are included in the article or uploaded as Supporting Information.
