Pediatric Kidney Stones—Avoidance and Treatment
Curr Treat Options Peds
Pediatric Kidney Stones-Avoidance and Treatment
David I. Chu
Gregory E. Tasian
Lawrence Copelovitch 2
0 Division of Urology and Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia , Philadelphia, PA , USA
1 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA
2 Division of Nephrology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA , USA
Nephrolithiasis I Medical expulsive therapy (MET) I Lithotripsy I Pediatric
Pediatric stone disease is increasing in incidence and healthcare costs. With more years
atrisk for stone recurrence during their lifetimes, children with nephrolithiasis constitute a
high-risk patient population that requires focused intervention through both medical and
surgical means. Through high-quality future studies to compare methods of stone
prevention and treatment, the burden of stone disease on the youngest members of society
may be ameliorated.
Nephrolithiasis in children has been increasingly
recognized as a major source of morbidity and cost
in the USA. The disease incidence has risen 6–
10 % annually over the last two decades (
1 , 2
with accompanying increases in frequency of
hospitalizations, emergency department (ED) visits,
a n d s u r g i c a l i n t e r v e n t i o n s (
1 , 3 , 4 , 5
Population-based observational studies have
estimated contemporary incidence to range from
36 to 145 per 100,000 children (
1 , 3, 4
study noted a more than fourfold increase in
incidence over a 12-year span (
). Of note, one
specific subpopulation of children that appears to be
at particularly higher risk is adolescent females (
3, 4 , 6
), though the etiology is not clear. Recent
estimates of the economic burden related to
pediatric nephrolithiasis have been $229 million
per year for hospital admissions and $146 million
per year for emergency room encounters (7). As a
result, this disease process has necessitated
strategies to optimize the evaluation and treatment
of children with kidney stones and to reduce
recurrence risk through preventive medical and dietary
Presentation and diagnosis
Children with nephrolithiasis may present clinically with a spectrum of
symptoms, depending on age (
). Localization of pain to the abdomen or flank is
easier in adolescents and older children, while younger children may have more
vague symptoms of nausea, vomiting, and irritability. Gross hematuria is not
uncommon. Patients may also be diagnosed with stones as an incidental
finding on imaging for other indications such as urinary tract infections (
In adults, use of computerized tomography (CT) with its inherent ionizing
radiation is broadly considered first-line in diagnosis of nephrolithiasis given its
excellent cross-sectional anatomic detail. Recently, however, a large
randomized-controlled trial comparing ultrasound versus CT scan in adults
with suspected nephrolithiasis showed no difference in 30-day complications
between the two modalities (
) with the ultrasound arm showing less
6month cumulative radiation exposure. Importantly, a secondary analysis of
patients in the CT arm of the trial demonstrated significant and inappropriate
variability in CT radiation dosages, further emphasizing the potential harms of
CT scans (
In children with suspected nephrolithiasis, due to the concern for
cumulative effects of radiation exposure, first-line imaging is a renal and bladder
ultrasound, with CT reserved for nondiagnostic results but high clinical
). The sensitivity, specificity, positive predictive value, and negative
predictive value of ultrasound for stone detection, compared to CT as the gold
standard, are 70, 100, 96, and 62 %, respectively. The stones that were missed by
ultrasound could be considered to be clinically insignificant in size (14). The
accuracy of ultrasound also may depend on stone location, with higher rates of
detection in the kidney as opposed to the ureter alone (
Despite the concerns of radiation exposure, ultrasound is infrequently used
as the initial imaging for suspected nephrolithiasis in children (
). Use of CT
as first-line imaging modality has been directly associated with nonteaching
hospitals and weekend ED visits (
), older age (
17, 18, 19
), and public
insurance status (
). On the contrary, certain EDs that utilized clinical care
pathways emphasizing ultrasound as first-line imaging were noted to have
lower odds of undergoing CT (
), as were EDs that cared for more children
When an obstructive stone has been diagnosed in a child, management options,
in addition to pain control, include observation with medical expulsive therapy
(MET) or surgery. Studies on spontaneous passage rates without MET suggest
higher rates of passage in older than younger children and with stones found in
the lower ureter than kidney or upper ureter (
). As in adults, utilization of
MET with alpha-blockers or calcium-channel blockers in children with
nephrolithiasis has been increasingly employed. The rationale behind MET is
the abundance of alpha-1a, alpha-1d, and calcium channel receptors found in
the smooth muscle of the distal ureter. By blocking these receptors, the tone of
the ureter, in theory, relaxes and thus dilates the ureter, facilitating stone
While numerous trials and meta-analyses of MET exist in the adult literature,
showing decrease in time to stone passage, reduced analgesic use, and increased
cost-effectiveness compared to analgesics alone (
22 , 23
), only a few studies
have evaluated the efficacy of MET in children.
Three small randomized-controlled trials have been performed, all of which
examined distal ureteral stones in children and included fewer than 65 patients
21, 24, 25
). Although far from conclusive, two of the three trials found a
significantly improved passage rate favoring alpha-blockers (
recently, a multi-institutional retrospective cohort study demonstrated that
MET was associated with 55 % spontaneous passage rate which was
significantly higher compared to 44 % with analgesics alone, with over threefold increased
odds of spontaneous passage (26).
Between 25 and 50 % of children with nephrolithiasis are estimated to undergo
surgical intervention (
). Current commonly used surgical options for
nephrolithiasis include extracorporeal shockwave lithotripsy (SWL), retrograde
i n t r a r e n a l s u r g e r y ( R I R S ) w i t h u r e t e r o s c o p y , an d p e r c u t a n e o u s
nephrolithotomy (PCNL). Open pyelolithotomy is rarely used in the
contemporary era. While historically most stones in children were treated with SWL,
technological advancements in miniaturization and optics of endoscopy have
allowed an increase in utilization of RIRS and PCNL (
). According to the
American Urologic Association 2007 guidelines, RIRS is now considered
firstline surgical treatment along with SWL for children with ureteral or renal calculi
). PCNL is usually reserved for large staghorn stones, large infection stones
where clearance is essential, or renal stones in kidneys with abnormal anatomy,
such as patients with horseshoe kidneys or urinary diversions (
Various studies have compared stone-free rates among the surgical
treatment modalities. These rates for PCNL range 70–97 %, RIRS 85–
88 %, and SWL 80–83 %, although the study populations were
). Because the evidence in the pediatric population is
limited, higher quality data may be extrapolated from the adult literature. A
meta-analysis comparing SWL, RIRS, and PCNL in adults for lower pole
stones G2 cm in size favored PCNL over SWL and RIRS over SWL,
particularly in stones 10–20 mm in size (
). Another meta-analysis
compared PCNL to RIRS in adults for any kidney stone and noted
higher stone-free rates with PCNL techniques but also higher
complication rates, greater blood loss, and longer hospital stay (
these results are applicable to children remains controversial.
One key issue that has made considerable progress recently has been
the reduction of radiation exposure during surgical interventions for
nephrolithiasis. All the surgical modalities excluding open surgery
typically incorporate plain films (SWL) or fluoroscopy (RIRS and PCNL),
both of which carry ionizing radiation. As the radiation safety concept
of as low as reasonably achievable (ALARA) emphasizes, recent
techniques that utilize ultrasound for RIRS (
) and PCNL (
) have sought
to minimize radiation exposure in children.
Kidney stone recurrence
Prevention and medical management
A major contributor to the morbidity associated with nephrolithiasis is disease
recurrence. Among adults with nephrolithiasis, up to 50 % recurrence may be
expected within 10 years after the initial stone episode (
35 , 36
). In children,
estimated nephrolithiasis recurrence rates range from 19 to 34 % at a mean
follow-up of 2–3 years (
). As such, children are regarded as high-risk
recurrent stone formers and must be treated as such.
The primary determinant of the likelihood of kidney stone recurrence is
whether there is an associated urinary metabolic abnormality with
hypercalciuria and hypocitraturia being the most common (
). Other risk factors include
anatomic abnormalities such as ureteropelvic junction obstruction and rare
genetic conditions such as cystinuria or primary hyperoxaluria (
Analyses of stone compositions in children have shown a similar breakdown to
adults, with 70–80 % of stones containing calcium oxalate, 10 % containing
calcium phosphate, 10–15 % containing struvite, and 5 % being pure uric acid
(39). Nearly 70 % of children have been found to have a metabolic
derangement found on 24-h urine collections that predisposes to stone formation (
Of note, children without any identifiable metabolic abnormalities have a
substantially lower risk of recurrence (
After the management of acute renal colic is complete, the primary focus
is the prevention of new stone formation and secondary prevention of
growth of any retained stones. These preventive strategies depend on
modifying the metabolic milieu that predisposes to stone formation.
It is recommend that first-time stone-formers at high-risk of stone
recurrence undergo both serum and 24-h urine studies (
electrolytes should include sodium, potassium, bicarbonate, creatinine,
calcium, magnesium, phosphorus, and uric acid. A 24-h urine collection
should include calcium, oxalate, citrate, uric acid, sodium, creatinine,
pH, cystine, volume, and supersaturation levels of calcium oxalate,
calcium phosphate, and uric acid. Importantly, the accuracy of collected
24-h samples is checked using well-established 24-h creatinine values by
weight, with a normal range of 15–25 mg/kg/24 h. However, normal
values of creatinine excretion in children have not been published. In
younger patients that have not yet been toilet trained, a Bspot^ urine
sample can be used to test for urinary calcium, oxalate, and
citrate-tocreatinine ratios. The definition of hypercalciuria varies by age, with a
normal value of less than 0.2 mg/mg being established by age 6, which
is the upper limit of normal for adults (40).
If any underlying metabolic abnormalities are diagnosed, the next
step is often prevention through dietary modification, followed by
pharmacologic intervention if dietary changes are insufficient. In adults with
hypercalciuria and recurrent stones, diets containing normal calcium
levels, low protein, and low sodium were shown to reduce recurrence
41, 42 , 43
). In children, the recommendations regarding protein
restriction should not be strictly followed, given how important protein
is for normal growth and a paucity of data in this age group. In general,
children should consume the recommended dietary allowance of
calcium, as calcium restriction may increase intestinal oxalate absorption and
stone risk. Pediatric stone-formers also are encouraged to eat fruits and
vegetables, which are high in citrate and potassium, two known
inhibitors of stone formation (
42 , 43
). Lastly, limiting sodium intake has
been strongly associated with lower urinary calcium excretion in
hypercalciuric stone formers (44).
Of note, one of the most important dietary modifications to reduce
stone recurrence risk is adequate fluid intake to increase urinary volume
and decrease urinary supersaturation and crystal formation (
9, 35, 41,
42 , 43, 45 , 46
). In adults, the recommended minimal intake is 2 L
per day or enough fluids to generate over 2.5 L of urine output per day
9, 35 , 42 , 45 , 46
). In children, some authors have recommended a
minimum fluid intake of 750 mL per day in infants, 1000 mL per day
in children up to age 5, 1500 mL per day in children up to age 10, and
over 2000 mL per day in older children and adolescents (47). The
Institute of Medicine also has dietary references for water intake by
age, ranging from 700 mL per day in infants to 3300 mL in 14–
18 year-olds (48).
In patients in whom dietary modifications alone fail, pharmacologic
intervention may be indicated. The specific therapies depend on the
underlying metabolic abnormalities as detected on the stone composition and
24h urine collections (
9, 35 , 46, 49
). In patients with calcium-based stones,
which constitute the majority of children with nephrolithiasis (39), the
underlying metabolic abnormalities often include hypocitraturia and
). Citrate is a known direct inhibitor of stone formation and
furthermore alkalinizes urinary pH to increase the solubility of various
crystals, including cystine and uric acid. As such, alkali therapy, usually in
the form of potassium citrate, constitutes a major class of targeted
pharmacologic therapy for stone prevention.
Two prospective cohort studies in children with hypocitraturia and
calcium-based stone burden have found that administration of
potassium citrate was significantly associated with decreased stone recurrence
). Other indications for potassium citrate include hyperuricosuria
with pure uric acid stones, cystinuria, and distal renal tubular acidosis
The second major class of pharmacologic interventions is thiazide
diuretics, which work by reducing urinary calcium excretion within the
distal convoluted tubules of the nephron. They are recommended in
patients with calcium stones and hypercalciuria but do require limiting
dietary sodium load to optimize success. While the data examining
thiazide efficacy in children is lacking, several trials in adults show
approximately 50 % reduced risk of recurrent calcium stone formation
compared to placebo or control (46).
Overall, the quality and quantity of studies in pediatric patients with
nephrolithiasis remain limited. Much of the evidence driving current clinical
practice is extrapolated from the adult literature. Key similarities to adults exist
in the treatment of primary stone episodes among children, with MET and
advancements in technology enabling less invasive techniques for stone
removal. Preventive strategies to reduce recurrence, including adequate fluid intake,
dietary changes, and select use of pharmacologic therapies, also may be
applicable to pediatric stone patients. However, children do simultaneously
represent a very different risk population than adults. Unnecessary radiation
exposure must be reduced given a child’s greater years at risk for stone recurrence and
additional diagnostic imaging or treatment. Additionally, with the rising
incidence of pediatric nephrolithiasis, the disease burden on society can be
expected to increase, both clinically and financially. Future research directions should
include comparative effectiveness studies of various primary and secondary
treatment strategies and randomized trials evaluating efficacy and safety of
MET and pharmacologic interventions.
Compliance with Ethical Standards
Conflict of Interest
David I. Chu has received grant number T32-DK07785 from the National Institute of Diabetes and Digestive and
Gregory E. Tasian and Lawrence Copelovitch declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been
Of major importance
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