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Essentials in Pediatric Urology, 2012: 79-88 ISBN: 978-81-308-0511-5

Editor: George Sakellaris

8. Pediatric urolithiasis

Nikolaos Partalis1 and George Sakellaris2

1
Pediatric Surgery, University Hospital, Heraklio, Greece; 2Consultant Pediatric Surgeon
Department of Pediatric Surgery, University Hospital of Heraklion, Greece

Introduction
While pediatric urinary stone disease once considered rare, now is evident
that children form urinary tract stones and the incidence of this disease is
increasing, particularly in females. There are many opinions regarding the
management of the pediatric patient who is presented with a stone, but any
patient who has a surgically active stone should have it removed expeditiously.
With the technological advance, stone management has transformed into
techniques that are significantly less invasive. A number of factors must be
taken into account when selecting ones choice of therapy for urinary tract
stone in children such as the size of the stone, its location, composition, and
the anatomy of the urinary tract.

Epidemiology
Between 5 and 10% of the human population suffer from urinary stone
disease during their lifetime, and of these cases 2-3% are children [1].
Although a rare disease in children living in developed countries, with a
prevalence of between 1:1000 and 1:7,600 in different parts of the USA, the
number of pediatric patients per capita, has increased (2-4). In Europe, kidney
Correspondence/Reprint request: Dr. Nikolaos Partalis, Pediatric Surgery, University Hospital, Heraklio, Greece.
80 Nikolaos Partalis & George Sakellaris

stones occur in 1-2children per million population per year. In developing

countries, children more frequently have endemic bladder stones than renal
stones, where dietary protein is derived from plant sources. These areas
include Eastern Europe, Southeast Asia, India, and Middle East. Upper urinary
calculi connected to urease producing bacterial infection occur in England and
Europe (5). Overall, in patients under 20 years of age, the sex ratio was 70%
female and 30% male. Under 5 years of age, the male to female ratio was
60:40%, but, as the children grew, this difference reversed to the point that,
between the ages of 16 and 20, 77% of the patients were female. Reasons for
the change in gender specific incidence remain unclear (6).
Children can present with stones at any age and calcium stones are most
common. The approximate frequency of kidney stone types in the pediatric age
group is calcium with phosphate or oxalate 57%, struvite (magnesium
ammonium phosphate) (24%), uric acid (8%), cysteine (6%), endemic (2%),
mixed (2%) and other types (1%) (5). Kidney stones are not usually fatal,
although primary conditions that produce urinary stones may lead to death.
Infected stones can lead to urosepsis and death. In children, stone recurrence
rates range widely (from 3.6 to 67%), and appear mainly in children with
metabolic abnormalities (1,7,8). As a result, it is important to receive a
therapy that will render the patients stone free for as much time as possible.

Pathogenesis
The underlying causative factors that have been found to be responsible
for the etiology of the disease are metabolic abnormalities, urinary tract
infections, anatomical abnormalities and endemic factors. In two large
pediatric series, metabolic conditions were found to be responsible for more
than 50% of diagnoses and varieties of urinary tract anomalies have been
found in about 30% of children with urolithiasis (1,7,9).
Hypercalciuria is the most common metabolic abnormality accounting for
up to 34% of all pediatric stones with hyperuricosuria (usual in Lesch-Nyhan
disease) following in 8% of all cases. Although infection-related stones have
an incidence of 2-24%, as many as 75% of stones in European children have
been found to be associated with urinary tract infections, usually in boys
younger than six years of age and with associated genitourinary anomalies.
Cystinuria accounts for 2-7% of children with metabolic urolithiasis in
industrialized countries. Last but not least, calcium oxalate calculi are found in
primary hyperoxaluria and stones consisting of 2,8-dihydroxyadenine in
children suffering from 2,8-Dihydroxyadeninuria (9, 10).
In some patients the development of stones is secondary to the presence of
another condition or disease. For instance immobilization, hyperparathyroidism
Pediatric urolithiasis 81

and sarcoidosis frequently cause hypercalciuria; distal renal tubular acidosis

(dRTA) hypercalciuria and hypocitraturia; and myeloproliferative disorder
hyperuricosuria. Additionally, stones can be caused iatrogenically. Loop
diuretics, corticosteroids, and excess vitamin D cause hypercalciuria; ketogenic
diet hypocitraturia and hyperuricosuria; and parenteral nutrition in premature
infants hyperoxaluria. In other instances, it is the medication itself or its
metabolites, which precipitate and form stones, as in the case of indinavir,
ceftriaxone, felbamate and others (11, 12).

Presentation and diagnosis

Nonspecific symptoms are common in very young children. In older
children stone disease presents as intense pain that suddenly occurs in the back
and radiates downward and certainly towards the lower abdomen or groin; as
hematuria, occurring with or without pain; as asymptomatic random stones or
infection related; and as persistent microscopic hematuria.

Algorithm 1.- (14)

82 Nikolaos Partalis & George Sakellaris

Ultrasound should be the first line of imaging and non-contrast CT

scanning or intravenous urography may be required in some cases for
diagnostic purposes (13). The diagnosis sequence is best shown by the
algorithm 1 (14). In a study, the diagnosis of microlithiasis was made in 44%
of the children, and in 28% the microlithiasis resolved over the course of
follow-up. Vesico-ureteric reflux was present in 99% of children and an
anatomical abnormality was found in 8.9%. Plain radiography remains
important for both treatment planning and follow-up (15).

Non pharmacological intervention

The most important component of the treatment of all kinds of kidney stones
is increased urine volume, thereby decreasing solute concentration and
supersaturation (16). A urine flow of >1ml/kg per hour is a cut fold that almost
eliminates the risk of supersaturation for calcium oxalate (17). Milk and other
fruit juices do not have an effect in direction, therefore they (plus tea) become
the beverages of choice for children. It seems that, even after they have been
provided with the recommendation of high fluid intake, children with calcium
stones continued to have high urine specific gravity, used as a surrogate for urine
volume that was not different from that of healthy, age-matched, controls (18).
Multiple studies have shown the parallel route between high dietary
sodium intake, which mostly finds its way to the urine, and hypercalciuria
(19). On the other hand, high potassium intake has the opposite effect on urine
calcium (20). In hypercalciuric stone formers, another way to decrease urine
calcium and at the same time increase urine citrate (except eating fruits and
vegetables) is by changing the diet to be less acidic, by reducing animal-
protein intake. When comes to calcium consumption, in the past, dietary
calcium restriction or binding with cellulose-phosphate was used to decrease
absorptive hypercalciuria. This maneuver is not practiced any more, due to the
fact that it results in increased oxalate absorption in the gut and has the
potential to affect the bone adversely (21, 22).

Pharmacological intervention
Treatment of patients with calcium stones due to idiopathic hypercalciuria
with potassium (K)-citrate has the dual advantage of decreasing urine calcium
and increasing urine citrate. Furthermore, it improves the bone mineral status
of these patients (23). Thiazides are time-proven preparations for the treatment
of hypercalciuria and it may be advantageous to use them in combination with
plus k-sparing diuretics such as amiloride or with k-citrate. Approximately
one-third of hypercalciuric children have decreased bone mineral density but
Pediatric urolithiasis 83

treatment of these patients with alendronate, decreased urine N-telopeprides, a

marker of bone resumption and calciuria (24).
The traditional treatment of hyperoxaluria includes high fluid intake,
thiazide diuretics, magnesium oxide, citrate and pyrophosphates. Restriction of
dietary oxalate is mostly used in absorptive hyperoxaluria in addition to the
correction of the basic GI tract anomaly and increased calcium intake. It has
been known for some time that 30-50% of patients with type I disease lower
their urine oxalate in response to treatment with pyridoxine (vitamin B6). Oral
intestinal colonization with Oxalobacter formigenes is a novel approach, which
not only degrades intestinal oxalate but also enhances colonic secretion of
endogenously produced oxalate (25).
The goal of treatment for cystinuria is to keep urine cysteine soluble at a
concentration below 250 mg/l (normal :< 30mg/l). The fluid intake should be
increased and urine pH should be kept between 7.0 and 7.5 as cysteine
solubility increases dramatically in alkaline urine. Besides beverages and food
containing alkali, the optimal agents to alkalinize the urine are potassium
citrate and potassium bicarbonate. Additional therapy is D-penicillamine and
tiopronin, which cleave cysteine into two parts 50-times more soluble than
cysteine.
Infection related stones are now seen almost only in cases of underlying
anatomic predispositions. They are mostly composed of struvite and carbonate
apatite. Sterilization of the urinary tract and correction of the anatomic
abnormalities is the line of cure. In addition, urine acidification with acid-
phosphate preparation may keep the milieu in the kidney unfavorable for
formation of such stones.
The first line of treatment for uric acid stones is urine alkalinization,
optimally by potassium citrate. If needed, allopurinol can be added or dietary
purine restriction can be done. In the case of 1.8 dihydroxyadeninuria, the
stones formed are amenable to preventive treatment with allopurinol and a low
purine diet; however, in contrast to uric acid stones, their solubility decreases
in alkaline urine.

Extracorporeal shockwave lithotripsy

ESWL is the preferred treatment in pediatric patients with calculi <20 mm
and given its minimally invasive features, ESWL has become a primary mode
of treatment for pediatric patients with reno-caliceal stones (26). In most
pediatric series, the treatment of proximal ureteral stones has achieved similar
success rates to renal stones. Treatment of mid to distal ureteral calculi has
historically been avoided in children due to difficulties with localization over
the sacroiliac joint and concern regarding possible injury to the developing
84 Nikolaos Partalis & George Sakellaris

reproductive system (27, 28). In suspected cystine stones, the maximum

diameter should not exceed 15 mm because of the hardness of the stone.
Spontaneous stone passage is easier in children compared with adults, and
ureter stenting is not needed as often (only 5 37%) as it is in adults (29).
Nevertheless, these patients should receive pharmacological support to pass
their stone fragments; acetaminophen and ibuprofen are the medication of
choice. Nowadays not all therapeutic approaches require anesthesia, as
intravenous sedation can be used in older pediatric patients (27). Studies show
that ESWL has no defect on renal function or blood pressure, and there is no
sign of renal scarring in children. In addition, hematuria and proteinuria
resolved after patients were stone free (30). There are short-term effects such
as perirenal hematomas, hematuria, and reduced GFR directly after ESWL
therapy, but there has been no evidence for long-term damage in children.
Stone free rates ranging from 57 to 97% during short-term follow-up and 57 to
92% during long-term follow-up have been reported in the literature. Re-
treatment rates range from 13.9 to 53.9%, while ancillary procedures and/or
additional interventions range from 7 to 33% (1).
Ureteral stenting before ESWL remains a controversial issue, and often
depends on both the stone size and patient's anatomy. Preoperative stenting is
generally reserved for children with solitary kidney, severely obstructing
stones or abnormal anatomy (31).

Percutaneous nephrolithotomy
According to the guidelines of the European Association of Urology,
ESWL should be the first choice for most renal pediatric stones, but a
percutaneous approach could be used for bigger and more complex calculi.
The gradual acceptance of this technique in children was due to concerns
regarding long-term renal damage, small kidney size, relatively large
instruments, radiation exposure and the risk of major complications such as
bleeding. However, as the experience in this field grew, the results of relatively
large series demonstrated that there can be only minimal scarring and
insignificant loss of renal function after PCNL. Radioisotope scans before and
after PCNL have revealed unchanged differential function and no evidence of
significant renal scars (1). Indications for PCNL in children include a large
stone burden, significant renal obstruction with urinary infection, failure of
ESWL and significant volume of residual stones after open surgery. With the
availability of smaller instruments and with ultrasound guidance, the procedure
can now be performed safely in experienced hands. With the clinical
introduction of smaller nephroscopes, miniperc procedures are feasible
where hol: YAG laser, smaller pneumatic lithoclast and ultrasound probes can
Pediatric urolithiasis 85

be used during PCNL in children. Concerning the appropriate age of the

patients, PCNL has been performed in children as young as 19 months (32).
Although PCNL is an invasive treatment, it achieves excellent stone free
rates of about 90% (ranging from 67 to 100%) and comes with a relatively low
risk in experienced hands, especially if performed as mini-perc (29). Reported
complications of PCNL include postoperative fever (30%) and bleeding, with
the latter being the most reported complication associated with PCNL. The risk
for blood transfusions is generally very low, with rates ranging from 0% to
23.9% (29).

Uretero-renoscopy
Today, ureteroscopy may be applied for diagnostic and/or therapeutic
purposes, and with the clinical introduction of fine, smaller-calibre instruments
this modality has become the treatment of choice in middle and distal ureteric
stones in children. Currently, calculi throughout the entire upper urinary tract
in children can be treated endoscopically using semi-rigid or flexible
ureteroscopes with proven effectiveness and safety (33,34), and by using
mostly Holmium:YAG laser lithotripsy-the intracorporeal lithotriptor of choice
(35). The efficacy is good particularly for mid- and lower ureteral stones, with
the reported success rate ranging from 87.5 to 100%. However, the results
obtained in upper ureteral stones are less encouraging, with smaller success
(1). The stone-free rate following ureteroscopic lithotripsy for ureteral stones
has been reported as high as 98.5-100%. Intraoperative complications, defined
as ureteral injury (ischemia, perforation, and avulsion) or postoperative
complications (mainly ureteral stricture) have shown to be extremely rare (0%
to 5.2%). To achieve access to pediatric ureter either active dilatation is used
or, alternatively, a (1-2 weeks) pre-stenting with an indwelling ureteral stent is
followed (35).
Ureteroscopy may provide more efficient stone clearance, and should be
preferred for distal ureteral stones, larger stones and impacted stones.
Complications may occur after ureteroscopy in 07% of the patients, and
include ureteral avulsion, perforation, hematuria, infection and ureteral
stricture (36).

Laparoscopic/open surgery
In developed countries, open surgery remains the treatment of choice for
0.35.4% of children. In general patients with anatomical abnormalitiesi.e.
ureteropelvic junction obstruction, obstructive megaureter, urolithiasiswill
receive open surgery if stone removal and anatomical correction can be
86 Nikolaos Partalis & George Sakellaris

combined in one operation (37). In developing countries, open surgery is used

in 14% of cases, due to the fact that open surgery is more cost effective in
those countries (36). A 95.4% stone-free rate is reported in the treated children
and even 100% for single stones (Zargooshi et al) (29). The role of
laparoscopy in the management of pediatric stone disease remains to be
explored.

Cystolithotomy
The majority of the stones located in the bladder is usually large and hard,
and can be treated by either transurethral or percutaneous suprapubic
lithotripsy or litholopaxy. The major concern with the transurethral approach is
the possible damage to the male urethra. Nowadays suprapubic cystolithotomy
has evolved to a safe and effective alternative technique in such cases that
could even be performed on an outpatient basis. Approaches for bladder stones
are the endoscopic, suprapubic percutaneous access and open surgery routes.
Subrapubic cystolithotomy is appropriate in cases of large, hard vesical calculi
(38, 39).

Retrograde intra- renal surgery (RIRS)

Along with the increasing experience of retrograde intra-renal surgery
(RIRS) in adults, a few reports of successful ureterorenoscopic management of
inferior calyceal stones in children have been published. In future, RIRS may
be used more frequently to treat residual stones after SWL, inferior calyceal
stones and cystine stones.

Conclusion
The management of stones in children poses a specific technical challenge
to the urologist. Improvements in technology (i.e. availability of smaller-
calibre, rigid and actively deflectable endoscopes) and growing experience,
along with the refinement of ESWL and improvements to PCNL and URS
techniques, have resulted in greater acceptance of minimally invasive
techniques.

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