Introduction

Background
Urolithiasis, kidney stones, renal stones, and renal calculi are interchangeably used to refer to the accretion of
hard, solid, nonmetallic minerals in the urinary tract. Nephrocalcinosis is a term that refers to increased calcium
content in the parenchyma of the kidney.

Pathophysiology
Renal, urologic, endocrine, and metabolic disorders may lead to the development of crystallized material in the
urinary system. Stones are most often classified into groups based on their chemical components. Materials
that produce stones in the urinary tract of children include (1) calcium with phosphate or oxalate, (2) purine
derivatives, (3) magnesium ammonium phosphate (struvite), (4) cysteine, (5) combinations of the preceding
items, and (6) drugs or their metabolites (eg, phenytoin, triamterene).

In fluids contained within the urinary system, interaction between factors that promote and factors that inhibit
crystallization is continuous. When solutes in solution are at concentrations below their solubility product
(subsaturation of stone-forming compounds in the urine), added crystals dissolve (undersaturated region).
Spontaneous precipitation can occur when concentration of constituents is above the formation product. The
metastable region lies between solubility product and formation product. Existing crystals can grow, but
spontaneous precipitation does not occur.

Frequency
United States

Frequency of urolithiasis in children has not been studied in a systematic population-based fashion. Institutional
and case reports indicate regional variation. In the United States, the incidence of urolithiasis varies between 1
case per 1000 and 1 case per 7600 hospital admissions. Urolithiasis is relatively uncommon in the United
States compared with some other areas of the world, possibly because of diet or public health measures.
Endemic bladder stones (uric acid and ammonium acid urate) are common in the developing countries but are
rare in the United States. Endemic bladder stones are frequent in areas where dietary protein is mostly derived
from cereal grains rather than meat. The southeast region of the United States has a higher frequency of
kidney stone formation in adults than do other regions of the United States. Regional rates of stone formation in
children have not been reported.

The reason for a higher incidence of stone formation in the southern United States is unknown. Suggested
factors include climate, diet, genetics, state of hydration, and bacterial colonization. Urinary tract stones in
children are a relatively infrequent problem.

International

Stones are more common in certain areas. In Europe, kidney stones occur in 1-2 children per million population
per year. In underdeveloped countries, children more frequently have endemic bladder stones than renal
stones. Endemic bladder calculi are common in developing countries where dietary protein is derived from
plant sources. These areas include Eastern Europe, Southeast Asia, India, and the Middle East. Upper urinary
calculi associated with urease-producing bacterial infection occur in England and Europe.

Mortality/Morbidity
Kidney stones are not usually fatal, although some primary conditions that produce kidney stones (eg, Lesch-
Nyhan syndrome, oxalosis) can lead to death from problems associated with the primary disease or
complications of renal failure. Infected stones may lead to urosepsis and death. Complete untreated renal
outflow obstruction causes renal failure. When urolithiasis occurs during childhood it has important lifelong
implications.

Acute renal colic may be very painful. Infected stones may produce pain, sepsis, or both. Children who develop
frequent painful stones or stones that require painful treatment such as urologic stone removal or
extracorporeal shockwave lithotripsy (ESWL) may experience considerable morbidity.

Race
No population-based studies have been performed, but institutional reports indicate that, in the United States,
white children develop urolithiasis more frequently than children who are black, Asian American, or Latin
American.

Sex
Stones are more frequent in men than in women (4:1), although the boy-to-girl ratio (3:2) is closer to equal.

Age
Peak presentation for adults is middle age. Children can present with stones at any age (eg, premature
newborn to teenager). Adults are most often afflicted with calcium oxalate or calcium phosphate stones. In
some cases, the primary cause of stone formation cannot be identified. In children, 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 (24%), uric acid (8%), cystine (6%), endemic (2%), mixed (2%), and other
types (1%). With children, particularly younger children, the primary cause of stone formation (eg,
hypercalciuria, hyperuricosuria) can usually be identified with a through evaluation.

Clinical

History
Stones are classified by their composition. Knowledge of composition may help to design preventive therapy,
but the chemical composition of a stone usually has little to do with the clinical manifestations. The clinical
manifestations are more related to (1) the size of the stone (larger stones tend to be more symptomatic,
although some large stones produce few symptoms), (2) the location of the stone, (3) the production of urinary
outflow obstruction, (4) the movement of the stone (eg, from the renal pelvis to bladder), and (5) the presence
of infection.

• Presentation usually depends on age; symptoms such as flank pain and hematuria are more common
in older children. Nonspecific symptoms (eg, irritability, vomiting) are common in very young children.
• The following are 5 fairly typical presentations of stone disease in children:
o Intense pain that suddenly occurs in the back and radiates downward and centrally toward the
lower abdomen or groin
o Hematuria, usually gross, occurring with or without pain: Hematuria may or may not be
present. In a series of adults in whom helical CT scanning was used to identify lithiasis in the
emergency department, one third had 5 or fewer RBCs per high-powered field.1 No similar
study has been performed in children, but many pediatric nephrologists have identified stone
disease children with symptoms, stones, and no hematuria.
 o Infection leading to radiologic imaging in which a stone is identified
o Asymptomatic stones, which are sometimes identified when abdominal imaging is performed
for another reason
o Persistent microscopic hematuria, which consists of 5 or more RBCs per high-power field in 3
of 3 consecutive centrifuged urine specimens obtained at least 1 week apart
• Some renal stone diseases may be inherited. In some reports, as many as 70% of children with
idiopathic hypercalciuria (see Hypercalciuria) have a family history of stones. The cause of idiopathic
hypercalciuria is unknown, but it may be transmitted as an autosomal dominant trait. Cystinuria is an
autosomal recessive defect of amino acid transport that leads to cystine kidney stones. Glycinuria is a
rare inherited renal tubular defect producing oxylate stones. Xanthinuria is an autosomal recessive
disorder that produces xanthine urolithiasis. Primary hyperoxaluria is produced by an autosomal
disorder leading to oxylate stones. Several inherited disorders in purine metabolism lead to uric acid
stones (Lesch-Nyhan disease is probably the best known); therefore, a careful family history to identify
other family members with stones is important.
• History should include questions to identify frequent urinary tract infections, frequent bouts of
abdominal pain, hematuria (gross or microscopic), passage of previous calculus, dietary intake, drug
intake, vitamin intake, fluid intake, habitual fluid type, chronic disease (eg, renal tubular acidosis or
short-gut syndrome), prior urologic surgery, or recent immobilization (vide infra).
o Numerous dietary items may contribute to renal stone production. A high oxalate intake may
contribute to calcium oxalate stone production. Excessive purine intake may contribute to the
production of stones containing uric acid and uric acid plus calcium components. A ketogenic
diet, prescribed to reduce seizures, places children at risk for both uric acid and calcium stone
formation. In general, urinary calcium increases with dietary calcium intake (see
Hypercalciuria). Urinary calcium increases in patients with high sodium chloride intake.
Dietary phosphate restriction, if severe, increases urine calcium excretion. A diet high in
protein from animal sources, glucose or sucrose increases urinary calcium and, in some
cases, may contribute to stone formation.2 Fructose consumption is also associated with an
increased risk of kidney stones.3
o Drug intake may contribute to stone formation in 3 basic ways. First, the drug or its
metabolites may precipitate as stones (eg, phenytoin, triamterene, sulfadiazine, felbamate,
ceftriaxone4 ). Second, the drug may increase the concentration of stone-forming minerals by
increasing the filtered load or decreasing the tubular reabsorption. For example, anticancer
agents increase the filtered load of uric acid and glucocorticoids increase the filtered load of
calcium. Allopurinol increases the filtered load of xanthine in patients with tumor lysis to
produce xanthinuria. Furosemide decreases tubular calcium reabsorption, leading to
increased urine calcium concentration. Third, the drug may alter urine pH, decreasing the
solubility of a stone-forming agent. In children with distal renal tubular acidosis, bicarbonate
probably contributes to stone formation by further alkalinizing the urine.

Stone Formation

Open table in new window

Primary Stone
Mechanism of Stone Formation Drug
Composition

Crystallization of highly excreted, Phenytoin, triamterene, Drug or its

poorly soluble drug or metabolite sulfonamides, felbamate, ceftriaxone, metabolites
 causes stone formation. indinavir, ciprofloxacin,
guaifenesin/ephedrine

Drug may increase the 1. Anti-cancer drugs 1. Uric acid

concentration of stone-forming 2. Glucocorticoid 2. Calcium
minerals. 3. Allopurinol (if used in tumor lysis) 3. Xanthine
4. Loop diuretics 4. Calcium
5. Calcium and vitamin D oxalate
5. Calcium

Drug inhibits activity of carbonic Topiramate, zonisamide, Calcium

anhydrase enzymes in the acetazolamide phosphate
kidney, causing metabolic
acidosis, hypocitraturia, and
elevated urine pH.

Primary Stone
Mechanism of Stone Formation Drug
Composition

Crystallization of highly excreted, Phenytoin, triamterene, Drug or its

poorly soluble drug or metabolite sulfonamides, felbamate, ceftriaxone, metabolites
causes stone formation. indinavir, ciprofloxacin,
guaifenesin/ephedrine

Drug may increase the 1. Anti-cancer drugs 1. Uric acid

concentration of stone-forming 2. Glucocorticoid 2. Calcium
minerals. 3. Allopurinol (if used in tumor lysis) 3. Xanthine
4. Loop diuretics 4. Calcium
5. Calcium and vitamin D oxalate
5. Calcium

Drug inhibits activity of carbonic Topiramate, zonisamide, Calcium

anhydrase enzymes in the acetazolamide phosphate
kidney, causing metabolic
acidosis, hypocitraturia, and
elevated urine pH.

o Vitamins A and D can contribute to calcium urolithiasis when taken in excessive amounts.
o Fluid intake is important quantitatively and qualitatively. A low fluid intake leads to
concentrated urine and increases the risk of stone formation. Water may have a high mineral
content in some areas. Milk contains significant calcium and vitamin D. Orange juice may be
supplemented with calcium. Tea contains oxalate and often sucrose. Many drinks (eg, sports
drinks) contain sodium chloride and sucrose.
o Chronic illnesses may be a manifestation of stone disease. Prolonged unexplained fever may
reflect an infected staghorn calculus. Some diseases, or the medications used to treat them,
increase stone formation risk. Examples include distal renal tubular acidosis, short-gut
syndrome, inflammatory bowel disease, intractable seizures, and cystic fibrosis.
o Urolithiasis is not uncommon in pediatric patients who have undergone a kidney transplant.5
Factors associated with post–kidney transplant urolithiasis include retention of suture material,
recurrent urinary tract infection, hypercalciuria, and urinary stasis.

Physical
The physical examination in children with urolithiasis is influenced by several factors. The most important
include age, pain, infection, and underlying process producing the stone. An infant with pain may have
inconsolable crying; a teenager may have obvious costovertebral angle tenderness. Infection may range from
no physical abnormalities to fever to a physical picture consistent with urosepsis (eg, fever, tachycardia,
hypotension, cold clammy skin). Conditions such as Lesch-Nyhan disease, inflammatory bowel disease, and
cystic fibrosis have findings specific for the disease.

• A routine physical examination should be performed, including anthropometric data. Many children
with kidney stones have normal physical examination findings.
o Height
o Weight
o Muscle mass
• Systemic diseases associated with stones, including the following, may produce decreased growth:
o Distal renal tubular acidosis
o Oxalosis
o Inflammatory bowel disease
o Cystic fibrosis
o Short-gut syndrome
• Exceptions to normal findings on physical examination include the following:
o Hypertension (may be present with urinary obstruction or pain)
o Tachycardia in children with pain
o Costovertebral angle tenderness
o Oxalosis (flecked retina)
o Adolescents with primary hyperparathyroidism in whom stones are the presenting feature (eg,
hypertension associated with hypercalcemia)
o Rickets, stones as part of Dent disease

Causes

• Renal stones occur as a result of the following 3 factors:

o Supersaturation of stone-forming compounds in urine
o Presence of chemical or physical stimuli in urine that promote stone formation
o Inadequate amount of compounds in urine that inhibit stone formation (eg, magnesium,
citrate)
• Additional risk factors include the following:
o Habitually low urine volume
o High urine excretion of calcium
o High urine excretion of uric acid
o High urine excretion of oxalate
o Low urine pH: Uric acid and cysteine are less soluble in acid urine.
o High urine pH: Struvite and calcium phosphate are less soluble in alkaline urine.
o Nidus for crystal precipitation: A nidus for crystal precipitation (eg, uroepithelial surface
properties that affect crystal retention) occurs when the crystalline lattice structure of one
crystal is similar to another crystal and the second crystal grows on the first.
• Factors such as developmental abnormalities of the urinary tract, urinary obstruction, urinary stasis,
and infection with urea-splitting microorganisms may also be important