Gregory E. Tasian, MD, MSc
Douglas A. Canning, MD, FACS
BASICS
DESCRIPTION
• Urolithiasis can be found anywhere in the urinary tract of a child.
• Urolithiasis is much less common in children than adults
– Urolithiasis is an increasingly common disease of childhood.
• The most commmon stones in children are calcium (calcium oxalate and calcium phosphate), uric acid, Struvite and cysteine.
EPIDEMIOLOGY
Incidence
• In adolescents, the incidence of nephrolithiasis has increased 6–10% per year over the last 20 yr (1,2).
• White > African American
• Male = Female
• Increased incidence in the Southwest United States.
Prevalence
The prevalence is unclear.
RISK FACTORS
• When a metabolic evaluation is performed, an abnormality can be identified in 40–50% of children.
– Most common metabolic abnormalities are hypercalciuria and hypocitraturia.
PATHOPHYSIOLOGY
• Urine contains inhibitors of crystallization and thus can sustain large concentrations of solute (eg, Ca, uric acid) in a metastable state; however, perturbations of the equilibrium between inhibitors and promoters of stone formation may destabilize the urine to a point where solute cannot be held in solution and spontaneous nucleation occurs.
• Infection:
– Urea-splitting organisms produce urease, which catalyzes the hydrolysis of urea.
– Magnesium ammonium phosphate (struvite) and calcium phosphate stones
– Urine is alkaline due to urease.
– Most often present in patients with an anatomic abnormality that leads to chronic infection (neurogenic bladder, reflux, obstruction, etc.)
• Anatomic:
– Ureteropelvic/vesical obstruction
– Neurogenic bladder
– Previous bladder neck surgery
• Hypercalciuria:
– Renal: Impaired tubular reabsorption of calcium causes increased parathyroid hormone release, which normalizes serum calcium.
– Absorptive: Increased absorption from intestines causes decreased parathyroid hormone and therefore decreased calcium tubular reabsorption:
Type 1: Severe
Type 2: Mild
– Resorptive (exceedingly rare):
Results from primary hyperparathyroidism
Elevated PTH and serum calcium, low serum phosphorous, high urine calcium
– Iatrogenic (medications): Loop diuretics (furosemide), corticosteroids, methylxanthines (theophylline, aminophylline)
– RTA: Inability to acidify urine in response to an acid load:
Metabolic acidosis; high urine pH
Type I (distal) most common: Disorder of hydrogen ion excretion that leads to bone demineralization and thus hypercalciuria
Most common stone is calcium phosphate, which results from hypercalciuria, hypocitraturia, and elevated urine pH
• Uric acid stones/hyperuricosuria:
– Rare in children; high purine intake, uricosuric drugs (probenecid, sulfinpyrazone, allopurinol), renal tubular disorders, cyanotic congenital heart disease, hemolysis, and myeloproliferative disorders
– Lesch–Nyhan syndrome and type I glycogen storage disease: Increased uric acid
• Cystinuria: Autosomal recessive disorder of amino acid transport; impaired reabsorption of cystine
• Hyperoxaluria:
– Primary types I and II are rare autosomal recessive disorders with hepatic enzyme defects
– Secondary: Excessive intake of ethylene glycol, ascorbic acid, methoxyflurane, or increased intestinal absorption due to bowel disease/resection, gastric bypass
ASSOCIATED CONDITIONS
• Bartter syndrome
• Cystinuria
• Diabetes, obesity, and sugary drinks are associated with an increased risk of nephrolithiasis in adults. These risk factors have not been well studied in children.
• Distal RTA
• Gout (Hypoxanthine-guanine phosphoribosyl transferase deficiency and phosphoribosyl pyrophosphate synthetase superactivity) is rare in children unless associated with a genetic disorder
• Hyperparathyroidism
• Hypervitaminosis D
• Intestinal malabsorption (Crohn disease, bowel resection, cystic fibrosis)
• Ketogenic diet (high-fat, low-carbohydrate)
• Medications (furosemide, acetazolamide, protease inhibitors, and anticonvulsants such as topiramate and zonisamide).
• Primary hyperoxaluria
• Prolonged immobility
• Recurrent UTIs
• Rickets (associated with Dent disease and hereditary hypophosphatemic rickets with hypercalciuria)
• Tetany (familial hypomagnesemia with hypercalciuria and nephrocalcinosis and autosomal dominant hypocalcemic hypercalciuria)
• Urinary tract abnormalities (spina bifida, horseshoe kidney, UPJ obstruction, VUR)
• William syndrome
GENERAL PREVENTION
• Maintain adequate hydration and fluid volume
• Treat underlying disorders (anatomic or metabolic)
DIAGNOSIS
HISTORY
• Patient: Prematurity, medications, dietary habits, fluid consumption, malignancies, previous intestinal disorder/surgery, hematuria
• Family: Cystinuria, primary hyperoxaluria, RTA, uric acid lithiasis
• Abdominal/flank pain ± nausea/vomiting
PHYSICAL EXAM
• Hypertension associated with acute pain or obstruction
• Occasional abdominal or flank tenderness
• Growth charts may identify decreased growth patterns associated with certain childhood diseases associated with stones(cystic fibrosis, distal RTA, hyperoxaluria, etc.).
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Acute Episode: Urinalysis
– Macroscopic or microscopic hematuria is found in 85% of children with nephrolithiasis (3).
• Metabolic evaluation
– Following the resolution of the acute stone episode, obtain at least one 24-hr urine collection in children who are toilet-trained
– Analyze for calcium, oxalate, uric acid, sodium, citrate, creatinine levels, volume, pH, and cystine. It is essential to evaluate the results with respect to weight and creatinine level to accurately interpret the results.
– Hypercalciuria is defined by a urinary calcium excretion of greater than 4 mg/kg over 24 hr while ingesting a routine diet.
– Urine creatinine excretion (normal 15–25 mg/kg/d) is useful in assessing the adequacy of the urine collection.
– Urine calcium—creatinine ratios (UCa/Cr) from a spot urine sample should be obtained in children who have not been toilet-trained.
Except for neonates, there is an inverse relationship between age and UCa/Cr.
At approximately 5 years of age, UCa/Cr approaches 0.21, the upper limit of normal for adults (4).
Imaging
• Ultrasound: Reliable when it identifies a kidney stone, but it has only moderate sensitivity particularly for stones in the mid-ureter.
• CT: Accurate but delivers ionizing radiation, concerns for increased cancer risk, particularly with exposure at young ages
• A reasonable approach is to use US as the initial study. A non-contrast CT is indicated in children with persistent symptoms of nephrolithiasis and a non-diagnostic US.
Diagnostic Procedures/Surgery
N/A
Pathologic Findings
• Stone analysis to determine composition
• Calcium oxalate stones are most common, followed by calcium phosphate.
• The prevalence of struvite, cystine, and uric acid stones is each <10%.
DIFFERENTIAL DIAGNOSIS
See Section I: “Urolithiasis, Adult, General.”
TREATMENT
GENERAL MEASURES
• Indications for surgery: fever in the presence of an obstructing stone, pain refractory to oral analgesics, acute kidney injury, and an obstructing stone in a solitary kidney.
• Evaluate all children for underlying metabolic disorder.
• Goal is to decrease stone-promoting risk factors (urinary calcium, sodium, oxalate, uric acid, and low urine volume), and increase protective factors (urine pH, citrate, magnesium)
• Hydration:
– Water preferred; avoid caffeine, sodium, and sugary drinks (sports drinks)
• Dietary modifications when applicable
MEDICATION
First Line
• Should a trial of spontaneous passage be indicated, appropriate oral analgesics are important (ie, narcotics).
• Tamsulosin may increase passage of distal ureteral stones in children (5).
Second Line
• Hypercalciuria:
– Hydrochlorothiazide:
1–2 mg/kg/d in children
25–100 mg/d in adults
• Hypocitraturia
– Potassium citrate
2–4 mEq/kg/d
adults 30–90 mEq/d
• Uric acid stones:
– Limit dietary sodium
– Alkalinization of urine to pH >6.5:
– Allopurinol (decrease uric acid production) 200 mg/d
• Cystinuria:
– Create high urine volume (>1.5 L/m2/d)
– Chelating agents (bind cystine):
Thiola
D-penicillamine
• Hyperoxaluria:
– Limit sodium and oxalate-rich foods (eg, spinach, rhubarb, nuts, tea, bran, strawberries)
– Supplemental citrate, magnesium, phosphorous (stone inhibitors)
SURGERY/OTHER PROCEDURES
• The optimal management based on the size, location, and presumptive stone composition, as well as the age, size, and health of the patient.
• Extracorporeal Shock Wave Lithotripsy (ESWL)
– Renal/proximal ureteral stones, <1 cm, all ages
– Use for distal stones not well defined
– Success rate depends upon many variables:
Stone size and location, energy utilized, density of stone, anatomic abnormalities
– Complications
Subcapsular hematoma: Self-limiting
Interstitial fibrosis: Insignificant unless multiple procedures
Injury to surrounding organs:
• Ureteropyeloscopy:
– Rigid and flexible endoscopes permit access to almost all areas of the collecting system in nearly all children:
– Pre-placement of stent is sometimes necessary to passively dilate the ureter.
– Access sheaths (with/without pre-stenting) facilitate procedures requiring multiple endoscope passes.
– All forms of lithotripsy are safe; holmium laser most effective
• Percutaneous nephrolithotomy (PCNL):
– Appropriate for large intrarenal/proximal ureteral stones:
– Also failed primary procedures (SWL, ureteroscopy), and with associated anatomic abnormalities (congenital, acquired, etc.)
– Access at same time as or prior to surgery:
– Sheath size as small as possible to allow for success of procedure and to accommodate flow of irrigant around scope
– Renal access: best access to stone burden.
Multiple tracts are safe.
Irrigation (saline): Warmed for children
– Postoperative management: Appropriate drainage; chest x-ray in recovery room (upper pole access)
– Complications:
Bleeding: Place tube (traction if necessary); embolize if significant
Perforation/extravasation: If significant, stop procedure and place nephrostomy tube
Infection: Appropriate antibiotics; confirm patency of tube/stent
Pleural effusion/pneumothorax: Chest tube, needle drainage
Intestinal injury: Expectant management; colostomy tube
• Open/laparoscopic pyelolithotomy (rare): Large pelvic/staghorn stones
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
Adequate hydration to dilute urine
ONGOING CARE
PROGNOSIS
• Up to 50% of children will develop recurrent stones within 10 yr of initial occurrence, which is similar to rates in the adult population.
• The odds of recurrence is up to 5× higher in children with an identifiable metabolic abnormality.
COMPLICATIONS
Obstruction, infection, lost productivity, impaired renal function
FOLLOW-UP
Patient Monitoring
• Repeat 24-hr urine 3–4 mo after instituting therapy and if stone recurs after initial stabilization.
• Assess periodically for stone growth or new stone disease with US.
Patient Resources
National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov/kudiseases/pubs/stoneschildren/
REFERENCES
1. Dwyer ME, Krambeck AE, Bergstralh EJ, et al. Temporal trends in incidence of kidney stones among children: A 25-year population based study. J Urol. 2012;188:247.
2. Routh JC, Graham DA, Nelson CP. Epidemiological trends in pediatric urolithiasis at United States freestanding pediatric hospitals. J Urol. 2010;184:1100–1104.
3. Persaud AC, Stevenson MD, McMahon DR, et al. Pediatric urolithiasis: Clinical predictors in the emergency department. Pediatrics. 2009;124(3):888–894.
4. Sargent JD, Stukel TA, Kresel J, et al. Normal values for random urinary calcium to creatinine ratios in infancy. J Pediatr. 1993;123:393–397.
5. Mokhless I, Zahran AR, Youssif M, et al. Tamsulosin for the management of distal ureteral stones in children: A prospective randomized study. J Pediatr Urol. 2011:1–5.
See Also (Topic, Algorithm, Media)
• Cystinuria
• Hypercalcuria (Absorptive, Renal, and Resorptive)
• Renal Tubular Acidosis
• Urolithiasis, Adult, General
• Urolithiasis, Cystine and Cystinuria
• Urolithiasis, Pediatric, General Considerations Images 
CODES
ICD9
• 275.49 Other disorders of calcium metabolism
• 592.0 Calculus of kidney
• 592.9 Urinary calculus, unspecified
ICD10
• E83.52 Hypercalcemia
• N20.0 Calculus of kidney
• N20.9 Urinary calculus, unspecified
CLINICAL/SURGICAL PEARLS
• Kidney stones can occur at any age, even in premature infants.
• Most occur in teens, with teen girls having the highest incidence in adolescents.