Kidney stones in children: Prevention of recurrent stones

INTRODUCTION — The management of pediatric nephrolithiasis is divided into two parts.

●Acute episode – During the acute phase when the stone is being passed, management is directed towards pain control, and facilitating passage or removal of the stone(s).

●Prevention of recurrent disease – After the acute episode, management is directed towards prevention of recurrent stone disease. This includes an evaluation to identify any underlying cause or risk factors for stone formation. Based upon this assessment, interventions are tailored to reduce the risk of recurrent stone formation.

The prevention of recurrent childhood nephrolithiasis will be reviewed here. The acute management, epidemiology, risk factors, clinical manifestations, and diagnosis of nephrolithiasis in children are discussed separately. (See "Kidney stones in children: Acute management" and "Kidney stones in children: Epidemiology and risk factors" and "Kidney stones in children: Clinical features and diagnosis".)

EPIDEMIOLOGY — In children and adolescents with nephrolithiasis, kidney stones recur frequently. This was illustrated in a large case series of 221 children from the Mayo Clinic that demonstrated two-thirds of the patients developed one or more additional stones at a mean follow-up of 59 months [1]. Other centers have reported a lower but still substantial recurrence rate of approximately 30 percent [2-4]. The incidence of recurrent nephrolithiasis increases if there is an identified underlying metabolic abnormality that contributes to stone formation [2,3].

GOAL — Children who present with nephrolithiasis are at risk for recurrent disease. Thus, prevention of recurrent stone disease is a major clinical goal for any child with nephrolithiasis. Our practice of minimizing risk factors by identifying and correcting any metabolic abnormality associated with nephrolithiasis is, we believe, a reasonable approach in preventing recurrent disease in children.

The rationale for our approach is based upon the following observations:

●Recurrent stone disease frequently occurs in children and adolescents with nephrolithiasis. Children with an underlying metabolic abnormality are more likely to have recurrent stones. (See 'Epidemiology' above.)

●Several case series have demonstrated that over half of the children with nephrolithiasis will have an underlying metabolic abnormality that increases the risk of stone formation [5]. (See "Kidney stones in children: Epidemiology and risk factors".)

●In adults, outcome data demonstrate that medical intervention reduces the rate of recurrent stone disease. Although similar data are not readily available for children, we believe these findings are directly applicable to the prevention of recurrent stones in children. These data in adults are discussed elsewhere. (See "Kidney stones in adults: Prevention of recurrent kidney stones".)

●Recurrent episodes of nephrolithiasis are associated with pain, school absenteeism, loss of work hours for the parent/caregiver(s), and clinical costs. In addition, there is evidence that recurrent stone disease may have long-term deleterious effects upon kidney function. (See 'Outcome' below.)

Additionally, identifying and evaluating a metabolic abnormality may diagnose an underlying genetic cause, which may have specific management implications.

EVALUATION FOR UNDERLYING RISK FACTORS

Stone analysis — Any stone that is retrieved either through spontaneous passage or through surgical intervention should be sent to a laboratory with expertise in stone analysis to determine the stone composition. Knowing the composition of the stone can help focus the metabolic evaluation and guide therapeutic decisions. (See "Kidney stones in children: Epidemiology and risk factors" and 'Preventive management' below.)

Metabolic evaluation

General principles — As discussed above, all children with a kidney stone should be evaluated for underlying metabolic disorders that increase the risk of stone formation. (See 'Goal' above and "Kidney stones in children: Epidemiology and risk factors", section on 'Overview of risk factors'.)

●The metabolic evaluation should be performed while the patient is at home, fully ambulatory (assuming they are ambulatory at baseline), consuming a regular diet, and free of infection.

●If a stone has been retrieved and analyzed, the evaluation can be focused upon the specific components of the stone. As an example, in a child with calcium oxalate stones, urinary measurement of cystine is not necessary.

●If a stone is not retrieved, we perform a complete metabolic evaluation that consists of both serum and urine testing as discussed in the following sections.

Serum tests — Serum testing includes measurements of:

●Complete blood count

●Basic metabolic panel

●Calcium, phosphorus, magnesium

●Uric acid

●Alkaline phosphatase

●If calcium or phosphorus concentrations are abnormal:

•Parathyroid hormone

•25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations

Results of these studies may suggest potential etiologies:

●Hypercalcemic or hypophosphatemic – If the patient is hypercalcemic or hypophosphatemic, measurement of serum parathyroid hormone levels is required to assess features of calcium and phosphorus homeostasis. For instance, primary hyperparathyroidism could be the cause of hypercalcemia and kidney stones. (See "Primary hyperparathyroidism: Clinical manifestations", section on 'Symptomatic primary hyperparathyroidism'.)

The presence of hypophosphatemia raises the possibility of an underlying genetic disorder, such as hypophosphatemic rickets with hypercalciuria. (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia", section on 'Hypophosphatemic rickets with hypercalciuria'.)

●Low bicarbonate level – The presence of a low serum bicarbonate concentration raises the possibility of distal renal tubular acidosis (or other forms of chronic metabolic acidosis) as an underlying cause of nephrolithiasis. (See "Nephrolithiasis in renal tubular acidosis".)

●Hypomagnesemia – The presence of hypomagnesemia raises the possibility of an underlying genetic disorder, such as familial hypomagnesemia with hypercalciuria and nephrocalcinosis. (See "Hypomagnesemia: Causes of hypomagnesemia", section on 'Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)'.)

●Hyperuricemia – The presence of hyperuricemia is seen in lymphoproliferative and myeloproliferative disorders, or rare genetic disorders such as Lesch-Nyhan syndrome (hypoxanthine-guanine phosphoribosyl transferase deficiency), and glycogen storage diseases. However, nephrolithiasis is not generally a presenting finding in these disorders.

Urine tests — Urine metabolic abnormalities are detected by using the following:

●24-hour urine collection – Urinary abnormalities are best detected by measurements of urinary solute excretion from 24-hour urine collections (table 1). Most commercial laboratories can measure all parameters on a single specimen. However, in some laboratories, two or three separate collections may be required if they test for different solutes using separate solutions. As examples, uric acid is measured in an alkaline solution, calcium and oxalate in hydrochloric or nitric acid, and citrate in an acidified solution. Clinicians need to check with the clinical laboratory that will be performing the studies to obtain the correct containers and instructions for collection. (See "Patient education: Collection of a 24-hour urine specimen (Beyond the Basics)".)

To adequately assess kidney stone risk factors, 24-hour urine should be analyzed for volume, osmolality, creatinine, calcium, oxalate, uric acid, sodium, potassium, magnesium, phosphorus, ammonium, sulfate, and citrate, as well as crystal supersaturation for calcium oxalate, calcium phosphate, and uric acid. The measurement of creatinine excretion can help determine the completeness of the 24-hour collection. The normal creatinine excretion rate varies by the ratio of lean body mass to total body mass of the individual, which is usually manifested by the age and sex of the patient. Composite normal 24-hour urinary creatinine excretion values based upon age for White children are listed in table 2 (table 2) [6].

Similar data for children of other ethnicities are lacking. Until such data exist, we have continued to use the above parameters in all children to check for completion of a 24-hour urine collection. Under collection can be inferred if the creatinine excretion is below the expected normative range and over collection if the creatinine excretion is above the expected normative range. Similarly, data regarding normal ranges for many urinary analytes related to kidney stone risk are not very robust, so clinical interpretation and judgement are warranted.

●Spot urine sample – In some cases obtaining a 24-hour urine collection is difficult, especially in infants and children who are not toilet trained. As a result, normative values based upon a single urine sample have been developed (table 3). Of note, in infants and small children, the solute to creatinine ratios are generally higher in random urine samples because of the lower creatinine excretion rates.

●Urinalysis – Although urinalysis is performed during the acute presentation and diagnosis of nephrolithiasis, subsequent urinalysis performed when the patient is back to their normal daily routine may be useful in identifying and/or treating modifiable risk factors:

•A high specific gravity or osmolality is indicative of a concentrated urine, which increases solute supersaturation and the risk for stone formation.

•A low urine pH demonstrates an acidic urine, which decreases the solubility of some solutes, such as uric acid and cystine, but increases solubility of calcium phosphorus.

•Crystals detected by examination of the sediment may point towards a specific cause for nephrolithiasis. The presence of hexagonal cystine crystals (picture 1) is diagnostic of cystinuria, while the presence of phosphate crystals in the urine sediment when the urine pH is above 7 (picture 2) is suggestive of calcium phosphate or struvite calculi. (See "Cystinuria and cystine stones".)

•Proteinuria can be seen in Dent disease, an X-linked recessive disorder of the proximal tubules that is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, kidney stones, kidney failure, and rickets. If proteinuria is detected in a patient with kidney stones or nephrocalcinosis, further testing for LMWP should be performed. (See "Dent disease (X-linked recessive nephrolithiasis)", section on 'Diagnosis'.)

Definitions of specific urine metabolic abnormalities — Several case series have documented metabolic urine abnormalities in approximately half of the evaluated children with nephrolithiasis. Specific metabolic findings and their frequency in children with an identifiable metabolic abnormality include the following:

●Hypercalciuria – 50 percent

●Hyperoxaluria – 10 to 20 percent

●Hyperuricosuria – 2 to 8 percent

●Cystinuria – 5 percent

●Hypocitraturia – 10 percent

These metabolic abnormalities are defined below and discussed in detail separately. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Metabolic risk factors'.)

●Hypercalciuria – Thresholds for hypercalciuria depend on age:

•For children greater than two years of age, hypercalciuria is defined as a urinary calcium excretion rate that is greater than 4 mg/kg per 24 hours (table 1) [7,8]. However, urinary calcium excretion may normally be at this level during periods of rapid adolescent growth [9]. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hypercalciuria'.)

•Children younger than two years old are often unable to perform a 24-hour urine collection, and so we screen for hypercalciuria by measuring the total calcium/creatinine ratio (mg/mg) on a spot urine sample (table 3) [10,11]. Infants (one year of age or less) have higher urinary calcium excretion and lower urinary creatinine excretion than older children. As a result, the normal urine calcium/creatinine ratio for infants is higher than for older children [7,8,12,13]:

-Infants below six months of age – <0.8 mg/mg (2.25 mmol/mmol)

-Infants 6 to 12 months of age – <0.6 mg/mg (1.7 mmol/mmol)

-Children two years of age or older – <0.2 mg calcium/mg creatinine (0.6 mmol/mmol)

Urine calcium excretion on random urine may be difficult to interpret in formula/breast fed infant, on tube feeds or parenteral nutrition. In patients with an elevated ratio, we attempt to perform a 24-hour urine collection, if possible (ie, toilet trained, on chronic intermittent catheterization), and use the 24-hour specimen to confirm the presence of hypercalciuria prior to initiation of treatment.

●Hyperoxaluria – Hyperoxaluria is defined as a urinary oxalate excretion rate that is greater than 0.7 mmol (62 mg)/1.73 m² per 24 hours (table 1) [7].

An alternative method of quantitative assessment is measurement of the total oxalate/creatinine ratio on a spot urine sample, with which a ratio greater than normal for age defines hyperoxaluria. However, normative values by age vary depending on the assay method, and clinicians should be aware of the specific normative reference values for the assay used [7,14-16]. This was illustrated in a prospective study of 30 healthy infants in which the mean oxalate/creatinine ratio was 0.08 mg/mg (0.1 mmol/mmol) when using an enzymatic oxalate assay but was 0.13 mg/mg (0.16 mmol/mmol) when using a chemical-colorimetric method [14]. In addition, normative values were higher in infants who were formula-fed compared with those who were breastfed. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hyperoxaluria'.)

●Hyperuricosuria – For children three years of age or greater, normal uric acid excretion adjusted for glomerular filtration rate (GFR) is constant at a value less than 0.56 mg/dL (0.03 mmol/dL) based upon a random urine sample (table 3). This value is calculated using the following equation, where UCr and PCr are the urine and plasma creatinine concentrations, respectively:

Age-specific reference values are also available. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hyperuricosuria'.)

●Cystinuria – Cystinuria is defined as an elevated cystine on a 24-hour urine collection. The normal rate of cystine excretion is <30 mg/day (0.13 mmol/day) (table 1). In comparison, patients with cystinuria generally excrete more than 400 mg/day (1.7 mmol/day). For very young children who are unable to complete a 24-hour urine collection, we collect a random urine sample and estimate cystine excretion using the urine cystine-to-creatinine ratio (table 3). Normal urine cystine-to-creatinine ratios vary with age, and many children with cystinuria have concentrations >315 mg/g creatinine (>150 micromol/mmol creatinine) (See "Cystinuria and cystine stones" and "Kidney stones in children: Epidemiology and risk factors", section on 'Cystinuria'.)

●Hypocitraturia – We diagnose hypocitraturia in children with a urinary citrate excretion rate that is less than 300 mg/g of creatinine in a 24-hour urine collection (table 1) [17,18]. Citrate excretion is greater in children than adults. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hypocitraturia'.)

Genetic testing in selected cases — In some cases, the combination of serum and urine findings suggest the possibility of underlying genetic causes of nephrolithiasis, particularly if other associated clinical features are present. Some such causes are presented in the table (table 4). Workup for these genetic disorders are discussed in the dedicated topic reviews.

PREVENTIVE MANAGEMENT

Supportive evidence — Preventive measures are directed towards reducing risk factors associated with stone formation. In adults, clinical trials have demonstrated the benefits of medical therapeutic interventions in reducing new stone formation in patients with underlying metabolic abnormalities. Although similar data are not available for children, we believe the evidence demonstrating beneficial results in adults are directly applicable to the prevention of recurrent stones in children. (See "Kidney stones in adults: Epidemiology and risk factors" and "Kidney stones in adults: Prevention of recurrent kidney stones" and "Kidney stones in adults: Surgical management of kidney and ureteral stones", section on 'Medical therapy'.)

Fluid intake — In all children with nephrolithiasis, adequate fluid intake is a key component to reducing the risk of recurrent stones. High fluid intake increases the urine flow rate and lowers the urine solute concentration, thereby reducing the likelihood of new stone formation. Fluid intake is targeted to maintain the following approximate 24-hour urine volumes based upon age [19]:

●Infants – ≥750 mL

●Small children below five years of age – ≥1000 mL

●Children between 5 and 10 years of age – ≥1500 mL

●Children greater than 10 years of age – ≥2000 mL

●Adolescents – ≥2.5-3L

Metabolic interventions — Preventive interventions are targeted to correct specific metabolic abnormalities that increase the risk of stone formation. The most common are briefly reviewed in this section. More complete discussions of many of these disorders are found separately.

Hypercalciuria

●Diet – Dietary measures to reduce urinary calcium excretion include the following:

•Low-sodium diet enhances sodium and calcium renal tubular reabsorption, thereby reducing urinary calcium excretion.

•Dietary calcium is not restricted and calcium intake is maintained at the United States Recommended Dietary Allowance (USRDA) for age. Calcium restriction below the USRDA is not recommended because of the risk of osteopenia and secondary hyperoxaluria. However, calcium excess should be avoided.

•Vitamin D supplementation is avoided unless the patient if vitamin D deficient because elevated serum calcitriol (1,25-dihydroxyvitamin D3) levels can enhance urinary calcium excretion both by increasing intestinal calcium absorption (absorptive hypercalciuria) and by promoting bone resorption (resorptive hypercalciuria).

•Other measures include limiting animal protein intake to the USRDA, maintaining a diet high in fruits and vegetables, and ensuring adequate potassium intake, as potassium deficiency is associated with increased calcium excretion.

●Thiazide diuretics – We suggest the administration of thiazide diuretics in a child or adolescent with recurrent calcium stones if high fluid and dietary measures over a three to six month period fail to reduce urinary calcium levels. Thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone) enhance sodium and calcium reabsorption in the distal renal tubule leading to a reduction in urinary calcium excretion [20]. Some patients may benefit from a combination of thiazide diuretics and amiloride, because amiloride increases calcium reabsorption in the cortical collecting tubule, further lowering calcium excretion and hence this is sometimes utilized in cases of severe hypercalciuria. Monitoring of serum electrolytes is warranted in smaller children since these medications can cause electrolytes disturbances. The use of thiazide diuretics in patients with hypercalciuria is discussed in greater detail elsewhere. (See "Diuretics and calcium balance", section on 'Distal tubule and thiazide diuretics' and "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'High urine calcium'.)

●Potassium citrate – A potential alternative is potassium citrate supplementation since citrate binds free calcium in the urine and makes it unavailable for crystal and stone formation. However, it should only be used with caution in patients with calcium phosphate stones because citrate also increases urine pH, which promotes calcium phosphate stone formation. (See "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'High urine calcium' and "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'Calcium phosphate stones'.)

Hyperoxaluria and oxalosis — Preventive measures in children with hyperoxaluria depend on the underlying cause.

●Idiopathic hyperoxaluria – Preventive measures are directed towards diminishing oxalate absorption. The regimen consists of:

•High fluid intake, as discussed above (see 'Fluid intake' above).

•Oral calcium carbonate or citrate with meals to bind oxalate in the intestinal lumen. Maintaining adequate calcium intake (USRDA) is also important, as low calcium intake enhances enteric oxalate absorption.

•Lowering dietary oxalate intake as necessary. Oxalate rich foods include beet and turnip greens, rhubarb, strawberries, star fruit, sweet potatoes, wheat bran, tea, cocoa, pepper, chocolate, parsley, beets, spinach, dill, nuts, and citrus juices [21]. Excessive consumption of vitamin C can lead to hyperoxaluria because Vitamin C is metabolized to oxalate.

•Avoiding excess Vitamin D intake.

●Enteric hyperoxaluria – In addition to those listed above for idiopathic hyperoxaluria, additional preventive measures for children with secondary hyperabsorption of oxalate due to fat malabsorption include:

•Low-fat diet.

•Magnesium and pyrophosphate supplementation. These solutes, when excreted in the urine, inhibit calcium oxalate precipitation.

•Cholestyramine, which binds both intestinal bile acids and oxalate, but side effects may be limiting.

In children with fat malabsorption who have kidney stones, appropriate therapy should also be targeted towards correcting the underlying malabsorptive process. (See "Overview of the causes of chronic diarrhea in children in resource-abundant settings", section on 'Fat malabsorption'.)

●Primary hyperoxaluria – Primary hyperoxaluria types I, II, and III are rare autosomal disorders of glyoxalate metabolism that result in increased production of oxalate and hyperoxaluria, and should be a diagnostic consideration in any child in whom urine testing reveals hyperoxaluria. Treatment of primary hyperoxaluria is challenging and should be provided by clinicians with expertise in this disorder; this is discussed in detail elsewhere. (See "Primary hyperoxaluria", section on 'Management'.)

Hyperuricosuria — There are three forms of therapy to reduce urinary uric acid concentration.

●Fluid – Initial therapy is increased fluid intake to maintain a targeted 24-hour urine volume based upon the age of the child as previously discussed. (See 'Fluid intake' above.)

●Urinary alkalinization – Alkalinization of the urine with administration of potassium citrate-citric acid or potassium bicarbonate, which increases the solubility of uric acid. Alkalinization prevents uric acid precipitation and, in some cases, can lead to dissolution of uric acid crystals and stones. Potassium bicarbonate or potassium citrate-citric acid is the preferred therapy for urinary alkalization, as the administration of sodium salt (eg, sodium bicarbonate) induces volume expansion. The sodium-induced volume expansion increases sodium and secondarily calcium excretion resulting in hypercalciuria, which increases the risk of stone formation. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine uric acid'.)

●Allopurinol or febuxostat – These decrease the production of uric acid and are generally reserved for children with a known disorder of uric acid metabolism, such as Lesch-Nyhan syndrome. (See "Kidney stones in children: Epidemiology and risk factors", section on 'Hyperuricosuria'.)

Restriction of dietary purine is of limited value because most children do not consume significant quantities of purine-rich foods, such as anchovies, mussels, and goose brain, kidney and liver. Dietary sodium restriction may decrease uric acid and calcium excretion and reduce the risk of recurrent stone formation.

A more complete discussion on the management of uric acid stones is presented separately. (See "Kidney stones in adults: Uric acid nephrolithiasis".)

Cystinuria — In children with cystinuria, the initial conservative therapy used to prevent new stone therapy consists of:

●Fluid – High fluid intake targeted to dilute urine and reduce the urinary cystine concentration below 250 mg/dL.

●Urinary alkalinization – Alkalinization of the urine with administration of potassium citrate-citric acid (0.5 to 4 mEq bicarbonate/kg/day in two to four divided doses up to 30 to 80 mEq bicarbonate/day) or potassium bicarbonate formulations (table 5), each titrated to achieve a urine pH equal to or above 7.0.

●Sodium and protein restriction – Dietary restriction of sodium and animal protein can reduce urinary cystine excretion.

If the urine cystine excretion remains elevated despite these measures, cystine-binding drug therapy is administered. Medications, such as tiopronin and D-penicillamine, bind cystine and form highly soluble complexes. These drugs can be associated with side effects and should be used in consultation with a clinician familiar with their use. In one study of 18 children and young adults with cystinuria, medical therapy including the use of cystine-binding drugs that maintained the urine cystine to creatinine ratio below 0.2 mg/dL (0.1 mmol/mmol) reduced the formation of new stones from 0.28 to 0.03 per year [22]. In six patients, the size of pre-existing stones was reduced.

Cystine stones and their management are discussed in greater detail separately. (See "Cystinuria and cystine stones".)

Hypocitraturia — Increasing urinary citrate excretion is the goal in patients with hypocitraturia, because citrate inhibits stone formation by forming a soluble complex with calcium resulting in a reduction of available calcium for binding with oxalate or phosphate. Citrate excretion can be enhanced by alkalinizing the plasma by the daily administration of potassium citrate-citric acid (0.5 to 4 mEq bicarbonate/kg/day in two to four divided doses up to 30 to 80 mEq bicarbonate/day) or potassium bicarbonate formulations (table 5), each titrated to the target pH for the individual stone composition [23-25]. (See "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'Low urine citrate'.)

Struvite — Prevention of infection is the main component in reducing the risk of recurrent struvite stones. A complete evaluation of the kidney and urinary tract should also be performed because these children have an increased risk for renal and urinary tract abnormalities that predisposes them to infection and stone formation. Both the evaluation and management of recurrent urinary tract infection and the evaluation of congenital anomalies of the kidney and urinary tract are reviewed separately. (See "Urinary tract infections in children: Long-term management and prevention" and "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)".)

Complementary and alternate therapies — Data on the efficacy and safety of complementary and alternate therapies in the treatment of pediatric nephrolithiasis are not available. Nevertheless, both herbal and acupuncture therapies have commanded widespread interest and use, especially in Asian countries. We do not recommend these therapies as their safety and efficacy remain unproven. This discussion is to provide information on what complementary and alternate therapies are being used.

●Most of the herbal agents used in treating nephrolithiasis are believed to have mild diuretic effects, which may reduce stone formation by increasing urinary flow and volume. Chocolate vine (Mu Tong, Akebia quinata) and Centella asiatica (gotu kola) are traditional Chinese medicine. Kamala (Mallotus philippinensis) and cumin (Cuminum cyminum) are popular treatments in India, although cumin may be of concern in pregnancy because it also is used to induce abortion. Other plants include cleavers (Galium aparine) and burdock (Arctium lappa).

Aloe vera and yellow dock (Rumex crispus) contain calcium binders that reduce crystal growth rate, but the high levels of oxalate in yellow dock may negate any beneficial effect.

●Acupuncture and acupressure are used to treat nephrolithiasis in China.

MONITORING — Monitoring includes imaging to detect new stone formation or increasing size of previous stones, and laboratory evaluation to assess the response to preventive medical therapy.

The frequency and degree of monitoring in children with nephrolithiasis depends upon the type of stone, the number of stones and recurrence rate, and the presence and severity of any metabolic abnormality. As an example, a child with multiple stones and a significant metabolic problem, such as primary hyperoxaluria or cystinuria, is at greater risk for recurrent nephrolithiasis than a child with a single stone and no evidence of an underlying metabolic abnormality. In the child with a high-risk of recurrent stones, more frequent and intensive monitoring is required.

Imaging — In children, ultrasonography is generally used to monitor for new stone formation and change in size of previous stones. Although non-contrast helical computed tomography (CT) is the most sensitive imaging modality in the detection of kidney stones, the higher radiation, especially in small children, and cost compared with ultrasonography limits its use in routine follow-up [26].

The frequency of imaging is dependent upon the type and number of stones, and the presence and severity of any underlying metabolic abnormality. In most circumstances and in the absence of symptoms or infections, an examination is performed one year after the initial episode. If the study demonstrates no stone recurrence or change in residual stone size, the study can be performed every other year.

Acute symptoms should prompt reevaluation. In this setting, the choice of imaging modality is based upon the clinical circumstances and the availability of appropriate equipment and the expertise of the personnel. (See "Kidney stones in children: Clinical features and diagnosis", section on 'Imaging'.)

Metabolic surveillance — If preventive measures are initiated to correct a metabolic abnormality, repeat laboratory assessment with 24-hour urine collection specimens is warranted to evaluate the impact of the intervention.

In general, we obtain the appropriate 24-hour urine studies at six to eight weeks after therapy has begun. If the intervention has successfully corrected the metabolic abnormality, we obtain repeat values at six months, and then at a yearly or every two-year interval. If biochemical abnormalities persist, additional adjustment of the metabolic intervention and subsequent evaluation six to eight weeks later is required.

If it is difficult to obtain a 24-hour urine collection, random spot urine samples can be obtained.

Monitoring the specific gravity of the urinalysis is useful in determining whether increased fluid intake has resulted in a dilute urine.

OUTCOME

Recurrent stone disease — In children, there are limited data comparing the effects of metabolic intervention to conservative therapy of increased fluid intake on the rate of stone recurrence. Data that do exist primarily involve children with severe metabolic abnormalities and nephrolithiasis, such as cystinuria and primary hyperoxaluria.

As discussed above, in adults there is evidence that dietary measures and some pharmacologic agents decrease recurrent stone formation in patients with the more common metabolic abnormalities of hypercalciuria, hyperoxaluria, and hypocitraturia. (See "Primary hyperoxaluria" and "Cystinuria and cystine stones" and "Kidney stones in adults: Prevention of recurrent kidney stones".)

Renal outcome — Data are limited regarding the effects of nephrolithiasis upon long-term kidney function. The risk of developing chronic kidney disease (CKD) is primarily dependent upon the presence and severity of an underlying metabolic defect.

CKD frequently develops in patients with severe metabolic disorders, such as primary hyperoxaluria and Dent disease. Long-term outcome data demonstrate that most patients with cystinuria develop CKD but do not develop end-stage kidney disease. Therapeutic intervention reducing urinary cystine excretion appears to preserve kidney function. (See "Primary hyperoxaluria" and "Dent disease (X-linked recessive nephrolithiasis)" and "Cystinuria and cystine stones".)

Adults with idiopathic calcium oxalate stones have a low risk of CKD, estimated as 1.7 percent [27]. The risk for CKD for children with either idiopathic hypercalciuria or hyperoxaluria is unknown. However, renal tubular damage, demonstrated either by increased urinary excretion of N-acetyl-beta-glucosaminidase or impaired renal acidification, has been reported in small case series of children with nephrolithiasis and/or hypercalciuria [28-30].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney stones" and "Society guideline links: Pediatric nephrolithiasis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Kidney stones in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – In children and adolescents with nephrolithiasis, repeat kidney stones occur frequently, with reported recurrence rates between 30 and 60 percent. Children with an underlying metabolic abnormality are more likely to have recurrent stone formation. (See 'Epidemiology' above.)

●Evaluation – Over one-half of children with nephrolithiasis will have an underlying metabolic abnormality. As a result, in our practice, we routinely evaluate all children with nephrolithiasis for an underlying metabolic disorder. Evaluation includes stone analysis, whenever possible, and serum and urine testing to detect increased solute concentrations either in the serum and/or urine. These tests should be performed when the child is at home, fully ambulatory, consuming a regular diet, and without infection. (See 'Evaluation for underlying risk factors' above.)

•Serum tests – Serum testing includes measurements of calcium, phosphorus, bicarbonate, creatinine, magnesium, and uric acid. (See 'Serum tests' above.)

•Urine tests – To adequately assess kidney stone risk factors, 24-hour urine should be analyzed for volume, osmolality, creatinine, calcium, oxalate, uric acid, sodium, potassium, magnesium, phosphorus, ammonium, sulfate, and citrate, as well as crystal supersaturation for calcium oxalate, calcium phosphate, and uric acid. In some cases, obtaining a 24-hour urine collection is difficult, especially in children who are not toilet trained. As a result, normative values based upon a single urine sample have been developed and complement the age-based standard values for a 24-hour urine collection (table 1 and table 3). (See 'Urine tests' above.)

Urinalysis can provide additional information regarding urinary concentration and acidity and the possible presence of crystals that point to a specific underlying metabolic risk factor for stone formation.

●Preventive management

•Fluid intake – In all children with nephrolithiasis, high fluid intake is required to reduce the risk of recurrent stones. We use targeted 24-hour urine volumes based upon age along with urine osmolality or specific gravity to determine if the fluid intake is adequate. (See 'Fluid intake' above.)

•Metabolic interventions – The therapeutic preventive interventions are based upon the underlying metabolic condition as follows for the three most common disorders:

-Hypercalciuria – We suggest that children with hypercalciuria be initially managed with dietary measures and not with pharmacologic therapy (Grade 2C). These measures include a low sodium diet and limiting calcium intake based on the United States Recommended Dietary Allowance for age.

For children with recurrent calcium stones in whom dietary measures over a three to six month period fail to reduce urinary calcium levels, we suggest adding thiazide diuretic therapy and continue dietary measures versus only nonpharmacologic management (Grade 2C). (See 'Hypercalciuria' above.)

-Hyperoxaluria – Children with hyperoxaluria should be evaluated to determine the cause. For initial management of children with hyperoxaluria that is not due to primary hyperoxaluria, we suggest due measures to reduce enteric oxalate absorption (Grade 2C). These include a high fluid intake, oral sodium or potassium carbonate or potassium citrate-citric acid with meals to bind intestinal oxalate, and lowering dietary oxalate intake. Other therapeutic options, such as magnesium and pyrophosphate supplementation or cholestyramine, are generally needed in patients with secondary hyperabsorption of oxalate, and not in patients with idiopathic hyperoxaluria. Patients with suspected primary hyperoxaluria should be managed in consultation with an expert in the disorder. (See 'Hyperoxaluria and oxalosis' above and "Primary hyperoxaluria", section on 'Management'.)

-Hypocitraturia – In children with hypocitraturia, we suggest enhancing citrate excretion with administration of potassium citrate-citric acid (Grade 2C). (See 'Hypocitraturia' above.)

●Monitoring – Monitoring includes imaging to detect new stone formation or increasing size of previous stones, and laboratory evaluation to assess the response to preventive medical therapy. Kidney ultrasonography is generally used as the imaging modality because of its lower radiation exposure and cost compared with noncontrast helical computed tomography. Ongoing adjustment of the metabolic interventions is based upon the results of laboratory monitoring. (See 'Monitoring' above.)