•Some affected individuals have neurodevelopmental abnormalities, particularly sensorineural deafness.

–Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency:

•This is an X-linked inborn error of purine metabolism caused by mutations in the HPRT1 gene associated with overproduction of uric acid.

•Complete deficiency of HPRT activity is associated with the Lesch-Nyhan syndrome, characterized by mental retardation, spastic cerebral palsy, choreoathetosis, uric acid calculi, and selfinjurious behavior.

•Children with partial HPRT deficiency can be phenotypically similar to patients with complete deficiencies or may have more subtle or mild neurologic symptoms.

•Renal stones, uric acid nephropathy, renal obstruction, or gout may be the first presenting signs of the disease.

9.3Classification of Urolithiasis

•Urolithiasis are considered relatively rare in children.

•In Europe, kidney stones occur in one to two children per million population per year.

•This however is not the case nowadays and a significant increase in the number of children diagnosed with and treated for urolithiasis has occurred in the last decade.

•Children with stones now account for 1 in 685 pediatric hospitalizations in the United States.

•Surprisingly, more than half the patients are younger than 13 years at hospitalization.

•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 mostly derived from plant sources rather than meat. These areas include:

–Eastern Europe

–Southeast Asia

–India

–The Middle East

•Upper urinary calculi associated with ureaseproducing bacterial infection occur in England and Europe.

•In children, calcium stones are most common.

•In children urolithiasis occur with almost equal frequency among boys and girls. The boy-to-girl ratio is 3:2.

•Urinary stones are typically classified by their location or by their chemical composition.

•Urinary stones are classified according to their location as follows:

–Renal

–Ureteric

–Vesical

–Urethral

•Urinary stones are classified according to their chemical composition as follows:

–Calcium-containing

–Struvite

–Uric acid

–Other compounds

•Calcium oxalate is a major constituent of most urinary stones.

•Knowledge of composition of urinary stones is important as this may help to design preventive therapy.

•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 %)

–Other types (1 %).

•With children, particularly younger children, the primary cause of stone formation (e.g., hypercalciuria, hyperuricosuria) can usually be identified with a thorough evaluation.

9.4Clinical Features

•The clinical manifestations of urolithiasis depends on the following factors:

–The size of the stone

–The location of the stone

–The production of urinary outflow obstruction

–The movement of the stone

–The presence of infection

•Larger stones tend to be more symptomatic, although some large stones produce few symptoms.

•Sometimes small stones produce severe symptoms as a result of their movement.

•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 (e.g., oxalate, purine, calcium, phosphate, fructose, animal protein)

–Drug intake (e.g., anticancer drugs, glucocorticoids, allopurinol, loop diuretics)

–Vitamin intake (A, D)

–Fluid intake, habitual fluid type (e.g., water, milk, tea, sports drinks),

•History should include questions to identify chronic disease:

–Renal tubular acidosis

–Inflammatory bowel disease

–Short-gut syndrome

–Intractable seizures

–Cystic fibrosis

–Prior urologic surgery (e.g., kidney transplant)

–Recent immobilization

•A careful family history to identify other family members with stones is important.

–In some reports, as many as 70 % of children with idiopathic hypercalciuria have a family history of stones. The cause of idiopathic hypercalciuria is unknown, but it may be transmitted as an autosomal dominant trait.

•Other inherited conditions to be considered during evaluation include:

–Cystinuria, an autosomal recessive defect of amino acid transport that leads to cystine kidney stones.

–Glycinuria, a rare inherited renal tubular defect producing oxalate stones.

–Xanthinuria, an autosomal recessive disorder that produces xanthine urolithiasis.

–Primary hyperoxaluria, produced by an autosomal disorder leading to oxalate stones.

–Several inherited disorders in purine metabolism lead to uric acid stones (LeschNyhan disease is probably the best known).

•The clinical presentation of urolithiasis are variable and include:

–Symptoms differ according to the location of the stone.

–Intense pain that suddenly occurs in the back and radiates downward and centrally toward the lower abdomen or groin.

–The pain may be dull aching localized to the renal area or lower abdomen in those with urinary bladder stones.

–The pain may be nonspecific localized to the abdomen, flank, or pelvis.

–Sometimes the pain is severe colicky localized to the flanks, abdomen or pelvis or radiates from the flank downwards towards the urinary bladder and urethra.

–In infants and children and because of rarity of urolithiasis, the pain may be attributed to intestinal colic.

–Hematuria, usually gross, occurring with or without pain.

–Hematuria may or may not be present or may be microscopic.

–Macroscopic or microscopic hematuria can occur in up to 90 % of children with urolithiasis.

–Urinary tract infection may be the first presentation of urolithiasis.

–Unexplained sterile pyuria or recurrent urinary tract infections (UTIs) should raise the level of suspicion for urolithiasis, especially in the younger child.

–Urolithiasis may be discovered incidentally during radiological investigation of children with urinary tract infection.

–Asymptomatic urolithiasis may be discovered during radiological investigation for another reason.

–Persistent microscopic hematuria, which consists of five or more RBCs per highpower field in three of three consecutive centrifuged urine specimens obtained at least 1 week apart may be the presentation of urolithiasis in children.

–Ureteral stones are much more likely to cause obstruction that leads to severe

colicky or non-specific flank or abdominal pain.

–Renal stones may be found incidentally and remain present for years without causing symptoms.

–Approximately 10 % of calculi can present with fever, dysuria and urinary frequency and are usually localized to the lower urinary tract.

–Urolithiasis may also be complicated by urinary tract infection. These patients may be asymptomatic or present with dysuria and frequency. Pyuria may also be present without bacteriuria or infection.

–Rarely, a urethral stone can present with acute urinary obstruction and urine retention.

•Nephrocalcinosis:

–Nephrocalcinosis is mostly asymptomatic, especially during infancy and early childhood.

–Sometimes, nephrocalcinosis is discovered incidentally on an imaging study performed for other reasons.

–Nephrocalcinosis may also be discovered when symptoms of reduced concentrating capacity of the renal tubules are obvious.

–It is not unusual for nephrocalcinosis to be diagnosed during systematic renal ultrasound examination of high-risk infants or as part of the diagnostic evaluation of urinary tract infection.

–The first clinical symptoms, if any of nephrocalcinosis, are gross or microscopic hematuria and/or sterile leukocyturia that may be misdiagnosed as urinary tract infection.

9.5Investigations

•Complete blood count (CBC)

•Electrolyte, blood urea nitrogen (BUN), creatinine

•Serum calcium, phosphorus, alkaline phosphatase, uric acid, total protein, albumin, parathyroid hormone (PTH), and vitamin D metabolite levels

•Urinalysis and culture

•Estimating the ratio of calcium, uric acid, oxalate, cystine, citrate, and magnesium to creatinine.

•A 24-h urine collection for calcium, phosphorus, magnesium, oxalate, uric acid citrate, cystine, protein, and creatinine clearance.

•Renal ultrasonography is very effective for identifying stones in the urinary tract.

•Generally, ultrasonography should be used as a first study.

–US remains the initial study of choice in the assessment of calculi in children.

–Ultrasound has the ability to detect 90 % of calculi confined to the kidney.

–The sensitivity for detecting ureteral calculi and smaller calculi (<5 mm) is poor.

•If no stone is found but symptoms persist, abdominal CT-scan is indicated.

•Abdominal CT-scan is the most sensitive test for identifying stones in the urinary system. It is safe, rapid, and has been shown to have 97 % sensitivity and 96 % specificity.

•Many radiopaque stones can be identified with a simple abdominal radiogram (Figs. 9.1 and 9.2).

•Calculi composed of uric acid, cystine, xanthine, or indinavir are usually radiolucent.

•The typical stone location is within the renal pelvis and/or the renal calyces or the ureter and less often within the bladder.

•The most common ureteral calcification is a stone that has migrated down from the kidney. These stones typically become impacted at anatomic sites of narrowing and are especially difficult to detect when they overlie bony structures such as the sacrum.

•Detection of a ureteral stone via ultrasonography is difficult, but the stone may lead to obstruction (hydroureter or hydronephrosis) and may, thus, be suspected, even if not directly visualized.

•Non-contrast-enhanced CT is more effective than intravenous urography (IVU) in identifying and locating ureteral stones.

•Intravenous pyelography is rarely used in children (Fig. 9.3).

•An intravenous urography can be considered in children with hypercalciuria in whom medullary sponge kidney is suspected.

Fig. 9.3 An intravenous urography showing a large left staghorn calculus

•The content of the stone (i.e., cysteine versus calcium versus uric acid) may be the most important element in developing a treatment program to prevent further stone formation.

•Specific Metabolic Investigations:

–Urolithiasis developing during childhood carry a life-long risk of stone formation.

–Approximately 16–20 % of children develop recurrences within 3–13 years of the first attack.

–Children with an identifiable metabolic abnormality have an up to fivefold increased risk of having a recurrence as compared with children with no identifiable metabolic disorder.

–All children should undergo a comprehensive initial evaluation.

–An infrared spectroscopy or radiograph diffraction analysis of a passed stone is important.

–If a cystine or struvite stone is found, the analysis will be diagnostic.