–Serum and urine studies should be obtained in patients in whom stone analysis could not be performed or for those with either calcium or uric acid-based stones.

–A serum creatinine level is essential to evaluate for possible acute kidney injury or chronic kidney disease.

–Serum calcium, phosphorous, bicarbonate, magnesium, and uric acid levels are effective in screening for hypercalcemiaand hypocalcemia-associated calculi, hyperuricemia, HHRH, Bartter syndrome, dRTA, and FHHNC.

–Primary hyperparathyroidism is rare in children and measurement of parathyroid hormone level is indicated if there is evidence of hypercalcemia and hypophosphatemia.

–A 25-hydroxyvitamin D level should be evaluated in all patients with hypercalcemia.

–A spot urine beta-2 microglobulin (low- molecular-weight protein) is a useful screening test for Dent disease.

–A 24-h urine collection should be analyzed for calcium, oxalate, uric acid, sodium, citrate, creatinine levels, volume, pH, and cystine.

–Measuring the ratio of calcium, uric acid, citrate, and oxalate levels to creatinine level in a random urine sample.

9.6Complications of Urolithiasis

•The primary complications of urolithiasis include:

–Obstruction of the urinary tract

–Renal parenchymal damage

–Recurrent urinary tract infection

9.7Management

•The management of children with urolithiasis include:

–To diagnose children with asymptomatic urolithiasis and treat those with symptomatic urolithiasis.

–To prevent renal damage, which may lead to loss of renal parenchyma.

–To expedite passage or removal of any stones present.

–To treat associated urinary tract infection.

–To diagnose those with predisposing conditions for urolithiasis.

–To prevent new stones from forming.

•A child presenting with acute renal colic can be managed with analgesics.

•This can be accomplished using simple nonsteroidal analgesics.

•Narcotics may be required in those with severe pain, as well as enteral or parenteral hydration.

•In the absence of oligoanuric renal failure or a complete urinary obstruction, an intravenous infusion rate of 1.5–2 times their maintenance is recommended.

•A small stone stuck at the ureteropelvic or ureterovesical junction may pass spontaneously and these patients should be treated initially conservatively.

•A stone that completely obstructs the bladder outlet should be treated with catheterization using a Foley’s catheter to relive the obstruction.

–The obstructing stone can then be removed from the urinary bladder.

–There are several methods to remove the stone:

•Vesicostomy and stone removal

•Cystoscopy, stone crushing and removal

•Lithotripsy

•Children with asymptomatic stones detected while screening for another problem should have blood and urine testing performed to identify underlying metabolic abnormalities.

•The specific aims of surgical treatment of urolithiasis include:

–Drainage and removal of the obstruction of the urinary tract

–Removal of stones present in the urinary tract

–Surgical correction of anatomic abnormalities, which may promote additional stone formation.

•A child with an infected stone and urinary tract infection should be treated with antibiotics and drainage of the urinary tract in the presence of obstruction.

•Stones removal technique used usually depends on the stone size and location and these include:

–Ureteroscopic stone extraction

–Percutaneous nephrolithotomy

–Open stone extraction

–Extracorporeal shockwave lithotripsy (ESWL).

•Alpha-1 adrenergic blocker agents, such as doxazosin, have been used as medical expulsive treatment in children with distal uretral stones.

•Dietary considerations depend on the type of stone.

•A high fluid intake leading to increased urine output is safe and generally beneficial for children with all types of stones.

•A dietitian is important in those with dietary induced urolithiasis. Children with stones composed of calcium and who have excessive calcium intake or idiopathic gastrointestinal absorptive hypercalciuria may benefit from lowered dietary calcium intake.

•The goal is to lower urinary calcium such that no new stones are formed without producing calcium deficiency.

•Fluids that increase urinary pH and citrate excretion such as orange juice, lemonade, and black currant juice, as well as those that increase urinary volume such as coffee, tea, beer, and wine, reduce the risk of calcium stone formation.

•Grapefruit juices seem to increase the risk of calcium-based stones.

•Increased sodium intake is known to promote calciuria by competing for reabsorption at the level of the renal tubules.

•A low salt diet corresponding to less than 2–3 mEq/kg/day in children or less than 2.4 g/ day in adolescents or adults is generally recommended for patients with hypercalciuria or calcium-containing stones.

•A low salt diet may also reduce urinary cystine excretion in patients with cystinuria.

•A higher calcium containing diet is associated with a reduced risk of stone formation.

•Higher calcium intake effectively binds dietary oxalate in the gut, thereby reducing intestinal absorption and eventual urinary oxalate excretion.

•Calcium restriction is not recommended, in part, because of the long-term risk of osteoporosis.

•Excess consumption of vitamin D with or without calcium supplements can also induce excessive urinary calcium excretion.

•Excessive dietary animal protein intake causes increased urinary calcium excretion and reduced urinary pH and citrate excretion.

•Children with idiopathic hypercalciuria caused by renal tubular calcium leak may benefit from treatment with a thiazide.

•In those with idiopathic gastrointestinal absorptive hypercalciuria and not responding to a low-calcium diet, neutral sodium phosphate may be beneficial in reducing dietary calcium absorption.

•Hypocitraturia is treated with oral potassium citrate. Supplemental citrate leads to correction of hypocitraturia.

•Struvite stones require treatment with an appropriate antibiotic.

–Surgical intervention or ESWL may be necessary if the stone produces high-grade obstruction, if antibiotic therapy is not adequately eliminating infection, or after infection is cleared to remove stone fragments.

•Uric acid stones require alkalinization of urine with sodium bicarbonate or potassium citrate in four divided doses.

–Urine pH levels should be maintained at 7.5 or greater.

–Uric acid is much more soluble in alkaline than acid urine.

–Allopurinol is indicated in children with uric acid stones whose daily uric acid excretion exceeds the reference range.

–The consumption of excessive amounts of dietary animal protein also results in increased purine intake, increased uric acid production, and may contribute to both uricosuria and more acidic urine.

–The treatment of children with uric acid calculi includes:

• A high urine flow rate

• Alkalization of the urine

• Allopurinol (4–10 mg/kg/day, adult maximum 300 mg/day) is indicated in

those with hyperuricemia and hyperuricosuria, such as PRPSS or HPRT deficiency.

•Inhibition of xanthine dehydrogenase by allopurinol may lead to the accumulation and urinary excretion of xanthine.

•Rarely, a secondary xanthinuria with xanthine calculi is observed in children on long-term therapy.

•Allopurinol may also be the agent of choice for treating hyperuricosuric calcium oxalate urolithiasis if there is no concomitant evidence of hypercalciuria, hyperoxaluria, or hypocitraturia.

•The medical management of cystinuria consists of:

–Hyperhydration

–Urine alkalization

–Sulfhydryl agents such as tiopronin

–Reducing animal protein intake might be helpful by increasing urinary pH

•Patients with calcium oxalate stones who demonstrate evidence of hyperoxaluria should have limited dietary oxalate ingestion.

–Foods that contain high levels of oxalate include certain nuts (almonds, peanuts, cashews, walnuts, and pecans), spinach, soy beans, tofu, rhubarb, beets, sweet potatoes, wheat bran, okra, parsley, chives, black raspberries, star fruit, green tea, and chocolate.

•Vitamin C supplements have been associated with increased risk of calcium oxalate stone formation because oxalate is a byproduct of ascorbic acid metabolism.

•Vitamin C supplements should be discontinued in calcium oxalate stone formers with hyperoxaluria.

•Potassium-rich foods such as fruits and vegetables usually contain large amounts of citrate, which are protective against the formation of calcium oxalate stones.

•A diet high in potassium is protective against urolithiasis.

•A potassium-restricted diet can cause increased urinary calcium excretion and overt hypokalemia, leading to hypocitraturia.

•Higher dietary magnesium has been associated with a lower risk of stone formation, and magnesium supplement may be helpful in the treatment of children with secondary hyperoxaluria.

•Carbohydrate ingestion has been associated with hypercalciuria, and sucrose ingestion has been found to be associated with urolithiasis.

•Phyate, a dietary factor found in many high fiber-containing foods (cereals, legumes, vegetables, and nuts), seems to bind calcium avidly and may inhibit the formation of calcium oxalate stones.

•Medications:

–A thiazide diuretic is often required for children with hypercalciuria who do not respond to a restricted sodium diet.

–The usual recommendation is hydrochlorothiazide 1–2 mg/kg/day (adult 25–100 mg/day).

–Amiloride can be added for its potassiumsparing effect as well as for its ability to independently reduce calcium excretion.

–Thiazide diuretics have also been used in an attempt to reduce calcium excretion in patients with Dent disease, FHHNC, and PH.

–Treatment with either potassium citrate (2–4 mEq/kg/day) or potassiummagnesium citrate has been shown to reduce the recurrence of calcium oxalate stone formation in patients with low or normal citrate excretion.

–Sodium citrate is generally considered less ideal because it is associated with increased sodium delivery to the nephron.

–Potassium citrate is also used to alkalinize the urine in patients with Dent disease, FHHNC, dRTA, uric acid urolithiasis (goal of urine pH >6.5), cystinuria (goal of urine pH >7), and hyperoxaluria.

–Thiol-containing agents (d-penicillamine and α-mercaptopropionylglycine) are used

exclusively for patients with cystinuria in whom fluid and dietary modifications as well as urinary alkalization are ineffective in preventing stone recurrences or dissolving preexisting stones.

–The thiol group combines with cysteine to form a more soluble cysteine-drug product combination, which is be excreted.

–Approximately 10–30 % of children with primary hyperoxaluria type I are pyridoxine sensitive. The treatment should be initiated (2–5 mg/kg/day) and increased gradually (8–10 mg/kg/day). Large doses of pyridoxine have been known to induce sensory neuropathies.

Further Reading

1. Avci Z, Koktener A, Uras N, et al. Nephrolithiasis associated with ceftriaxone therapy: a prospective study in 51 children. Arch Dis Child. 2004;89(11): 1069–72.

2. Bartosh SM. Medical management of pediatric stone disease. Urol Clin North Am. 2004;31:575–87.

3. Bass NH, Emmanuel B. Nephrolithiasis in childhood. J Urol. 1966;95:749–53.

4. Cameron MA, Sakhaee K, Orson WM. Nephrolithiasis in children. Pediatr Nephrol. 2005;20:1587–92.

5. Cameron MA, Sakkhae K, Moe OW. Nephrolithiasis in children. Pediatr Nephrol. 2005;20:1587–92.

6.Evan A, Lingeman J, Coe FL. Randall’s plaque: pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int. 2006;69:1313–8.

7.Johnson EK, Lightdale JR, Nelson CP. Risk factors for urolithiasis in gastrostomy tube fed children: a

case-control study. Pediatrics. 2013;132(1):e167–74. 8. Khositseth S, Gillingham KJ, Cook ME, Chavers BM. Urolithiasis after kidney transplantation in pediatric recipients: a single center report. Transplantation.

2004;78(9):1319–23.

9. Mandeville JA, Gnessin E, Lingeman JE. Imaging evaluation in the patient with renal stone disease. Semin Nephrol. 2011;31(3):254–8.

10.McKay CP. Renal stone disease. Pediatr Rev. 2010; 31(5):179–88.

11.Milliner DS, Murphy ME. Urolithiasis in pediatric patients. Mayo Clin Proc. 1993;68:241–8.

12. Moe OW, Pearle MS, Sakhaee K. Pharmacotherapy of urolithiasis: evidence from clinical trails. Kidney Int. 2001;79:385–92.

13. Palmer JS, Donaher ER, O’riordan MA. Diagnosis of pediatric urolithiasis: role of ultrasound and computerized tomography. J Urol. 2005;174:1413–6.

14.Pietrow PK, Pope IV JC, Adams MC. Clinical outcome of pediatric stone disease. J Urol. 2002;167: 670–3.

15.Sarica K. Pediatric urolithiasis: etiology, specific

pathogenesis and medical treatment. Urol Res. 2006; 34:96–101.

16. Stapleton FB. Clinical approach to children with urolithiasis. Semin Nephrol. 1996;3:116–24.

17. Van’t Hoff WG. Aetiological factors in paediatric urolithiasis. Nephron Clin Pract. 2004;98:c45–8.

18. VanDervoort K, Wiesen J, Frank R. Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome. J Urol. 2007; 177(6):2300–5.