(1)
Pediatric Surgery, AlSadik Hospital, Qatif, Saudi Arabia
9.1 Introduction
Urolithiasis (from Greek oûron, “urine”, + lithos, “stone”, + -iasis) are calculi formed or located anywhere in the urinary system.
It comprises:
Nephrolithiasis (the formation of kidney stones)
Ureterolithiasis (the formation of stones in the ureters)
Cystolithiasis (the formation of bladder stones)
Nephrocalcinosis refers to increased calcium content in the parenchyma of the kidney.
Urolithiasis is a fairly common disease in adults with an estimated prevalence of 3–5 %.
Urolithiasis has been regarded as an uncommon condition in children.
Childhood urolithiasis however, is an increasingly recognized condition.
The estimated incidence in the United States from the 1950s to the 1970s is approximately 1–2 % that of adults. More recent studies from the United States suggest an increase in the incidence and prevalence of childhood urolithiasis, with one study demonstrating a nearly fivefold increase in the incidence in the last decade.
Calculi are particularly uncommon in children of African descent.
In certain regions, such as Southeast Asia, the Middle East, India, and Pakistan, calculi are endemic.
The endemic calculi observed in developing nations are often confined to the bladder and comprise predominantly ammonium acid, urate, and uric acid, and seem to correlate with a decreased availability of dietary phosphates.
Most calculi in the United States are found in the kidneys or ureters. They are composed of either calcium oxalate or calcium phosphate, and often associated with a metabolic abnormality.
The exact incidence of urolithiasis in childhood is not known but it is believed to be approximately 10 % of that in adults, which is around 5 % in developed countries.
Urolithiasis in childhood differs substantially from that in adults with regard to:
Etiology
Clinical features
Diagnostic techniques
Treatment.
Approximately 40 % of children with urolithiasis have a positive family history of kidney stones.
Most of the children with urolithiasis have an underlying metabolic etiology.
Materials that produce stones in the urinary tract of children include the following:
Calcium with phosphate or oxalate
Purine derivatives
Magnesium ammonium phosphate (struvite)
Cysteine
Combinations of the above items
Drugs or their metabolites (e.g., phenytoin, triamterene)
Melamine-contaminated milk powder consumption
9.2 Etiology
The development of urinary stones depends on the following three factors:
Supersaturation of stone-forming components in urine
The presence of chemical or physical stimuli in urine that promote stone formation
Inadequate amount of chemicals in urine that inhibit stone formation (e.g., magnesium, citrate)
The followings are contributing factors to urinary stones developments:
Dietary factors
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 stones.
A ketogenic diet, prescribed to reduce seizures, places children at risk for both uric acid and calcium stone formation.
The development of calcium urolithiasis is attributed to by increased urinary calcium.
Urinary calcium increases:
With increased dietary calcium intake.
With increased sodium chloride intake.
Severe dietary phosphate restriction increases urine calcium excretion.
A diet high in protein from animal sources, glucose or sucrose increases urinary calcium.
Vitamins A and D can contribute to calcium urolithiasis when taken in excessive amounts.
Fructose consumption is also associated with an increased risk of kidney stones.
Drugs taken by the patients may contribute to the development of urolithiasis for the following reasons:
The drug or its metabolites may precipitate as stones (e.g., phenytoin, triamterene, sulfadiazine, felbamate, ceftriaxone).
The drug may increase the concentration of stone-forming minerals by increasing the filtered load or decreasing the tubular reabsorption.
Anticancer agents increase the filtered load of uric acid.
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.
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.
Fluid intake quantitatively and qualitatively is an important factor for the development of urolithiasis.
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 (e.g., sports drinks) contain sodium chloride and sucrose.
Several diseases, or the medications used to treat them, increase the risk of urolithiasis development. These include:
Distal renal tubular acidosis
Short-bowel syndrome
Inflammatory bowel disease
Intractable seizures
Cystic fibrosis
Urolithiasis is also a known complication following renal transplant for the following reasons:
Retention of suture material
Recurrent urinary tract infection
Hypercalciuria
Urinary stasis
Gastrostomy tube–fed children are at higher risk of urolithiasis for the following reasons:
The concomitant use of Topiramate (an anticonvulsant)
Urinary tract infection
Subclinical chronic dehydration
Risk factors for pediatric urolithiasis include the following:
Habitually low urine volume
High urine excretion of calcium
High urine excretion of uric acid
High urine excretion of oxalate
Low urine pH: Uric acid and cysteine are less soluble in acid urine.
High urine pH: Struvite and calcium phosphate are less soluble in alkaline urine.
Nidus for crystal precipitation
In children, hypercalciuria is a significant risk factors for urolithiasis.
Other risk factors for urolithiasis include:
Developmental abnormalities of the urinary tract
Urinary obstruction
Urinary stasis
Urinary tract infection with urea-splitting microorganisms
Functional or anatomic obstruction predisposes children to stone formation by promoting stasis of urine and infection.
Only 1–5 % of children with urologic abnormalities develop calculi, suggesting a concomitant metabolic abnormality in patients with both urologic abnormalities and calculi.
Although infection is commonly associated with kidney stones, it is unlikely to be causative of non–struvite calculi.
Genitourinary anomalies are found in approximately 30 % of children with urolithiasis. These include:
Hydronephrosis
Duplex ureter
Posterior uretheral valves
Bladder exstrophy
Urolithiasis is associated with an identifiable metabolic abnormality in approximately 40–50 % of children.
The major metabolic abnormalities associated with urolithiasis include:
Hypercalciuria
Hyperoxaluria
Hypocitraturia
Cystinuria
Hyperuricosuria
Hypercalciuria or hypocitraturia are the most frequently reported abnormalities in children.
In the United States the chemical composition of urolithiasis is as follows:
40–65 % are calcium oxalate
14–30 % are calcium phosphate
10–20 % are struvite (magnesium ammonium phosphate)
5–10 % are cysteine
1–4 % are uric acid
Rarely, stones may also comprise xanthine, or 2, 8-dihydroxyadenine.
Metabolic abnormalities known to be associated with increased risk for urolithiasis include:
Hypercalciuria
Hypercalciuria is formally defined as calcium excretion of greater than 4 mg/kg/day in children older than 2 years.
Hypercalciuria is found in approximately 30–50 % of children with urolithiasis.
The most common cause in children and adults is idiopathic hypercalciuria.
Idiopathic hypercalciuria is defined as hypercalciuria that occurs in the absence of hypercalcemia in patients in whom no other cause can be identified.
Familial idiopathic hypercalciuria appear to be transmitted in an autosomal dominant fashion with incomplete penetrance.
Approximately 4 % of asymptomatic healthy children demonstrate evidence of idiopathic hypercalciuria, and 40–50 % of those children have a positive family history of urolithiasis.
In school-aged children, a calcium to creatinine ratio of 0.2 mg/mg or less is considered normal, although higher values are reported in younger children.
When hypercalciuria is observed, several conditions must be excluded before establishing a diagnosis of idiopathic hypercalciuria.
In children with hypercalcemic hypercalciuria, the following possibilities should be excluded:
Hyperparathyroidism
Hypervitaminosis D
Prolonged immobilization
Sarcoidosis
Malignancy
Juvenile idiopathic arthritis
Corticosteroid excess
Adrenal insufficiency
William syndrome
In children with hypocalcemic hypercalciuria, the following possibilities should be excluded:
Hypoparathyroidism
Autosomal, dominant hypocalcemic hypercalciuria
Other causes of hypercalciuria include:
Idiopathic hypercalciuria
Prematurity
Diuretics (furosemide and acetazolamide)
Anticonvulsants (topiramate and zonisamide)
Ketogenic diet
Dent disease
Bartter syndrome
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)
Distal renal tubular acidosis (dRTA)
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
Medullary sponge kidney
Dent disease:
This is an X-linked inherited condition caused by a mutation in the CLCN5 gene.
The condition is characterized by low-molecular-weight proteinuria, nephrocalcinosis, normocalcemic hypercalciuria, nephrolithiasis, and chronic kidney disease.
Bartter syndrome:
This is an autosomal recessive condition characterized by renal salt wasting, hypokalemia, metabolic alkalosis, hypercalciuria, and normal serum magnesium levels.
Children younger than 6 years typically present with salt craving, polyuria, dehydration, emesis, constipation, and failure to thrive.
Severe polyhydramnios, prematurity, and occasionally sensorineural deafness are the hallmark features.
There are four types of Bartter syndrome deepening on the mutation.
Mutations in the SLC12A, KCNJ1, and BSND genes (Bartter syndrome type I, type II, and type IV, respectively) typically result in severe dysfunction of the thick ascending limb of the loop of Henle in the neonatal period (neonatal Bartter syndrome).
Mutations in the ClCKB gene (Bartter syndrome type III) usually cause milder dysfunction of the thick ascending limb of the loop of Henle and often present outside the neonatal period (classic Bartter syndrome).
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC):
FHHNC is an autosomal recessive condition caused by mutations in either the CLDN-16 or CLDN-19 genes.
FHHNC often presents in childhood with seizures or tetany caused by hypomagnesemia.
Other clinical manifestations include frequent urinary tract infections (UTI), polyuria, polydipsia, failure to thrive, nephrolithiasis, and progressive renal failure.
Homozygous CLDN-16 or -19 mutations are associated with impaired tight junction integrity in the thick ascending limb of the loop of Henle, urinary magnesium and calcium wasting, and hypomagnesemia.
Patients usually develop the characteristic triad of hypomagnesemia, hypercalciuria, and nephrocalcinosis.
Profound visual impairment characterized by macular coloboma, significant myopia, and horizontal nystagmus can been seen in association with CLDN-19 mutations.
Distal renal tubular acidosis (dRTA):
Primary dRTA is an inherited condition characterized by systemic acidosis as a result of the inability of the distal tubule to adequately acidify the urine.
Failure to thrive, polyuria, polydipsia, hypercalciuria, hypocitraturia, nephrocalcinosis, renal calculi, and hypokalemia are common presenting signs in infancy.
Primary dRTA may be a dominant (SLC4A1 gene) or a recessive condition (ATP6V1B1 or ATP6V0A4 genes).
The inability to secrete H+ ions from the α-intercalated cells of the distal tubule is caused by either a defective vacuolar H+-ATPase (ATP6V1B1 or ATP6V0A4 genes) or a defective Cl−/HCO3− anion exchanger-1 (SLC4A1 gene).
Sensorineural hearing loss may be found in patients with ATP6V1B1 mutations.
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH):
HHRH is a rare, autosomal recessive disorder caused by mutations in the SLC34A3 gene, resulting in loss-of-function of the type IIc sodium phosphate cotransporters of the proximal tubule.
The decreased renal phosphate reabsorption can result in profound hypophosphatemia, normocalcemia, rickets, and bone pain.
Hypercalciuria and nephrolithiasis are also commonly observed and may be the result of a hypophosphatemia-induced stimulation of 1, 25-dihydroxyvitamin D synthesis.
The increased synthesis causes increased gastrointestinal absorption of calcium and excessive urinary calcium losses in the face of normal serum calcium levels.
Hyperoxaluria:
Oxalate is an end product of the metabolic pathways for glyoxylate and ascorbic acid and is primarily excreted by the kidneys.
The vast majority (80–85 %) of daily urinary oxalate excretion is derived from normal metabolic homeostasis.
The remainder (10–15 %) is from dietary intake.
Daily urine oxalate excretion is generally less than 50 mg/day/1.73 m2 of body surface area.
The random urine oxalate to creatinine ratio can be used to estimate oxalate excretion.
Increased urinary oxalate excretion may be caused:
By an inherited metabolic disorder (primary hyperoxaluria [PH]).
Or, more commonly, as a secondary phenomenon caused by increased oxalate absorption or excessive intake of oxalate precursors.
Primary hyperoxaluria (PH):
PH type I and II are relatively rare, autosomal recessive disorders of endogenous oxalate production.
Overproduction of oxalate by the liver causes excessive urinary oxalate excretion with resultant nephrocalcinosis and nephrolithiasis.
The calcium oxalate deposition results in progressive renal damage; however, the clinical presentation can vary from end-stage renal failure in the neonate to occasional stone passage into adulthood.
Because of the clinical variability, the diagnosis is often overlooked and only realized after the loss of a transplanted kidney.
PH type I is caused by mutations in the AGXT gene, which result in a functional defect of the hepatic peroxisomal enzyme alanine–glyoxylate aminotransferase (AGT).
The deficit leads to accumulation of glyoxylate, glycolate, and oxalate in the urine.
Pyridoxine is an essential cofactor for proper AGT activity and, rarely, profound vitamin B6 deficiency can mimic PH type I.
PH type II is caused by mutations in the GRHPR gene with resultant deficient glyoxylate reductase–hydroxypyruvate reductase enzyme activity.
Excessive amounts of oxalate and l-glyceric acid are excreted by the kidney.
PH type II is somewhat milder compared with PH type I but is not benign.Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
