INTRODUCTION — Kidney stones are increasingly recognized in children. The epidemiology and etiology of kidney stones in children will be reviewed here. The clinical manifestations, diagnosis, acute management, and prevention of recurrence are discussed separately. (See "Kidney stones in children: Clinical features and diagnosis" and "Kidney stones in children: Acute management" and "Kidney stones in children: Prevention of recurrent stones".)
EPIDEMIOLOGY
The diagnosis of pediatric kidney stones has increased as illustrated by the following:
●A study using data from a commercial health claims database reported the annual rate of pediatric cases for urinary stone disease in the United States rose from 2005 to a peak of 65.2 cases per 100,000 person years in 2011 [1].
●A population-based study of children who were younger than 18 years of age from a single county in Minnesota that reported a yearly increase in the incidence of kidney stones from 7.2 to 14.5 per 100,000 person-years between the two time periods of 1984 to 1990 and 2003 to 2008 [2]. In this study, it remains uncertain whether there was a true increase in the risk of pediatric kidney stones or if there was improvement in making the diagnosis of stone disease with the use of computerized tomography.
●An Israeli study based reported histories during compulsory medical evaluations of 17-year-old military enlistees found the average prevalence rate increased from 69 to 120 cases per 100,000 individuals between the two time periods of 1980 to 1995 and 2010 to 2012 [3]. During the same time period, the authors also noted an increase in body mass index and hypothesized whether a possible association existed.
Data from the United States Pediatric Health Information System (PHIS) have shown a proportional increase in hospitalizations due to pediatric kidney stones with a diagnosis of kidney stones made in 1 case for every 685 pediatric hospitalizations [4,5].
Additional factors that may affect the prevalence of kidney stones include:
●Age – The incidence of kidney stones is lower in children than in adults, and the incidence increases with age, with adolescents having the highest risk of kidney stones [1,2].In a population-based United States study of patients over 10 years of age, adolescents between 10 and 19 years of age accounted for only 4 percent of the total episodes of kidney stones [6]. For the total population, the incidence of kidney stones was 109 per 100,000 men per year and 36 per 100,000 women per year. The explanation for the lower pediatric incidence is unknown, but may be due in part to the higher concentrations of crystal formation inhibitors such as citrate and magnesium in the urine of children compared with adults [7,8].
●Sex – Children do not have the strong male predominance seen in adults with kidney stones. Some studies do show a slightly higher prevalence in boys [5,9-14], whereas a Taiwanese study and the previously mentioned United States report found a higher prevalence in girls compared with boys [1,15].
In the United States, sex distribution varied with age in children who were hospitalized for kidney stones [16]. Boys were more commonly affected in the first decade of life and girls in the second decade. This sex variation may reflect that boys are more likely to have obstructive urinary malformations resulting in kidney stones that typically presents early, whereas there is an increase in the rate of urinary tract infections, another risk factor for kidney stones, in postpubertal sexually active girls.
●Race – Numerous studies have demonstrated that kidney stones are more common in White children and occur rarely in Black children [1,5,17,18].
●Geography – Similar to adults, the incidence of kidney stones in children varies worldwide, with the highest incidence occurring in endemic areas, such as in Turkey and Thailand. Data from the National Health Insurance Research Database reported that the risk of kidney stones was greater in children who lived in urban areas and in those with urinary tract infection [15].
OVERVIEW OF RISK FACTORS — In children with kidney stones, an underlying risk factor is identified in as high as 75 to 85 percent of affected children [9-14]. In most children, kidney stones are associated with a urinary metabolic abnormality, urinary tract infection, and/or a structural kidney or urinary tract abnormality [9-14,17,19].
METABOLIC RISK FACTORS
Pathogenesis — The two mechanisms by which metabolic factors enhance stone formation include:
●Solute excess – High urinary concentrations of calcium, oxalate, uric acid, and cystine due to increased renal excretion and/or low urine volume cause solute excess. This leads to solute supersaturation and precipitation, and results in the formation of crystals, which may aggregate into a stone.
●Decreased levels of inhibitors of stone formation – Natural inhibitors of urinary stone formation include citrate, magnesium, and pyrophosphate. Low levels of these inhibitors, particularly hypocitraturia, are associated with kidney stones in both adults and children.
In two case series of children with kidney stones, approximately 90 percent of patients had at least one metabolic risk factor [20,21]. Common risk factors include low urine flow rate, hypercalciuria and hypocitraturia.
Stone composition — In general, stone composition varies based on age and sex in both adults and children (figure 1). Based upon case series, the frequency of different stone composition in children is as follows [17,18]:
●Calcium oxalate – 45 to 65 percent
●Calcium phosphate – 14 to 30 percent
●Struvite – 13 percent
●Cystine – 5 percent
●Uric acid – 4 percent
●Mixed or miscellaneous – 4 percent
Hypercalciuria
Overview — Hypercalciuria is the most common metabolic abnormality associated with pediatric stone disease [22,23]. It is identified as the major contributing factor in at least half of the children with a metabolic cause for kidney stones [9,17].
Hypercalciuria may also cause nephrocalcinosis, a condition in which calcium salts precipitate out of solution within the kidney and urologic system. Hematuria, dysuria, and urinary frequency can be seen in children with hypercalciuria [24-26]. (See "Evaluation of gross hematuria in children" and "Evaluation of microscopic hematuria in children".)
Definition — Hypercalciuria is defined as urinary calcium excretion rate that is greater than 4 mg/kg per 24 hours in a child greater than two years of age, while ingesting a routine diet (table 1) [27,28]. However, urinary calcium excretion may normally be at this level during periods of rapid adolescent growth [29].
At times, it may be difficult to obtain a 24-hour sample. An alternative method of quantitative assessment is measurement of the total calcium/creatinine ratio (mg/mg) on a spot urine sample (table 2) [30,31]. We suggest that a spot urine calcium/creatinine ratio be used for screening for hypercalciuria. In patients with an elevated ratio, a 24-hour urine collection should be obtained to confirm the presence of hypercalciuria prior to initiation of treatment.
Infants (one year of age or less) have higher urinary calcium excretion and lower urinary creatinine excretion. As a result, the normal urine calcium/creatinine ratio for infants is higher than for older children as follows [27,28,32,33]:
●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)
Pathogenesis — Three mechanisms contribute to higher urinary calcium excretion [34-38]:
●Increased intestinal absorption ("absorptive hypercalciuria") in which there is an increase in intestinal calcium absorption resulting in excess serum calcium and high urinary calcium excretion.
●Increased renal losses ("renal hypercalciuria") in which there is a defect in renal tubular calcium reabsorption resulting in an increase in urinary calcium excretion.
●Increased bone resorption ("resorptive hypercalciuria") in which the source of the excess calcium is bone.
Both genetic and environmental factors can affect these mechanisms, thereby increasing urinary calcium excretion and the risk for kidney stones.
Genetic factors — There is evidence that many cases (and likely a majority of cases) of idiopathic hypercalciuria represent a complex interaction among many genes and environmental factors [39,40]. Proposed specific involvement includes genes that affect the calcium sensing receptor, calcium channels in the intestine and kidney, vitamin D receptor, intestinal oxalate exchangers, renal and bone resorption, and renal excretion of calcium, oxalate, and citrate. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Family history'.)
Less commonly, a monogenic defect can cause hypercalciuria via any of the three physiologic mechanisms that results in kidney stones or nephrocalcinosis [38-40].
●Monogenic disorders that increase intestinal absorption of calcium include hypophosphatemia and absorptive hypercalciuria, Blue diaper syndrome, and congenital malabsorption disorders (ie, congenital lactase deficiency, congenital sucrase-isomaltase deficiency, and glucose/galactose malabsorption). (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia" and "Etiology of hypercalcemia", section on 'Congenital lactase deficiency'.)
●Monogenic disorders that impair renal tubular calcium reabsorption include the following:
•Dent disease, also referred to as X-linked recessive kidney stones (see "Dent disease (X-linked recessive nephrolithiasis)")
•Bartter syndrome (see "Inherited hypokalemic salt-losing tubulopathies: Pathophysiology and overview of clinical manifestations")
•Wilson disease (see "Wilson disease: Clinical manifestations, diagnosis, and natural history", section on 'Other manifestations')
•Glycogen storage disease type 1a (see "Glucose-6-phosphatase deficiency (glycogen storage disease I, von Gierke disease)", section on 'Clinical features')
•Hereditary distal renal tubular acidosis (RTA) with identified mutations in either the basolateral chloride-bicarbonate cotransporter or in the apical hydrogen-ATPase (see "Etiology and diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis", section on 'Distal (type 1) RTA' and "Nephrolithiasis in renal tubular acidosis" and "Overview and pathophysiology of renal tubular acidosis and the effect on potassium balance")
•Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (see "Hypomagnesemia: Causes of hypomagnesemia", section on 'Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)' and "Hypomagnesemia: Causes of hypomagnesemia")
●Monogenic disorders that increase bone absorption include multiple endocrine neoplasia type 1 syndrome with hyperparathyroidism [41], and McCune-Albright syndrome. (See "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)
Environmental factors — The following environmental factors can increase urinary calcium excretion [19,34-37]:
●Dehydration due to exertion or environmental conditions without adequate fluid replacement resulting in decreased urine volume.
●Immobilization with increased bone resorption [14,42].
●Medications such as loop diuretics, which increase calcium renal excretion (especially in neonates), and glucocorticoids, which increase bone resorption. (See "Nephrocalcinosis in neonates".)
●Excessive amounts of vitamin D.
The role of calcium, routine dietary vitamin D supplementation, and other solutes as risk factors in kidney stone formation is unclear and is discussed separately. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Dietary factors'.)
Other factors — Secondary forms of hypercalciuria include hyperparathyroidism [41], chronic metabolic acidosis in association with hypocitraturia, hypercalcemia from any cause, and hypophosphatemia. (See "Primary hyperparathyroidism: Clinical manifestations" and 'Hypocitraturia' below and "Etiology of hypercalcemia" and "Hypophosphatemia: Causes of hypophosphatemia".)
Hyperoxaluria and oxalosis — In case series of pediatric kidney stone disease, hyperoxaluria is detected in 10 to 20 percent of children [9,17].
●Definition – Hyperoxaluria is defined as a urinary oxalate excretion rate that is greater than 50 mg/1.73 m2 per 24 hours (table 1) [27].
An alternative method of quantitative assessment is measurement of the total oxalate/creatinine ratio on a spot urine sample. However, normative values vary depending on the age of the patient and the assay method [27,43-45]. This was illustrated in a prospective study of 30 healthy infants that demonstrated a mean oxalate/creating ratio of 0.08 mg/mg (0.1 mmol/mmol) using an enzymatic oxalate assay, compared with a mean value of 0.13 mg/mg (0.16 mmol/mmol) using a chemical-colorimetric method. In addition, normative values were higher in infants who were formula-fed compared with those who were breastfed. As a result, it is important that the clinician knows the normative reference values for the laboratory that is used for this analysis.
●Etiology – Idiopathic hyperoxaluria is the most commonly diagnosed cause for children with oxalate stones. It often occurs in conjunction with hypercalciuria resulting in calcium oxalate crystals and stones (picture 1A-B). The underlying pathogenesis of idiopathic hyperoxaluria is unknown. It has been proposed that affected patients have increased urinary oxalate excretion because of increased oxalate production or enhanced gastrointestinal oxalate absorption.
Other causes of hyperoxaluria include the following:
•Primary hyperoxaluria – Primary hyperoxaluria type I and II, rare autosomal disorders, are characterized by enhanced conversion of glyoxalate to poorly soluble oxalate resulting in increased serum oxalate and hyperoxaluria. These disorders are discussed in greater detail separately. (See "Primary hyperoxaluria".)
•Fat malabsorption – Children with fat malabsorption may have an enhanced enteric absorption of oxalate. Excess fatty acid binds calcium resulting in less available calcium to combine with oxalate, and thus, more free oxalate is absorbed. Children with inflammatory bowel disease [46], extensive bowel resection, pancreatitis, and cystic fibrosis are at risk for hyperoxaluria and kidney stones. In addition, Orlistat, a new antiobesity agent that inhibits gastrointestinal lipase, causes secondary hyperoxaluria [47]. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'High urine oxalate' and "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Malabsorption' and "Chronic complications of short bowel syndrome in children", section on 'Hyperoxaluria and kidney stones'.)
In these patients, the degree of hyperoxaluria is dependent on the dietary intake of oxalate. Urinary oxalate excretion can be reduced by decreasing dietary oxalate, eating a low-fat diet, adding dietary calcium supplements, and increasing fluid intake.
•Excessive oxalate ingestion – Ethylene glycol, ascorbic acid, and methoxyflurane are metabolized to form oxalate. Excessive ingestions of these products result in increased serum oxalate and hyperoxaluria. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis".)
Hyperuricosuria — Hyperuricosuria is detected in 2 to 8 percent of children with kidney stones. Determining whether uric acid excretion is abnormally elevated in children can be challenging. Uric acid excretion is highest in infants and remains high in children until adolescence when values decrease to adult values. In infants, the normal urinary uric acid excretion is so high that crystals may precipitate in the diaper and be misidentified as blood (picture 2A-B and picture 3).
●Definition – Reference values that are age-specific are available, however, 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 2). This value is calculated using the following equation, where UCr and PCr are the urine and plasma creatinine concentrations, respectively:
Urine uric acid x PCr
Uric acid/GFR, mg/dL = --------------------
UCr
●Etiology – Increased urinary excretion of uric acid can result from either enhanced renal excretion or increased production of uric acid.
Idiopathic hyperuricosuria is thought to be due to a defect in renal tubular uric acid excretion and is often seen in conjunction with hypercalciuria. It is also frequently present in families and is generally asymptomatic. However, in some families, formation of uric acid stones occurs, usually in individuals with constantly acidic urine.
In childhood, pure uric stones are uncommon and are generally due to overproduction of uric acid due to tumor lysis syndrome, lymphoproliferative and myeloproliferative disorders, or rare genetic disorders such as Lesch-Nyhan (hypoxanthine-guanine phosphoribosyl transferase deficiency), and glycogen storage diseases. In addition, a high dietary intake of purines or hemolysis has been associated with uric acid kidney stones. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors" and "Treatment of acute lymphoblastic leukemia/lymphoma in children and adolescents" and "Hyperkinetic movement disorders in children", section on 'Lesch-Nyhan syndrome' and "Glucose-6-phosphatase deficiency (glycogen storage disease I, von Gierke disease)" and "Phosphofructokinase deficiency (glycogen storage disease VII, Tarui disease)".)
●Clinical significance – Many of the conditions with hyperuricosuria can also lead to acute kidney failure due to precipitation of uric acid within the renal tubules. (See "Uric acid kidney diseases", section on 'Acute uric acid nephropathy'.)
Cystinuria — Cystine stones account for 5 percent of pediatric kidney stone disease and are caused by cystinuria, an autosomal recessive disorder of renal tubular transport. Cystinuria is characterized by excessive excretion of the dibasic amino acids cystine, arginine, lysine, and ornithine. It appears to be caused by mutations and/or genomic rearrangements in two genes, SLC3A1 and SLC7A9. (See "Cystinuria and cystine stones".)
In children, normal urinary cystine excretion rates are less than 60 mg of cystine/1.73 m2 body surface area (BSA) per day (table 1). Patients with cystinuria often excrete more than 400 mg/1.73 m2 BSA per day and patients with nonspecific proximal renal tubule aminoaciduria may excrete as much as 200 mg cystine/1.73 m2 BSA per day. An alternative method of quantitative assessment is measurement of the total cystine/creatinine ratio (mg/mg) on a spot urine sample, which is normally less than 0.02 mg/mg (0.01 mmol/mmol) (table 2).
The colorless, flat, hexagonal cystine crystals found in the urinary sediment are diagnostic, but are only identified in 20 to 25 percent of individuals with this disorder (picture 4). Recurrent kidney stones appear to be the only manifestation of cystinuria.
Hypocitraturia — Citrate is an inhibitor of calcium oxalate and calcium phosphate crystallization. In adult patients with idiopathic kidney stones, hypocitraturia is a frequent finding. Hypocitraturia has also been reported in 10 percent of children with kidney stones [48]. In one study, citrate excretion was lower in 78 children with calcium stones compared with a control group of 24 healthy nonstone-forming children [49].
Citrate excretion is greater in children than adults. In children, hypocitraturia is defined as a urinary citrate excretion rate that is less than 400 mg/g of creatinine in a 24-hour urine collection (table 1) [50].
Citrate combines with calcium in the tubular lumen to form a nondissociable but soluble complex resulting in less free calcium available to combine with oxalate. Citrate also appears to inhibit crystal agglomeration, in which individual calcium oxalate crystals combine to form a stone.
Children with chronic metabolic acidosis have an increased risk of kidney stones. In these patients, because of enhanced proximal renal tubular citrate reabsorption, citrate excretion is decreased, leading to stone formation. Chronic diarrhea (ie, cystic fibrosis), administration of carbonic anhydrase inhibitors (ie, topiramate [51]), and renal tubular acidosis (RTA) including acquired forms due to medications (ie, ifosfamide) or recreational drugs (eg, toluene exposure from glue sniffing) are associated with chronic metabolic acidosis and kidney stones.
Although the cause of idiopathic hypocitraturia is unknown, proposed etiologies include ingestion of a high protein diet and polygenetic factors. (See "Kidney stones in adults: Epidemiology and risk factors", section on 'Low urine citrate'.)
Melamine exposure — Melamine is a synthetic product used to form resins with formaldehyde and is found in a variety of products in which resin-based coatings are used. The stones are not radiopaque and therefore not seen on plain films; however, they are easily visualized by abdominal ultrasonography or computed tomography.
Increased melamine exposure has been linked to urolithiasis in both children and adults. This risk was highlighted by the 2008 melamine-tainted baby formula in China that resulted in over 50,000 affected infants, including 13,000 who were hospitalized for acute kidney failure due to urinary obstruction, and six deaths [52,53]
Several retrospective studies have shown that infants with exposure to formula with a high melamine content (>500 ppm) were most likely to develop kidney stones [54-56]. However, kidney stones was also observed in patients with either exposure to formula with moderate (<150 ppm) or low content (6.2 to 17 ppm). In most patients, there was a lack of urinary symptoms and abnormalities. In these studies, ultrasonographic evaluation was the main imaging study used to make the diagnosis of melamine-associated kidney stone. However, the available data suggest that ultrasound screening for melamine-associated stones should be reserved only for individuals who have been exposed to products with high melamine concentration exceeding a minimum value of 150 ppm.
Follow-up studies showed that kidney stones resolved in most patients with conservative therapy (eg, increased fluid intake, urine alkalinization, and diuresis) [57,58]. In some cases, further interventions were undertaken including extracorporeal shock wave lithotripsy, retrograde ureteral catheterization, and other more invasive surgical procedures (ureteral lithectomy, percutaneous nephrostomy or nephrolithotomy, and ureteroscopic lithotripsy) . [58,59] (See "Kidney stones in children: Acute management".)
The United States Food and Drug Administration (FDA) published guidelines that established a tolerable daily melamine intake of 0.5 mg/kg [52]. Thus, in an infant who weighs 5 kg, the greatest tolerable amount of melamine would be 2.5 mg per day, which is equivalent to an intake of 750 mL of formula with a concentration of melamine of 3.3 mg/L (ppm). By comparison, the Sanlu product that has been incriminated in the cases in China had concentration of melamine that resulted in a 100-fold greater melamine intake than the suggested tolerable level [52].
However, melamine exposure remains a potential source of kidney stones, especially with the use of melamine tableware. Hot soup consumption using melamine bowls results in a continuous low-dose exposure to melamine, which has been associated with kidney stones [60].
Other metabolic causes — There are a wide range of disorders that result in urine solute excretion abnormalities that increase the risk of kidney stones. They include the following:
●High animal protein diet – Diets with a high content of animal protein can result in high urinary excretion rates of uric acid, calcium, and oxalate, and low urinary excretion rate of citrate. These changes in urinary solute excretion may predispose the child to the formation of calcium oxalate crystals and stones.
●Ketogenic diet – Kidney stones are reported in 3 to 10 percent of children treated with a ketogenic diet for management of their seizures disorders [61-64]. Urinary metabolic abnormalities include hypercalciuria, hyperuricosuria, and hypocitraturia. In patients with kidney stones, the stone composition varies and includes calcium oxalate, uric acid, and ammonium urate, as well as mixed stones of calcium and uric acid. (See "Ketogenic dietary therapies for the treatment of epilepsy".)
●Cystic fibrosis – Patients with cystic fibrosis have an increased risk of kidney stones, most commonly due to calcium oxalate, and nephrocalcinosis [65,66]. Although hyperuricosuria, hypercalciuria, and hypocitraturia can be present, hyperoxaluria due to enhanced enteric oxalate absorption is thought to be the primary contributor to stone formation. In addition, tubular dysfunction from cotrimoxazole and ceftazidime therapy may play a role in kidney stones [66].
●Drugs – Many drugs alter solute excretion such as furosemide, acetazolamide, and allopurinol, resulting in stone formation. A rare complication of allopurinol therapy is secondary xanthinuria and hypouricosuria. In contrast, stone formation due to indinavir, a HIV protease inhibitor, is due to precipitation of the drug itself, which has a low solubility at a urine pH of 6.0 (picture 5). Some classes of oral antibiotics (oral cephalosporins, fluoroquinolones, sulfas, nitrofurantoin, and broad-spectrum penicillins) have been associated with increased risk of kidney stones [67]. The greatest risk was observed among younger children and most recent use.
●Inborn errors of metabolism – Inborn errors of metabolism associated with kidney stones include abnormalities in purine and pyrimidine metabolism, such as the following:
•Adenine phosphoribosyltransferase deficiency, a rare inborn error of purine metabolism, is an autosomal recessive trait that is associated with radiopaque calculi composed of 2,8-dehydoxyadenine [68,69].
•Xanthine oxidase deficiency, an autosomal disorder of purine metabolism, results in xanthine calculi in one-third of affected patients [70]. These patients have a low urinary excretion of uric acid.
•Orotic aciduria is a rare inborn error of pyrimidine metabolism that is recessively inherited. This disorder is characterized by an onset in early infancy, growth failure, developmental delay, hypochromic anemia, and excessive urinary excretion of orotic acid, an intermediary of uridine synthesis [71].
•Another inborn error of metabolism, alkaptonuria, is a disorder of tyrosine metabolism that is usually associated with kidney stones in adulthood, but there are cases of kidney stones reported in childhood [72]. (See "Disorders of tyrosine metabolism", section on 'Alkaptonuria'.)
INFECTION — In 20 to 25 percent of children with kidney stones, urinary tract infection (UTI) is detected or there is a history of a UTI. Infection may be the primary cause of a stone or occur concomitantly with a underlying urinary metabolic abnormality or structural abnormality.
Functional or anatomic obstruction of the urinary tract predisposes children to stasis and infection, which promote stone formation. Because boys are more likely to have obstructive uropathy, 80 percent of children with stones associated with infections are male. Infection-associated stones are usually detected before five years of age. All races are equally affected. Improvements in the detection and repair of obstructive uropathy have reduced the incidence of stones due to infections.
Bacteria that produce the enzyme urease are strongly associated with pediatric kidney stones and include Proteus, Providencia, Klebsiella, Pseudomonas, and enterococci. Urease breaks down urea to form ammonium and bicarbonate, which creates a favorable biochemical milieu for the formation of struvite stones (magnesium ammonium phosphate). Struvite stones, which can contain carbonate apatite, tend to branch, enlarge, and often fill the renal calyces, producing a "staghorn" appearance (image 1 and image 2). (See "Kidney stones in adults: Struvite (infection) stones".)
In addition, infections may also produce a soft radiolucent mucoid substance called "matrix concretion" that may calcify readily and account for the rapid formation of some infection-related calculi.
Xanthogranulomatous pyelonephritis is a rare, severe chronic infection of the kidney that leads to renal parenchymal destruction and chronic inflammation characterized by lipid-laden macrophages [73-75]. In 70 percent of affected children, obstruction is caused by kidney stones, resulting in a nonfunctioning or poorly functioning kidney. Nephrectomy or partial nephrectomy is often required to treat these patients [76]. (See "Xanthogranulomatous pyelonephritis".)
CONGENITAL/STRUCTURAL ABNORMALITIES — In case series of children with kidney stones, structural abnormalities are reported in 10 to 25 percent of patients [17,77,78]. Congenital and structural abnormalities that are accompanied by urinary stasis are associated with kidney stones. Urinary stasis predisposes to crystal and stone formation.
Kidney and urinary tract abnormalities associated with urinary stasis and kidney stones include:
●Medullary sponge disease (see "Medullary sponge kidney", section on 'Kidney stones and nephrocalcinosis')
●Autosomal dominant polycystic kidney disease (see "Autosomal dominant polycystic kidney disease (ADPKD): Kidney manifestations", section on 'Nephrolithiasis')
●Ureteropelvic junction obstruction (see "Congenital ureteropelvic junction obstruction")
●Horseshoe kidney (image 3) (see "Renal ectopic and fusion anomalies", section on 'Horseshoe kidney')
●Bladder exstrophy
●Augmentation of the bladder – Patients who have surgically augmented bladders are at risk for kidney stones, most commonly bladder stones composed of struvite [79]
●Neurogenic bladder
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: 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 5th to 6th 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 10th to 12th 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.)
●Basics topic (see "Patient education: Kidney stones in children (The Basics)")
SUMMARY
●Pathogenesis – Urinary stones develop when there is precipitation of solutes because of urinary solute supersaturation. (See 'Pathogenesis' above.)
This is due to two mechanisms:
•Solute excess due to increased urinary concentration of solutes due to increased renal excretion and/or low urine volume.
•Decreased levels of inhibitors of stone formation, including citrate.
●Risk factors – An underlying risk factor is identified in 75 to 85 percent of children with kidney stones. Predisposing conditions include a urinary metabolic abnormality, infection, and/or structural abnormality of the kidney or urinary tract. (See 'Overview of risk factors' above.)
•Metabolic risk factors – A urinary metabolic abnormality is identified in approximately 40 to 50 percent of children with kidney stones. The most common disorder is hypercalciuria, followed by hyperoxaluria, and hypocitraturia. Hyperuricosuria and cystinuria are less commonly seen in children with pediatric kidney stones. (See 'Metabolic risk factors' above.)
•Urinary tract infection – In 20 to 25 percent of children with kidney stones, a urinary tract infection (UTI) is detected or there is a history of a UTI. Infection may be the primary cause of pediatric kidney stones or occur concomitantly with underlying urinary metabolic abnormality or structural abnormality. Bacteria that produce the enzyme urease are strongly associated with pediatric kidney stones and include Proteus, Providencia, Klebsiella, Pseudomonas, and enterococci. (See 'Infection' above.)
•Structural abnormalities – Structural abnormalities are reported in 10 to 25 percent of children with kidney stones. In these children, urinary stasis predisposes to crystal formation and stone formation. (See 'Congenital/structural abnormalities' above.)
