Levels of evidence (1a-4) and grades of recommendation (A-C) are defined at the end of the "Major Recommendations" field.
Stone Formation Mechanisms, Diagnosis of Causative Factors and Medical Treatment for Specific Stone Types
Urinary stone formation is the result of a complex process involving metabolic, anatomical factors and presence of infection.
When supersaturated in urine calcium, oxalate, uric acid and cystine molecules may cause stone formation. A decreased concentration of crystallization inhibitors (citrate, magnesium, pyrophosphate, macromolecules and glycosaminoglycans) may sometimes be the sole factor playing a role in the formation of urinary stones. Urinary pH changes also affect stone formation.
An impaired flow of urine due to abnormal morphology may facilitate stasis and increase the concentration of stone-forming substances.
Calcium Stones
Hypercalciuria. This is defined by a 24-hour urinary calcium excretion of more than 4 mg/kg/day in a child weighing less than 60 kg. In infants younger than 3 months, 5 mg/kg/day is considered to be the upper limit of normal for calcium excretion.
A good screening test for hypercalciuria compares the ratio of urinary calcium to creatinine. The normal calcium-to-creatinine ratio in children is less than 0.2. If the calculated ratio is higher than 0.2, repeat testing is indicated. Neonates and infants have a higher calcium excretion and lower creatinine excretion than older children. If the follow-up ratios are normal, then no additional testing for hypercalciuria is needed. However, if the ratio remains elevated, a timed 24-hour urine collection should be obtained and the calcium excretion calculated.
The 24-hour calcium excretion test is the criterion standard for the diagnosis of hypercalciuria. If calcium excretion is higher than 4 mg/kg/day (0.1 mmol/kg/day), the diagnosis of hypercalciuria is confirmed and further evaluation is warranted. Further evaluation includes levels of serum bicarbonate, creatinine, alkaline phosphatase, calcium, magnesium, pH, and parathyroid hormone. Freshly voided urine should be measured for pH.
A 24-hour urine collection should also be collected for measurement of calcium, phosphorus, sodium, magnesium, citrate and oxalate. Meanwhile dietary manipulations should be tried to normalize urine calcium.
Initial management is always to increase fluid intake and urinary flow. Dietary modification is a mandatory part of effective therapy. The child should be referred to a dietician to assess accurately the daily intake of calcium, animal protein, and sodium. Dietary sodium restriction is recommended as well as maintenance of calcium intake consistent with the daily needs of the child.
A brief trial of a low-calcium diet can be carried out to determine if exogenous calcium intake is contributing to a high urinary calcium. However, great caution should be used when trying to restrict calcium intake for long periods (Level of evidence: 3; Grade of recommendation: B).
Hydrochlorothiazide and other thiazide-type diuretics may be used to treat hypercalciuria at a dosage of 1-2 mg/kg/day (Level of evidence: 3; Grade of recommendation: C). Citrate therapy is also useful if citrate levels are low or if hypercalciuria persists, despite other therapies (Level of evidence: 4; Grade of recommendation: C).
Hyperoxaluria. Oxalic acid is a metabolite excreted by the kidneys. Only 10%-15% of oxalate comes from diet. Normal school children excrete less than 50 mg (0.57 mmol)/1.73m2/day, while infants excrete four times as much.
The diagnosis of primary hyperoxaluria is made upon laboratory findings of severe hyperoxaluria and clinical symptoms. The definitive diagnosis requires liver biopsy to assay the enzyme activity.
The majority of children who have high levels of oxalate excretion in urine may not have any documented metabolic problem or any dietary cause. This is known as idiopathic 'mild' hyperoxaluria, with urine oxalate levels elevated only mildly in these cases.
The treatment of hyperoxaluria consists of the promotion of high urine flow, restriction of dietary oxalate and regular calcium intake. Pyridoxine may be useful in reducing urine levels, especially in primary hyperoxaluria (Level of evidence: 4; Grade of recommendation: C).
Hypocitraturia. Low urine citrate may be a significant cause of calcium stone disease. In adults, hypocitraturia is the excretion of citrate in urine of less than 320 mg/day (1.5 mmol/day) for adults; this value must be adjusted for children depending on body size.
Due to the increased stone risk in hypocitraturia, the restoration of normal citrate levels is advocated to reduce stone formation. Although some studies have shown that citrate replacement therapy reduces the risk of stone formation in an adult population, there are few relevant studies in children. Hypocitraturia is treated by potassium citrate at a starting dose of 1 mEq/kg, given in two divided doses (Level of evidence: 3; Grade of recommendation: B).
Uric Acid Stones
Uric acid stones are responsible for urinary calculi in 4-8% of children. Uric acid is the end product of purine metabolism. Hyperuricosuria is the main cause of uric acid stone formation in children. A daily output of uric acid of more than 10 mg/kg/day is considered to be hyperuricosuria.
Uric acid stones are non-opaque stones. Plain X-rays are insufficient to show uric acid stones, and renal sonography and spiral computed tomography (CT) are used for diagnosis.
Alkalinization of urine is the mainstay of therapy and prevention for uric acid stones. Citrate preparations are useful as alkalinizing agents. Maintaining a urine pH of 6 to 6.5 is sufficient to prevent uric acid stones.
Cystine Stones
Cystinuria is the cause of cystine stone formation and accounts for 2-6% of all urinary stones in children.
Cystine solubility is pH-dependent, with cystine precipitation beginning at pH levels <7.0. Other metabolic conditions, such as hypercalciuria, hypocitraturia and hyperuricosuria, may accompany cystinuria, so leading to the formation of mixed-composition stones.
Cystine stones are faintly radiolucent and may be difficult to show on regular radiograph studies. They are also hard in texture and more difficult to disintegrate by extracorporeal shock-wave lithotripsy (ESWL).
The medical treatment for cystine stones aims to reduce cystine saturation in urine and increase its solubility. The initial treatment consists of maintaining a high urine flow and the use of alkalinizing agents, such as potassium citrate to maintain urine pH at above 7.0. If this treatment fails, the use of alpha-mercaptopropionyl glycine or D-penicillamine may reduce cystine levels in urine and prevent stone formation. Use of these drugs can be associated with severe side effects, such as bone marrow depression and nephrotic syndrome (Level of evidence: 4; Grade of recommendation: C).
Infection Stones (Struvite Stones)
Infection-related stones constitute nearly 5% of urinary stones in children.
In addition to bacterial elimination, stone elimination is essential for treatment, as stones will harbour infection and antibiotic treatment will not be effective. Consideration should be given to investigating any congenital problem that causes stasis and infection. Genitourinary tract anomalies predispose to formation of such stones.
Clinical Presentation
Presentation tends to be age-dependent, with symptoms such as flank pain and haematuria being more common in older children. Non-specific symptoms (e.g., irritability, vomiting) are common in very young children. Haematuria, usually gross, occurring with or without pain, is less common in children. However, microscopic haematuria may be the sole indicator and is more common in children. In some cases, urinary infection may be the only finding leading to radiological imaging in which a stone is identified.
Diagnosis
Imaging
Generally, ultrasonography should be used as a first study. Renal ultrasonography is very effective for identifying stones in the kidney. Many radiolucent stones can be identified with a simple abdominal flat-plate examination.
If no stone is found but symptoms persist, spiral CT scanning is indicated. The most sensitive test for identifying stones in the urinary system is non-contrast helical CT scanning. It is safe and rapid, with 97% sensitivity and 96% specificity (Level of evidence: 2; Grade of recommendation: B). Intravenous pyelography is rarely used in children, but may be needed to delineate the caliceal anatomy prior to percutaneous or open surgery.
Metabolic Evaluation
Due to the high incidence of predisposing factors for urolithiasis in children and high stone recurrence rates, every child with urinary stone should be given a complete metabolic evaluation.
Metabolic evaluation includes:
- Family and patient history of metabolic problems.
- Analysis of stone composition (following stone analysis, metabolic evaluation can be modified according to the specific stone type).
- Electrolytes, blood urea nitrogen (BUN), creatinine, calcium, phosphorus, alkaline phosphatase, uric acid, total protein, carbonate, albumin, and parathyroid hormone (if there is hypercalcaemia).
- Spot urinalysis and culture, including ratio of calcium to creatinine.
- Urine tests, including a 24-hour urine collection for calcium, phosphorus, magnesium, oxalate, uric acid citrate, cystine, protein, and creatinine clearance.
Figure 3 in the original guideline document provides an algorithm of how to perform metabolic investigations in urinary stone disease in children and to plan medical treatment accordingly.
Management
With the advance of technology stone management has changed from open surgical approach to endoscopic techniques that are less invasive. Deciding the form of treatment depends on the number, size, location, composition and anatomy of the urinary tract.
Currently, most paediatric stones can easily be managed by extracorporeal shock-wave lithotripsy (ESWL). Endoscopic treatment can be applied easily for ureteric and bladder stones. Percutaneous removal of stones is also possible for kidney stones in children. Only a small portion of children will need an open surgical approach.
Extracorporeal Shock-Wave Lithotripsy (ESWL)
Many reports confirm that shock-wave lithotripsy (SWL) can be performed in children with no suspicion of long-term morbidity of the kidney.
The mean number of shock waves for each treatment is about 1800 and 2000 (up to 4000 if needed) and the mean power set varies between 14kV and 21kV. The use of ultrasonography and digital fluoroscopy has significantly decreased the radiation exposure, and it has been shown that children are exposed to significantly lower doses of radiation compared to adults. Concerns about anaesthesia do not seem to be a problem anymore because of advances in technique and medication, even in the infant period. The type of anaesthesia should be general or dissociative for children under 10 years of age, whereas conventional intravenous sedation or patient-controlled analgesia is an option for older children who are able to co-operate (Level of evidence: 2b).
Stone-free rates are significantly affected by various factors. Regardless of the location, as the stone size increases, the stone-free rates decrease and re-treatment rate increases. The stone-free rates for <1 cm, 1-2 cm, >2 cm and overall were reported as nearly 90%, 80%, 60% and 80%, respectively. As the stone size increases, the need for additional sessions increases.
Localization of the calculi has been described as a significant factor affecting the success rates in different studies. Stones in renal pelvis and upper ureter seem to respond better to SWL. In these mentioned sites, the stone clearance rates are nearly 90%. However, SWL was found to be less effective for caliceal stones particularly the lower caliceal stones. Several studies reported stone-free rates for isolated lower caliceal stones varying between 50% and 62%.
ESWL treatment can also be used to treat ureteral calculi. However, this is a more specific issue and with controversies. The success rates with ESWL are less for distal ureteric stones. There may also be technical problems with localization and focusing of ureteric stones in children.
The type of machine used has a strong effect on success rates and complications. First-generation machines can deliver more energy to a larger focal zone, resulting in higher fragmentation rates in a single therapy. However, general anaesthesia is usually required due to the intolerable discomfort associated with a first-generation machine. Later-generation machines have a smaller focal zone and deliver less energy, and have a lower risk of pulmonary trauma. However, additional treatments may be needed with later-generation machines. The success rate is higher in younger children.
Although stenting does not affect stone clearance, overall complication rates are higher and hospital stay is longer in the unstented patient. Stenting is essential in solitary kidneys undergoing ESWL treatment. Children with a large stone burden have a high risk of developing Steinstrasse and urinary obstruction and should be followed more closely for the risk of prolonged urinary tract obstruction after ESWL. Post-ESWL stent or nephrostomy tube placement may be needed in prolonged obstruction.
ESWL in children may have complications, but these are often self-limiting and transient. The most frequently observed complications are:
- Renal colic
- Transient hydronephrosis
- Dermal ecchymosis
- Urinary tract infection
- Formation of Steinstrasse
- Sepsis
- Haemoptysis, rarely
In children with sterile pre-operative urine cultures, antibiotic prophylaxis to decrease the infectious complications is not recommended. However, every effort should be made to sterilize the urine before performing ESWL, ureteroscopy (URS), or percutaneous nephrolithotomy.
Percutaneous Nephrolithotomy (PCNL)
ESWL is the first choice for treating most renal paediatric stones. However, percutaneous renal surgery can be used for larger and complex stones. Pre-operative evaluation, indication and surgical technique are similar in children compared to adults. PCNL is used as monotherapy in most cases, but is also used as an adjunctive procedure to other therapies.
The use of adult-sized instruments, in association with an increased number of tracts and sheath size, seems to increase the blood loss. However, small-calibre instruments have now been developed and there are some advantages for PCNL in children (particularly smaller children), such as smaller skin incision, single-step dilation and sheath placement, good working access for paediatric instruments, variable length, and lower cost. Now that appropriate-size instruments are available, age is no longer a limiting factor for PCNL.
As monotherapy, PCNL is considerably effective and safe. The reported stone-free rates in the recent literature are between 86.9% and 98.5% after a single session. These rates increase with adjunctive measures, such as second-look PCNL, ESWL and URS. Even in complete staghorn cases, a clearance rate of 89% has been achieved following a single session.
The most frequently reported complications of PCNL in children are bleeding, post-operative fever or infection, and persistent urinary leakage. Bleeding requiring transfusion is reported in 0.4% to 23.9% and is closely associated with stone burden, operative time, sheath size and number of tracts. Post-operative fever and infection has been reported up to 29.3% and 5.5%, respectively; the origin of fever is not thought to be the infection.
The mean post-operative hospital stay is similar to adults. It is reported as 3 to 4 days in all the previously mentioned studies and is much shorter than open surgery. The less invasive nature of this technique has made it a promising alternative to open surgery for treating renal stones in children (Level of evidence: 2; Grade of recommendation: B).
Ureterorenoscopy
The increasing availability of smaller size endourological equipment has made it possible to manage paediatric ureteral stones using endoscopic techniques.
The technique used in children is similar to the one used in adults. It is strongly recommended that guide wires are used and the procedure is performed using direct vision. Routine balloon dilation of ureterovesical junction and ureteral stenting are controversial. In general, ureteric dilatation is being done less and less and only in selected cases. The general tendency is to use hydrodilation more as it is shown to be as effective (Level of evidence: 3; Grade of recommendation: B).
Different lithotripsy techniques, including ultrasonic, pneumatic and laser lithotripsy, have all been shown to be safe and effective. Because of the smaller size of the probes, laser energy is easier to use in smaller instruments and is more useful for paediatric cases.
All studies reporting the use of endoscopy for ureteric stones in children have clearly demonstrated that there is no significant risk of ureteric strictures or reflux with this mode of therapy (Level of evidence: 1; grade of recommendation: A).
Open Stone Surgery
Most stones in children can be managed by ESWL and endoscopic techniques. Yet in some situations, open surgery is inevitable. Good candidates for open stone surgery include very young children with large stones and/or a congenitally obstructed system which also requires surgical correction. Severe orthopaedic deformities may limit positioning for endoscopic procedures. Open surgery would also be a necessity for such children.
Bladder stones in children can usually be managed by endoscopic techniques. Open surgery may also be used for very large bladder stones or for bladder stones caused by an anatomical problem.
Recommendations for interventional management are given in the Table below.
Table. Recommendations for Interventional Management in Paediatric Stones
| Stone Size and Location* |
Primary Treatment Option |
Level of Evidence (LE) |
Secondary Treatment Option |
|
| Staghorn stones |
Percutaneous Nephrolithotomy (PCNL) |
2b |
Open/SWL |
Multiple sessions and accesses with PCNL may stones be needed
Combination with SWL may be useful
|
| Pelvis <10 mm |
Shock-wave lithotripsy (SWL) |
1a |
Retrograde Intrarenal Surgery (RIRS)/PCNL |
|
| Pelvis 10-20 mm |
SWL |
2b |
PCNL/Open |
Multiple sessions with SWL may be needed
PCNL has similar recommendation grade
|
| Pelvis >20 mm |
PCNL |
2b |
SWL/Open |
Multiple sessions with SWL may be needed |
| Lower pole calix <10 mm |
SWL |
2c |
RIRS/PCNL |
Anatomical variations are important for complete clearance after SWL |
| Lower pole calix >10 mm |
PCNL |
2b |
SWL |
Anatomical variations are important for complete clearance after SWL |
| Upper ureteric stones |
SWL |
2b |
PCNL/URS/Open |
|
| Lower ureteric stones |
Ureteroscopy (URS) |
1a |
SWL/Open |
Additional intervention need is high with SWL |
| Bladder stones |
Endoscopic |
2b |
Open |
Open is easier and with less operative time with large stones |
* Cystine and uric acid stones excluded.
Definitions:
Levels of Evidence
1a Evidence obtained from meta-analysis of randomized trials
1b Evidence obtained from at least one randomized trial
2a Evidence obtained from at least one well-designed controlled study without randomization
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities
Grades of Recommendation
- Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomized trial
- Based on well-conducted clinical studies, but without randomized clinical studies
- Made despite the absence of directly applicable clinical studies of good quality
