Description of the condition
Although more frequent in adults, urinary tract stones (urolithiasis) occur in children, with reported incidence of 2% to 3% and a male to female ratio of 1:1 (Malek 1975; Pietrow 2002). Urinary tract stones in children account for 1/1000 to 1/7600 hospital admissions, according to data from the 1970s to 1990s (Nimkin 1992; Troup 1972; Walther 1980). However, recent reports suggest that urinary calculi are being recognised at an increasing frequency in children (Dwyer 2012; Trinchieri 1996; VanDervoort 2007).
In the US there are over 2 million outpatient visits annually for renal colic at an estimated annual cost of $2 billion (Pearle 2005). Recent studies have also found an 86% increase in emergency department visits secondary to kidney stones in children from 1999 to 2008 (Kairam 2013). There is a 27% to 50% risk of developing a recurrent stone within the first five years of the initial stone episode and approximately 70% of children who form stones will continue with recurrent stone disease during childhood and adulthood (Kocvara 1999; Milliner 1993). Thus, most of these children have chronic, painful and debilitating disease that erratically interrupts their education and the work life of their parents and carers. Because of these factors, prevention of future episodes is critical.
Excluding genetic and secondary causes of stone disease (i.e. medication induced or intestinal malabsorption), there are many nutritional risk factors for the formation of idiopathic nephrolithiasis as the composition of urine is largely determined by diet( Heilberg 2013). For example, high dietary sodium intake decreases proximal tubular sodium reabsorption which reduces renal calcium reabsorption causing hypercalciuria secondary to increased calcium excretion (Heilberg 2013). High animal protein intake, a source of purines, contributes to hyperuricosuria as well as leads to hypercalciuria secondary to increased bone resorption and lower tubular calcium reabsorption (Heilberg 2013). On the other hand, dietary modifications are also protective against stone disease. Citrates increase the solubility of stone-forming calcium salts and inhibit calcium oxalate crystal growth as well as induce a systemic alkalisation which reduces calcium excretion (Heilberg 2013). In addition, as metabolic acidosis results increased in bone resorption, increased citrate intake may also improve bone mineral density (Arrabal-Polo 2013). Potassium may also be protective as decreased potassium intake increases calcium excretion and citrate reabsorption, and ingested potassium will accompany organic ions such as citrate that will be metabolized to bicarbonate (Saxena 2010). Finally, low urinary volume is a well-known risk factor for stone disease and increased water intake results in excretion of a less saturated and higher volume of urine, which benefits all types of stone-formers (Borghi 1996).
Description of the intervention
After the initial acute stone event, long-term management of urinary stone disease focuses on the prevention of recurrent or new urinary stones. Urinary stones may be composed of a variety of constituents including calcium oxalate, calcium phosphate, uric acid, and struvite. The prevention of recurrent stones focuses on improving the balance between the crystal-forming and crystal-inhibiting substances in the urine (Fink 2013). The most basic interventions are dietary and include increasing water intake, restricting consumption of animal protein and salt, and increasing ingestion of fibre, calcium, and potassium (Kocvara 1999). Pharmacologic interventions include thiazide diuretics, potassium salts, allopurinol, and phosphate.
How the intervention might work
Prevention of urinary stones revolves around improving the concentration of various substances in the urine to prevent the precipitation of salts which form into stones. This can be achieved with a variety of dietary and pharmacologic interventions. Simply increasing water intake causes an increase in urine volume. This should in turn decrease the concentration of calcium, oxalate, phosphorus and uric acid in the urine, and thus subsequently reduce the saturation of the salts that form stones (Borghi 1996). An increase in urine volume to > 2.5 L/d has been previously shown in adults to decrease the time to and total number of stone recurrences (Borghi 1996).
With regard to specific diets, it has been hypothesised that excess animal protein intake increases urinary calcium, oxalate and uric acid, and decreases urinary citrate (Dussol 2008). In addition, a high fibre diet also may decrease urinary calcium (Dussol 2008). Oversaturation of urine with calcium is one of the most important risk factors for calcium nephrolithiasis and paradoxically, studies have shown that diets low in calcium actually have increased risks for stone disease possibly secondary to an increase in urinary oxalate (Heilberg 2013). As expected, urinary oxalate excretion increases as dietary oxalate intake increases and thus a low oxalate diet is also thought to be protective (Heilberg 2013). High sodium intake reduces renal tubular calcium reabsorption and thus increases calcium excretion and the risk for stone formation (Heilberg 2013). Citrate is protective against the formation of urinary tract stones because urinary citrate increases the solubility of stone-forming calcium salts and so inhibits calcium oxalate crystal growth (Heilberg 2013).
There are also a variety of medications that can alter the urinary parameters and are hypothesised to prevent urinary stones. Thiazide diuretics cause enhanced calcium reabsorption in the distal renal tubule and decrease the urinary concentration of calcium (Escribano 2009). Because urinary citrate inhibits stone formation, the administration of citrate salts is also hypothesised to prevent recurrent stone disease. Allopurinol, a xanthine oxidase inhibitor, reduces uric acid synthesis and lowers urinary uric acid, has proven to be effective in reducing recurrence of uric acid and calcium stones which form via heterogeneous nucleation (Escribano 2009). Finally, neutral phosphates, sodium/potassium phosphate or both may be used as urinary chelators to reduce stone formation.
Why it is important to do this review
Urinary tract stone disease is a major public health issue; one in 33 children will be affected. Given the increasing incidence of urinary tract stones in children any treatments aimed at preventing recurrent disease will diminish pain and distress, surgical interventions, and medical health costs. To date, there have been very few small studies that have explored the use of any pharmacologic or dietary interventions for prevention of recurrent urinary tract stone disease in children. It is anticipated that this review will stimulate further studies in interventions for the prevention of urinary tract stones in children.