The risk of urinary stone recurrence can be decreased with dietary changes and medications
By Margaret S. Pearle, MD, PhD
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IN THE United States, the incidence of urinary stone disease is about 12% in men and 7% in women, and evidence suggests that these numbers are increasing. For patients who form stones, the likelihood of a recurrence is nearly 50% within five years and up to 95% over a lifetime. Stone disease comes with a hefty price tag. Annual spending for urolithiasis care in 2000 was estimated to be nearly $2.1 billion (J Urol. 2005;173:848-857). A meta-analysis of randomized medical therapy trials has shown that drug and dietary therapy can reduce the risk of urinary stone recurrence by 22.6% (J Endourol. 1999;13:679-685), but many patients with recurrent stone disease go undiagnosed or fail to receive a thorough metabolic evaluation or counseling about diets and medications that could help them. Clinicians may find that the evaluation process is complicated or that their understanding of the pathophysiology of stone disease is limited. They also might be reluctant to prescribe drugs that require close follow-up, are associated with adverse effects, and can be expensive.
Pathophysiology
Among the metabolic abnormalities that can lead to stone formation are hypercalciuria, hypocitraturia, and gouty diathesis. Hypercalciuria is characterized by intestinal hyperabsorption of calcium. It occurs in 35%-65% of recurrent stone formers, and can result in bone loss. Osteoporosis occurs in up to 25% of patients with this disorder. Hypocitraturia stems from intracellular acidosis, which results from various environmental, dietary, and metabolic factors, including strenuous physical exercise, sodium load, animal protein excess, distal renal tubular acidosis, potassium deficiency, and chronic diarrhea. A decline in citrate leads to enhanced crystallization of stone-forming calcium salts such as calcium oxalate and calcium phosphate.
In gouty diathesis, uric acid stones may develop from defective ammoniagenesis (Curr Opin Nephrol Hypertens. 2004;13:181-189). The hallmark of this condition is low urinary pH (less than 5.5) that causes an increased amount of poorly soluble undissociated uric acid, resulting in uric acid stones.
Researchers have found that uric acid nephrolithiasis occurs in 34% of diabetics and 6% of non-diabetics and that a significant inverse relationship exists between urinary pH and body weight (Urology. 2003;61:523-527). It is thought that obesity leads to insulin resistance, which in turn results in a drop in urinary pH.
In contrast, a urinary pH greater than 5.5 can lead to hyperuricosuric calcium nephrolithiasis. Increased dissociation of uric acid results in high saturation of monosodium urate that in turn causes calcium oxalate crystallization that may lead to calcium stones.
Role of diet
Citrus fruits can play a beneficial role in stone prevention by delivering an alkali load. The amount of alkali delivered depends on the potassium content of fruit. Potassium-rich fruit juices confer an alkali load, but potassium-poor citrus fruits do not. Lemon and cranberry juices contain little or no potassium, whereas apple and pineapple contain moderate amounts and grapefruit and orange juice contain large amounts.
In two metabolic trials evaluating the effect of citrus juices on urinary stone risk factors, our group at the University of Texas Southwestern Medical Center in Dallas found that orange juice showed benefit with respect to stone risk whereas cranberry juice did not. In a two-phase, randomized crossover trial, both urinary pH and citrate were observed to increase during orange juice consumption compared with a control water consumption phase (J Urol. 1993;149:140-148).
Animal proteins hike risk
Animal proteins (red meat, fish, and poultry) confer an acid load, which can cause hyperuricosuria, a condition that could lead to calcium stones. The UT Southwestern group recently investigated the effects of a high animal protein diet typified by the Atkins diet in 10 obese non-stoneforming subjects (Am J Kidney Dis. 2002;40:265-274). Both the induction and maintenance diets significantly increased urinary calcium, reduced urinary citrate, and raised net acid excretion. Overall, this study suggests that animal protein is associated with increased risk of stone formation and bone loss.
There is considerable controversy regarding the role of dietary calcium in stone formation, with some advocating dietary calcium restriction and others warning against it for fear of increased stone risk and bone loss.
We recently investigated the relative effects of urinary calcium and oxalate on stone-forming propensity in a large number of calcium stone formers. Contrary to the commonly held notion that urinary oxalate is a more important contributor than urinary calcium to urinary saturation of calcium oxalate, we found that urinary calcium and oxalate contribute equally. Several factors influence the effect of dietary calcium on stone formation, including oxalate intake, the state of intestinal calcium absorption, and the type of dietary restriction, whether it consists of calcium alone or comprises a broad dietary restriction.
Management
For recurrent stone formers, the first step is to obtain a 24-hour urine sample that should be analyzed for calcium and other risk factors. Clinicians should also obtain serum SMA and have the stones analyzed. We recommend that patients then be stratified into three groups based on urinary calcium levels (Group I: moderate to severe hypercalciuria; Group II: mild hypercalciuria; and Group III: normocalciuria [Kidney Int. 2005;68:2264-2273]). Exclude secondary causes such as primary hyperparathyroidism, enteric and primary hyperoxaluria, gouty arthritis, infection and cystinuria.
For Group I patients, we recommend dietary calcium restriction plus potassium citrate and indapamide or a thiazide diuretic. For Group II patients, we advise modest calcium restriction plus potassium citrate along with a hypocalciuric agent when necessary. In Group III, we advise liberal calcium intake, as calcium restriction does not lower urinary calcium, and we add potassium citrate.
Conclusion
Ultimately, physicians need to identify the etiology and then treat with dietary modification and medications that can prevent further stone production. Taking the time to evaluate and classify patients into the proper categories simplifies medical treatment and may ultimately lower overall medical costs and morbidity.
Dr. Pearle is professor of urology at the University of Texas Southwestern Medical Center in Dallas.
