Nephrolithiasis: Treatment, causes, and prevention

Calcium restriction is not advised

For several reasons, a calcium-restricted diet is not advised for patients with idiopathic hypercalciuria. ²⁶ Dietary calcium restriction can put the patient into negative calcium balance. Further, it is thought that with less calcium to bind to dietary oxalate, more unbound oxalate can be absorbed in the colon and eventually excreted in the urine. This increase in urinary oxalate can be to the point of supersaturation, even though urinary calcium levels remain unchanged.^25,27,28 This, in turn, increases the likelihood of stone formation.

Several studies showed that a higher intake of dietary calcium is actually associated with fewer calcium stone events in both men and women.^25,27,28

Further, a study in 120 Italian patients with hypercalciuric calcium oxalate stones concluded that a diet that is normal in calcium, low in sodium, and low in animal protein was associated with a lower frequency of calcium stones than a low-calcium diet.²⁹ Although both diets were associated with a reduction in urinary calcium concentrations, urinary oxalate excretion rose in those on a low-calcium diet and fell in those on a normal-calcium diet. The reduction in urinary oxalate excretion in patients on a normal-calcium diet was attributed to intestinal binding of dietary oxalate by dietary calcium, thus lessening the amount of free oxalate available for absorption. Although calcium oxalate excretion fell in both groups, it fell more in those on a normal calcium intake. Compared with those on a low-calcium diet, the patients on the normal-calcium, low-sodium, low-protein diet had a 50% lower risk of stones at 5 years.

Hyperparathyroidism

Primary hyperparathyroidism can cause hypercalciuria and nephrolithiasis. In one series,³⁰ 56 (4.9%) of 1,132 consecutive patients with nephrolithiasis had a confirmed diagnosis of hyperparathyroidism. Parathyroidectomy prevented subsequent stone disease in 48 patients.

However, only 17% to 24% of patients with primary hyperparathyroidism have urinary stones composed of calcium oxalate or calcium phosphate.^31,32 In many studies, it was difficult to determine why a minority of these patients develop stones, but two studies shed some light on this.

Parks et al³⁰ found that, compared with nephrolithiasis patients with idiopathic hypercalciuria, those with primary hyperparathyroidism have elevated serum calcium levels (but usually < 11.5 mg/dL), greater degrees of hypercalciuria (352 mg/day vs 252 mg/day, P < .001), and lower serum phosphate levels (2.45 vs 3.10 mg/dL, P < .001).

Odvina et al³³ found, in a study of 131 patients with proven primary hyperparathyroidism, that 78 had nephrolithiasis and 53 did not. Those with stones excreted more calcium (343 mg/day) than those without stones (273 mg/day), had a higher urinary saturation of calcium oxalate and brushite, and excreted twice as much calcium following a 1-g oral calcium load.

These studies suggest that in patients with primary hyperparathyroidism, the risk of forming stones is related to the degree of hypercalciuria, and in particular to the increased intestinal absorption of dietary calcium.

Renal tubular acidosis

Features of distal renal tubular acidosis are systemic metabolic acidosis, alkaline urine, hypokalemia, hypercalciuria, hypocitraturia, and nephrolithiasis. The chronic metabolic acidosis results in loss of bone calcium, contributes to hypercalciuria, and is responsible for the hypocitraturia.³⁴ Stone formation is the result of excessive urinary calcium excretion, the deficiency of the urinary crystal inhibitor citrate, and persistently alkaline urine.

Treatment with sodium bicarbonate or potassium citrate corrects the metabolic acidosis, reduces the loss of calcium from bone, corrects hypokalemia, and increases urinary citrate.

Too much uric acid in the urine

Elevated urinary uric acid excretion (> 800 mg/day in men, > 750 mg/day in women) is associated with formation of calcium oxalate stones³⁵ and, in conjunction with low urine pH, with uric acid stones. An increase in dissolved uric acid salts induces heterogeneous calcium oxalate nucleation.³⁶ In one randomized clinical trial,³⁷ giving allopurinol (Zyloprim) lowered urinary uric acid excretion and was associated with a lower rate of calcium stone disease.

Too much oxalate in the urine

The 95th percentile for urinary oxalate excretion is 45 mg/day in women and 55 mg/day in men.³⁸ Hyperoxaluria increases calcium oxalate supersaturation and contributes to calcium stone formation.

Normally, 90% of dietary oxalate binds to dietary calcium in the small intestine and passes into the stool as calcium oxalate; 10% of dietary oxalate remains free and is absorbed in the colon and subsequently excreted in the urine.

Hyperoxaluria may simply be a result of high dietary oxalate intake. However, increased enteric absorption of dietary oxalate can occur in those on a low-calcium diet (in which less calcium is available to bind to dietary oxalate, as described above) and may partially explain why a low-calcium diet has been associated with increased frequency of calcium stone disease.

Patients with enteric malabsorption of fat (eg, due to inflammatory bowel disease or intestinal bypass surgery for obesity) may also develop hyperoxaluria. This occurs because the excess enteric fat binds dietary calcium and allows free oxalate to be more readily absorbed in the colon.³⁹

Rarely, hyperoxaluria is caused by one of several recessively inherited disorders of oxalate metabolism.⁴⁰

The growing number of people with obesity has resulted in an upsurge in gastric bypass surgery. Although the current procedures do not pose the same metabolic risks as were noted in the 1970s when a different type of bypass was performed, the incidence of kidney stones does appear to be higher after these procedures. A recent analysis of 1,436 patients undergoing Roux-en-Y gastric bypass surgery found that 60 of them developed calcium stones afterward. Of these, 31 who underwent metabolic studies were found to have higher oxalate and lower citrate levels at 12 months of follow-up.⁴¹

Not enough citrate, a stone inhibitor

Hypocitraturia is defined as a daily urine citrate excretion less than 500 mg in women and 434 mg in men.⁴² As already mentioned, citrate plays an important role in inhibiting calcium crystal formation and preventing stone formation.

Urinary citrate excretion is mainly determined by tubular reabsorption, which is increased by acid loads and decreased by alkali loads.⁴³ Low urine citrate levels are often seen in conditions that cause chronic metabolic acidosis, such as inflammatory bowel disease, intestinal malabsorption, and renal tubular acidosis—all of which are associated with increased occurrence of nephrolithiasis. However, in most nephrolithiasis patients with hypocitraturia, the cause is not apparent, and the mechanism of the hypocitraturia cannot be determined.⁴⁴

In recent years, high-protein, low-carbohydrate diets have become popular for weight reduction, but they also have metabolic effects that increase the risk of stones.⁴⁵ The metabolism of a diet high in animal protein produces more hydrogen ions that are buffered by bone, releasing calcium from bone and increasing urinary calcium excretion. These diets also cause intracellular acidosis, resulting in decreased urinary excretion of citrate. As a result of these effects, the stone-forming propensity of the urine is increased.