Nephrolithiasis: Treatment, causes, and prevention
ABSTRACTFactors that promote stone formation include low daily urine volumes; saturation of the urine with calcium, oxalate, calcium phosphate, uric acid, or cystine; acidic urine; and bacterial infection. The author identifies the mechanisms of stone formation and outlines management aimed at preventing recurrences.
KEY POINTS
- During an acute stone event, medical management focuses on pain control. Hydration and certain drugs may help the stone to pass.
- Most stones are composed of calcium oxalate or calcium phosphate. Less common are uric acid, magnesium ammonium phosphate, and cystine stones.
- To prevent stones from recurring, patients who have had any type of stone should maintain an adequate fluid intake to keep the urine dilute.
- Paradoxically, calcium restriction is not warranted for patients who have had calcium stones, and may even be harmful.
- Alkalinization of the urine may help prevent recurrent uric acid stones and cystine stones.
PREVENTING RECURRENT STONES: PRINCIPLES AND SPECIFICS
Urinary stone disease recurs in 30% to 50% of patients within 5 years.1,13,14
In preventing recurrent stones, some principles apply to all patients and some are specific to the type of stone the patient had.
Stones form when the urine is supersaturated
Nephrolithiasis occurs when the concentration of stone-forming salts such as calcium oxalate, calcium phosphate, or uric acid is high. When the concentration is high enough to allow crystals to form or preformed crystals to grow, the urine is said to be supersaturated.
Several facors are the major determinants of whether the urine is supersaturated by different salts:
- Calcium oxalate—low urine volume and high concentrations of calcium and oxalate
- Calcium phosphate—a high urine calcium concentration and alkaline urine
- Uric acid—acidic urine
- Cystine—a high urinary cystine concentration and acidic urine.
Increasing daily fluid intake
Since the urinary concentration of stone-forming salts is strongly affected by the daily urine volume, it follows that increasing daily fluid intake is important in preventing recurrent stone disease.
In one study,15 199 patients with a first calcium stone were randomized to a program of high oral fluid intake or no intervention. Five years later, 12 (12%) of the 99 patients in the high-fluid intake group had had a second stone, compared with 27 (27%) in the untreated group (P = .008). Of interest, the baseline 24-hour urine volumes were significantly lower in patients with stones than in 101 normal controls (P = .001), suggesting that habitual low daily fluid intake is a risk factor for calcium stone disease.13
PREVENTING CALCIUM STONES
Most stones are composed of calcium oxalate or calcium phosphate. Calcium stone disease occurs most often in the 3rd to 5th decades of life.
Naturally occurring inhibitors of calcium crystal formation in the urine include citrate, nephrocalcin, uropontin, and magnesium. Of these, only citrate and magnesium levels are routinely measured; low levels of citrate are treated as a cause of calcium stone disease. It follows that the risk of calcium nephrolithiasis is the result of the interplay between the supersaturated state and the level of urinary inhibitors.16
Hypercalciuria and calcium oxalate stones
Calcium oxalate stones begin as crystals that form on the surface of the renal papillae over collections of suburothelial calcium phosphate particles called Randall plaque.17 The driving force for calcium oxalate overgrowth on plaque is calcium oxalate supersaturation, which is strongly linked to high urinary calcium excretion. The fraction of papillary surface covered by plaque in patients with idiopathic calcium oxalate stones correlates directly with the urine calcium level and inversely with urine volume and pH.18
Most patients with calcium oxalate stones have hypercalciuria (defined as 24-hour urinary calcium excretion > 300 mg in men, > 250 mg in women, or > 4 mg/kg in men or women).
Hypercalciuria can be idiopathic
Hypercalciuria can occur in primary hyperparathyroidism, sarcoidosis, vitamin D excess, corticosteroid treatment, renal tubular acidosis, hyperthyroidism, and malignant neoplasms. If none of these conditions is present, elevated urinary calcium excretion is considered idiopathic.
Some patients with idiopathic hypercalciuria have a strong family history of hypercalciuria and, likely, a genetic basis for the disease. This condition has been categorized by the presumed site of the primary abnormality:
Absorptive hypercalciuria. Most patients with idiopathic hypercalciuria absorb too much calcium from the intestine. In many of them, 1,25 dihydroxyvitamin D levels are slightly high and serum phosphorous levels are slightly low; the hypothesis is that they produce more 1,25 dihydroxyvitamin D or are more sensitive to it.19 However, Breslau et al20 showed that not all patients with idiopathic hypercalciuria have absorptive hypercalciuria mediated by 1,25 dihydroxyvitamin D, which suggests that the intestinal hyperabsorption of calcium has other mechanisms.
Resorptive hypercalciuria occurs if increased bone turnover leads to urinary loss of bone calcium.
Renal leak is due to a primary defect in renal tubular transport that causes loss of calcium into the urine and a secondary increase in intestinal calcium absorption or mobilization from bone.
This categorization is based on measuring fasting and 24-hour urine calcium, urinary calcium responses to a low-calcium diet, and responses to an oral calcium load.21 However, these studies are difficult to do and have been shown to have minimal clinical value.
To reduce calcium in the urine, limit sodium, give thiazides
Idiopathic hypercalciuria is worsened by a diet high in sodium22,23 and animal protein.24 Thiazide diuretics lower urinary calcium excretion and promote mineral retention.25 Therefore, treatment of idiopathic hypercalciuria consists of high fluid intake, dietary sodium restriction, and thiazide diuretics.
