URIC ACID–RELATED NEPHROLITHIASIS

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Uric acid stones account for 5% to 8% of renal calculi in Western countries.24, 67 Uric acid–related nephrolithiasis, which includes hyperuricosuric calcium stones, accounts for up to 40% of stones in some series.47 Unlike most forms of urolithiasis, medical therapy has a pivotal role in active treatment and prophylaxis against stone recurrences. Understanding the pathophysiology and biochemical nature of uric acid leads to a rational treatment approach in patients with uric acid–related urinary stone disease.

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SOLUBILITY CHARACTERISTICS

Uric acid (2,6,8-trioxypurine) is a weak acid with solubility characteristics dependent on concentration and environmental pH (Fig. 1). Urinary volume and uric acid excretion influence concentration; however, urinary pH is the principal determinant of uric acid solubility. A pKa of 5.5 governs the loss of the first dissociable proton from uric acid to form anionic urate.18 A second pKa of 10.3 controls the loss of a second proton from urate but is physiologically unimportant in humans. The

SOURCES OF URIC ACID

Uric acid is an end product of purine metabolism with no known physiologic activity in humans. Purines come from three sources: (1) dietary, (2) de novo synthesis, and (3) cellular RNA from tissue catabolism (Fig. 3). The average daily turnover of uric acid is 600 to 800 mg. Endogenous purine production from de novo purine synthesis and tissue catabolism under most normal conditions is constant at 300 to 400 mg/d. Clinical conditions associated with endogenous overproduction include gout,

ELIMINATION

Once formed, uric acid is eliminated principally through renal excretion or intestinal uricolysis. Renal excretion accounts for approximately two thirds of uric acid disposal, whereas extrarenal routes excrete the remaining one third. Renal compromise results in a compensatory increase in extrarenal disposal.61

CLASSIFICATION

Uric acid solubility is determined by three main factors: (1) urinary volume, (2) uric acid excretion, and (3) urinary pH. Patients with excessive uric acid excretion or who are dehydrated chronically have high urinary concentrations of uric acid and are prone to uric acid stone formation. Most importantly, any clinical condition resulting in a persistently acidic urinary environment predisposes to uric acid nephrolithiasis. A classification scheme based on these three factors for uric acid

HYPERURICOSURIA AND CALCIUM UROLITHIASIS

Although uric acid stone formation is associated with hyperuricosuria, dehydration, and acidic urinary pH less than 5.5, hyperuricosuric calcium oxalate nephrolithiasis (HUCN) is characterized by calcium oxalate or calcium phosphate stone formation in the setting of hyperuricosuria, urinary pH greater than 5.5, and normocalciuria.42 The pKa of uric acid promotes the formation of monosodium urate in uric acid solutions containing sodium at pH greater than 5.5.50 Monosodium urate promotes calcium

DIAGNOSIS

The diagnosis and treatment of uric acid urolithiasis is based on an understanding of the pathophysiology of stone formation. Any patient presenting with renal colic found to have acidic urine (pH < 5.5) or a clinical history that predisposes them to hyperuricosuria or chronic dehydration, or patients with a past history of uric acid lithiasis, should be suspected as having a uric acid stone. Uric acid stones are most common in middle-aged white men. In addition to comorbidities, a thorough

STONE FEATURES

Uric acid stones can range from small rounded calculi that spontaneously pass to fully branched staghorn calculi that fill the entire renal collecting system. Unlike calcium oxalate stones, which often are jagged, uric acid stones are typically smooth and round and more readily passed spontaneously. They have an affinity for urochromes and typically appear yellow to deep brown in color but also can be black.

Pure uric acid stones are classically radiolucent on standard radiographs. Other

TREATMENT

Treatment of uric acid stones can be classified as active for an existing stone versus prophylactic against stone recurrences. Uric acid stones are unique in that they are the only common renal stone readily amenable to dissolutional therapy. Active and prophylactic therapy focus on altering the urinary environment to optimize the solubility characteristics of uric acid. Consequently, treatment of uric acid stones is directed at increasing urinary volume, alkalinizing urinary pH, and decreasing

TREATMENT OF HYPERURICOSURIC CALCIUM OXALATE STONES DISEASE

HUCN accounts for 10% to 15% of patients with calcium urolithiasis.12, 45 Treatment for HUCN involves reducing the propensity for monosodium urate–induced calcium oxalate crystallization. This is accomplished by decreasing urinary uric acid excretion and limiting dietary sodium intake (<150 mEq/d). The hyperuricosuria of HUCN most often is attributed to overindulgence of dietary proteins and successful prophylactic therapy often results from dietary protein reduction.12 Hyperuricosuria in

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    *

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