Uric acid stones are responsible for 5 to 10% of all stones seen in a stone clinic. Stones composed of uric acid or the sodium salt of this crystal, sodium hydrogen urate, may become clinically manifest as crystalluria, obstruction, dysuria, or bleeding. Elevated serum uric acid may cause interstitial deposition of crystals with inflammation of the renal parenchyma. Crystalluria may occur in the presence or absence of hyperuricemia or hyperuricosuria. Low urine pH may cause crystals in the urine of normal subjects. Uric acid stones occur in a variety of clinical settings (Table 10).
Table 10. Pathophysiologic Classification of Uric Acid Stone Formation
|
Uric acid stones are more frequent in patients with primary gout, and stone formation may occur prior to gouty articular symptoms (51,52,53). The frequency of stone formation among gouty patients is estimated to be about 35%, with increasing frequency of stones as serum or urine uric acid levels rise. Urine pH is the major determinant of urine uric acid supersaturation. Uric acid may appear in the urine as monohydrogen sodium urate as the first of two hydrogen ions dissociates from uric acid with a pK of 5.34. Urate is more soluble in the urine than uric acid, therefore urate stones are rare, and supersaturation refers to the state of uric acid.
Urine pH has a greater influence on uric acid stone formation than the 24-hour urine excretion of uric acid. A decline in urine pH from 6.0 to 5.0 increases urine uric acid six-fold, while increases in excretion due to production only two-fold. Therefore, uric acid stone formation is more determined by pH than by urine volume or urine uric acid concentrations. The normal range for uric acid excretion 500 to 600 mg per 24 hour, and excretions greater than 750 mg for women and 800 mg for men are considered elevated. Clinically significant crystal and stone formation require persistent hyperuricosuria, dehydration, or marked reduction in urine pH. The cause of the low urine pH in uric acid stone-formers is not completely understood, but reductions in urine ammonium excretion appears to play an important role. Dehydration, which reduces urine volume also promotes a decline in urine pH and thereby increases urine uric acid concentration. Stone formers who over-excrete uric acid do so either as a result of excess dietary purine ingestion and metabolic conversion to uric acid, or to excess production of uric acid. Marked overproduction of uric acid may rarely be due to hereditary enzyme deficiency states such as Lesch-Nyhan syndrome (Table 10).
Treatment of a variety of disorders including myeloproliferative disorders, adult chronic granulocytic leukemia, and childhood acute leukemia may be complicated by uric acid stone formation as a result of chemotherapy-induced massive cell necrosis and release of purines. Renal precipitation may be extensive under these conditions, leading to bilateral obstruction and acute renal insufficiency.
Acute diarrheal states and chronic inflammatory bowel disease may be associated with water loss and dehydration. With plasma volume contraction, urine pH falls and predisposes to stone formation. Patients with ileostomy are at increased stone risk due to intestinal bicarbonate losses. Patients with ileal resection may have hyperoxaluria and hyperuricosuria and have stones composed of both uric acid and calcium oxalate.
Hyperuricosuria may be induced by large doses of aspirin or probenecid. In patients with high purine intake, these agents may increase urine uric acid excretion and stone formation.
Familial uric acid nephrolithiasis occurs at a younger age and follows an autosomal dominant pattern of inheritance. Men and women are equally affected. Sporadic cases often begin in the early to mid-adult years, with high rates of recurrence. Serum and urine uric acid levels are normal in both conditions, and urine pH is low and related to reduced renal ammonium production.