Endocrinology and Metabolism Clinics of North America
Review articleHyperuricosuric calcium nephrolithiasis
Section snippets
Definition of hyperuricosuric calcium nephrolithiasis
Patients who form kidney stones with calcium as the major component but are found to have hyperuricosuria (>750 mg/day for women and >800 mg/day for men) as their primary metabolic defect, are classified as having hyperuricosuria calcium nephrolithiasis (HCN). Hyperuricosuria may sometimes be associated with uric acid stones or mixed stones of uric acid and calcium oxalate. In this article on HCN, only the formation of calcium oxalate stones in association with hyperuricosuria is considered.
Stone analysis
Patients with hyperuricosuria form either pure calcium stones or a mixture of uric acid and calcium stones [2], [3]. Herring reported in 1962 that of 4303 calcium oxalate stones sent to their laboratory, 5% contained a uric acid nucleus [4]. In an analysis of 3158 stones, Alvarez et al [5] found 5% of stones containing a mixture of calcium and uric acid. In patients with gout and nephrolithiasis, Gutman and Yü [6] reported that 8.3% of their stones were composed of calcium oxalate, 4.2% were
Radiographic findings
Calcium containing calculi are radiodense [8]. As such, patients with HCN form stones that are visible on a plain radiographic film of the kidneys, ureters, and bladder (KUB). In contrast to calcium-containing stones that are radiopaque, pure uric acid stones are radiolucent on KUB [9]. Occasionally HCN patients may develop calcium stones with a small uric acid core which has a unique appearance on KUB; the uric acid core is more radiolucent while the calcium shell is more radiodense.
Clinical presentation
The acute clinical presentation of patients with hyperuricosuria calcium urolithiaisis is similar to the typical signs and symptoms of renal colic. The history and clinical findings of acute renal colic are reviewed in the article by Preminger in this issue.
Patients with HCN do not have an increased risk of stone recurrence compared to stone forming patients with other metabolic disorders [1], [7], [10], [11], [12]. However, whether these patients have an increased risk for requiring surgical
Metabolic abnormalities
Hyperuricosuria has been somewhat arbitrarily defined over the years [15]. Gutman and Yü defined hyperuricosuria as greater than 750 mg per day (4.5 mmol/day) for women and 800 mg per day (4.8 mmol/day) for men [6]. Using this definition, about one-third of normal patients and one third of calcium oxalate stone formers are found to excrete excessive uric acid [1], [11], [16], [17], [18]. However, only 15% of these patients excrete more than 1000 mg (5.9 mmol) of uric acid per day [1]. Of all
Physicochemistry
While clinical and epidemiology studies continue to implicate hyperuricosuria in calcium nephrolithiasis, studies in the laboratory have not been able to define a specific physicochemical mechanism. Hypotheses that attempt to explain how hyperuricosuria promotes calcium oxalate growth fall into four categories [2]:
- (1)
Growth of calcium oxalate on solid forms of uric acid or sodium urate.
- (2)
Consumption of calcium oxalate crystallization inhibitors by uric acid or sodium urate.
- (3)
promotion of calcium
Pathophysiology of hyperuricosuria
As previously mentioned, 70% of hyperuricosuric patients are thought to have hyperuricosuria from high dietary purine intake, while thirty percent are hyperuricosuric because of increased endogenous production of uric acid [20]. The metabolism of purine to uric acid is discussed in the article by Moe et al in this issue.
Gout and calcium stones
Yü and Gutman [1] observed that 22% of their gout patients passed urinary stones. Of the stones formed by these patients, 83.3% were pure uric acid, 4.2% were mixed uric acid
Surgical management
The surgical treatment of HCN stones is similar to the surgical treatment of all calcium stones and includes extracorporeal shock wave lithotripsy (SWL), percutaneous nephrolithomy (PNL), ureteroscopy/renoscopy with stone extraction and/or lithotripsy, and open surgical procedures. The majority of renal and upper ureteral stones can be managed with SWL; however, studies show the success rate for SWL rapidly decreases for renal stones greater than 2.5 cm. For renal stones greater than 2.5 cm and
Summary
Since the findings of Yü and Gutman [1], the hyperuricosuric calcium stone former is a unique clinical entity. While an impressive number of clinical and epidemiologic studies implicate hyperuricosuria in calcium stone formation, the exact physicochemical mechanism by which uric acid affects calcium oxalate crystallization has not been proven. Allopurinol decreases stone recurrences and is the drug of choice for patients with isolated HCN.
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