Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 54-year-old man is evaluated during a follow-up visit for five previous episodes of nephrolithiasis. Two of these stones were composed primarily of uric acid. After his third episode, potassium citrate was initiated. Medical history is notable for type 2 diabetes mellitus, hypertension, and hyperlipidemia. He does not have a known history of gout. He eats a fairly high protein diet, and his fluid intake is inconsistent. Other medications are metformin, metoprolol, amlodipine, atorvastatin, and aspirin.
On physical examination, blood pressure is 136/82 mm Hg, and pulse rate is 68/min. BMI is 32. There is no costovertebral angle tenderness. The remainder of the examination is unremarkable.
Laboratory studies:
| Blood urea nitrogen | 15 mg/dL (5.4 mmol/L) |
| Calcium | 8.5 mg/dL (2.1 mmol/L) |
| Serum creatinine | 1.1 mg/dL (97.2 µmol/L) |
| Uric acid | 7.8 mg/dL (0.46 mmol/L) |
| Urine studies: | |
| Calcium excretion | 220 mg/24 h (5.5 mmol/24 h) |
| Citrate excretion | 400 mg/24 h (normal range, 320-1240 mg/24 h) |
| Oxalate excretion | 26 mg/24 h (296 µmol/24 h) (normal range, 9.7-40.5 mg/24 h [111-462 µmol/24 h]) |
| Uric acid excretion | 710 mg/24 h (4.19 mmol/24 h) |
| Urinalysis | Specific gravity 1.025; pH 6.2; no blood, protein, or leukocyte esterase |
| Urine volume | 1600 mL/24 h |
In addition to increased fluid intake and dietary changes, which of the following is the most appropriate treatment for this patient?
A: Acetazolamide
B: Allopurinol
C: Calcium carbonate
D: Chlorthalidone
MKSAP Answer and Critique
The correct answer is B: Allopurinol.
Allopurinol is indicated for this patient who has recurrent uric acid stones despite alkalinization of the urine. Patients who develop uric acid stones typically have low urine volume or hyperuricosuria. The latter may result from a high protein diet (as in this patient) or rapid purine metabolism as in tumor lysis syndrome. Other risk factors include gout, conditions associated with uric acid overproduction, diabetes mellitus, the metabolic syndrome, and chronic diarrhea. This patient also has inconsistent fluid intake, a relatively high urine uric acid level, and low urine volume, all of which are significant risk factors for development of uric acid nephrolithiasis. Treatment with potassium citrate to alkalinize the urine is often sufficient to decrease the risk for recurrent stones, with the goal of increasing the urine pH to greater than 6.0. This patient continues to have recurrent uric acid nephrolithiasis despite his urine pH being appropriately alkaline. In addition to encouraging more aggressive daily oral hydration and a diet with limited animal protein, seafood, and yeast, the next appropriate step in management is to begin a xanthine oxidase inhibitor to lower uric acid production and urine excretion.
Acetazolamide can alkalinize the urine, but chronic use may lead to a metabolic acidosis and is therefore not typically used for this purpose. Instead, efforts at increasing the urine alkalinization, if necessary, would focus on the dose and frequency of potassium citrate.
Calcium carbonate is often utilized for high urine oxalate excretion from enteric hyperoxaluria, which is not seen in this patient.
A thiazide diuretic such as chlorthalidone is not appropriate for this patient, because thiazide diuretics tend to increase the serum uric acid level and could increase his propensity to develop gout.
Key Point
- In addition to urine alkalinization, treatment with allopurinol is indicated for patients who have recurrent uric acid stones.
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