MKSAP: 28-year-old man is evaluated for recurrent nephrolithiasis

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 28-year-old man is evaluated for recurrent nephrolithiasis. Medical history is significant for Crohn disease complicated by multiple small bowel strictures requiring resection. He began developing kidney stones 3 years ago following his last bowel surgery. Analysis of the stones has consistently shown calcium oxalate, and he has been adherent to a low oxalate diet, oral hydration to maintain urine output of at least 2 L/d, and intake of 2 g of calcium carbonate with each meal. However, he has continued to have periodic episodes of kidney stones. Medical history is otherwise unremarkable. Medications are infliximab and calcium carbonate.

On physical examination, temperature is 37.1 °C (98.8 °F), blood pressure is 131/78 mm Hg, pulse rate is 84/min, and respiration rate is 12/min. BMI is 22. The abdominal examination shows healed surgical incisions and is otherwise unremarkable. The remainder of the examination is normal.

Laboratory studies, including complete blood count, electrolytes, and kidney function, are normal. Urinalysis is normal; 24-hour urine chemical analysis shows normal levels of calcium, citrate, and uric acid, but elevated oxalate.

Plain abdominal radiographs show multiple small stones in both kidneys.

Which of the following is the most appropriate additional treatment for this patient?

A. Cholestyramine
B. Hydrochlorothiazide
C. Potassium citrate
D. Pyridoxine

MKSAP Answer and Critique

The correct answer is A: Cholestyramine.

Treatment with cholestyramine is an appropriate additional therapy for this patient with enteric hyperoxaluria. Hyperoxaluria predisposes to calcium oxalate stone formation. Excessive oxalate in the urine may result from excessive intake (from foods such as chocolate, spinach, rhubarb, or green and black tea) or in situations in which there is significant restriction in dietary calcium intake, which decreases binding of calcium to dietary oxalate in the gut and increases oxalate absorption. Enteric hyperoxaluria results from malabsorption when excessive free fatty acids in the gastrointestinal lumen bind calcium, increasing free oxalate absorption in the colon as may be seen in patients with small bowel disease or bowel resection. In addition to maintaining an adequate urine output of at least 2 L/d and ensuring adequate dietary calcium intake, patients with enteric hyperoxaluria may benefit from the bile salt binder cholestyramine, which also binds oxalate in the gut. This therapy is indicated in this patient with recurrent calcium oxalate nephrolithiasis following small bowel resection unresponsive to other treatments.

Thiazide diuretics, such as hydrochlorothiazide, are used in patients with idiopathic hypercalciuria to reduce calcium excretion in the urine by inducing mild hypovolemia that results in increased sodium reabsorption and passive calcium reabsorption in the proximal tubule. However, this patient does not have evidence of hypercalciuria, and thiazide therapy would not decrease the excessive oxalate in the urine.

Urine citrate inhibits stone formation by binding calcium in the tubular lumen, preventing it from precipitating with oxalate. Citrate excretion can be enhanced in patients with low urine citrate levels by alkalinizing the serum with potassium citrate, which decreases uptake of filtered citrate from the tubular lumen. However, this patient does not have evidence of hypocitraturia and would not be expected to benefit from additional urine citrate.

Pyridoxine is indicated in some patients with primary hyperoxaluria to improve glyoxylate metabolism and reduce overproduction of oxalate. However, this would not be effective in this patient with enteric hyperoxaluria.

Key Point

  • Patients with enteric hyperoxaluria and calcium oxalate nephrolithiasis may benefit from treatment with bile salt binders to decrease intestinal oxalate absorption.

This content is excerpted from MKSAP 17 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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