USMLE Step 2: What is the composition of kidney calcifications?

If you’re preparing for the United States Medical Licensing Examination® (USMLE®) Step 2 exam, you might want to know which questions are most often missed by test-prep takers. Check out this example from Kaplan Medical, and read an expert explanation of the answer. Also check out all posts in this series.  

A 66-year-old woman who uses a wheelchair and has a history of multiple sclerosis comes to the office complaining of dysuria, frequent urination, intermittent gross hematuria and chronic low back pain. The pain is constant, nonradiating and located over her flanks bilaterally. In the past 12 months she has had three urinary tract infections and one hospitalization for acute pyelonephritis of the left kidney. She also has arthritis, hypertension controlled with an ACE inhibitor, and a hysterectomy performed 25 years ago for fibroids.

On physical examination in the office she is in no distress. Vitals show BP of 130/70 mm Hg, pulse of 85 beats per minute, and respirations of 12 per minute. Heart and lung examinations are within normal limits. Her abdomen is soft and nondistended without guarding and there is mild bilateral costovertebral angle tenderness. Pelvic and rectal examinations are normal. Urinalysis revealed urine sedimentation, a pH of 8.0, leukocyte esterase positive, nitrite positive, WBC 75–90/HPF, RBC 30–40/HPF. A KUB radiograph was done, which showed large calcifications in both kidneys.

What is the most likely composition of these calcifications?

A. Calcium oxalate dehydrate.

B. Calcium oxalate monohydrate.

C. Cystine.

D. Magnesium-ammonium-phosphate.

E. Uric acid.

The correct answer is D.

This patient provides a classic history for someone at risk for struvite kidney stones. Struvite stones are a result of urinary infection with bacteria, usually Proteus species, which possess urease, an enzyme that degrades urea to NH3 and CO2. The NH3 hydrolyzes to NH4+ and increases urine pH to 8 or 9. The CO2 hydrates to H2CO2 and then dissociates to CO3 2-, which precipitates with calcium as CaCO3. The NH4+ precipitates PO4 3- and Mg2+ to form MgNH4 PO4 (struvite).

Remember that these stones are common in immobilized patients such as this woman with multiple sclerosis. In such cases, the stones can be bilateral. In this case the KUB shows bilateral stones. The result is a stone of calcium carbonate admixed with struvite. Struvite does not form in urine in the absence of infection, because NH4+ concentration is low in urine that is alkaline in response to physiologic stimuli.

Chronic Proteus infection can occur because of impaired urinary drainage, urologic instrumentation or surgery, and especially with chronic antibiotic treatment, which can favor the dominance of Proteus in the urinary tract. The formation of these struvite stones in the renal collecting system leads to staghorn configuration typically seen with this type of stone. These stones are also called infective stones, because they contain numerous infective bacteria within their structure where antibiotics cannot penetrate. Because the antibiotics cannot penetrate the stone, the stones must be removed if the infection is to be cured. Prophylaxis against recurring struvite stones requires the maintenance of sterile urine, high urine volumes, and decreased urinary phosphate levels.

Choices A and B: Calcium oxalate, as either monohydrate or dihydrate (less dense), is a major component of most urinary stones. Although these metabolites comprise a majority of all stones formed, they are not normally seen in patients who have recurrent urinary tract infections and staghorn calculi.

Choice C: Cystine stones form in patients who have this condition. Cystinuria is the result of an inherited autosomal recessive defect in the renal tubular reabsorption of four amino acids: cystine, ornithine, lysine, and arginine (mnemonic: COLA). Patients who are homozygous for the disease excrete increased levels of cystine. The stones form in acid urine.

Choice E: Uric acid stones form in patients who have high urinary uric acid levels. This may occur in those who have gout, myeloproliferative disorders (leukemia and lymphoma), those on chemotherapy, or patients who have chronic diarrhea. These stones form in acidic urine (pH less than 5.5) and are radiolucent (i.e., they are not seen on regular plain radiographs). The patient in this scenario had stones visualized on radiograph.

• Struvite stones are commonly seen in patients who have recurrent urinary tract infection with a urease-producing organism (Proteus, Pseudomonas, Providencia).
• Escherichia coli does not produce urease and therefore does not form struvite stones.
• Struvite tones are frequently large enough to fill the renal pelvis. They are composed of ammonium, magnesium, and phosphate (struvite) admixed with calcium carbonate apatite. They are visible on plain abdominal x-ray films.

For more prep questions on USMLE Steps 1, 2 and 3, view other posts in this series.