What is the most likely cause of kidney stones in a 24-year-old man with a family history of kidney stones, mild hypertension, normal calcium levels, and no calcific densities on X-ray, who has previously passed a kidney stone?

Most Likely Cause: Uric Acid Stones

In a 24-year-old man with a strong family history of kidney stones (father and brother affected), mild hypertension, normal serum calcium (400 mg/dL appears to be a transcription error—likely 10.0 mg/dL), and radiolucent stones on X-ray (no calcific densities), the most likely diagnosis is uric acid nephrolithiasis. 1, 2

Key Diagnostic Features

The radiolucent nature of the stones on X-ray is the critical distinguishing feature:

• Radiolucent stones that do not appear on plain radiography are characteristic of uric acid stones, which account for 5-10% of all kidney stones 1
• Calcium-containing stones (calcium oxalate and calcium phosphate) are radiopaque and would show calcific densities on X-ray 3
• The absence of calcific densities effectively rules out calcium stones as the primary stone type 3

Supporting Clinical Context

Family History

• A positive family history substantially increases stone risk, with a relative risk of 2.57 for incident stone formation 4
• Genetic factors account for approximately 45% of heritability in kidney stone disease 5
• The strong family history (father and brother) suggests an inherited metabolic predisposition 2, 4

Hypertension Association

• Hypertensive patients have a 5.5-fold increased odds ratio for stone formation compared to normotensive subjects 6
• Hypertensive males demonstrate higher urinary uric acid levels (707 vs. 586 mg/day in normotensives) and increased uric acid supersaturation 6
• During follow-up studies, 26% of stones formed by hypertensive patients were uric acid calculi 6

Normal Serum Calcium

• Normal serum calcium effectively excludes primary hyperparathyroidism, which would present with elevated or high-normal calcium 1, 3
• This makes calcium-based metabolic disorders less likely as the primary etiology 3

Metabolic Workup Required

This patient requires comprehensive 24-hour urine metabolic testing to confirm the diagnosis and guide treatment:

• Analysis should include total urine volume, pH, uric acid, calcium, oxalate, citrate, sodium, potassium, and creatinine 1, 7
• Urine pH is particularly critical: acidic urine (pH <5.5) promotes uric acid stone formation, while alkaline urine would suggest calcium phosphate stones 2
• Hyperuricosuria (>800 mg/day in men) would confirm uric acid as the primary metabolic abnormality 1
• Two 24-hour urine collections are preferred for accuracy 1, 7

Additional Diagnostic Considerations

Stone Analysis

• When the stone is available, formal stone composition analysis should be performed to definitively confirm uric acid composition 3, 7
• Stone composition can guide specific preventive measures 7

Serum Studies

• Serum electrolytes, creatinine, and uric acid should be measured 3, 7
• Elevated serum uric acid would support the diagnosis of uric acid nephrolithiasis 3

Common Pitfalls to Avoid

• Do not assume calcium stones based solely on family history—stone composition varies even within families 7
• Do not restrict dietary calcium without confirming stone type, as this paradoxically increases calcium oxalate stone risk by increasing oxalate absorption 1, 2
• Do not delay metabolic workup in young patients with family history, as early intervention prevents recurrence (30-50% recurrence rate within 5 years without treatment) 2

Alternative Considerations

While uric acid stones are most likely given the radiolucent presentation:

• Cystine stones are also radiolucent but are rare and typically present in childhood with hexagonal crystals on urinalysis 1, 3
• Xanthine stones are extremely rare and associated with xanthinuria 1
• The family history pattern and hypertension make uric acid stones far more probable than these rare entities 6, 4