Diagnostic Testing for Hypercalciuria and Hyperuricosuria
The gold standard for diagnosing hypercalciuria and hyperuricosuria is a 24-hour urine collection with measurement of calcium and uric acid excretion, which should be performed at least twice to establish the diagnosis. 1
24-Hour Urine Collection Protocol
For Hypercalciuria:
- Collect all urine over a 24-hour period
- Normal values:
- Adults: <4 mg/kg/day of calcium
- Children: <3.75 mg/kg/day 2
- Diagnostic threshold for hypercalciuria: >4 mg/kg/day in adults
- At least two positive assessments are required to establish the diagnosis 1
For Hyperuricosuria:
- Collect all urine over a 24-hour period
- Normal values vary by age group:
- Adolescents: <600 mg/day or <13 mg/kg/day
- School-age children: <450 mg/day or <15 mg/kg/day
- Preschool children: <320 mg/day or <18 mg/kg/day 2
- Adult diagnostic threshold: >800 mg/day for men, >750 mg/day for women
Alternative Testing Methods
When 24-hour collection is not feasible:
Spot Urine Testing:
- Fasting morning urine sample can be used 2
- Express results as ratio to creatinine:
- Calcium/creatinine ratio: Normal <0.25 mg/mg
- Uric acid/creatinine ratio: Normal <0.47 mg/dl GFR 2
- Positive correlation exists between spot samples and 24-hour collections 2
Fasting and Calcium Load Test:
For differentiating types of hypercalciuria 3:
- Collect 2-hour urine sample after overnight fast
- Administer 1g oral calcium load
- Collect 4-hour urine sample
- Measure calcium, cyclic AMP, and creatinine
Interpretation:
- Absorptive hypercalciuria: Normal fasting calcium (<0.11 mg/mg creatinine), high post-load (≥0.2 mg/mg creatinine)
- Resorptive hypercalciuria: High fasting calcium, high cyclic AMP after calcium load
- Renal hypercalciuria: High fasting calcium, high/high-normal fasting cyclic AMP 3
Additional Testing
Serum Tests:
- Calcium
- Phosphorus
- Parathyroid hormone (PTH)
- 1,25(OH)₂D₃ (calcitriol)
- Creatinine (to assess kidney function) 4, 5
Urine Tests:
- Urinary pH
- Citrate (hypocitraturia often coexists)
- Oxalate (if primary hyperoxaluria is suspected)
- Sodium (high sodium intake increases calcium excretion)
- Creatinine (for normalization and GFR estimation) 1
Sample Handling
- Keep urine samples at 4°C after collection
- Acidification of samples can be done in the laboratory within 24 hours 6
- Use age-related reference values when interpreting results, especially for children 6, 2
Clinical Correlation
- Hypercalciuria and hyperuricosuria may cause hematuria even in the absence of kidney stones 7
- Family history of kidney stones increases likelihood of metabolic abnormalities 7
- Consider genetic testing in patients with suspected primary hyperoxaluria who have hyperoxaluria with hypercalciuria 6
Follow-up Testing
- Monitor response to treatment with repeat 24-hour urine collections
- For patients on treatment, the citrate/creatinine ratio in fasting urine samples can be used to monitor hypocitraturia 2
- A decrease in urine calcium of at least one-third is required to confirm response to treatment 6
Remember that proper diagnosis guides appropriate treatment: thiazide diuretics for hypercalciuria and allopurinol for hyperuricosuria, along with dietary modifications and increased fluid intake to achieve at least 2-2.5 liters of urine output daily 1, 5.