Calcium-Creatinine Clearance Ratio Calculator
Calcium-Creatinine Clearance Ratio Calculator
Separate familial hypocalciuric hypercalcaemia from primary hyperparathyroidism using the 24-hour calcium-creatinine clearance ratio.
Calcium-Creatinine Clearance Ratio
FHH vs PHPTUrine calcium 8 mg/dL, serum creatinine 0.9 mg/dL, serum calcium 10.8 mg/dL, urine creatinine 90 mg/dL
Formula
- urine calcium, urine creatinine
- from the same 24-hour collection, both in mg/dL
- serum calcium, serum creatinine
- measured on the same day as the collection, both in mg/dL
- result
- a unitless ratio — the units cancel, so any consistent concentration unit works as long as it is used throughout
Worked example
Urine calcium 8 mg/dL, serum creatinine 0.9 mg/dL, serum calcium 10.8 mg/dL, urine creatinine 90 mg/dL
8 × 0.9 = 7.2
10.8 × 90 = 972
7.2 ÷ 972 = 0.0074
Interpreting the ratio
| CCCR | Favours |
|---|---|
| < 0.01 | Familial hypocalciuric hypercalcaemia |
| 0.01 – 0.02 | Indeterminate |
| > 0.02 | Primary hyperparathyroidism |
Why this ratio is worth calculating before surgery
The calcium-creatinine clearance ratio (CCCR) exists to separate two conditions that look identical on a calcium and parathyroid hormone alone: familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT). Both present with mild hypercalcaemia and an inappropriately normal or raised parathyroid hormone. The distinction matters enormously in practice, because PHPT may warrant parathyroidectomy while FHH is a benign, lifelong, inherited condition that needs no treatment at all — and does not respond to it.
A ratio below 0.01 strongly suggests FHH; above 0.02 suggests primary hyperparathyroidism; and 0.01 to 0.02 is genuinely indeterminate and should not be forced into either category. The ratio is not perfectly discriminating: around 20% of genetically confirmed FHH patients fall above the 0.01 cut-off, so a raised value does not exclude the diagnosis on its own. Where the family history, age of onset or an indeterminate ratio leaves doubt, genetic testing for CASR, GNA11 and AP2S1 — the three genes underlying FHH — is the definitive test.
The ratio is also invalidated by several common confounders that independently lower urinary calcium: vitamin D deficiency, thiazide diuretics, lithium therapy and renal impairment. Each should be corrected or accounted for before the ratio is interpreted. Operating on a patient with unrecognised FHH does not cure their hypercalcaemia, exposes them to surgical risk for no benefit, and is precisely the outcome this calculation is meant to prevent.
Frequently asked questions
What does a calcium-creatinine clearance ratio below 0.01 mean?
It strongly suggests familial hypocalciuric hypercalcaemia (FHH) rather than primary hyperparathyroidism. FHH is benign and inherited, and does not need or respond to parathyroidectomy.
Does a ratio above 0.01 rule out FHH?
No. About 20% of genetically confirmed FHH patients have a ratio above 0.01. Genetic testing for CASR, GNA11 and AP2S1 is the definitive test where doubt remains.
What lowers urinary calcium and invalidates the ratio?
Vitamin D deficiency, thiazide diuretics, lithium and renal impairment all lower urinary calcium and can push the ratio falsely toward FHH. Correct or account for these before interpreting the result.
Why does this distinction matter clinically?
Primary hyperparathyroidism may be treated with parathyroidectomy, while FHH is a benign inherited condition that surgery does not cure. Operating on unrecognised FHH exposes the patient to surgical risk with no benefit.
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References
- Christensen SE, Nissen PH, Vestergaard P, et al. Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcaemia and primary hyperparathyroidism. Clin Endocrinol (Oxf). 2008;69(5):713–720.
- Hannan FM, Thakker RV. Investigating hypercalcaemia. BMJ. 2017;356:i6183.