Chapter 15 Calcium

Serum calcium is regulated by PTH and vitamin D:

Hypercalcaemia can be classified as PTH-dependent or PTH-independent:

Drug causes of hypercalcaemia:

Mechanism Drugs
Impaired urinary Ca2+ excretion thiazide diuretics
calcium-containing antacid preps (milk-alkali)
lithium
Increased absorption vitamin D preparations
calcium-containing antacid preps (milk-alkali)
Stimulation of PTH secretion lithium
Reduced bone buffering vitamin A
anti-oestrogens

15.1 Investigations in hypercalcaemia:

15.2 Urine calcium

Urine calcium excretion will vary according to calcium intake and urinary sodium excretion (with UCa and UNa changing in parallel) (Foley & Boccuzzi, 2010). There is also diurnal variation.

Therefore urine calcium excretion is best assessed on 24 hr collection, rather than spot samples.

Results may be expressed either as:

  • total calcium excretion (as mg per kg BW per day)
  • 24hr calcium-creatinine clearance ratio, CCCR
  • calcium / creatinine excretion ratio (as mg/mg or mmol/mmol)

(The CCCR is often referred to as the FECa, but given the extent to which serum calcium is protein-bound, it may not be appropriate to think of it as such.)

CCCR performs best as a screening test for familial hypocalciuric hypocalcaemia (Christensen et al., 2008).

Random spot urine samples may be used (but are less accurate) and are normally interpreted as:

  • calcium / creatinine ratio (mg/mg or mmol/mmol)

15.3 Interpreting the results

15.3.1 Unit conversions

Ca: 1 mg = 0.025 mmol Cr: 1 mg = 0.0088 mmol

Therefore, a Ca/Cr of x mg/mg = 2.84x mmmol/mmol.

15.3.2 Normal calcium excretion:

  • 1–4 mg/kg/day (0.025–0.1 mmol/kg/day)
  • Ca/Cr ratio < 0.14 mg/mg

15.3.3 Hypercalciuria (e.g. in hyperPTH, other causes of hypercalcaemia, RTA):

  • >4 mg per kg per day
  • >300 mg (= 7.50 mmol) per day (men) or >250 mg (= 6.25 mmol) per day (women)
  • Ca/Cr ratio > 0.6 mmol/mmol = 0.20 mg/mg (adults) - or > 0.15 mg/mg in second void urine after an overnight fast
  • FECa > 2 % (CCCR > 0.020)

In an observational study of stone-formers (Curhan, KI 2001), stone risk elevated at thresholds lower than these classical cut-offs of 300 mg (M) or 250 mg (F) - but stone risk obviously complex and related to other urinary salts / pH etc.

15.3.4 Hypocalciuria (e.g. FHH, Gitelman):

  • FECa < 1 % (CCCR < 0.010)

In a small Japanese cohort of adult patients with Gitelman syndrome, calcium excretion was ~ 10-fold lower than in matched controls (Cheng et al., 2007):

  • 24hr excretion ~20 vs ~200 mg
  • FECa ~0.15% vs ~1.5%
  • Ca/Cr ~0.006 vs ~0.06 mg/mg (= ~0.02 vs ~0.2 mmol/mmol)