Familial Hypocalciuric Hypercalcaemia I: Renal Handling of Calcium, Magnesium and Phosphate

Abstract

Ten hypercalcaemic members from three generations of a family with familial hypocalciuric hypercalcaemia (FHH) were compared with age and sex matched healthy subjects. Two of the former had undergone unsuccessful subtotal parathyroidectomy. Our results showed that the hypercalcaemia was mainly attributable to an increased capacity for tubular reabsorption of calcium, but in part also to an increased release of calcium from bone. The relative hypermagnesaemia had a similar dual origin. The serum phosphate concentration was low and this could be accounted for in full by a decrease in renal tubular reabsorption of phosphate, as assessed by the renal threshold phosphate concentration (TmPO4/GFR). The results of PHT measurements with two radioimmunoassays were equivocal. Most patients had normal serum PTH values, but with one assay mean serum PTH was significantly higher in the hypercalcaemic group. We conclude that the abnormalities of the divalent cation and phosphate metabolism cannot be accounted for in full by increased circulating PTH activity, and are predominantly due to an intrinsic renal abnormality.

Magnesium stimulates renal phosphate reabsorption

“…Therefore, these experiments show for the first time on the molecular level how Mg 2ϩ influences renal P i excretion. Moreover, these data also confirm previous findings that Mg 2ϩ influences PTH secretion not only in vitro but also in vivo (2,5,10,16,23,26,33).…”

“…Heterozygous inactivating mutations of the CaSR cause familial hypocalciuric hypercalcemia (FHH), which is characterized by hypocalciuric hypercalcemia often associated with hypomagnesiuric hypermagnesemia (26). Affected individuals may display hypophosphatemia due to decreased renal P i reabsorption (16). Homozygous or compound heterozygous inactivating mutations of the CaSR result in neonatal severe hyperparathyroidism (NSHPT), which is generally lethal unless a parathyroidectomy is performed (26).…”

Epithelial Ca2+ and Mg2+ Channels in Health and Disease

“…Inactivation of the CaSR likely leads to inappropriate reabsorption of Ca 2ϩ and Mg 2ϩ in the TAL (91) and Mg 2ϩ transport in DCT (92). Therefore, renal excretion of Ca 2ϩ and Mg 2ϩ is reduced, which leads to hypercalcemia and in some cases hypermagnesemia (93). It should be noted that the CaSR plays a role in controlling renal Ca 2ϩ and Mg 2ϩ secretion independent of its role in regulating PTH release.…”

Renal tubular reabsorption of calcium in familial hypocalciuric hypercalcaemia

“…The hypercalcaemic members of our FHH family and the ten normal controls were described in details else¬ where (Kristiansen et al 1985). However, in the present study one patient (male, 18 years) refused to partici¬ pate.…”

“…Total serum calcium and serum creatinine were measured on a Technicon 12/90 multichannel analyser. The values of total serum cal¬ cium were converted into serum ultrafiltrable concen¬ trations by multiplication with the average of the ultra¬ filtrable fractions of calcium as previously determined in the FHH patients (0.631) and normals (0.603) (Kristiansen et al 1985).…”