Tubular calcium reabsorption and other aspects of calcium homeostasis in primary and secondary hyperparathyroidism.

Aims: Primary hyperparathyroidism (PHPT) causes hypercalcemia by increasing tubular calcium reabsorption. Because chronic kidney disease (CKD) is associated with normocalcemia, we inferred that calcium reabsorption is also normal, and hypothesized that normal reabsorption requires excessive parathyroid hormone (PTH) in CKD.

Methods: The following were obtained in controls and patients with CKD or PHPT: estimated GFR (eGFR); concentrations of PTH 1-84, 1,25-dihydroxyvitamin D, and ultrafilterable and ionized calcium ([PTH], [1,25(OH)2D], [Ca]uf, [Ca]i); and ratios of calcium excreted or reabsorbed per volume of filtrate (ECa/Ccr, TRCa/Ccr). Pertinent linear regressions were examined.

Results: In CKD, [PTH] was increased, but ECa/Ccr, TRCa/Ccr, [Ca]uf, and [Ca]i equaled control values. [PTH] was inversely related to eGFR but unrelated to [1,25(OH)2D]. TRCa/Ccr was constant at all [PTH]. In PHPT, [PTH] was no higher than in CKD, but TRCa/Ccr, [Ca]uf, and [Ca]i were increased. [1,25(OH)2D] correlated with [PTH]. In controls, TRCa/Ccr varied directly with [1,25(OH)2D] and inversely with [PTH].

Conclusions: In controls, calcium reabsorption rose with [1,25(OH)2D], and [PTH] fell in response. In PHPT, [PTH] determined [1,25(OH)2D]; together, the hormones increased calcium reabsorption and caused hypercalcemia. In CKD, normal calcium reabsorption required high [PTH].