Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.

Abstract

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PIH) secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79±0.09 mg/dl and gradually increased up to 5.30±0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64±7.7 to 118±21 pg/ml. Serum 1,25(0H-)D3 decreased from 25.4±3.8 to 12.2±3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8±3.5 to a maximum of 69.6±4A pg/ml. In the second group the levels of serum 1,25(0H)D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3.In summary, the dogs at no time developed hypocalcemia however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.

Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium.

“…The radioimmunoassay for PTH employed the antiserum CH9N which was developed in our laboratory. The characteristics ofthis amino-terminal assay have been described previously (17). Plasma levels of 1,25(OH)2D were measured by the method of Reinhardt et al (18).…”

Structure-Activity Relation of NH2-terminal Human Parathyroid Hormone Fragments

“…All fragments show the loop region and the COOHterminal helix. His-14 to Leu-28 (loop and COOH-terminal helix) comprises the major part of the receptor binding region that is known to reside within His-14 to Phe-34 (5,6,68). The NH 2 -terminal helix, however, is present only in the in vivo bioactive fragments hPTH-(1-37) and hPTH-(2-37), but not in the inactive fragments hPTH-(3-37) and hPTH-(4 -37) (Table II).…”

“…In addition to the cyclic adenosine monophosphate (cAMP) pathway, involvement of the phosphatidylinositol hydrolysis signaling pathway is postulated for these functions (4). The receptor binding region mediating the calcium regulatory activity is located within sequence His-14 to Phe-34 (5,6). The complete NH 2 -terminal part of hPTH-(1-34) is required for stimulation of the cAMPdependent pathway (4), and the minimum sequence affecting bone and kidney comprises amino acids 2-27 (1,7).…”

A Forgotten Method to Induce Experimental Chronic Renal Failure in the Rat by Ligation of the Renal Parenchyma

“…It is widely accepted that a decrease in serum calcium plays a role in the development of 2HPT. However, Lopez-Hilker et al [10] demonstrated that a decrease in calcium is not necessary, and that some other factors may be involved. Furthermore, increases in serum calcium in animals with 2HPT have been described before [11].…”