Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure.
Several studies have suggested that phosphorus (P) restriction, independent of serum levels of ionized calcium and 1,25-(OH)2D3, may prevent parathyroid hyperplasia and secondary hyperparathyroidism in patients and animals with chronic renal failure. A direct role of phosphorus in the pathogenesis of these abnormalities is, however, still controversial. Thus, studies were performed to examine the direct role of phosphorus on the development of these abnormalities. Female Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation. The animals were then divided into two dietary groups (High-P: 0.8% P diet, Low-P: 0.2% P diet). Six to eight rats per group per time-point were killed at the following intervals: 0, 1, 2, and 4 days, and 1, 2, 3, and 4 weeks. Serum intact parathyroid hormone (PTH) levels in uremic rats fed the high-P diet increased 1 day after nephrectomy, and high levels persisted for the duration of the study. Parathyroid gland growth in uremic rats fed the high-P diet was apparent within 2 days of uremia and increased nearly twofold by 2 weeks. These abnormalities, however, did not develop in uremic rats fed the low-P diet. Serum P levels in uremic rats fed the high-P diet were significantly higher than those of uremic rats fed the low-P diet, but there was no significant difference in serum ionized calcium or 1,25-(OH)2D3 levels. These results demonstrate that phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure, and that phosphorus restriction prevents these abnormalities independent of changes in serum ionized calcium and 1,25-(OH)2D3.
Denda
M
M
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Finch
J
J
Slatopolsky
E
E
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000097:blood; D005260:Female; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006965:Hyperplasia; D007676:Kidney Failure, Chronic / Q000150:complications*; D009392:Nephrectomy; D009929:Organ Size; D010280:Parathyroid Glands / Q000473:pathology*; D010758:Phosphorus / Q000009:adverse effects* / Q000097:blood / Q000502:physiology; D016226:Phosphorus, Dietary / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D016226:Phosphorus, Dietary; D010758:Phosphorus; D002118:Calcium