Phosphorus restriction reverses hyperparathyroidism in uremia independent of changes in calcium and calcitriol

Abstract

Phosphorus is a well-known modulator of renal 1 alpha-hydroxylase activity. In early and moderate renal failure it is proposed that dietary Pi reduction ameliorates secondary hyperparathyroidism through increased circulating levels of calcitriol (i.e, 1 alpha, 25-dihydroxycholecalciferol). To gain further insight into the mechanisms by which a low-Pi diet ameliorates secondary hyperparathyroidism in advanced renal insufficiency, studies were performed in five dogs before and 6 mo after the induction of uremia by 5/6 nephrectomy. Glomerular filtration rate decreased from 69.0 +/- 2.3 to 10.5 +/- 0.5 ml/min, immunoreactive parathyroid hormone (irPTH) increased from 66.0 +/- 8.8 to 321.0 +/- 46 pg/ml, and calcitriol decreased from 39.0 +/- 10.4 to 27.0 +/- 6.2 pg/ml. Thereafter, dietary Pi was decreased gradually every 2 wk from 0.95% to 0.6, 0.45, and 0.3%, respectively. Dietary Ca was reduced from 1.6 to 0.6% to prevent development of hypercalcemia. Ionized Ca (ICa) decreased from 5.4 +/- 0.04 to 5.2 +/- 0.05 mg/dl (P less than 0.02), and plasma Pi decreased from 6.3 +/- 0.7 to 4.7 +/- 0.2 mg/dl (P less than 0.05). Calcitriol remained low (23.3 +/- 4.7 pg/ml). However, irPTH gradually decreased from 321.0 +/- 46.0 to 94.7 +/- 22.9 pg/ml (P less than 0.005). These studies indicate that a decrease in dietary Pi from 0.95 to 0.3% suppressed irPTH by approximately 70%. Reduction of irPTH was observed in the absence of a concomitant increase in levels of ICa or calcitriol. These studies suggest that reduction in dietary Pi in advanced renal insufficiency improves secondary hyperparathyroidism by a mechanism that is independent of the levels of calcitriol or plasma ICa.

Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D.

“…In all these clinical situations the stimulus was hypocalcemia but hyperphosphatemia may have an independent role. Serum phosphate is invariably raised in chronic renal failure and correction of serum phosphate alone with no changes in serum calcium or 1,25(OH)2D3 corrects secondary hyperparathyroidism (39)(40)(41) and it is possible but not proven that phosphate may have a direct effect on the PT cell similar to that of calcium (3). In patients with intestinal malabsorption both the serum calcium and 1,25 (OH)2D3 levels would be decreased.…”

Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro.

“…However, this mechanism may not be operative in advanced renal insufficiency because the decrease in renal mass may limit the production of 1,25-(OH) 2 D 3 (3)(4)(5). Lopez-Hilker and collaborators (6) demonstrated in dogs with advanced renal insufficiency and severe secondary hyperparathyroidism that a gradual reduction of phosphorus in the diet was accompanied by a significant decrease in the levels of PTH without changes in ICa or 1,25-(OH) 2 D 3 . Although these data clearly demonstrated that the effect of phosphorus on PTH secretion was independent of changes in serum ICa and 1,25-(OH) 2 D 3 , they did not evaluate the role of phosphorus on parathyroid cell growth or establish if phosphorus directly affected the synthesis or secretion of PTH.…”

Online Hemodiafiltration: Clinical Results and Economic Evaluation

“…Ее клиническими по-следствиями являются ренальная остеодистрофия и прогрессирование вторичного гиперпаратиреоза [30,31], кальцификация мягких тканей и сосудов. Последняя четко связана с сердечно-сосудистой патологией [32,33].…”