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

S. Lopez-Hilker, A. S. Dusso, N. S. Rapp, K. J. Martin, E. Slatopolsky

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224 Scopus citations

Abstract

Phosphorus is a well-known modulator of renal 1α-hydroxylase activity. In early and moderate renal failure it is proposed that dietary P(i) reduction ameliorates secondary hyperparathyroidism through increased circulating levels of calcitriol (i.e., 1α,25-dihydroxycholecalciferol). To gain further insight into the mechanisms by which a low-P(i) 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 P(i) 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 < 0.02), and plasma P(i) decreased from 6.3 ± 0.7 to 4.7 ± 0.2 mg/dl (P < 0.05). Calcitriol remained low (23.3 ± 4.7 pg/ml). However, irPTH grdually decreased from 321.0 ± 46.0 to 94.7 ± 22.9 pg/ml (P < 0.005). These studies indicate that a decrease in dietary P(i) from 0.95 to 0.3% suppressed irPTH by ~ 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 P(i) in advanced renal insufficiency improves secondary hyperparathyroidism by a mechanism that is independent of the levels of calcitriol or plasma ICa.

Original languageEnglish
Pages (from-to)F432-F437
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume259
Issue number3 28-3
DOIs
StatePublished - 1990

Keywords

  • calcitriol
  • phosphorus retention
  • uremia
  • vitamin D

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