Effect Of Phosphorus In The Pathogenesis Of Secondary Hyperparathyroidism

Objective To study the effects of high phosphorus (P) independent of serum levels of ionized calcium and 1,25-(OH)2D3 on promoting parathyroid hyperplasia and parathyroid hormone secretion;To research the effects of the Renagel?and Phosphonoformic acid(PFA) on preventing parathyroid hyperplasia and parathyroid hormone(PTH) secretion; To research the parathyroid gland senses extracellular inorganic P by the sodium-dependent phosphate cotransporter and the sodium-dependent phosphate cotransporter PiT-1 of vascular muscle in uremic rats.Methods Male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation. The animals were then divided into two dietary groups(High-P:1.2% P and calcium 1.6% diet, Low-P:0.2% P and calcium 0.5% diet) at random.In high phosphorus dietary groups, there are six normal rats,six uremic rats nothing treated,six uremic rats treated with Renagel?six uremic rats that injected PFA 150mg/kg through intraperitoneal and six uremic rats injected the equivalent dissolvent of PFA .In low phosphorus dietary groups,there are six normal rats and six uremic rats nothing treated.Blood was taken for creatinine, ionized calcium, phosphorus, 1,25-(OH)2D3, and intact PTH determinations at thefollowing intervals day,7 day, and 14 day. Parathyroid glands were removed for immunohistochemistry of PCNA at 14th day.PiT-1 of blood vessel in uremic rats was detected by reverse transcription Polymerase chain reaction(RT-PCR).Results (1) Serum P and iPTH levels in uremic rats fed the high-P diet were significantly higher than those of uremic rats fed the low-P diet and sham operational rats, but there was no significant difference inserum ionized calcium or 1,25-(OH)2D3 levels(P<0.05). (2)Serum P and iPTH level of UHP rats were higher than the UHP rats.(3)Serum iPTH levels in PFA-treated rats were lower than UHP rats,but there was no significant difference in serum ionized calclum,P or 1,25-(OH)2D3 levels(P<0.05).(4) There was no significantly difference in all indexes between the UHP and those injected the equivalent dissolvent of PFA. (5) Nuclear proliferation Indexes of parathyroid in PFA-treated rats, ULP, NHP, NLP and Renagel?treated rats were littler than those of UHP rats(P<0.05).(6) There were 540bp strap of PiT-1 in gel electrophoresis.Conclutions These results demonstrate that high phosphorus accelerates the development of parathyroid hyperplasia and PTH secretion in rats with renal failure, and that phosphorus restriction prevents these abnormalities independent of changes in serum ionized calcium and 1,25-(OH)2D3 Renagel?and PFA can prevent the develpment of parathyroid hyperplasia and secretion of PTH. The parathyroid gland may be senses extracellular inorganic P by the sodium-dependent phosphate cotransporter PiT-1.There is the sodium-dependent phosphate cotransporter PiT-1 in vascular muscle of uremic rats.