Cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD). E... more Cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD). Extraosseous calcifications, particularly vascular calcifications (VC), are frequently observed in patients with CKD and represent an important risk factor for cardiovascular death (1,2). Changes in mineral metabolism, which are related to the development of secondary hyperaparathyroidism, play an important role in the pathogenesis of VC. Uremic patients may develop both calcifications of the intima (atherosclerosis) and calcifications of the media (arteriosclerosis), although the latter seem to be more prevalent (3). Patients with CKD frequently develop metabolic acidosis (MA) due to the failure of the kidney to excrete the acids originated from protein metabolism and to generate the bicarbonate necessary for acid buffering (4). The influence of acidosis on the development and progression of secondary hyperparathyroidism is not well understood. Our research group has investigated the eff...
Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experi... more Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet...
OBJECTIVE: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hor... more OBJECTIVE: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hormone (PTH) response to hypocalcemia. DESIGN: The PTH response to hypocalcemia has been evaluated in three groups of rabbits: Group I, normal rabbits, Group II, normal rabbits subjected to an acute hypercalcemic clamp (induced by CaCl(2) infusion) and Group III, rabbits with chronic hypercalcemia (due to surgical reduction of renal mass). RESULTS: In Group I (baseline Ca(2+)=1.69+/-0.02 mM), hypocalcemia resulted in stimulation of PTH secretion which reached a maximum (PTHmax) of 91.7+/-6.4 pg/ml. In rabbits from Group II, which also had normal baseline Ca(2+) (1.70+/-0.02 mM), plasma Ca(2+) was maintained at an elevated level for 2 h, at around 2.05 mM. The PTH response to hypocalcemia in Group II was attenuated and the PTHmax in these rabbits was 45.6+/-7.4 pg/ml. In rabbits from Group III, baseline Ca(2+) was elevated (2.06+/-0.06 mM) for 1 month. The PTH response to hypocalcemia in Gr...
Objective—To establish reference values for protein-bound, ionized, and weak-acid complexed fract... more Objective—To establish reference values for protein-bound, ionized, and weak-acid complexed fractions of calcium and magnesium in equine serum and determine stability of ionized calcium (iCa) and ionized magnesium (iMg) in serum samples kept under various storage conditions. Animals—28 clinically normal horses. Procedure—Total calcium (tCa) and magnesium (tMg) in equine serum were fractionated by use of a micropartition system that allows separation of protein-bound calcium (pCa) and magnesium (pMg) and ultrafiltrable calcium (μCa) and magnesium (μMg) fractions. Serum concentrations of iCa and iMg were measured in the ultrafiltrate by use of selective electrodes. Serum concentration of complexed calcium (cCa) or magnesium (cMg) was calculated by subtracting iCa or iMg from μCa or μMg, respectively. Results—Mean ±SE serum tCa concentration was 3.26 ± 0.06 mmol/L. Calcium fractions were as follows: pCa, 1.55 ± 0.03 mmol/L (47.4 ± 0.9%); iCa, 1.58 ± 0.03 mmol/L (48.5 ± 0.7%); and cCa, ...
Objective—To provide reference values for serum biochemical variables that are used for evaluatio... more Objective—To provide reference values for serum biochemical variables that are used for evaluation of mineral metabolism in donkeys and compare values with those in horses. Animals—18 donkeys and 18 horses. Procedures—Total calcium (tCa), total magnesium (tMg), and inorganic phosphorus (P) concentrations were measured in serum samples via spectrophotometry. Ionized calcium (iCa) and magnesium (iMg) concentrations were quantified with selective electrodes. By use of a micropartition system, tCa and tMg were fractionated to separate protein-bound (pCa, pMg) and ultrafiltrable fractions. Complexed calcium (cCa) and magnesium (cMg) concentrations were calculated by substracting ionized fractions from ultrafiltrable fractions. Parathyroid hormone (PTH) and calcitriol (CTR) concentrations were measured via radioimmunoassay. Results—Serum tCa concentration in donkeys (3.37 ± 0.21 mmol/L) was composed of pCa (1.59 ± 0.21 mmol/L [47.0 ± 4.2%]), iCa (1.69 ± 0.04 mmol/L [50.4 ± 3.0%]), and cCa...
American Journal of Physiology-Renal Physiology, 2009
The purpose of the present study was to test the hypothesis that extraskeletal calcification regr... more The purpose of the present study was to test the hypothesis that extraskeletal calcification regresses in uremic rats after reduction in phosphorus intake and treatment with calcimimetics. Extraosseous calcification was induced in five to six nephrectomized rats fed a high-phosphorus (1.2%) diet who received calcitriol (80 ng/kg ip) every other day for a period of 14 days. Next, dietary phosphorus was reduced to 0.6%, and rats were treated with vehicle ( n = 20), calcitriol [80 ng/kg ip/48 h ( n = 20)], or the calcimimetic AMG 641 [1.5 mg/kg sc/48 h ( n = 20)]. Aortic and soft-tissue calcium and phosphorus content was evaluated after 14 and 28 days. At 28 days, reduction of phosphorus intake resulted in a significant decrease in tissue mineral content in vehicle- and AMG 641-treated rats but not in rats receiving calcitriol. Aortic calcium and phosphorus was lower in rats treated with AMG 641 (96.7 ± 26.4 mg/g) than in rats receiving vehicle (178.3 ± 38.6 mg/g). An infiltrate of pha...
This report describes two cases of marked bone loss (osteopenia) occurring in a 9-week-old German... more This report describes two cases of marked bone loss (osteopenia) occurring in a 9-week-old German shepherd puppy and in a 6-month-old tiger. In both cases the animals were fed a diet which was exclusively boneless meat. The diets in both cases contained approximately 40 mg of calcium and 1000 mg of phosphorus per pound resulting in both calcium deficiency and phosphorus excess, resulting in a phosphorus-to-calcium ratio of 25:1, well beyond the amounts known to cause marked loss of bone experimentally. This has been termed nutritional secondary hyperparathyroidism (NSH). Both animals presented with severe bone pain, difficulty in ambulation, and difficulty in chewing food. Radiographs showed marked osteopenia and spontaneous fractures. Both responded clinically and radiographically to calcium supplementation and a diet with an appropriate phosphorus-to-calcium ratio. The importance of calcium and phosphorus in the human diet is briefly discussed.
American Journal of Physiology-Renal Physiology, 2008
To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expr... more To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR...
To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy i... more To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy intake, in vivo and in vitro experiments were conducted. Three groups of rats were fed diets with high (HC), normal (NC) and low (LC) caloric content that resulted in different energy intake. In vitro, UMR106 cells were incubated in high (HG, 4.5 g/l) or low glucose (LG, 1 g/l) medium. Additional treatments included phosphorus (P), mannitol, rapamycin and everolimus. Intestinal absorption of P and plasma P concentrations were similar in the three groups of rats. As compared with NC, plasma FGF23 concentrations were increased in HC and decreased in the LC group. A significant correlation between energy intake and plasma FGF23 concentrations was observed. In vitro, mRNA FGF23 was significantly higher in UMR106 cells cultured in HG than in LG. When exposed to high P, mRNA FGF23 increased but only when cells were cultured in HG. Cells incubated with HG and mechanistic target of rapamycin (mTO...
This study was designed to evaluate the influence of phosphorus (P) restriction on the deleteriou... more This study was designed to evaluate the influence of phosphorus (P) restriction on the deleterious effects of high fat diets on mineral metabolism. Twenty-four rats were allotted to 3 groups (n = 8 each) that were fed different diets for 7 months. Rats in group 1 were fed normal fat-normal P (0.6%) diet (NF-NP), rats in group 2 were fed high fat- normal P diet (HF-NP) and rats in group 3 were fed high fat-low P (0.2%) diet (HF-LP). Blood, urine and tissues were collected at the end of the experiments. When compared with the control group (NF-NP), rats fed HF diets showed increases in body weight, and in plasma concentrations of triglycerides and leptin, and decreased plasma calcitriol concentrations. In rats fed HF-NP plasma fibroblast growth factor 23 (FGF23) was higher (279.6±39.4 pg/ml vs 160.6±25.0 pg/ml, p = 0.018) and renal klotho (ratio klotho/GAPDH) was lower (0.75±0.06 vs 1.06±0.08, p<0.01) than in rats fed NF-NP. Phosphorus restriction did not normalize plasma FGF23 or ...
High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal diseas... more High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets. Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half we...
Alterations in phosphate homeostasis play an important role in the development of secondary hyper... more Alterations in phosphate homeostasis play an important role in the development of secondary hyperparathyroidism in renal failure. Until recently, it was accepted that phosphate retention only increased parathyroid hormone (PTH) secretion through indirect mechanisms affecting calcium regulation and calcitriol synthesis. However, recent in vitro studies have suggested that phosphate may directly affect PTH secretion. Our goal was to determine whether in vivo an intravenous phosphate infusion stimulated PTH secretion in the absence of changes in serum calcium. Three different doses of phosphate were infused intravenously during 120 minutes to increase the serum phosphate concentration in dogs. Sulfate was also infused intravenously as a separate experimental control. A simultaneous calcium clamp was performed to maintain a normal ionized calcium concentration throughout all studies. At the lowest dose of infused phosphate (1.2 mmol/kg), serum phosphate values increased to ∼3 mM, but PT...
Objective—To characterize the dynamics of calcitonin secretion in response to experimentally indu... more Objective—To characterize the dynamics of calcitonin secretion in response to experimentally induced hypercalcemia in cats. Animals—13 healthy adult European Shorthair cats. Procedures—For each cat, the calcitonin response to hypercalcemia (defined as an increase in ionized calcium concentration > 0.3mM) was investigated by infusing calcium chloride solution and measuring circulating calcitonin concentrations before infusion (baseline) and at various ionized calcium concentrations. Calcitonin expression in the thyroid glands of 10 of the cats was investigated by immunohistochemical analysis. Results—Preinfusion baseline plasma calcitonin concentrations were very low in many cats, sometimes less than the limit of detection of the assay. Cats had a heterogeneous calcitonin response to hypercalcemia. Calcitonin concentrations only increased in response to hypercalcemia in 6 of 13 cats; in those cats, the increase in calcitonin concentration was quite variable. In cats that responded...
Cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD). E... more Cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD). Extraosseous calcifications, particularly vascular calcifications (VC), are frequently observed in patients with CKD and represent an important risk factor for cardiovascular death (1,2). Changes in mineral metabolism, which are related to the development of secondary hyperaparathyroidism, play an important role in the pathogenesis of VC. Uremic patients may develop both calcifications of the intima (atherosclerosis) and calcifications of the media (arteriosclerosis), although the latter seem to be more prevalent (3). Patients with CKD frequently develop metabolic acidosis (MA) due to the failure of the kidney to excrete the acids originated from protein metabolism and to generate the bicarbonate necessary for acid buffering (4). The influence of acidosis on the development and progression of secondary hyperparathyroidism is not well understood. Our research group has investigated the eff...
Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experi... more Rats with normal renal function (Experiment 1, n = 12) and uninephrectomized (1/2Nx) rats (Experiment 2, n = 12) were fed diets with normal P (NP) and either normal (NF) or high fat (HF). Rats with intact renal function (Experiment 3, n = 12) were also fed NF or HF diets with high P (HP). Additionally, uremic (5/6Nx) rats (n = 16) were fed HP diets with NF or HF. Feeding the HF diets resulted in significant elevation of plasma FGF23 vs rats fed NF diets: Experiment 1, 593 ± 126 vs 157 ± 28 pg/ml (p < 0.01); Experiment 2, 538 ± 105 vs 250 ± 18 pg/ml (p < 0.05); Experiment 3, 971 ± 118 vs 534 ± 40 pg/ml (p < 0.01). Rats fed HF diets showed P retention and decreased renal klotho (ratio klotho/actin) vs rats fed NF diets: Experiment 1, 0.75 ± 0.06 vs 0.97 ± 0.02 (p < 0.01); Experiment 2, 0.69 ± 0.07 vs 1.12 ± 0.08 (p < 0.01); Experiment 3, 0.57 ± 0.19 vs 1.16 ± 0.15 (p < 0.05). Uremic rats fed HF diet showed more severe vascular calcification (VC) than rats fed NF diet...
OBJECTIVE: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hor... more OBJECTIVE: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hormone (PTH) response to hypocalcemia. DESIGN: The PTH response to hypocalcemia has been evaluated in three groups of rabbits: Group I, normal rabbits, Group II, normal rabbits subjected to an acute hypercalcemic clamp (induced by CaCl(2) infusion) and Group III, rabbits with chronic hypercalcemia (due to surgical reduction of renal mass). RESULTS: In Group I (baseline Ca(2+)=1.69+/-0.02 mM), hypocalcemia resulted in stimulation of PTH secretion which reached a maximum (PTHmax) of 91.7+/-6.4 pg/ml. In rabbits from Group II, which also had normal baseline Ca(2+) (1.70+/-0.02 mM), plasma Ca(2+) was maintained at an elevated level for 2 h, at around 2.05 mM. The PTH response to hypocalcemia in Group II was attenuated and the PTHmax in these rabbits was 45.6+/-7.4 pg/ml. In rabbits from Group III, baseline Ca(2+) was elevated (2.06+/-0.06 mM) for 1 month. The PTH response to hypocalcemia in Gr...
Objective—To establish reference values for protein-bound, ionized, and weak-acid complexed fract... more Objective—To establish reference values for protein-bound, ionized, and weak-acid complexed fractions of calcium and magnesium in equine serum and determine stability of ionized calcium (iCa) and ionized magnesium (iMg) in serum samples kept under various storage conditions. Animals—28 clinically normal horses. Procedure—Total calcium (tCa) and magnesium (tMg) in equine serum were fractionated by use of a micropartition system that allows separation of protein-bound calcium (pCa) and magnesium (pMg) and ultrafiltrable calcium (μCa) and magnesium (μMg) fractions. Serum concentrations of iCa and iMg were measured in the ultrafiltrate by use of selective electrodes. Serum concentration of complexed calcium (cCa) or magnesium (cMg) was calculated by subtracting iCa or iMg from μCa or μMg, respectively. Results—Mean ±SE serum tCa concentration was 3.26 ± 0.06 mmol/L. Calcium fractions were as follows: pCa, 1.55 ± 0.03 mmol/L (47.4 ± 0.9%); iCa, 1.58 ± 0.03 mmol/L (48.5 ± 0.7%); and cCa, ...
Objective—To provide reference values for serum biochemical variables that are used for evaluatio... more Objective—To provide reference values for serum biochemical variables that are used for evaluation of mineral metabolism in donkeys and compare values with those in horses. Animals—18 donkeys and 18 horses. Procedures—Total calcium (tCa), total magnesium (tMg), and inorganic phosphorus (P) concentrations were measured in serum samples via spectrophotometry. Ionized calcium (iCa) and magnesium (iMg) concentrations were quantified with selective electrodes. By use of a micropartition system, tCa and tMg were fractionated to separate protein-bound (pCa, pMg) and ultrafiltrable fractions. Complexed calcium (cCa) and magnesium (cMg) concentrations were calculated by substracting ionized fractions from ultrafiltrable fractions. Parathyroid hormone (PTH) and calcitriol (CTR) concentrations were measured via radioimmunoassay. Results—Serum tCa concentration in donkeys (3.37 ± 0.21 mmol/L) was composed of pCa (1.59 ± 0.21 mmol/L [47.0 ± 4.2%]), iCa (1.69 ± 0.04 mmol/L [50.4 ± 3.0%]), and cCa...
American Journal of Physiology-Renal Physiology, 2009
The purpose of the present study was to test the hypothesis that extraskeletal calcification regr... more The purpose of the present study was to test the hypothesis that extraskeletal calcification regresses in uremic rats after reduction in phosphorus intake and treatment with calcimimetics. Extraosseous calcification was induced in five to six nephrectomized rats fed a high-phosphorus (1.2%) diet who received calcitriol (80 ng/kg ip) every other day for a period of 14 days. Next, dietary phosphorus was reduced to 0.6%, and rats were treated with vehicle ( n = 20), calcitriol [80 ng/kg ip/48 h ( n = 20)], or the calcimimetic AMG 641 [1.5 mg/kg sc/48 h ( n = 20)]. Aortic and soft-tissue calcium and phosphorus content was evaluated after 14 and 28 days. At 28 days, reduction of phosphorus intake resulted in a significant decrease in tissue mineral content in vehicle- and AMG 641-treated rats but not in rats receiving calcitriol. Aortic calcium and phosphorus was lower in rats treated with AMG 641 (96.7 ± 26.4 mg/g) than in rats receiving vehicle (178.3 ± 38.6 mg/g). An infiltrate of pha...
This report describes two cases of marked bone loss (osteopenia) occurring in a 9-week-old German... more This report describes two cases of marked bone loss (osteopenia) occurring in a 9-week-old German shepherd puppy and in a 6-month-old tiger. In both cases the animals were fed a diet which was exclusively boneless meat. The diets in both cases contained approximately 40 mg of calcium and 1000 mg of phosphorus per pound resulting in both calcium deficiency and phosphorus excess, resulting in a phosphorus-to-calcium ratio of 25:1, well beyond the amounts known to cause marked loss of bone experimentally. This has been termed nutritional secondary hyperparathyroidism (NSH). Both animals presented with severe bone pain, difficulty in ambulation, and difficulty in chewing food. Radiographs showed marked osteopenia and spontaneous fractures. Both responded clinically and radiographically to calcium supplementation and a diet with an appropriate phosphorus-to-calcium ratio. The importance of calcium and phosphorus in the human diet is briefly discussed.
American Journal of Physiology-Renal Physiology, 2008
To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expr... more To investigate whether the effect of the calcimimetic AMG 641 and calcitriol on CaSR and VDR expression could be separated from their ability to reduce parathyroid cell proliferation, five-sixth nephrectomized (5/6 Nx) rats received vehicle, AMG 641, calcitriol, or AMG 641+calcitriol either daily for 13 days (long-term protocol) or in a single dose (short-term protocol). In the long-term protocol, AMG 641, calcitriol, and their combination significantly reduced the percentage of proliferating parathyroid cells. Proliferation was uncontrolled in the short-term protocol. A significant increase in CaSR mRNA (% vs. β-actin) was detected in rats treated with both calcitriol (1.60 ± 0.30) and AMG 641 (1.66 ± 0.25) for 13 days ( P = 0.01 vs. 5/6 Nx+vehicle, 0.89 ± 0.09); and there was a further increase when both drugs were administered simultaneously (2.46 ± 0.33). In the short-term protocol, only rats receiving AMG 641 alone (2.01 ± 0.33, P < 0.001) showed increased expression of CaSR...
To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy i... more To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy intake, in vivo and in vitro experiments were conducted. Three groups of rats were fed diets with high (HC), normal (NC) and low (LC) caloric content that resulted in different energy intake. In vitro, UMR106 cells were incubated in high (HG, 4.5 g/l) or low glucose (LG, 1 g/l) medium. Additional treatments included phosphorus (P), mannitol, rapamycin and everolimus. Intestinal absorption of P and plasma P concentrations were similar in the three groups of rats. As compared with NC, plasma FGF23 concentrations were increased in HC and decreased in the LC group. A significant correlation between energy intake and plasma FGF23 concentrations was observed. In vitro, mRNA FGF23 was significantly higher in UMR106 cells cultured in HG than in LG. When exposed to high P, mRNA FGF23 increased but only when cells were cultured in HG. Cells incubated with HG and mechanistic target of rapamycin (mTO...
This study was designed to evaluate the influence of phosphorus (P) restriction on the deleteriou... more This study was designed to evaluate the influence of phosphorus (P) restriction on the deleterious effects of high fat diets on mineral metabolism. Twenty-four rats were allotted to 3 groups (n = 8 each) that were fed different diets for 7 months. Rats in group 1 were fed normal fat-normal P (0.6%) diet (NF-NP), rats in group 2 were fed high fat- normal P diet (HF-NP) and rats in group 3 were fed high fat-low P (0.2%) diet (HF-LP). Blood, urine and tissues were collected at the end of the experiments. When compared with the control group (NF-NP), rats fed HF diets showed increases in body weight, and in plasma concentrations of triglycerides and leptin, and decreased plasma calcitriol concentrations. In rats fed HF-NP plasma fibroblast growth factor 23 (FGF23) was higher (279.6±39.4 pg/ml vs 160.6±25.0 pg/ml, p = 0.018) and renal klotho (ratio klotho/GAPDH) was lower (0.75±0.06 vs 1.06±0.08, p<0.01) than in rats fed NF-NP. Phosphorus restriction did not normalize plasma FGF23 or ...
High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal diseas... more High fat diets are implicated in the pathogenesis of metabolic syndrome, obesity and renal disease. Previous studies have revealed that high fat diets promote vascular calcification in uremic rats. Moreover, vitamin E has been shown to prevent uremic calcifications in genetically obese Zucker rats fed standard diet. The objective of this study was to investigate the influence of vitamin E supplementation on the development of extraskeletal calcifications in non-obese (wild type) uremic rats fed high fat diets. Wistar rats (n = 32) were preconditioned by feeding either a normal (NF) or high fat (HF) diet for 45 days and subsequently were subjected to 5/6 nephrectomy (Nx). Just before performing the first Nx step, a blood sample (Pre-Nx) was obtained. After Nx rats were switched to a diet with 0.9% phosphorus and supplemented with calcitriol. Also, after Nx, half of the rats from each group (NF and HF) were treated with vitamin E (VitE) in the diet (30,000 mg/kg) and the other half we...
Alterations in phosphate homeostasis play an important role in the development of secondary hyper... more Alterations in phosphate homeostasis play an important role in the development of secondary hyperparathyroidism in renal failure. Until recently, it was accepted that phosphate retention only increased parathyroid hormone (PTH) secretion through indirect mechanisms affecting calcium regulation and calcitriol synthesis. However, recent in vitro studies have suggested that phosphate may directly affect PTH secretion. Our goal was to determine whether in vivo an intravenous phosphate infusion stimulated PTH secretion in the absence of changes in serum calcium. Three different doses of phosphate were infused intravenously during 120 minutes to increase the serum phosphate concentration in dogs. Sulfate was also infused intravenously as a separate experimental control. A simultaneous calcium clamp was performed to maintain a normal ionized calcium concentration throughout all studies. At the lowest dose of infused phosphate (1.2 mmol/kg), serum phosphate values increased to ∼3 mM, but PT...
Objective—To characterize the dynamics of calcitonin secretion in response to experimentally indu... more Objective—To characterize the dynamics of calcitonin secretion in response to experimentally induced hypercalcemia in cats. Animals—13 healthy adult European Shorthair cats. Procedures—For each cat, the calcitonin response to hypercalcemia (defined as an increase in ionized calcium concentration > 0.3mM) was investigated by infusing calcium chloride solution and measuring circulating calcitonin concentrations before infusion (baseline) and at various ionized calcium concentrations. Calcitonin expression in the thyroid glands of 10 of the cats was investigated by immunohistochemical analysis. Results—Preinfusion baseline plasma calcitonin concentrations were very low in many cats, sometimes less than the limit of detection of the assay. Cats had a heterogeneous calcitonin response to hypercalcemia. Calcitonin concentrations only increased in response to hypercalcemia in 6 of 13 cats; in those cats, the increase in calcitonin concentration was quite variable. In cats that responded...
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