Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat

Bover, Jordi; Rodriguez, Mariano; Trinidad, Pedro; Jara, Aquiles; Martı́nez, Marı́a Eugenia; Machado, Lorraine; Llach, Francisco; Felsenfeld, Arnold J.

doi:10.1038/ki.1994.129

Cited by 70 publications

(36 citation statements)

References 37 publications

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“…Dietary phosphate and vitamin D status are known to affect the development of hyperparathyroidism in both the normal and the azotemic state. Studies in normal and azotemic rats have shown that high dietary phosphate greatly increases PTH values (15,40). Conversely, dietary phosphate restriction reduces PTH values in normal rats and minimizes increases in PTH values in azotemic rats (13,41).…”

Section: Basal Pthmentioning

confidence: 99%

“…Phosphorus restriction and an increased serum calcitriol shift the EOP to the left (12)(13)(14) because less PTH is needed to maintain the same serum calcium concentration. Conversely, phosphorus loading, a deficiency of calcitriol, and renal failure shift the EOP to the right (15)(16)(17)(18)(19) because more PTH is needed to maintain the same serum calcium concentration.…”

Section: Bifunctional Relationship Between Pth and Serum Calciummentioning

confidence: 99%

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Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Felsenfeld

Rodríguez

Aguilera–Tejero

2007

Clinical Journal of the American Society of Nephrology

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This review examines the dynamics of parathyroid hormone secretion in health and in various causes of secondary hyperparathyroidism. Although most studies of parathyroid hormone and calcium have focused on the modification of parathyroid hormone secretion by serum calcium, the relationship between parathyroid hormone and serum calcium is bifunctional because parathyroid hormone also modifies serum calcium. In normal animals and humans, factors such as phosphorus and vitamin D modify the basal parathyroid hormone level and the maximal parathyroid hormone response to hypocalcemia. Certain medications, such as lithium and estrogen, in normal individuals and sustained changes in the serum calcium concentration in hemodialysis patients change the set point of calcium, which reflects the serum calcium concentration at which parathyroid hormone secretion responds. Hypocalcemia increases the basal/maximal parathyroid hormone ratio, a measure of the relative degree of parathyroid hormone stimulation. The phenomenon of hysteresis, defined as a different parathyroid hormone value for the same serum calcium concentration during the induction of and recovery from hypo-and hypercalcemia, is discussed because it provides important insights into factors that affect parathyroid hormone secretion. In three causes of secondary hyperparathyroidism-chronic kidney disease, vitamin D deficiency, and aging-factors that affect the dynamics of parathyroid hormone secretion are evaluated in detail. During recovery from vitamin D deficiency, the maximal parathyroid hormone remains elevated while the basal parathyroid hormone value rapidly becomes normal because of a shift in the set point of calcium. Much remains to be learned about the dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism. T his review examines the dynamics of parathyroid hormone (PTH) secretion in health and in various causes of secondary hyperparathyroidism with an emphasis on chronic kidney disease (CKD). For better understanding of factors that affect PTH secretion, the PTH-calcium relationship is evaluated with respect to (1) PTH secretion in the baseline state (basal PTH) and its sensitivity to the serum calcium concentration; (2) the maximal PTH response to hypocalcemia and factors that have been reported to modify the maximal PTH response to hypocalcemia; (3) shifts in the set point of calcium for PTH secretion in normal individuals as a result of treatment with medications such as lithium and estrogen and in hemodialysis patients during sustained changes in the serum calcium concentration; (4) the dynamics of PTH secretion in the secondary hyperparathyroidism of CKD, vitamin D deficiency, and aging; and (5) the phenomenon of hysteresis, defined as a different PTH value for the same serum calcium concentration during the induction of and recovery from both hypo-and hypercalcemia. A focus on hysteresis is justified because it provides important insights into how PTH secretion is modified by rate and directional changes in the serum c...

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Section: Basal Pthmentioning

confidence: 99%

Section: Bifunctional Relationship Between Pth and Serum Calciummentioning

confidence: 99%

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Felsenfeld

Rodríguez

Aguilera–Tejero

2007

Clinical Journal of the American Society of Nephrology

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“…In humans, it has been observed that although the overall urinary excretion of calcium is generally reduced, the fractional excretion of calcium (FECa) increases in advanced renal failure [4] but it does not happen the same in moderate renal failure [22]. The findings reported in animals [2,20] have not been able to clarify this matter. For this reason, further studies are needed to throw light on the pathogenesis of hyperparathyroidism subsequent to renal failure.…”

Section: Introductionmentioning

confidence: 48%

Renal handling of calcium and phosphorus in experimental renal hyperparathyroidism in dogs

et al. 2003

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-Twenty-four hour urinary excretion, fractional excretion and the filtered load of calcium and phosphorus were monitored as hyperparathyroidism evolved in a model of progressive canine renal failure. Thirteen beagles of both sexes aged four and a half months were used. Nine of them were subjected to a renal damaging schedule (neomycine, 60 mg/kg/48 h, IM, 32 weeks) in order to induce chronic renal failure leading to secondary hyperparathyroidism (2HPT group). The remaining four were kept as the control group. The experiment was conducted over 32 weeks. Blood and 24 h urine were collected every four weeks. Calcium, phosphorus and creatinine were analyzed. Plasma parathormone and calcitonin were determined at weeks 0, 12, 24 and 32. The level of renal function in the 2HPT animals was reduced to 25% of that of the controls (endogenous creatinine clearance was 0.45 ± 0.22 mL/min/kg as opposed to 1.81 ± 0.54 mL/min/kg). Hyperparathyroidism was confirmed by a progressive increase in the levels of the parathyroid hormone. Calcitonin levels were not modified. A tendency to hypocalcaemia was observed, reaching statistically significant levels from the twenty-eighth week of the study, when hyperphosphataemia also became significant. Daily urinary excretion of calcium and phosphorus remained at values considered normal throughout the experiment with no alteration imputable to the impaired renal function. This is explained by the decrease in the filtered load of these elements (in both cases statistically significant from the 24th week on) being associated with an increase in their fractional excretion. Thus, calcium and phosphorus urinary excretion values could be maintained in a normal range up to the end of the experiment, showing that renal calcium handling in dogs with experimentally induced renal failure seems to differ from that observed in human patients. renal hyperparathyroidism / calciuria / phosphaturia / parathyroid hormone / calcitonin / dog

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“…At first glance, this seems to be in disagreement with existing literature data. Indeed, in the study of Bover et al [26] of rats with only a mild degree of renal failure (serum creatinine 0.75-1 mg/dL) receiving a diet with comparable phosphorus content (0.6% P; 0.6% Ca), PTH levels almost doubled after 20 days of uremia. The reason for this discrepancy may be due to a difference in biological availability of the phosphorus in their diet versus that in the present study.…”

Section: Tablementioning

confidence: 99%

“…The good bioavailability of phosphorus in this diet is evidenced by the fact that animals receiving this food had distinctly higher urinary phosphorus concentrations compared to the rats receiving the STD. Although a high phosphorus diet has previously been used for the induction of secondary hyperparathyroidism in renal failure rats, [26] this is the first study in which bone histological parameters in animals fed a diet with low vs. high bioavailable phosphorus are compared. The development of sHPTH after phosphorus-loading may be attributed to the cumulative effect of various factors:…”

Section: Tablementioning

confidence: 99%

Role of Dietary Phosphorus and Degree of Uremia in the Development of Renal Bone Disease in Rats

et al. 2007

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The remnant kidney rat model has been extensively used for the evaluation of bone changes due to uremia. The present study aimed to assess the effect of the dietary phosphorus availability and of the severity of renal failure on bone histomorphometric changes and various biochemical markers over time in this model. Chronic renal failure (CRF) was induced in male Wistar rats by 5/6 th nephrectomy. Half of the number of animals received a standard rat diet (STD) (0.67% P, containing low bioavailable phosphorus of plant origin); the other animals were fed a high phosphorus diet (HPD) (0.93% P, containing inorganic phosphorus with high bioavailability). Every two weeks, blood and urine samples were collected. At sacrifice after 6 or 12 weeks, bone samples were taken for the measurement of histological and histodynamic parameters. Serum creatinine measurements indicated the development of mild to moderate renal failure in both diet groups. Phosphaturia was unexpectedly low in all animals that received the STD, indicating relative phosphorus depletion despite the normal dietary phosphorus content. In the HPD CRF group, a decrease in calcemia and a rise in phosphatemia were seen after 12 weeks of CRF, which were more pronounced in animals with higher serum creatinine. Serum iPTH levels were distinctly increased in CRF rats fed a HPD, especially those with more pronounced renal failure. Serum osteocalcin and to a lesser extend tartrate-resistant acid phosphatase and urinary pyridinoline and deoxypyridinoline crosslinks were higher in the CRF animals compared to the shams, particularly in the animals of the HPD group with more pronounced CRF. In both diet groups, the CRF animals had significantly higher amounts of osteoid compared to shams. Only the animals that received a HPD developed distinct histological signs of secondary hyperparathyroidism (sHPTH), that is, an increased bone formation rate, mineral apposition rate, osteoblast perimeter, and eroded perimeter. Again, this effect was most prominent in rats with more severe CRF. In conclusion, data of the present study indicate that in experimental studies using the remnant kidney rat model, both the dietary phosphorus bioavailability and the degree of renal failure in the development of hyperparathyroidism should be considered.

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Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat

Cited by 70 publications

References 37 publications

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Renal handling of calcium and phosphorus in experimental renal hyperparathyroidism in dogs

Role of Dietary Phosphorus and Degree of Uremia in the Development of Renal Bone Disease in Rats

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