Several key components of parathyroid gland function have yet to be fully characterized in chronic renal failure despite the central role of disturbances in parathyroid hormone (PTH) secretion in the pathogenesis of renal osteodystrophy. It is not known, therefore, whether the normal diurnal variations in serum ionized calcium and PTH levels are preserved in renal failure or whether pulsatile PTH secretion is maintained in either secondary hyperparathyroidism or adynamic renal osteodystrophy. Both factors may contribute to substantial short-term fluctuations in serum PTH levels in patients with end-stage renal disease. Because serum intact PTH measurements are widely used not only for the diagnosis of renal osteodystrophy but also to monitor therapy, disturbances in diurnal PTH secretion and/or pulsatile PTH release may serve as important modifiers of PTH secretion and of bone formation and turnover in chronic renal failure; such changes may directly affect the development and progression of selected types of renal osteodystrophy. To address these issues, cosinor analysis and deconvolution analysis will be used to assess diurnal PTH secretion and pulsatile PTH release in patients with secondary hyperparathyroidism, in those with adynamic renal osteodystrophy and in subjects with normal renal and parathyroid gland function. The impact of daily oral and thrice weekly intermittent oral doses of calcitriol on diurnal PTH secretion and pulsatile PTH release in patients with secondary hyperparathyroidism will also be evaluated, and the respective roles of hemodialysis and peritoneal dialysis as separate modifiers of diurnal and pulsatile PTH secretion in end-stage renal disease will be examined.
The specific aims of the current proposal are: 1) To measure and compare the diurnal variations in serum ionized calcium and PTH levels in patients with secondary hyperparathyroidism and adynamic renal osteodystrophy; 2) To measure and compare the components of pulsatile PTH secretion in patients with secondary hyperparathyroidism and adynamic renal osteodystrophy; 3) To determine whether continuous or intermittent calcitriol dosage regimens diminish or eliminate pulsatile PTH secretion and alter the diurnal patterns of ionized calcium and PTH in secondary hyperparathyroidism. The results of the studies proposed should provide new information about the regulation of PTH secretion in chronic renal failure, and they should also offer new insights into additional mechanisms that contribute to the pathogenesis of specific types of renal osteodystrophy.
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