ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Extracellular calcium ion concentration is the major determinant of parathyroid hormone (PTH) secretion from parathyroid cells. In dialysis patients with secondary hyperparathyroidism, higher calcium concentration is needed to suppress PTH secretion as demonstrated by the PTH-calcium curve. Such abnormal sensitivity to extracellular calcium ion has been recently explained by the decrease in number of calcium-sensing receptors, especially on cells in nodular hyperplasia, which is the advanced type of parathyroid hyperplasia in uremia. Modulation of the sensitivity of parathyroid cells to calcium has become partly possible through the use of newly developed calcimimetics.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Vitamin D’s biologically active metabolite, 1,25(OH)2D3,has important effects upon the parathyroid cell that are relevant to both the physiology of mineral metabolism and the regulation of the secondary hyperparathyroidism of chronic renal failure. 1,25(OH)2D3markedly decreases parathyroid hormone (PTH) gene transcription and thus PTH synthesis and secretion. It also acts to decrease parathyroid cell proliferation. Nonhypercalemic analogs of 1,25(OH)2D3are being developed that may have a wider therapeutic window than 1,25(OH)2D3itself. In the situations of chronic hypocalcemia and hypophosphatemia, there are interesting interrelationships between 1,25(OH)2D3and the post-transcriptional regulation of thePTHgene. In nodular secondary hyperparathyroidism, there is down-regulation of the vitamin D receptor in the parathyroid. Different vitamin D receptor genotypes may be associated with higher levels of serum PTH and a predisposition to autonomous hyperplasia.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Hyperplasia of the parathyroid glands and high levels of parathyroid hormone (PTH) are among the most consistent findings in patients with chronic renal failure. In early renal failure, alterations in vitamin D metabolism play a key role in the development of secondary hyperparathyroidism. Low levels of calcitriol and decreased expression of the vitamin D responsive element may allow greater synthesis and secretion of PTH. Phosphorus independent of serum calcium and calcitriol increases PTH synthesis and secretion by a post-transcriptional mechanism. Studies in vivo in uremic rats demonstrated that an increase in dietary phosphorus induces parathyroid gland hyperplasia. If the rats are then fed a low-phosphorus diet, the levels of serum PTH return to normal; however, the size of the parathyroid glands remains enlarged. No apoptosis was observed in the glands. To further characterize the effects of phosphorus on PTH synthesis and secretion, intact rat parathyroid glands were metabolically labeled during a 4-hour incubation in methionine-free medium containing 1.25 mM Ca2+, [35S]methionine, and either 2.8 mM or 0.2 mM phosphorus. Total PTH secretion, as measured in the medium, was increased more than 6-fold in glands incubated in high-phosphorus medium compared with glands incubated in the low-phosphorus medium. Thus, in the past 20 years, numerous investigators have provided strong evidence for the action of phosphorus on PTH secretion. Unfortunately, the absence of a parathyroid cell line is slowing the progress in understanding the molecular mechanism(s) involved in phosphorus regulation of PTH.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Marked parathyroid hyperplasia of heterogeneous degrees is often seen in chronic dialysis patients with severe secondary hyperparathyroidism. In uremia, parathyroid cell proliferation is initially stimulated by decreased concentration of calcium ions and calcitriol and also by direct effect of phosphate accumulation, leading to diffuse hyperplasia of the parathyroid. Then, small nodules caused by monoclonal cell proliferation form within diffuse hyperplasia, which progress to form nodular hyperplasia. Cells in nodular hyperplasia have a lower density of calcitriol receptor and calcium-sensing receptor than diffuse hyperplasia and are thus more resistant to medical therapy, including calcitriol pulse therapy. One of these nodules may grow more vigorously than the others and may finally occupy a large part of the enlarged gland. Genetic mutations and rearrangements of these cells in nodular hyperplasia remain to be fully elucidated in the near future to establish an effective method for the prevention of parathyroid hyperplasia in uremia.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The prevention and treatment of the secondary hyperparathyroidism of chronic renal failure by medical means relies on a number of different possible approaches, which should be tailored to each patient’s individual needs. Schematically, prevention should start early during the course of chronic renal failure (ie, when plasma intact parathyroid hormone is normal or only slightly elevated). Small calcium supplements prevent the development of a calcium deficit and may prevent parathyroid hormone oversecretion. The various therapeutic options that are available at present include: oral or intravenous vitamin D and vitamin D derivatives, in particular the 1&agr;-hydroxylated vitamin D compounds; oral calcium supplements (calcium carbonate and calcium acetate) to avoid calcium depletion and also to bind phosphate in the intestinal lumen; aluminum-containing phosphate binders, the use of which should be restricted; oral magnesium salts (magnesium carbonate and magnesium hydroxide), which often are not well tolerated; general measures, such as dietary restriction of phosphate intake; and, in the case of resistance to all these approaches, the possibility of attempting ultrasound-guided ethanol injection of grossly hyperplastic parathyroid glands. Finally, it is encouraging to know that new drugs are in development, including calcium-free, aluminum-free, nonabsorbable oral phosphate binders, potentially nonhypercalcemic vitamin D derivatives, and calcimimetics. Some of them already have entered the stage of clinical evaluation, and preliminary results are promising.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Advanced secondary (renal) hyperparathyroidism (HPT) induced by uremia is one of the most serious complications for long-term hemodialysis patients. Parathyroidectomy (PTx) is indicated in patients with severely advanced renal HPT that is refractory to medical treatment, including calcitriol pulse therapy. The clinical effect of PTx is striking. However, skeletal deformity, vessel calcification, and remarkable reduction of bone content is irreversible. Therefore, it is important to perform PTx at the right time. Based on histopathological and pathophysiological investigations, nodular hyperplasia is monoclonal neoplasia with abnormal parathyroid hormone response to extracellular calcium and vitamin D. When parathyroid hyperplasia progresses to nodular hyperplasia, PTx should be required. Total PTx with forearm autograft is the preferred procedure for renal HPT, especially for patients who need to continue hemodialysis treatment after PTx. Removal of all parathyroid glands, including supernumerary glands, at the initial operation and proper choice of adequate parathyroid tissue for autograft are important to prevent persistent and recurrent HPT. In this series of 782 patients, the function of autografted parathyroid tissue is almost satisfactory and no retransplantation of cryopreserved parathyroid tissue was necessary; however, graft-dependent recurrent HPT was not negligible. In conclusion, total PTx with forearm autograft is very effective and adequate treatment for advanced renal HPT and parathyroid function can be controlled after PTx.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Impaired calcitriol synthesis is one of the major factors contributing to the development of secondary hyperparathyroidism in patients with chronic renal failure. Vitamin D therapy, particularly 1&agr;-hydroxyvitamin D3, even in low doses, has been shown to be effective in the treatment of secondary hyperparathyroidism in patients with mild-to-moderate chronic renal failure. Complications associated with calcitriol and alfacalcidol therapy, which include hypercalcemia and progressive deterioration of renal function, have been reported in some patients. The majority of the studies reviewed, however, demonstrated that daily calcitriol and alfacalcidol doses below 0.25 &mgr;g are rarely associated with hypercalcemia, hyperphosphatemia, or progressive decline in renal function. In addition, these complications usually resolve with the reduction in dose or discontinuation of the medication. Thus, vitamin D therapy may be valuable in the treatment of patients with mild-to-moderate chronic renal failure who may be at high risk of developing secondary hyperparathyroidism.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Renal bone disease results in significant morbidity in patients with end-stage renal failure. Renal osteodystrophy is a mixture of different conditions with different pathogenetic factors involved. Most recently a new form of renal bone disease, adynamic bone disease, has emerged as the most frequent finding on bone biopsy of patients on dialysis therapy. The etiology of this new entity is not fully understood, but relatively low levels of intact serum parathyroid hormone are frequently associated with this disorder and may play an important role in its pathogenesis.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Dialysis-related amyloidosis (DRA) is a major complication of chronic renal failure and long-term renal replacement therapy. &bgr;2-Microglobulin is a major constituent of amyloid fibrils in DRA. Amyloid deposition can present as carpal tunnel syndrome, destructive arthropathy, or subchondral bone erosions and cysts. A definitive diagnosis of DRA can only be made using histological findings, but various analytical imaging methods often support diagnosis. Therapy of an established DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes can be used to delay DRA development. Recent studies have suggested a pathogenic role for a new modification of &bgr;2-microglobulin in DRA. Increased carbonyl compounds modify proteins, which leads to the augmentation of advanced glycation and lipoxidation end products. Thus, uremia might be a state of carbonyl overload with potentially damaging proteins, leading to a new modification of &bgr;2-microglobulin in amyloid fibrils and development of DRA.

ISSN:0002-9629    

出版商:OVID    

年代:1999

数据来源: OVID