Successful Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients with Oral Pulse 1-Alpha-Hydroxycholecalciferol Therapy

Rapoport, Jayson; Mostoslavski, Marcus; Ben-David, Alon; Knecht, Aaron; Blau, Alexander; Arad, Jacob; Zlotnik, Moshe; Chaimovitz, Cidio

doi:10.1159/000188833

Cited by 6 publications

(5 citation statements)

References 12 publications

(17 reference statements)

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“…Multiple studies have influenced the care dialysis patients receive. The efficacy of calcitriol in regulating calcium and suppressing PTH secretion has been shown [9]. Calcium-based phosphate binders have been substituted for aluminum-based binders because they have been found to be safer, and they provide calcium supplementation.…”

Section: Discussionmentioning

confidence: 99%

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

et al. 2001

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There are scant data on the frequency of parathyroidectomy (PTX) for end-stage renal disease (ESRD). Medical therapy for ESRD and secondary hyperparathyroidism has evolved to include better dialytic urea removal and the use of calcitriol. The aim of this study was to determine whether medical therapy has changed the frequency or indications for PTX in the management of renal failure. Hospital and clinic records were analyzed to gather information on all patients undergoing PTX for secondary hyperparathyroidism (2HPT) (n = 48) and tertiary hyperparathyroidism (3HPT) (n = 26) from 1986 through 1998 at our institution. Prospective computer databases were queried for information concerning both chronic dialysis and renal transplant patients at our center. The patients were divided based on date of operation before or after 1991, a divider that separated the patients into groups before or after the widespread adoption of intravenous calcitriol treatment during hemodialysis at our institution. Over the 12 year period, the proportion of our chronic dialysis patients undergoing PTX did not change significantly, ranging from 0% to 2.5% per year. Comparing all patients undergoing PTX for 2HPT during 1986-1991 versus 1992-1998, there was no significant difference in time on dialysis [7.0 +/- 4.2 (n = 11) vs. 7.5 +/- 4.6 (n = 36) years, mean +/- SD]. The later group had higher intact parathyroid hormone (iPTH) levels [765 +/- 415 (n = 6) vs. 1377 +/- 636 (n = 28) pg/ml; p = 0.03], lower serum calcium [11.2 +/- 1.0 (n = 12) vs. 9.9 +/- 1.5 (n = 34) mg/dl; p = 0.006], and higher serum phosphate [5.7 +/- 1.6 (n = 12) vs. 7.2 +/- 2.3 (n = 31) mg/dl; p = 0.042]. Among the population of patients with transplants undergoing PTX for 3HPT, the average percent per year undergoing PTX ranged from 0% to 4.2% and did not change during the study period. Comparing the 1986-1991 group to the 1992-1998 group, the time from transplantation to PTX did not change during the study period (3.3 +/- 2.3 vs. 2.9 +/- 3.0 years; p = 0.391), and there were no significant differences between preoperative calcium levels or iPTH levels. Despite advances in dialysis technique and pharmacologic therapy, there has been no change in the proportion of dialysis patients requiring PTX for 2HPT or 3HPT. There was also no change in the time on dialysis for patients with 2HPT or the time from transplant to PTX for patients with 3HPT. Analysis of preoperative biochemical markers as evidence of disease severity suggests there was no change in indications for PTX during our study. From this information we conclude that parathyroid pathophysiology is incompletely understood and medical therapy is not optimal, resulting in a continuing need for PTX in some patients.

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Section: Discussionmentioning

confidence: 99%

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

et al. 2001

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“…Several clinical studies have documented that PTH levels can be suppressed in most uremic patients and that this suppression can be maintained by continuous treatment with phosphate binders, vitamin D analogs, or calcimimetics (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). PTH levels return to pretreatment values, however, when the treatment is stopped (32,33,37).…”

Section: Can Parathyroid Hyperplasia Be Arrested or Reversed?mentioning

confidence: 99%

Can Hyperparathyroid Bone Disease Be Arrested or Reversed?

Ølgaard

Lewin

2006

Clinical Journal of the American Society of Nephrology

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Parathyroid hyperplasia, oversecretion of parathyroid hormone (PTH), and hyperparathyroid bone disease are characteristic features of chronic uremia; they develop early in the course of uremia and often in a progressive way. This review focuses on the potential for arrest or regression of hyperparathyroid-induced bone disease. For this purpose, the review addresses investigations that have used bone histology and not investigations that indirectly attempted to demonstrate changes in the skeleton by measurements of bone mineral density or laboratory indices of bone turnover, other than PTH. A prerequisite for inducing regression of the hyperparathyroid bone disease is a significant suppression of PTH secretion or reversal of hyperparathyroidism and uremia. It is concluded, on the basis of paired bone biopsy studies in patients with established hyperparathyroid bone disease, that bone histology can be improved or normalized after treatment that diminishes PTH levels. Oversuppression of PTH levels, however, might lead to adynamic bone disease.Clin J Am Soc Nephrol 1: 367-373, 2006367-373, . doi: 10.2215 R enal osteodystrophy (ROD) is a disabling skeletal disease in uremic patients that consists of a high-turnover bone disease, a low-turnover bone disease, or a mixture of both. The type of bone lesion is correlated to increased production or to oversuppression of parathyroid hormone (PTH) levels (1-3).The high-turnover bone disease, osteitis fibrosa (cystica), is related to the severity of the secondary hyperparathyroidism (sHPT). PTH in concert with locally produced cytokines and factors (some produced by bone marrow cells and some by osteoblast precursors) IL-1 and TNF and later IL-6, IL-11, GM-CSF, M-CSF, and the OPG/RANKL system induce recruitment and differentiation of osteoclast precursors, resulting in stimulation of bone resorption (4). Bone formation is impaired, but the mechanism is not completely understood. PTH inhibits the synthesis of collagen and inhibits the progression of the osteoblastic cell cycle. The net result of severe sHPT in uremia is accelerated bone resorption. Furthermore, these bone lesions are characterized by massive peritrabecular fibrosis, and it has been postulated that PTH stimulates proliferation of an osteoprogenitor (preosteoblastic cell), which leads to accumulation of fibroblastic cells that produce marrow fibrosis (4). Recent experimental evidence (5,6) documented that uremia, per se, decreases skeletal anabolic activity. Development of HPT might be considered an adaptive mechanism to override this abnormality in bone remodeling. In this respect, increased PTH functions as a surrogate for a missing factor, maintaining bone turnover. Bone morphogenic protein 7 is a candidate for such a renal-derived factor (7,8).The clinical consequences of osteitis fibrosa, fractures, skeletal deformities, tendon rupture, bone pain, and impaired skeletal growth in children are well described. In the total population of uremic patients, hyperparathyroid bone lesions still are the most frequen...

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“…Several clinical studies have documented that PTH levels can be suppressed in most uremic patients and this suppression can be maintained by continuous treatment with phosphate binders, vitamin D analogs or calcimimetics. [28][29][30][31][32][33][34][35][36][37][38] PTH levels return, however, to pre-treatment values when the treatment is stopped. 28,29,33 This rebound of PTH levels suggest that even with good control of parathyroid function under maintainance treatment, no involution of hyperplastic glands takes place.…”

Section: Clinical Versus Experimental Studies Of Parathyroid Growthmentioning

confidence: 99%

Influence of parathyroid mass on the regulation of PTH secretion

Lewin

Ølgaard

2006

Kidney International

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In advanced uremia, parathyroid hormone (PTH) levels should be controlled at a moderately elevated level in order to promote normal bone turnover. As such, a certain degree of parathyroid gland (PG) hyperplasia has to be accepted. No convincing evidence of apoptosis or of involution of PG hyperplasia exists. However, even considerable parathyroid hyperplasia can be controlled when the functional demand for increased PTH levels is abolished. When 20 isogenic PG were implanted into one parathyroidectomized (PTX) rat normalization of Ca(2+) and PTH levels and normal suppressibility of PTH secretion by high Ca(2+) was obtained. Similarly, normal levels of Ca(2+) and PTH and suppressibility of PTH secretion were obtained when Eight isogenic PG from uremic rats were implanted into normal rats or when long-term uremia and severe secondary hyperparathyroidism (sec. HPT) was reversed by an isogenic kidney transplantation. Normalization of PTH levels after experimental kidney transplantation took place despite a persistent decrease of vitamin D receptor (VDR) mRNA and calcium sensing receptor (CaR) mRNA in PG. Thus, in experimental models PTH levels are determined by the functional demand and not by parathyroid mass, per se. When non-suppressible sec. HPT is present in patients referred to PTX, nodular hyperplasia with differences in gene expression between different nodules has been observed in most cases. An altered expression of some autocrine/paracrine factors has been demonstrated in the nodules. Enhanced expression of PTH-related peptide (PTHrP) has been demonstrated in PG from patients with severe secondary HPT. PTHrP has been shown to stimulate PTH secretion in vivo and in vitro. PTH/PTHrP receptor was demonstrated in the parathyroids. The low Ca(2+) stimulated PTH secretion was enhanced by 300% by PTHrP 1-40. The altered quality of the parathyroid mass and not only the increased parathyroid mass, per se, might be responsible for non-controllable hyperparathyroidism in uremia and after kidney transplantation.

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Successful Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients with Oral Pulse 1-Alpha-Hydroxycholecalciferol Therapy

Cited by 6 publications

References 12 publications

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

Subtotal Parathyroidectomy in Renal Failure: Still Needed after All These Years

Can Hyperparathyroid Bone Disease Be Arrested or Reversed?

Influence of parathyroid mass on the regulation of PTH secretion

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