The 'oral 1,25-dihydroxyvitamin D3 pulse therapy' in hemodialysis patients with severe secondary hyperparathyroidism

Many hemodialysis patients are still suffering from secondary hyperparathyroidism although 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been used to treat renal osteodystrophy for the last two decades. The main reason for its failure to correct the secondary hyperparathyroidism is that in patients, hypercalcemia occurs before adequate parathyroid hormone (PTH) suppression is obtained when a large daily dose of 1,25(OH)2D3 is started. In this study, the oral dose of 1,25(OH)2D3 (4.0 micrograms) was administered only twice a week at the end of hemodialysis ('oral 1,25(OH)2D3 pulse therapy'), in 19 patients with severe secondary hyperparathyroidism. Serum immunoreactive PTH started to decrease after 6 weeks of therapy, and the original level of 41.2 +/- 7.24 was reduced to 24.4 +/- 6.12 ng/ml by the end of the 6-month therapy (p less than 0.001). Serum alkaline phosphatase also was reduced by 64.4%. Three out of 19 patients suffered from hypercalcemia during the 4th month of therapy. Calcium supplement given to 6 other patients with severe secondary hyperparathyroidism did not lower serum PTH levels significantly after 6 weeks of therapy, although serum calcium levels increased and were sustained above 10 mg/dl for the last 5 weeks. These findings strongly suggest that the suppressive effect of the oral 1,25(OH)2D3 pulse therapy was attained by a direct action of 1,25(OH)2D3 on the parathyroid gland rather than by its ability to elevate serum calcium levels. In conclusion, the oral 1,25(OH)2D3 pulse therapy effectively lowered PTH levels in hemodialysis patients who cannot tolerate large daily doses of 1,25(OH)2D3.     

Use of vitamin D analogs in chronic renal failure

Renal osteodystrophy is the term used to describe the spectrum of bone diseases associated with chronic renal failure. Deficiency of 1,25-dihydroxycholecalciferol (calcitriol) plays a major role in the development of renal osteodystrophy, in particular the evolution of secondary hyperparathyroidism. In recent decades, our understanding of the complex interactions between calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) has increased, resulting in a rational approach to therapy in which vitamin D analogs have become an essential component. The initial vitamin D analogs that have been in widespread clinical use include calcitriol (1,25-[OH](2)D(3)) and alfacalcidol (1alpha-[OH]D(3)). These agents have been extensively studied to optimize their effects on secondary hyperparathyroidism. The occurrence of significant hypercalcemia and hyperphosphatemia limiting their use has led to the development of alternative vitamin D analogs that effectively reduce PTH secretion without causing these complications. Recently, 3 such analogs, 22-oxa-1,25-(OH)(2)D(3) (OCT), 1alpha-(OH)D(2) (doxercalciferol), and 19-nor-1,25-(OH)(2)D(2) (paricalcitol), have been released for clinical use. Only paricalcitol has been studied in comparative human clinical trials with calcitriol in dialysis patients. Preliminary findings suggest a clinical advantage over calcitriol, however, analysis of the larger comparative studies are forthcoming.     

The consequences of uncontrolled secondary hyperparathyroidism and its treatment in chronic kidney disease

Secondary hyperparathyroidism (HPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Soft-tissue and vascular calcification, cardiovascular disease, and calcific uremic arteriolopathy (CUA) are additional serious consequences of the disorder that may contribute directly to cardiovascular morbidity and mortality in patients with CKD. Less widely appreciated manifestations include neurological disturbances, hematological abnormalities, and endocrine dysfunction. Secondary HPT arises from alterations in calcium, phosphorus, and vitamin D metabolism that develop early in the course of CKD and become more pronounced as kidney function declines. Treatment is often delayed, however, until the disease is well established. Current therapeutic strategies rely largely on the use of vitamin D sterols to diminish excess parathyroid hormone (PTH) synthesis and to lower serum or plasma PTH levels, but their use is often confounded by increases in serum calcium and phosphorus concentrations, changes that can aggravate soft-tissue and vascular calcification. As such, there is a need for new therapeutic interventions that can effectively lower serum or plasma PTH levels without producing untoward side effects. The current review summarizes the diverse manifestations of secondary HPT in patients with CKD. The consequences of inadequately controlled secondary HPT and the adverse effects of selected therapeutic interventions for the disorder on vascular calcification and cardiovascular disease in those with CKD are discussed.     

Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D.

Osteoblast activity and plasma 1,25(OH)2 vitamin D are increased in HPT but suppressed in HHM. To model HPT and HHM, we directly compared multiday continuous infusions of PTH versus PTHrP in humans. Continuous infusion of both PTH and PTHrP results in marked and prolonged suppression of bone formation; renal 1,25(OH)2D synthesis was stimulated effectively by PTH but poorly by PTHrP. INTRODUCTION: PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism (HPT) and humoral hypercalcemia of malignancy (HHM), respectively. Whereas HHM and HPT resemble one another in many respects, osteoblastic bone formation and plasma 1,25(OH)2 vitamin D are increased in HPT but reduced in HHM. MATERIALS AND METHODS: We performed 2- to 4-day continuous infusions of escalating doses of PTH and PTHrP in 61 healthy young adults, comparing the effects on serum calcium and phosphorus, renal calcium and phosphorus handling, 1,25(OH)2 vitamin D, endogenous PTH(1-84) concentrations, and plasma IGF-1 and markers of bone turnover. RESULTS: PTH and PTHrP induced comparable effects on renal calcium and phosphorus handling, and both stimulated IGF-1 and bone resorption similarly. Surprisingly, PTH was consistently more calcemic, reflecting a selectively greater increase in renal 1,25(OH)2 vitamin D production by PTH. Equally surprisingly, continuous infusion of both peptides markedly, continuously, and equivalently suppressed bone formation. CONCLUSIONS: PTHrP and PTH produce markedly different effects on 1,25(OH)2 vitamin D homeostasis in humans, leading to different calcemic responses. Moreover, both peptides produce profound suppression of bone formation over multiple days, contrasting with events in HPT, but mimicking HHM. These findings underscore the facts that the mechanisms underlying the anabolic skeletal response to PTH and PTHrP in humans is poorly understood, as are the signal transduction mechanisms that link the renal PTH receptor to 1,25(OH)2 vitamin D synthesis. These studies emphasize that much remains to be learned regarding the normal regulation of vitamin D metabolism and bone formation in response to PTH and PTHrP in humans.     

Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease

Chronic kidney disease (CKD) is associated with altered calcium-phosphate homeostasis and hyperparathyroidism due to decreased activity of 1alpha-hydroxylase and impaired activation of 25-hydroxyvitamin D3 [25(OH)D3]. In some patients these problems start earlier because of vitamin D deficiency. A retrospective review of patients followed in the chronic renal insufficiency clinic at Children's Hospital of Michigan assessed the prevalence of vitamin D deficiency in CKD stages 2-4 and evaluated the effect of treatment with ergocalciferol on serum parathormone (PTH). Blood levels of 1,25 dihydroxyvitamin D3, 25(OH)D3, and parathormone (PTH) were examined in 57 children (40 boys; mean age 10.6 years). Of 57 subjects, 44 (77.2%) had 25(OH)D3 levels 30 ng/ml was 67.84 +/- 29.09 ng/ml and in the remaining patients was elevated, at 120.36 +/- 86.42 ng/ml (p = 0.05). Following ergocalciferol treatment (22), PTH decreased from 122.13 +/- 82.94 ng/ml to 80.14 +/- 59.24 ng/ml (p < 0.001) over a period of 3 months. We conclude that vitamin D deficiency is common in children with CKD stages 2-4 and is associated with hyperparathyroidism in the presence of normal 1,25 dihydroxyvitamin D3. Its occurrence before significant renal impairment is noteworthy. Early diagnosis and appropriate treatment is emphasized.     

24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure

AIMS: This study compares the effects of 1,25(OH)2D3 and 24,25(OH)2D3 alone or in combination on renal osteodystrophy in rats with chronic renal failure (CRF). MATERIAL AND METHOD: One month subsequent to 5/6 nephrectomy animals were divided into four groups and treated for one or four weeks with either vehicle, 1,25(OH)2D3, 24,25(OH)2D3 or 1,25(OH)2D3 + 24,25(OH)2D3. A sham-operated group with normal renal function matched for age and weight was used as control. At the termination of the study blood chemistry, parathyroid hormone (PTH) level and bone histomorphometry were analyzed. RESULTS: The main findings were: amelioration of 1,25(OH)2D3-induced hypercalcemia by 24,25(OH)2D3, and similar suppression of PTH by the two metabolites of vitamin D when administered alone or in combination. Bone histomorphometry showed that 1,25(OH)2D3 alone exerts a potent proliferative effect on the osteoblasts but severely depresses their mineralizing capacity in a dose- and time-dependent manner. By contrast, 24,25(OH)2D3 improved the mineralizing activity with only a limited effect on osteoblast proliferation. Addition of 24,25(OH)2D3 potentiated the beneficial effect of 1,25(OH)2D3 on bone-resorbing parameters and corrected the mineralization failure. CONCLUSIONS: Based on the above observations we suggest that the combined treatment with 1,25(OH)2D3 and 24,25(OH)2D3 markedly improves the morphologic and metabolic abnormalities of renal osteodystrophy.     

Methylguanidine kinetics during oral active vitamin D pulse therapy for secondary hyperparathyroidism]

Active vitamin D (VD) metabolite preparations have been used in the management of secondary hyperparathyroidism (2 degrees HPT) due to impaired calcium and phosphorus metabolism and can allegedly be expected to prevent, to some extent, the progression of this pathological condition. Unfortunately, however, it is not uncommon for us in routine clinical practice to find 2 degrees HPT of moderate or greater severity embarrassingly unamenable to treatment with these VD preparations in ordinary oral therapeutic doses. Recent studies have gradually reported that intravenous administration of 1,25-(OH)2D3 and oral active VD pulse therapy has been therapeutic approach to 2 degrees HPT. Methylguanidine (MG) among other GCs, its precursor is already identified as creatinine and activated oxygen as well PTH and VD are known to participate in the process leading to its formation. In the present study, we administered oral 1,25-(OH)2D3 pulse therapy to patients with chronic renal failure for the treatment of 2 degrees HPT in an attempt to assess the effectiveness of this therapeutic regimen and to explore the clinical effect of MG on responsiveness to the therapy. The purpose of this paper is to present the results thus obtained. Oral 1,25-(OH)2D3 pulse therapy (6 micrograms once a week) was administered to 21 hemodialysis patients with for 12 weeks. Of these 21, 10 patients responded to the therapy with a more than 20% reduction in serum (PTH): (responsive group), whereas the remaining 11 did not (resistant group). Pretreatment serum PTH levels were significantly higher in the latter group than the former.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of intact parathyroid hormone and free 1,25-dihydroxyvitamin D levels in mild and moderate renal failure.

Parameters of calcium and phosphate metabolism were measured in 27 patients with mild renal failure [glomerular filtration rate (GFR) 40-90 ml/min], 12 patients with moderate renal failure (GFR 20-39 ml/min) and in 12 healthy subjects. GFR was determined by technetium-99m diethylenetriamine penta-acetic acid clearance. Intact parathyroid hormone (PTH) was measured by a sensitive immunochemiluminometric assay and somatomedin-C was determined by radioimmunoassay. Both 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin-D-binding protein were measured allowing calculation of the free 1,25(OH)2D index. By linear regression and multivariate analysis, PTH was negatively and independently correlated with GFR, plasma bicarbonate and 25-hydroxyvitamin D [25(OH)D] while free 1,25(OH)2D was positively correlated with GFR. Increased PTH secretion and reductions in 1,25(OH)2D were present in mild renal failure patients before any changes in plasma calcium, phosphate and bicarbonate were noted. Plasma alkaline phosphatase was significantly higher in mild chronic renal failure patients compared to normal subjects, possibly indicating early effects of the secondary hyperparathyroidism on the skeleton. Somatomedin-C did not correlate with the free 1,25(OH)2D index or a measure of 1,25(OH)2D production. It is concluded that the secondary hyperparathyroidism which occurs very early in the onset of chronic renal failure may be due to a reduction in the circulating concentration of 1,25(OH)2D consequent upon the renal failure. Low plasma bicarbonate and 25(OH)D also appear to be determinants of a raised PTH concentration. The compensatory increase in PTH presumably maintains extracellular calcium and phosphate levels constant but with possible deleterious effects on the skeleton.     

Vitamin D insufficiency: implications for the immune system

Chronic kidney disease (CKD) is characterized by a loss of kidney function and dysregulation of vitamin D metabolism. Well known are the defects in final activation of vitamin D to 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], resulting in renal osteodystrophy. However, in recent years, 1,25(OH)₂D₃ has been identified as having effects far beyond calcium and bone metabolism. In this review, specific attention is given to the effects of 1,25(OH)₂D₃ on the immune system and the implications of vitamin D deficiency, a feature of many patients with CKD, on immune function.     

Attenuated rise of 1,25 (OH)2 vitamin D3 in response to parathyroid hormone in patients with incipient renal failure

Despite elevated parathyroid hormone (PTH) levels, low normal or diminished serum 1,25(OH)2D3 concentrations are found in patients with incipient renal failure. To further assess (indirectly) the reserve capacity of renal production of 1,25(OH)2D3 we studied 9 patients with incipient or moderate renal failure (inulin clearance 31-68ml/min/1.73 m2) and 9 controls, using a novel stimulation test. We measured 1,25 (OH)2D3 levels, free 1,25(OH)2D3 index, cAMP excretion, calciuria and phosphaturia before and after infusion of 2 x 400 U of human (h) PTH (1-38). Baseline 1,25(OH)2D3 levels were not significantly different in patients (42.5 pg/ml, 21.6-51.1) compared with controls (45.0 pg/ml, 37.4-67.3). After infusion of hPTH(1-38), however, median increase in 1,25(OH)2D3 was only +25% versus +86% in controls, despite a greater proportional increase in cAMP/GF ratio. The data suggest subnormal stimulation of renal 1,25(OH)2D3 production in response to exogenous PTH in most patients with incipient renal failure. This may reflect partial exhaustion of biosynthetic reserve capacity.     

Chronic kidney disease mineral and bone disorder in children

Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.     

Lack of relationship between parathyroid hormone and 1,25-dihydroxyvitamin D in chronic renal failure

In the present study, concentrations of parathyroid hormone (PTH), determined by an intact PTH assay and a midregion/C-terminal PTH assay, 1,25-dihydroxyvitamin D [1,25(OH)2D3], ionized calcium and phosphate were measured in 15 patients with a stable creatinine clearance (Ccr) of 21.2 +/- 14.4 ml/min (mean +/- SD; group 1) and in 10 patients with a Ccr regularly undergoing hemodialysis (group 2, Ccr not measured). In group 1, the mean concentration of 1,25(OH)2D3 was significantly increased compared with the level in group 2, whereas no differences were found concerning the concentrations of intact PTH, midregion/C-terminal PTH, ionized calcium and phosphate. In group 1, the PTH concentration correlated inversely with ionized calcium concentration and Ccr, which in turn, was directly correlated. The concentration of 1,25(OH)2D3 correlated inversely with phosphate concentration, but did not correlate with either PTH or ionized calcium concentrations. In group 2 no correlation was found between any of the biochemical variables. The data demonstrate that in patients with stable renal failure, the concentration of ionized calcium still regulates PTH secretion but other variables such as parathyroid cell mass and setpoint may interfere with the interrelation. The elevated concentration of phosphate in renal failure may override PTH as a regulator of the renal 1,25(OH)2D3 formation. The lack of correlation in the hemodialyzed patients may be attributed to extrarenal production of 1,25(OH)2D3, reduced binding of 1,25(OH)2D3 to parathyroid tissue or the major changes in calcium homeostasis caused by the hemodialysis.     

In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3.

BACKGROUND: Although it effectively suppresses parathyroid hormone (PTH) secretion, vitamin D [1,25(OH)(2)D(3)] therapy often causes tissue calcification over the long term. In patients on chronic dialysis, cardiovascular calcification is clearly linked to an unfavourable prognosis. In pre-dialysis patients, renal calcification of the kidney leads to the deterioration of renal function. METHODS: We compared the propensities of 22-oxacalcitriol (OCT), with lesser calcaemic action, and 1,25(OH)(2)D(3) for producing their potential side effects in rats: (i) metastatic calcification of heart and aorta, and (ii) renal dysfunction with nephrocalcinosis, using the same effective doses for hyperparathyroidism. OCT (1.25 and 6.25 micro g/kg) or 1,25(OH)(2)D(3) (0.125 and 0.625 micro g/kg) solutions were administered intravenously to subtotally nephrectomized (SNX) rats three times weekly for 2 weeks. RESULTS: Despite the suppression of PTH to comparable levels, the calcification of the hearts, aortas and kidneys in the 1,25(OH)(2)D(3)-treated group was significantly greater than in the OCT-treated group. Of interest was that, in the OCT (6.25 micro g/kg) group, the degree of calcification in hearts, aortas and kidneys were distinctly lower than those in the 1,25(OH)(2)D(3) (0.125 micro g/kg) group despite the comparable serum Ca x Pi products. Therefore, there may be different mechanisms behind the calcifications resulting from OCT and 1,25(OH)(2)D(3). Deterioration of renal function, tubular changes, and atypical hyperplasia of proximal tubules associated with calcification were more severe in the 1,25(OH)(2)D(3)-treated group than in the OCT-treated group. CONCLUSIONS: These results indicate that OCT may be an effective agent for the suppression of PTH with a lesser risk of cardiovascular calcification or deterioration of residual renal function.     

Effect of 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol (2MbisP), an analog of vitamin D, on secondary hyperparathyroidism.

Vitamin D analogs are being developed that retain therapeutic effects but are less calcemic and phosphatemic, a concern in CKD patients who are prone to vascular calcification. We tested a new analog of vitamin D, 2MbisP, and found that it suppresses PTH at doses that do not affect serum Ca or P. INTRODUCTION: Calcitriol is used for the treatment of secondary hyperparathyroidism. However, its use is often limited by the development of hypercalcemia and hyperphosphatemia, an important consideration in patients with chronic kidney disease (CKD) because they are prone to vascular calcification. To minimize this toxicity, structural modifications in the vitamin D molecule have led to the development of calcitriol analogs with selective actions. MATERIALS AND METHODS: In this study, we compared the effects of 1,25(OH)(2)D(3) and a new analog, 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol (2MbisP), on the development of secondary hyperparathyroidism and established secondary hyperparathyroidism in uremic rats and on mobilization of calcium and phosphorus from bone in parathyroidectomized rats. The clearance from circulation, half-life, and binding affinities to the vitamin D-binding protein and vitamin D receptor of this compound were also evaluated. RESULTS: Uremia produced a marked rise in plasma PTH, but treatment every other day for 2 wk with either 1,25(OH)(2)D(3) (4 ng) or 2MbisP (250, 750, 1500, or 3000 ng) suppressed this increase by >50%. The suppression by 1,25(OH)(2)D(3), however, was accompanied by increases in ionized calcium, phosphorus, and the calcium x phosphorus product, whereas these three parameters were unchanged by 2MbisP. The binding affinity of 2MbisP was 10-20 times less for the vitamin D receptor and 1000 times less for the serum vitamin D-binding protein compared with 1,25(OH)(2)D(3). Also, 2MbisP was cleared more rapidly from the circulation (t1/2 = 10 min) than 1,25-(OH)(2)D(3) (t1/2=7-9 h). In parathyroidectomized rats fed calcium-or phosphorus-deficient diets, daily injections of 2MbisP (1500 or 3000 ng), unlike 1,25(OH)(2)D(3) (50 ng), had no effect on calcium or phosphorus mobilization from bone. CONCLUSIONS: In uremic rats, 2MbisP can suppress PTH at doses that do not affect plasma calcium, phosphorus, and calcium x phosphorus product. This new vitamin D analog may represent an important tool in the treatment of secondary hyperparathyroidism in patients with CKD.     

Vitamin D status in children with chronic kidney disease

Background

The role of vitamin D status in patients with renal insufficiency and its relation to dietary intake and parathyroid hormone (PTH) secretion is of utmost interest given the morbidity and mortality associated with the disordered mineral metabolism seen in chronic kidney disease (CKD).

Methods

We conducted a cross-sectional study of 100 pediatric patients with a diagnosis of CKD stage 1–5 at Children's Hospital Boston, measuring blood levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)₂D], and parathyroid hormone and obtaining data on nutrient intake and other variables related to vitamin D status.

Results

Subjects ranged in age from 6 months to 18?years, and 60 were male, 40 female. Of the 100 patients, 16 % were deficient in 25(OH)D (≤20?ng/mL) and another 24 % were insufficient (≤30?ng/mL), with 40 % in the suboptimal range. Serum 25(OH)D and dietary vitamin D intake were not correlated.

Conclusions

We found a high prevalence of hyperparathyroidism in early-stage CKD and a significant relationship between 25(OH)D and PTH regardless of calcitriol level. Our study results support the suggestion that optimization of vitamin D levels may provide additional benefit in preventing or improving hyperparathyroidism in patients with early CKD and likely remains important as an adjunctive therapy in children with advanced CKD.     

Progress of renal osteodystrophy during continuous ambulatory peritoneal dialysis

At present, only a few data are available on the effects of continuous ambulatory peritoneal dialysis (CAPD) on renal osteodystrophy. Twelve patients on CAPD were studied for one year, in order to evaluate the progress of renal osteodystrophy. Our results showed a downward trend of plasma calcium, a good control of phosphatemia, a significant increase of alkaline phosphatase and parathyroid hormone. We also found an important decrease of plasma vitamin D metabolites (25(OH)D3 and 1,25 (OH)2D3) and bone mineral content. Bone biopsy showed a general worsening of both secondary hyperparathyroidism and osteomalacia. Thus, we can conclude that CAPD alone is not able to control the evolution of renal osteodystrophy.     

The oral 1-25 dihydroxyvitamin D3 pulse therapy in hemodialysis patients for the early treatment of secondary hyperparathyroidism]

It is said that maintenance hemodialysis patients are already suffering from secondary hyperparathyroidism (2HPT) from early stage of chronic renal failure. The treatment of 2HPT in this stage is very important for preventing renal osteodystrophy (ROD). But many long-term dialysis patients are still afflicted with ROD although vitamin D have been used for treatment. In this study, an oral administration of 1-25 (OH)2 D3 (4 micrograms) with pulse therapy twice a week at the day before hemodialysis was started for 12 weeks. The concentration of 1-25 (OH)2D3, total calcium (Ca), ionized calcium (Ca++), alkaline phosphatase (ALP) and parathyroid hormone (PHT) in serum were measured not only before and after every 2 hours of administration a day, but also for 12 weeks after that. The peak of serum 1-25 (OH)2D3 could be sufficiently elevated after 8 hours, and the slight peak of Ca++ could be seen after 8 hours as well. But the level of total calcium could not increased. Although the level of only HS-PTH has not increased after 24 hours, a significant reduction in serum level of C-PTH, intact-PTH and HS-PTH could be recognized after 12 weeks finally. This pulse therapy was effective in reducing the serum level of PTH in this early stage from beginning hemodialysis. But, it needs further studies for the standard treatment.