Deterioration of renal function during treatment of chronic renal failure with 1,25-dihydroxycholecalciferol. A randomized trial of intermittent versus continuous oral alfacalcidol treatment of hyperparathyroidism in end-stage renal disease. Comparison of 1 alpha-OH-vitamin D3 and high doses of calcium carbonate for the control of hyperparathyroidism and hyperaluminemia in patients on maintenance dialysis. Intravenous vitamin D therapy reduces PTH-(1-84)/large C fragments ratio in chronic hemodialysis patients. The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study). Effect of 24,25-dihydroxycholecalciferol on intestinal absorption of calcium and phosphate and on parathyroid hormone secretion in chronic renal failure. A randomized trial of sevelamer hydrochloride (RenaGel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. A controlled study of vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. Prevention of hyperparathyroidism in patients on maintenance dialysis by intravenous 1-alpha-hydroxyvitamin D3 in association with Mg(OH)2 as sole phosphate binder. A randomized comparative study with the association CaCO3 +/- Mg(OH)2. [A comparison of phosphorus-chelating effect of calcium carbonate versus calcium acetate before dialysis]. Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients. Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Suppression of secondary hyperparathyroidism in children with chronic renal failure by high dose phosphate binders: calcium carbonate versus aluminium hydroxide. Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis. A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients. Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol. Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2. Double blind study on the need for vitamin D supplementation in prepubertal children. Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation. Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D. Comparison of the efficacy of two injectable forms of vitamin D3 and oral one-alpha in treatment of secondary hyperparathyroidism in patients on maintenance hemodialysis. Effects of a supplemented hypoproteic diet in chronic kidney disease. Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group. Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism. 19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism. Controlled trial of the effects of 1,25-dihydroxycholecalciferol in patients treated with regular dialysis. Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis. Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. Effect of supplementation with vitamin D3 and calcium on quantitative ultrasound of bone in elderly institutionalized women: a longitudinal study. Preventing bone loss in renal transplant recipients with vitamin D. Effect of the mode of calcitriol administration on PTH-ionized calcium relationship in uraemic patients with secondary hyperparathyroidism. A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD. Controlled trial of 1apha-hydroxycholecalciferol in chronic renal failure. Vitamin D administration to tuberculous children and its value. A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol. Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women.
A controlled study of the effects of the potent vitamin-D metabolite, 1, 25-dihydroxycholecalciferol (1,25[OH]2D3), and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure (C.R.F.). Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected. After 6 months' observation of the spontaneous course the patients were randomly allocated to 6 months' oral treatment with either 1, 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U., respectively, combined with 0.5 g calcium. 1,25(OH)2D3 quickly corrected hypocalcaemia, reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone, and more than doubled the urinary excretion rate of calcium. D3 had similar, but less pronounced effects. 7 out of 8 patients on 1,25(OH)2D3, developed hypercalcaemia which necessitated a reduction in dosage. None of the patients on D3 treatment developed hypercalcaemia. The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1, 25 (OH)2D3 (P less than 0.01) and in 7 of 9 patients on vitamin D3 treatment (though the group change here was not significant). Deterioration of renal function is a major limitation of the clinical use of 1, 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact, the decrased formation of 1, 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism. Secondary hyperparathyroidism, a major clinical problem in patients with chronic renal failure, develops in response to phosphate retention and impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy, particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be effective in the treatment of secondary hyperparathyroidism. The aim of this study was to compare the effect of a 12-week course of continuous versus intermittent oral alfacalcidol therapy on parathyroid hormone suppression.
                34 patients were selected and randomly divided into 2 groups to receive either intermittent or continuous oral alfacalcidol. Baseline data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH. All but the PTH were monitored monthly. PTH levels were measured again until the end of the protocol. The intervention was 2 microg of alfacalcidol given after each dialysis session (intermittent group) or 1 microg given 6 days/week (continuous group).
                Serum calcium and phosphorus showed a tendency to increase from baseline levels in both groups. Mean PTH levels for both groups showed a progressive reduction over time during the study period. This decrement showed no significant difference with regard to the schedule of alfacalcidol administration when comparing the 2 groups. There also was no difference in the incidence of side effects--hypercalcemia and hyperphosphatemia--between the intermittent and continuous intervention.
                Feedback regulation of PTH with oral alfacalcidol therapy is efficient in the treatment of hyperparathyroidism. However, intermittent and continuous oral administration are equally effective in suppressing an elevated PTH level in hemodialysis patients, with similar safety margins. 27 patients on hemodialysis (dialysate aluminium less than 0.7 mumol/l for 2 years, and 2 mumol/l before) whose plasma Ca and PO4 were adequately controlled for already 6 months by high doses of CaCO3 alone (mean +/- SD: 9 +/- 5 g/day), were randomly divided into 2 groups, a control group (c group) which was kept on the same treatment, and a group in which CaCO3 was reduced to 3 g/day but in which plasma Ca was kept normal due to 1 alpha-OH-vitamin D3 administration (1 microgram/day at the beginning, 0.3 microgram/day after 6 months; 1 alpha group) whereas plasma phosphate was kept below 6.0 mg/dl because of Al(OH)3 (2.7-5 g/day). Initially, the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca, phosphate, alkaline phosphatases, medium and C-terminal parathyroid hormone (PTH) and aluminium, but the control group had lower plasma 25-OH-vitamin D (25-OHD.) After 6 months, the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH (beta error 1%). However, plasma concentration of phosphate and the plasma Ca phosphate product, as well as the plasma aluminium were higher in the 1 alpha group whereas their PCO3H- was lower. Although the alkaline phosphatase values were not significantly different between the 2 groups, they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia (plasma 25-OHD 3 ng/ml), which was subsequently cured by physiological doses of 25-OHD3. The incidence of transient hypercalcemia (15 vs. 21 episodes) and worsening of soft tissue calcifications (3 in each group) was the same in the 2 groups. Renal osteodystrophy is one of the major complications in patients with chronic renal failure. Large C-PTH fragments are secreted from the parathyroid glands and exert antagonistic actions against PTH-(1-84). The PTH-(1-84)/large C-PTH fragments ratio reflects both biosynthesis and processing of PTH; however the alteration of the ratio under vitamin D therapy has not been investigated.
                Seventeen hemodialysis patients with intact PTH levels of >300 pg/ml were enrolled. Calcitriol or maxacalcitol were administered intravenously for 78 weeks. Intact PTH, PTH-(1-84), and the PTH-(1-84)/large C-PTH fragments ratio were measured at 0, 13, 26, 52 and 78 weeks.
                Intact PTH and PTH-(1-84) levels, which were 492.0 +/- 115.7 and 303.4 +/- 105.4 pg/ml, respectively, at baseline, significantly decreased at the end of the study to 268.9 +/- 121.9 (p < 0.0001) and 190.7 +/- 106.9 pg/ml (p = 0.0008), respectively. In contrast, large C-PTH fragments, which were 152.7 +/- 53.5 pg/ml at baseline, did not significantly change at 78 weeks (144.5 +/- 72.2 pg/ml, p = 0.7612). Consequently, the PTH-(1-84)/large C-PTH fragments ratio was significantly reduced from 2.25 +/- 1.31 to 1.47 +/- 0.89 (p = 0.0004).
                The PTH-(1-84)/large C-PTH fragments ratio reflects the change of PTH biosynthesis, processing and secretion from the parathyroid glands, and it may be a beneficial marker to evaluate the overall biological PTH action and predict bone turnover status in hemodialysis patients under intravenous vitamin D therapy.
                Copyright (c) 2004 S. Karger AG, Basel. Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease. Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial.
                Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment.
                Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups.
                Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4. Hyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.
                To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus </=5.5 mg/dL and Ca x P product </=55 mg(2)/dL(2), we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.
                Comparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08 mg/dL difference, P= 0.0006), higher serum calcium (0.63 mg/dL difference, P < 0.0001), and lower Ca x P (6.1 mg(2)/dL(2) difference, P= 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28-4.37, P= 0.0058], and 15% to 20% more likely to attain goal Ca x P (OR 2.16, 95% CI 1.20-3.86, P= 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8-13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).
                Calcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients. Twelve patients with chronic renal failure (CRF) requiring dialysis, 7 of whom were hypercalcaemic, were treated with 24,25-dihydroxycholecalciferol [24,25(OH)2D3; 10 micrograms daily for 3 months] or placebo and the treatment then crossed over for a further 3 months. Treatment with 24,25(OH)2D3 was associated with small but significant increments in the fractional rates of absorption of calcium (p less than 0.01) and phosphate (p less than 0.05) measured by a combined radioisotope test, but even during treatment, the absorption of both calcium and phosphate remained subnormal. A significant fall in immunoreactive parathyroid hormone (i-PTH) levels occurred during treatment (p less than 0.05) in the absence of significant changes in plasma ionised calcium and plasma phosphate levels. In 7 patients, treatment with 24,25(OH)2D3 converted parathyroid glands which were non-suppressible by calcium infusion before treatment to suppressible ones (greater than 50% suppression of i-PTH levels) at similar levels of ionised calcium. 24,25(OH)2D3 may have a role in the treatment of renal osteodystrophy, especially in patients with hypercalcaemic hyperparathyroidism. We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients.
                We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites.
                Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs.
                We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism. A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx. New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation. The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting.
                Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone were randomized to receive either 400 mg daily oral calcium (Ca group, n=44) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 (CaVitD group, n=46). Bone mineral density (BMD) was measured by dual energy absorptiometry at baseline and at 1 year.
                The overall population experienced a moderate but significant -2.3+/-0.9% loss of lumbar spine BMD (P<0.01) but no bone loss at the femoral neck and shaft during the first posttransplant year. Bone loss tended to be slightly higher in the CaVitD group, but the difference did not reach statistical significance. Patients in the CaVitD group had significantly higher 25(OH) but not 1,25(OH)2 vitamin D levels. We observed a highly significant negative correlation between 25(OH) vitamin D and intact parathyroid hormone (iPTH) serum levels.
                Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year. Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation. A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism.
                Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus.
                The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 +/- 280.1 pg/mL vs. 637 +/- 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH >or=30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study.
                The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism. The purpose of this study is to evaluate the place of intravenous 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in the prevention of radiologically obvious hyperparathyroidism (HPT) in patients on maintenance dialysis while excluding aluminium phosphate binder and using a dialysate calcium concentration of 1.62 mmol which keeps the intradialytic calcium balance neutral. Therefore, 47 patients without subperiosteal resorption and previously treated by oral CaCO3 and if necessary Mg(OH)2 as phosphate binder while their dialysate calcium had a Ca level of 1.62 and a Mg level of 0.2 mmol/l were randomized into a control group of 24 who were maintained on the same treatment and an experimental group of 23. This group discontinued CaCO3 and received intravenous 1 alpha-OH-D3 after each dialysis at increasing doses up to 4 micrograms and increased Mg(OH)2 as their sole phosphate binder. When plasma Ca increased above 2.7 mmol/l, the dose of 1 alpha-OH-D3 was decreased. When plasma PO4 increased above 2 mmol/l, the dose of Mg(OH)2 was increased to the highest dose not inducing diarrhea, hypermagnesemia (less than 2 mmol/l) or hyperkalemia (less than 6 mmol/l). In case of persistent hyperphosphatemia, the dose of 1 alpha-OH-D3 was decreased. Since mean plasma alkaline phosphatase was normal, HPT was monitored on the plasma concentration of 1-84 PTH for which a previous histological study showed that frank osteitis fibrosa was present only when they were above 70 pg/ml, i.e. (about twice the upper limit of the normal value). Before the study, plasma PTH was below this limit in 16 patients of the CaCO3 group and in 14 patients of the 1 alpha-OH-D3 group. After 6 months, they remained below this limit in all patients except 2 of each group. Plasma PTH was initially above 70 pg/ml in 8 of the CaCO3 and did not change significantly throughout the study, 2 patients having at 6 months a PTH level below 70 pg/ml. In contrast with intravenous 1 alpha-OH-D3, all the 9 patients with initial frank HPT decreased their PTH levels after 2 months, the levels being below 70 pg/ml in 6 cases. However, because of hypercalcemia and/or of hyperphosphatemia in spite of a highest tolerable dose of Mg(OH)2, 1 alpha-OH-D3 doses had to be decreased down to 0.4 microgram per dialysis at the 6th month so that at 6 months 6 of 9 patients had their PTH levels above 70 pg/ml, a number comparable to that of patients treated with CaCO3 (6 of 8).(ABSTRACT TRUNCATED AT 400 WORDS) The hyperphosphatemia, hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure. The phosphorus control is essential to prevent secondary hyperparathyroidism. There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients.
                To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients.
                The present study includes 28 patients with chronic renal failure (mean clearance of creatinine 21 ml/min). Patients were separated into two groups: Group 1: (n = 14) received calcium carbonate 2,500 mg/day (1,000 mg of calcium); Group 2: (n = 14) receives calcium acetate 1,000 mg (254 mg of calcium). Calcium and phosphorus were determined every 4 months; i-PTH, alkaline phosphatase and clearance of creatinine were determined every six months.
                Both groups were comparable regarding age, renal function, calcium, phosphorus, alkaline phosphatase and i-PTH on basal situation and the end of study were not different. The serum calcium increased, not significantly, in the calcium carbonate group (group 1) [from 9.2 to 9.8 mg/dl (p = 0.05)], however it was not modified in the calcium acetate group (group 2). The serum phosphorus decreased significantly (p < 0.05) in both groups, independently of the calcium levels. Alkaline phosphatase and i-PTH not was modified during the study period.
                1) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder. 2) The carbonate group required four fold greater doses of calcium that acetate group. 3) The calcium acetate has less hypercalcemic effect than calcium carbonate. to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients.
                a randomised double-blind controlled trial.
                two hundred and eighteen long-term inpatients aged over 65 years.
                the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg.
                plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months.
                the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP.
                vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels. Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported.
                In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed.
                A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001).
                In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations. Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether paricalcitol provides a therapeutic advantage to calcitriol.
                A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca x P < 75, and a PTH level > or =300 pg/mL were randomly assigned to receive either paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product.
                Paricalcitol-treated patients achieved a > or =50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients (P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (P = 0.008).
                Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy. Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines.
                We evaluated the effect of vitamin D supplementation on the survival rate and different biochemical variables in patients with CHF.
                One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and after 9 mo. The survival rate was calculated for a follow-up period of 15 mo.
                Ninety-three patients completed the study. Significant treatment effects were observed on logarithmic-transformed serum concentrations of 25-hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the D(-) group. Compared with baseline, parathyroid hormone was significantly lower and the antiinflammatory cytokine interleukin 10 was significantly higher in the D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha increased in the D(-) group but remained constant in the D(+) group. The survival rate did not differ significantly between the study groups during the follow-up period.
                Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new antiinflammatory agent for the future treatment of the disease. Our data provide evidence for the involvement of an impaired vitamin D-parathyroid hormone axis in the progression of CHF. Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure. This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product. Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors.
                We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia.
                In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic.
                Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients. Paricalcitol and doxercalciferol are effective in reducing parathyroid hormone PTH concentrations in patients with secondary hyperparathyroidism. The purpose of this study was to determine the relative dose of doxercalciferol (compared to paricalcitol) required to maintain equivalent PTH concentrations in dialysis patients.
                Chronic hemodialysis patients treated with a stable dose of paricalcitol for at least 3 months were randomized to receive doxercalciferol at either 35, 50, or 65% of the paricalcitol dose for 6 weeks. Serum iPTH, calcium, phosphorus, and albumin were determined at baseline and monitored every 2 weeks. A linear regression analysis of percent change in iPTH values by dose group was performed to determine the conversion factor.
                27 patients were enrolled. Initial iPTH, adjusted serum calcium, serum phosphorus, and CaxP were similar among the treatment groups. Linear regression analysis demonstrated a conversion factor of 0.57 for the dose of doxercalciferol relative to paricalcitol resulting in equivalent suppression of iPTH. Corrected serum calcium, phosphorus, CaxP product, as well as incidence of hypercalcemia, hyperphosphatemia and CaxP >50 were similar for all groups.
                In patients on a maintenance dose of paricalcitol, dosing doxercalciferol at 55-60% of the paricalcitol dose results in comparable inhibition of PTH. Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients. But it is often impossible to administer enough dose to suppress parathyroid hormone (PTH) level, because of hypercalcemia and hyperphosphatemia. New modalities with higher specificity for PTH suppression are desirable. We conducted a crossover comparative study of falecalcitriol, an active vitamin D3 analog, and alfacalcidol (1alpha[OH]D3). In this study, 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled. They received daily oral doses of alfacalcidol during an 8-week observation period. Based on serum calcium levels and intact PTH, the subjects were allocated into two groups, and a comparative study was conducted using unmasked crossover design of two drugs x two periods. The dosage of both drugs was adjusted to maintain the initial serum calcium levels, and the relative change (%change) of serum biochemical parameters were compared. Comparison of two drugs in period 1 was taken as primary efficacy evaluation. Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2. The percent change of PTH of falecalcitriol was lower than that of alfacalcidol: Those were, respectively, -7.89% and +30.42% for c-terminal PTH (P = 0.022), -4.39% and +38.88% for i-PTH (P = 0.077), and +3.68% and +30.52% for midregion PTH (P = 0.099). The similar changes were observed in the falecalcitriol group during period 2, confirming the reproducibility. Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels. In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT. Fifty-one healthy prepubertal schoolchildren were followed for 13 months in a double blind study. Twenty-four of them were supplemented with 400 IU of vitamin D2 5-7 times weekly, while 27 received a placebo. The children were examined in winter both at the beginning and at the end of the study, and in the middle of the study in autumn. Mean 25-hydroxyvitamin D levels in the supplemented group were significantly higher than those in the placebo group both in autumn and in winter, when the study ended. The vitamin D supplementation did not, however, affect other vitamin D metabolites, serum calcium, albumin, inorganic phosphorus, parathyroid hormone concentrations or alkaline phosphatase activity. Moreover, the supplementation caused no alterations in the weight or height gain or bone mineral content of the distal radius of the children, and thus subclinical rickets could not be shown. Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia.
                This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL).
                Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03).
                Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype. A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration. In the present study, we compared the efficacy of two intravenous forms of vitamin D3[Calcijex: 1,25(OH)2D3 and One-Alpha: 1(OH)D3] and that of oral One-Alpha in the treatment of secondary hyperparathyroidism in patients receiving maintenance hemodialysis. Twenty patients were assigned to 1 of 2 treatment groups (A and B) which were matched for age, sex, and duration of maintenance hemodialysis. None of the patients included had chronic liver disease or had received drugs known to interfere with hepatic enzymes. All patients had received a stable dose of oral calcium and One-Alpha for a minimum period of 1 year, which maintained corrected serum calcium at the upper limit of the normal range. At the start of the study, oral One-Alpha was replaced by Calcijex in group A and injectable One-Alpha in group B. Treatment was maintained for 3 months (phase I). Subsequently, injectable vitamin D3 was discontinued and all patients received their previous dose of oral One-Alpha for a period of 1 month. Finally, oral One-Alpha was discontinued again and the injectable forms of vitamin D3 were crossed over in the 2 treatment groups for another 3 months (phase II). The results showed that the serum concentrations of 1,25(OH)2D3, measured 48 h after intravenous injection of One-Alpha, were not different from that produced by an equivalent dose of Calcijex in the same group of patients. Furthermore, overall analysis of intact parathyroid levels during the cross-over, using ANOVA with repeated responses, indicated that the two analogues were equipotent as regards suppression of PTH secretion. In our study, treatment with intravenous vitamin D3 led to significant suppression of PTH secretion. These results were achieved by a lower drug dosage of vitamin D3 and at lower trough blood levels of 1,25(OH)2D3 as compared to those of oral One-Alpha. Our findings are in favor of the early use of either forms of injectable vitamin D3 in the treatment of secondary hyperparathyroidism. We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD).
                We performed a prospective, open-label, parallel, randomized, controlled trial.
                The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania.
                A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups.
                Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d).
                Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline.
                In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted.
                SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD. Vitamin D therapy for patients with end-stage renal disease (ESRD) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication. Obtaining a patient's dry weight can be difficult, and no correlation has been established between a patient's body weight and severity of secondary hyperparathyroidism. We conducted a double-blind, double-dummy, randomized, 12-week, multicenter trial to compare the incidence of hypercalcemia (single occurrence) between two dosing regimens: one regimen based on baseline intact parathyroid hormone (iPTH; PTH/80) level, and the other regimen based on patient body weight (0.04 microgram/kg). One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites. Before treatment, all patients were required to have PTH levels of 300 pg/mL or greater, calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less, and a calcium x phosphorus (Ca x P) product of 70 or less. Patients were randomized to one of two regimens: the nonrandomized treatment was also administered as a placebo dummy. No incidence of hypercalcemia occurred in either treatment group during the study. Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30% or greater more rapidly than patients treated based on body weight (P = 0.0306). Incidences of elevated Ca x P product levels were similar between treatment groups. Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients.
                In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses.
                This was a 40-week prospective nonmasked trial of 52 patients [parathyroid hormone (PTH) 150 to 600 pg/mL] who were randomized to receive escalating doses of either calcium carbonate (CaCO3) alone (calcium group, N = 11), daily oral calcitriol (oral group, N = 20), or intermittent intravenous calcitriol (IV group, N = 21). The groups were compared with regard to changes in serum intact PTH, serum bone-specific alkaline phosphatase (BAP), incidence of hypercalcemia (>10.5 mg/dL), and hyperphosphatemia (>6.5 mg/dL).
                PTH levels decreased in all groups (P < 0.01, paired t-test). In the calcium group, PTH (mean +/- SEM) decreased from 325 +/- 46.2 to 160 +/- 44.5 pg/mL. In the oral group, it decreased from 265 +/- 26.4 to 125 +/- 23.7 pg/mL, and in the IV group, it decreased from 240 +/- 27.7 to 65 +/- 10.0 pg/mL. Upon analysis of covariance, controlling for the initial PTH level, we found no differences in the PTH response between the groups (P > 0.10). In contrast, the BAP concentration increased from 20.7 +/- 7.6 to 27.5 +/- 7.0 microg/L in the calcium group (P = 0.17), decreased from 20. 6 +/- 3.9 to 17.8 +/- 4.5 microg/L in the oral group (P = 0.26), and from 19.1 +/- 2.6 to 10.6 +/- 1.1 microg/L in the IV group (P = 0. 007). Serum calcium increased significantly in all groups from 8.4 +/- 0.25 to 9.0 +/- 0.28, 8.5 +/- 0.16 to 9.2 +/- 0.27, and 8.7 +/- 0.16 to 9.4 +/- 0.18 mg/dL in the calcium, oral, and IV groups, respectively (P = NS difference between groups). Serum phosphorus was significantly lower in the calcium group throughout the study (P = 0.02). Hypercalcemic episodes were 2.0 +/- 0.8, 3.0 +/- 0.6, and 3. 4 +/- 0.6 per patient-year (P > 0.10), and hyperphosphatemic episodes were 0.9 +/- 0.56, 4.2 +/- 0.79 and 4.9 +/- 0.84 in the calcium, oral, and IV groups, respectively (P < 0.01).
                In mild secondary hyperparathyroidism, all three strategies are effective. High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile, but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease. The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus. Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow reduction in PTH with less hypercalcemia. Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia. In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease. Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients.
                Double blind, placebo-controlled.
                Hemodialysis units and pediatric subjects receiving hemodialysis.
                After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)).
                Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product.
                60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group.
                Low power to detect differences in safety between groups and a short-term study.
                Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study. Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism (2 degrees HPT). The effects of calcium carbonate (CaCO3) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT. Twenty-nine patients were randomly assigned to CaCO3 (n = 14) or sevelamer (n = 15), concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2 degrees HPT improved with both binders, and bone formation rates reached the normal range in approximately 75% of the patients. Overall, serum phosphorus levels were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS) with CaCO3 and sevelamer, respectively. Serum calcium levels and the Ca x P ion product increased with CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus 8.9 +/- 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (>10.2 mg/dl) occurred more frequently with CaCO3 (P < 0.01). Baseline PTH levels were 980 +/- 112 and 975 +/- 174 pg/ml (NS); these values decreased to 369 +/- 92 (P < 0.01) and 562 +/- 164 pg/ml (P < 0.01) in the CaCO3 and the sevelamer groups, respectively (NS between groups). Serum alkaline phosphatase levels also diminished in both groups (P < 0.01). Thus, treatment with either CaCO3 or sevelamer resulted in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT. Sevelamer, however, maintained serum calcium concentrations closer to the lower end of the normal physiologic range, thereby increasing the safety of treatment with active vitamin D sterols. Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density. Quantitative ultrasound (QUS) measurements can be performed in nursing homes, and easily repeated for follow-up. However, the effect of the correction of vitamin D deficiency on QUS parameters is not known. Therefore, 248 institutionalized women aged 62-98 years were included in a 2-year open controlled study. They were randomized into a treated group (n = 124), receiving 440 IU of vitamin D3 combined with 500 mg calcium (1250 mg calcium carbonate, Novartis) twice daily, and a control group (n = 124). One hundred and three women (42%), aged 84.5 +/- 7.5 years, completed the study: 50 in the treated group, 53 in the controls. QUS of the calcaneus, which measures BUA (broadband ultrasound attenuation) and SOS (speed of sound), and biochemical analysis were performed before and after 1 and 2 years of treatment. Only the results of the women with a complete follow-up were taken into account. Both groups had low initial mean serum 25-hydroxyvitamin D levels (11.9 +/- 1.2 and 11.7 +/- 1.2 micrograms/l; normal range 6.4-40.2 micrograms/l) and normal mean serum parathyroid hormone (PTH) levels (43.1 +/- 3.2 and 44.6 +/- 3.5 ng/l; normal range 10-70 ng/l, normal mean 31.8 +/- 2.3 ng/l). The treatment led to a correction of the metabolic disturbances, with an increase in 25-hydroxyvitamin D by 123% (p < 0.01) and a decrease in PTH by 18% (p < 0.05) and of alkaline phosphatase by 15% (p < 0.01). In the controls there was a worsening of the hypovitaminosis D, with a decrease of 25-hydroxyvitamin D by 51% (p < 0.01) and an increase in PTH by 51% (p < 0.01), while the serum calcium level decreased by only 2% (p < 0.01). After 2 years of treatment BUA increased significantly by 1.6% in the treated group (p < 0.05), and decreased by 2.3% in the controls (p < 0.01). Therefore, the difference in BUA between the treated subjects and the controls (3.9%) was significant after 2 years (p < 0.01). However, SOS decreased by the same amount in both groups (approximately 0.5%). In conclusion, BUA, but not SOS, reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women. Very rapid bone loss, osteopenia, and osteoporosis have been documented in the first 6 to 12 mo after renal transplantation. Investigated was the effect of treatment with active vitamin D on the prevention of posttransplantation bone loss. Forty adult men who were recent renal transplant recipients were enrolled onto the study. Patients were randomized into two groups: group 1 received daily alfacalcidol 0.5 micro g by mouth, and group 2 (control) received placebo. Every patient in both groups received daily 500-mg calcium carbonate supplements. Parameters of bone metabolism and bone mineral density measured at three sites were assessed before and after the study period. Bone mineral density was increased by 2.1%, 1.8%, and 3.2% at lumbar spine, femoral neck, and forearm, respectively, in group 1, whereas it decreased by 3.2%, 3.8%, and 1.8% at the same sites in the control group (P < 0.05). Serum intact parathyroid hormone level decreased significantly in group 1 compared with the control group (P = 0.003). Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol. Use of alfacalcidol early after transplantation is safe and well tolerated. To assess the effect of the different modes of calcitriol administration on PTH-ionized calcium relationship we conducted a prospective clinical trial in 33 patients on chronic haemodialysis with secondary hyperparathyroidism (four times upper normal limit intact PTH) who were randomly assigned, with stratification to PTH levels, to receive daily oral, intermittent oral, or intermittent intravenous calcitriol at the same dose of 0.045 micrograms/kg/weekly. PTH-iCa curves were generated by inducing hypo- or hypercalcaemia in sequential haemodialysis 1 week apart, before and after 10 weeks on treatment. All patients were dialysed against a dialysate calcium concentration of 2.5 mEq/l throughout the study period. After drop-outs, 26 patients completed the study: 11 on intravenous calcitriol (mean basal PTH +/- SD: 666 +/- 280 pg/ml), eight on intermittent oral calcitriol (mean basal PTH: 831 +/- 361), and seven on daily oral calcitriol (mean basal PTH: 719 +/- 280). Serum ionized calcium and phosphorus significantly increased in intravenous and daily oral groups after calcitriol treatment, but not in the intermittent oral group. Basal PTH did not significantly change in the three groups after 10 weeks on treatment. Maximal PTH significantly decreased in intravenous group (1449 +/- 660 versus 1122 +/- 691 pg/ml, P = 0.0085) and at the limit of statistical significance in the intermittent oral group (1701 +/- 774 versus 1445 +/- 634, P = 0.12), but it did not change in the daily oral group. Minimal PTH did not modify in the three groups. In all three groups, a shift to the right in the PTH-iCa relationships were observed, with significant changes in the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS) A multicenter, randomized, open-label, crossover study was performed to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder, with calcium acetate in pediatric patients with chronic kidney disease (CKD).
                Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly assigned to the following treatment scheme: 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were measured every 2 weeks, and phosphate binder dosages were adjusted, if needed. Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period. The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment.
                Forty-four patients were screened. Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for the crossover analysis. There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups. Total cholesterol (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate treatment, whereas metabolic acidosis was more frequent with sevelamer treatment (P < 0.005).
                Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer. 24 patients with chronic renal failure (glomerular filtration-rate (G.F.R.) 5-25 ml/min) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol (1alpha-H.C.C.) 1 mug daily for eleven weeks. This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks. It also induced a significant reduction of the raised serum levels of parathyroid hormone. No significant changes were induced in plasma-phosphorus, plasma-alkaline-phosphatase, or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone. The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group. The fall in G.F.R. over eleven weeks was 2-5 times greater in the 1alpha-H.C.C. group than in the placebo group, but this difference was not significant. It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium. Our study was done to assess the value of administration of vitamin D to tuberculous children. The study included twenty four newly diagnosed tuberculous children; eleven males and thirteen females. Their age ranged from one and half to thirteen years. Thirteen patients were extra thoracic type of T.B., while only seven were intrathoracic and the rest were mixed. They were randomly divided into two Groups according to the treatment administered: Group A patients were given Rifampicin, Isoniazid and Streptomycin. Group B received in addition vitamin D. After eight weeks therapy, the patients of each group were evaluated regarding clinical, laboratory, and radiological improvement. Vitamin D level is raised after treatment in both Groups A and B, but this rise is not significant. It also showed insignificant difference between the two groups. Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls (non tuberculous children). Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B. Phosphorous was highly significantly elevated after treatment in Group A, whereas in Group B it is just significantly elevated. Alkaline phosphatase level in both groups A and B were slightly decreased after treatment. However, this decrease was not significant. Clinical improvement was more evident in Group B patients (those taking vitamin D) as compared to Group A patients. The same was noted with X-ray and Sonographic findings. We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children, and its use is highly recommended. Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function. We hypothesized that paricalcitol, a new vitamin D derivative, will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone (PTH) levels were randomized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients achieved the target dose of paricalcitol. Twenty patients were anergic at the start of the study; 4 of 11 patients in the paricalcitol group and 0 of 9 patients in the placebo group converted to reactive (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma from stimulated lymphocytes were not different between the groups. In contrast to clinical immune effects, paricalcitol increased serum calcium levels and decreased PTH and bone alkaline phosphatase levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake than calcitriol in lymphocytes isolated from either dialysis patients or control subjects. Paricalcitol has a tendency toward improving delayed hypersensitivity reactions, but did not have other proimmune effects. However, as expected, paricalcitol had significant effects on calcium homeostasis compared with placebo. Thus, patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH. We treated nineteen haemodialysis patients with secondary hyperparathyroidism with increasing oral doses of 1,25 dihydroxycholecalciferol (calcitriol) over a 12-week period and used low calcium dialysate (1.0 mmol/l) to prevent hypercalcaemia. Nine patients received daily calcitriol and ten received calcitriol thrice weekly, and at the end of the study the mean doses were 2.0 micrograms daily and 2.6 micrograms thrice weekly respectively. The regimen was well tolerated with nine episodes of mild hypercalcaemia, none of which were symptomatic. Mean PTH and alkaline phosphatase concentrations decreased from 62.0 pmol/l (15-125) to 22.0 pmol/l(1-70) (P less than 0.01), and 144 IU/l (48-461) to 123 IU/l (61-346) (P less than 0.05) respectively. Mean serum calcium increased from 2.33 mmol/l (2.05-2.55) to 2.52 mmol/l (2.26-2.67) (P less than 0.01). There were no significant changes in serum phosphate, magnesium, or aluminium concentrations and there were no significant differences in outcome between patients receiving daily therapy compared to those receiving it thrice weekly. A combination of high-dose oral calcitriol and low calcium dialysate can reverse secondary hyperparathyroidism without causing hypercalcaemia and these results suggest a benefit over conventional low-dose calcitriol. Long-term vitamin D and calcium supplementation is effective in reducing nonvertebral fractures in elderly people. Increased bone fragility caused by secondary hyperparathyroidism (sHPT) and impaired balance are known risk factors for hip fractures. The hypothesis is that short-term therapy with calcium and vitamin D may improve body sway as well as sHPT more effectively than calcium monotherapy. The effects of 8 weeks of supplementation with vitamin D (cholecalciferol) and calcium on body sway and biochemical measures of bone metabolism were measured. The sample consisted of 148 women (mean [+/-SD] age, 74 +/- 1 years) with a 25-hydroxycholecalciferol level below 50 nmol/liter. They received either 1200 mg of calcium plus 800 IU of vitamin D or 1200 mg of calcium per day. We measured intact parathyroid hormone (PTH), markers of bone turnover, and body sway before and after treatment. Falls and fractures among the participants were followed over a 1-year period. Compared with calcium mono, supplementation with vitamin D and calcium resulted in an increase in serum 25-hydroxyvitamin D of 72% (p < 0.0001), a decrease in the serum PTH of 18% ( p = 0.0432), and a decrease in body sway of 9% (p = 0.0435). The mean number of falls per subject during a 1-year follow-up period was 0.45 for the calcium mono group and 0.24 for the calcium and vitamin D group (p = 0.0346). Short-term supplementation with vitamin D and calcium improves sHPT and body sway and therefore may prevent falls and subsequent nonvertebral fractures in elderly women.
We confirm that vitamin D compounds suppress PTH in people with CKD and requiring dialysis although treatment is associated with clinical elevations in serum phosphorus and calcium. All studies were inadequately powered to assess the effect of vitamin D on clinical outcomes and until such studies are conducted the relative importance of changes in serum PTH, phosphorus and calcium resulting from vitamin D therapy remain unknown. Observational data showing vitamin D compounds may be associated with improved survival in CKD need to be confirmed or refuted in specifically designed RCTs.