Topical application of 1,25-dihydroxyvitamin D3 (calcitriol) is an effective and reliable therapy to cure skin lesions in psoriatic children

We studied, in vivo, the effects of a calcitriol-containing ointment (3 micrograms of calcitriol per gram of petrolatum) topically applied on skin lesions in children affected by psoriasis vulgaris. Each patient was instructed to apply the ointment, about 1 g once a day at bedtime followed by occlusive dressing with plastic wrap, on one-side lesion (treated) and petrolatum alone on the equivalent controlateral site (placebo) (total weekly dose of calcitriol: approximately 21 micrograms/patient). After 4 weeks of topical treatment all children showed a complete clearing of their skin lesions on the treated side, without appreciable changes on the placebo side. Serum ionised calcium, calcium and calcitriol levels or urinary calcium excretion did not vary significantly throughout the period of therapy. These findings suggest that topical calcitriol may be an effective and safe alternative therapy for psoriasis in children.     

Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study

A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25-hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons.     

The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis

BACKGROUND: Calcipotriol is an effective treatment of chronic plaque psoriasis. We have previously demonstrated that it has a small effect on systemic calcium homeostasis even at recommended doses. OBJECTIVE: We attempted to determine the mechanism of the effect of calcipotriol on systemic calcium homeostasis so we could assess the possible consequences of long-term use. METHODS: Sixteen patients with extensive chronic plaque psoriasis were hospitalized and treated with high-dose topical calcipotriol. Up to 360 gm of calcipotriol (50 micrograms/gm) ointment was applied per week for 2 weeks under controlled conditions. RESULTS: There was a dose-dependent rise in intestinal absorption of calcium. No effect on bone turnover was demonstrated over this short period. Five patients became hypercalcemic, and there was a dose-dependent rise in serum total adjusted calcium, serum ionized calcium, serum phosphate, urine calcium, and urine phosphate. There was a dose-dependent fall in serum parathyroid hormone and serum 1,25 dihydroxyvitamin D3. CONCLUSION: Calcipotriol exerts its effects on systemic calcium homeostasis by increasing intestinal absorption of calcium and probably phosphate. This results in suppression of parathyroid hormone and 1,25 dihydroxyvitamin D3.     

1.25(OH)2 cholecalciferol pulse therapy and the effects of different dialysis membranes on serum PTH levels of haemodialysis patients

Either oral, intravenous or subcutaneous 1.25(OH)2 cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis. We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types of dialysis membranes used. In the polysulfone group, mean age was 43.7 +/- 0.97 years and the average dialysis period lasted 29.9 +/- 1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2 +/- 1.31 years and the average dialysis period lasted 16.2 +/- 0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l. According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently. After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered. Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63 pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy protocol applied. PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used. PTH and phosphorus clearances were 15.2 +/- 3 ml/min and 239.1 +/- 19.2 ml/min, respectively, in the polysulfone membrane group, and 1.1 +/- 0.3 ml/min and 112.8 +/- 9.88 ml/min, respectively, in the cuprophane membrane group (p < 0.05).     

Epidermal cell DNA content and intermediate filaments keratin 10 and vimentin after treatment of psoriasis with calcipotriol cream once daily, twice daily and in combination with clobetasone 17-butyrate cream or betamethasone 17-valerate cream: a comparative flow cytometric study

Calcipotriol and corticosteroids, two therapy modalities frequently prescribed in the treatment of psoriasis, are often used in combination. The aim of the present study was to determine whether the cell biological response pattern of concurrent use of calcipotriol and corticosteroids is different from calcipotriol monotherapy. Forty patients with chronic plaque psoriasis were divided at random in four parallel groups and treated for 8 weeks with: (1) calcipotriol cream (50 micrograms/g once daily); (2) calcipotriol cream twice daily; (3) calcipotriol and clobetasone 17-butyrate (0.5 mg/g) creams; and (4) calcipotriol and betamethasone 17-valerate (1 mg/g) creams. Before and after treatment keratotome biopsies were taken and single cell suspensions prepared for flow cytometric analysis. Flow cytometric multiparameter quantification of markers for proliferation (TO-PRO-3), differentiation (antikeratin 10) and inflammation (antivimentin) was used to evaluate all four therapy modalities. A statistically significant decrease of the percentage of basal cells in S- and G2M-phase (proliferation) was obtained with all therapy modalities, except for calcipotriol monotherapy applied once daily. A significant reduction of the number of vimentin-positive cells (non-keratinocytes) was observed following combined treatment with calcipotriol and clobetasone butyrate. In contrast, monotherapy with calcipotriol had virtually no effect on the number of vimentin-positive cells. It can be concluded that: (i) calcipotriol monotherapy, applied once daily was less antiproliferative compared with twice daily applications of calcipotriol or the combined treatment with corticosteroids and that (ii) the combination of calcipotriol and corticosteroids proved to have a marked effect on the percentage of non-keratinocytes, in contrast to the modest effect of calcipotriol.     

Myocardial infarction in france: Prognosis improvement?

BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.     

Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis

Plaque-type psoriasis has been successfully treated with oral calcitriol, but there has been no long-term follow-up on the safety and efficacy of this calciotropic hormone for psoriasis. In a single centre study, patients were enrolled in an open trial to evaluate the efficacy and safety of oral calcitriol for psoriasis. Of the 85 patients who received oral calcitriol, 88.0% had some improvement in their disease; 26.5, 36.2 and 25.3%, had complete, moderate and slight improvement in their disease, respectively. The mean baseline psoriasis area severity index score (PASI) of 18.4 +/- 1.0 was reduced to 9.7 +/- 0.8 and 7.8 +/- 1.3 after 6 and 24 months on oral calcitriol therapy. Serum calcium concentrations and 24 h urinary calcium excretion increased by 3.9% and 148.2%, respectively, but were not outside the normal range. Bone mineral density remained unchanged. The clearance of creatinine decreased by 13.4% from baseline during the first 6 months of treatment, and thereafter, remained unchanged after 3 years of follow up. An evaluation of creatinine, inulin and paraaminohypurate (PAH) clearance was performed in eight patients. After 6 months on oral calcitriol, there was a 22.5% decline in creatinine clearance but no significant changes were observed in either inulin or PAH clearance, suggesting that calcitriol alters creatinine metabolism or secretion but does not affect renal function. Oral calcitriol is effective and safe for the treatment of psoriasis.     

Separation from related compounds and assay of calcipotriol by high-performance liquid chromatography

In this paper, two methods are presented. One involves the separation of calcipotriol, a new synthetic analogue, from two related compounds, specifically cholecalciferol (Vitamin D3) and calcitriol (1,25-dihydroxyvitamin D3). The other involves the isolation and assay of calcipotriol from a topical ointment. The study was performed with reversed-phase high-performance liquid chromatography using an RP18 column and ultraviolet detection. Applying the method of Snyder, a mobile phase mixture containing methanol-acetonitrile-water (67:23:10, v/v) was found which achieved a total separation within 18 min. A mobile phase of methanol-water (80:20, v/v) attained a slower elution of calcipotriol. For isolation and assay of calcipotriol from an ointment (Daivonex), dissolution in chloroform gave the highest recovery (> 98%). The isolation and assay process can be performed within 2 h.     

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.     

The economic and social burden of Alzheimer disease on families in the Lombardy region of Italy

The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D3 (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a hairless guinea pig model, Randomized, occlusive patch testing for 2 days was used. Each group of 8 animals was tested simultaneously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5 micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of the patches) and again at day 3. Evaluation was blinded and based on a multiple parameter assessment of skin irritancy, comparing clinical scoring, skin perfusion using high resolution laser Doppler image scanning, skin colour (a*, Minolta ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Skin biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential for calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical irritation score, cutaneous blood flow, skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was dominated by vasodilation and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TEWL remained unaffected. The hairless guinea pig appears a valid model to test irritancy of topical D-vitamins since the same profile of irritancy was previously established in humans for 2 of the compounds tested, calcitriol and calcipotriol.     

Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus

Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and beta-endorphin (but not thyrotropin, follicle-stimulating hormone, or luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and beta-endorphin responses to hypoglycemia in subjects with IDDM. We performed 3-hour stopped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m2) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A1 [HbA1], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA1, 12.6% +/- 0.5%; P < .001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- 1 microgram/L at plasma glucose 5.0 mmol/L to 9 +/- 2 micrograms/L at plasma glucose 2.2 mmol/L), whereas prolactin levels increased markedly in the poorly controlled diabetic group (7 +/- 2 micrograms/L to 44 +/- 17 micrograms/L) and healthy volunteers (12 +/- 2 micrograms/L to 60 +/- 19 micrograms/L, P < .05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P < .05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 pmol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.4 mmol/L, P < .05 between IDDM groups). In conclusion, prolactin and beta-endorphin responses to a standardized hypoglycemic stimulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose levels required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are affected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients with strict glycemic control.     

Oral calcitriol pulse therapy in treatment of secondary hyperparathyroidism in patients with long term hemodialysis

Oral calcitriol pulse therapy slowly becomes a method of choice in the treatment of secondary hyperparathyroidism in hemodialysis patients. It appears to be equally effective and simultaneously significantly cheaper than an intravenous therapy. In last year we have applied such a treatment to 12 hemodialysis patients with severe secondary hyperparathyroidism (iPTH range: 447-1228 pg/ml). All of them were hemodialysed 3 times a week with dialysate Ca+2 level 1.25-1.75 mM/l. Calcium carbonate was administered to maintain serum Ca level between 9.0-11.0 mg/dl and phosphate below 6.0 mg/dl. The patients were given calcitriol at dose 0.1 microgram/kg once a week, but it was obligatory to take a drug at bedtime, at least two hours after the last meal, a day before hemodialysis. During the treatment we divided the patients into two groups: I-patients who responded to our treatment (7/12); II-treatment was unsuccessful (5/12). In this group we decided to increase the dose of calcitriol to 0.075 micrograms/kg twice a week after 6 months use of a previous one. We have achieved statistically significant decrease of parathormone (p < 0.001) and alkaline phosphatase (p < 0.02) in group I and after the increase the dose of calcitriol there occurred the decrease of parathormone (p < 0.05) and alkaline phosphatase (p < 0.002) in group II. Simultaneously we have observed a great clinical improvement. Our results confirm the fact that even severe secondary hyperparathyroidism can be successfully treated with oral calcitriol pulse therapy. Administering of high doses of calcitriol at bedtime increases safety of this procedure-we have not observed any case of hypercalcemia.     

Minor physical anomalies in schizophrenia and mood disorders

The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 microgram i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 microgram i.p./rat) or calcitriol (0.05 microgram i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 +/- 0.04 and 1.10 +/- 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 +/- 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 +/- 0.4 to 7.0 +/- 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 +/- 75 pg/ml (calcitriol) versus 632 +/- 46 pg/ml (OCT) compared with 897 +/- 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 microgram i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 microgram i.p./rat) in reducing circulating iPTH: 110 +/- 26 (calcitriol) and 281 +/- 64 (OCT) versus 624 +/- 135 pg/ml (control), P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of calcium acetate as a chelating of phosphorus in patients in hemodialysis with secondary hyperthyroidism

In this study, we prospectively evaluated the efficacy of calcium acetate in patients with chronic renal insufficiency on hemodialysis programme with secondary hyperparathyroidism and hyperphosphatemia, which are difficult to control by means of the usual finders (calcium carbonate and aluminium hydroxide) and who were treated with pulses of calcitriol. We studied 10 patients. The inclusion criteria were: a serum phosphorus higher than 6.5 mg/dl, a serum PTHi higher than 250 pg/ml and a serum calcium higher than 9.5. The former therapy was stopped at the time of the patient was included in the study. Calcium acetate was initially introduced with doses between 2.5-4 g/day according to previous calcium and phosphate values. Also, all patients were initially treated with intermittent subcutaneous bolus of Calcitriol were modified and adjusted according to serum concentrations of calcium, phosphorus and PTHi. The concentration of calcium in the dialyzed was of 1.25 mmol/l. Fortnightly total calcium, phosphate and alkaline phosphatase serum determinations and monthly aluminium and PTHi serum determinations were carried out. During the 6 months treatment, a decrease was observed in serum concentrations of phosphate (p < 0.01), aluminum (p < 0.02) and PTHi (p < 0.001) with no changes in the values of calcium (p = ns) nor alkaline phosphatase (p = ns). The incidence of hypercalcemia was low during the follow-up period (11% of all biochemical serum determinations) and was easily controlled. We can conclude that calcium acetate is a sure and effective finder of phosphorus with a very good tolerance. Administered together with pulses of calcitriol, and the use of a low calcium concentration in the dialysate, it does not increase the risk of hypercalcemia.     

Developing habits and knowing what habits to develop: a look at the role of virtue in ethics

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).     

Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low Ca2+ dialysate. Effects on bone metabolism in the course of paired filtration dialysis

To evaluate the 1-year effects of PFD performed with low Ca2+ dialysate (1 mmol/l) on calcium metabolism and on bone disease, the authors studied in eight patients who were previously treated with PFD performed with standard Ca2+ dialysate (1.75 mmol/l). On samples from these subjects, the following were evaluated: 1) serum Ca2+ and PO4 levels, 2) serum PTH levels, 3) serum Al levels, and 4) bone morphology. All the patients were hypercalcemic, four with high serum PTH levels (high turnover bone disease, group 1) and four with low serum PTH levels (low turnover bone disease, group 2). In both groups, a decrease in serum Ca2+ and an increase in serum PTH was observed within the third month. In group 2, PTH levels reached the normal range. Because serum Ca2+ levels decreased to normal in both groups, it was possible to administer oral CaCO3 (10.5 +/- 2 g/day) to control serum PO4 and to stop Al gels. This did not induce any increase in serum Ca2+, whereas serum Al fell significantly. In group 1, to prevent a further rise in PTH, patients were treated with intravenous calcitriol (5 +/- 2 micrograms/week). This induced a reduction in the serum PTH without increasing serum Ca2+ or PO4. Within 12 months, an improvement in bone morphology was seen in both groups. It is concluded that the use of low Ca2+ dialysate corrects hypercalcemia in patients with PFD treated with high oral doses of CaCO3, and improves low turnover bone disease. The combination of low Ca2+ dialysate and intravenous calcitriol also improves high turnover bone disease.     

Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration

BACKGROUND: Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD). METHODS: Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. RESULTS: Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion. CONCLUSION: Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.     

Protection afforded by a novel K channel opener (Y-26763), against glycerol-induced acute renal failure (ARF) in rats

Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel opener and has been reported to protect against ischemic acute renal failure (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before glycerol injection. Glibenclamide (20 mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after glycerol injection, Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol-induced ARF.