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

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

Intravenous 1,25(OH)2 vitamin D3 therapy in haemodialysis patients: evaluation of direct and calcium-mediated short-term effects on serum parathyroid hormone concentration

Eleven patients on chronic haemodialysis treatment thrice weekly received 1 microgram 1,25(OH)2D3 i.v. after each dialysis for 3 weeks. Phosphate binders were mainly CaCO3, supplemented in a few patients by moderate amounts of Al(OH)3. Ionised calcium was measured by ion-selective electrode, normal values being 1.28-1.42 mmol/l. PTH was estimated by an N-terminal-sensitive assay; normal values are less than 0.25 ng/ml. Results before and after 1,25(OH)2D3 were: ionised calcium before haemodialysis, 1.19 +/- 0.12 and 1.17 +/- 0.14; ionised calcium after haemodialysis, 1.33 +/- 0.07 and 1.30 +/- 0.09; PTH before haemodialysis, 1.39 +/- 0.71 and 1.38 +/- 0.69; PTH after haemodialysis, 0.64 +/- 0.22 and 0.60 +/- 0.17; Phosphate before haemodialysis, 1.85 +/- 0.48 and 2.18 +/- 0.43 (P less than 0.05). No change of PTH concentration and ionised calcium before and after haemodialysis treatment could be documented after i.v. 1,25(OH)2D3 treatment. Mild and severe hyperparathyroidism were indistinguishable. Increased serum calcium concentrations therefore appear to be required for the suppression of PTH secretion by i.v. 1,25(OH)2D3 therapy.     

Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease

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

Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture

Summary Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)₂D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25 (OH)₂D values were not different between the two groups. We conclude that although 250HD level in hip fracture patients is low, there is no evidence of secondary hyperparathyroidism, suggesting that the low 250HD levels may be a secondary phenomenon in response to the fracture.     

Treatment of refractory hyperparathyroidism in patients on hemodialysis by intermittent oral administration of 1,25(OH)2vitamin D3

Intermittent oral administration of high dose 1,25(OH)2vitamin D3 was conducted in 7 patients associated with treatment-resistant secondary hyperparathyroidism (2nd HPT) on hemodialysis (HD) therapy. Each patient had a long history of HD therapy (range: 101-181 months, 145 +/- 29 months). Although serum calcium levels were maintained under the upper limit of the normal range with the appropriate dose of 1 alpha(OH)vitamin D3 every day before the present therapy, 2nd HPT could not have been controlled. The dose of 2-3 micrograms of 1,25(OH)2vitamin D3 3 times a week could successfully suppress serum levels of parathyroid hormone (iPTH) in all 7 patients after 20-32 weeks. The vitamin was given in the evening before each HD session and the dose and frequency of administration were dependent of the serum calcium level in each patient. After 20 weeks the iPTH-C and iPTH-intact levels decreased significantly from 35.0 +/- 15.8 to 18.6 +/- 11.7 ng/ml and from 533.2 +/- 200.0 to 249.5 +/- 136.2 pg/ml, respectively. The frequency of harmful elevations of serum calcium levels was not significantly increased in comparison with that in the previous period of the study, because serum calcium levels were strictly monitored with frequent checks. In conclusion, we could safely obtain an effect similar to the intravenous administration of the vitamin through the intermittent administration of a high oral dose 1,25(OH)2vitamin D3 in the treatment of refractory 2nd HPT in patients on HD therapy.     

Oral high dose 1,25(OH)2D3 pulse therapy

To 13 uremic patients with secondary hyperparathyroidism, 4 micrograms of 1,25(OH)2D3 were given orally twice a week for 4 weeks. Intact PTH values fell from 488.3 +/- 84.2 to 235.2 +/- 59.6 pg/ml (Mean +/- SE, p less than 0.01), while serum total and ionized calcium elevated from 10.3 +/- 0.2 to 11.8 +/- 0.6 mg/dl (p less than 0.01), from 1.43 +/- 0.03 to 1.64 +/- 0.06 mmol/l (p less than 0.05), respectively, in 9 patients whose initial intact PTH level had been below 1000 pg/ml. The other 4 patients, of whom intact PTH level had been above 1000 pg/ml, did not show significant change in intact PTH values, though serum ionized calcium elevated slightly after this treatment. The correlation curve, determined by ionized calcium and intact PTH values in each period, was found to shift in only 2 out of 5. During the 4 weeks of high dose oral 1,25(OH)2D3 therapy, mean blood pressure elevated from 92.4 +/- 3.3 to 103.5 +/- 3.5 mmHg (p less than 0.01) in general, and 7 patients out of 13 complained of mental irritability. These data suggest that oral administration of high dose 1,25(OH)2D3 suppresses PTH secretion of uremic patients directly, however, reliability of this effect is still controversial. Indication of this therapy and adverse effects caused by rapid increase in serum calcium should be studied in more detail.     

Phosphorus administration in patients with profound hypophosphatemia

The influence of severe hypophosphatemia (less than or equal to 1.0 mg/dl) on vitamin D metabolism was prospectively determined in 11 patients before and after intravenous phosphorus administration. Evidence of liver dysfunction was present in ten patients. The mean (+/- SE) plasma 25 hydroxycholecalciferol [25(OH)D] was significantly decreased before phosphorus therapy when compared to control subjects (9.4 +/- 1.3 vs. 17.8 +/- 1.3 ng/ml, P less than 0.001). With phosphorus administration, serum phosphorus increased from 0.59 +/- 0.07 to 2.58 +/- 0.09 mg/dl while 1,25 dihydroxycholecalciferol [1,25(OH)2D] decreased from 34.6 +/- 4.3 to 14.3 +/- 2.9 pg/ml (P less than 0.001). Plasma 25(OH)D, plasma immunoreactive PTH (both amino and carboxyterminal) and serum calcium did not change after phosphorus administration, suggesting that phosphorus alone was responsible for the change in plasma 1,25(OH)2D concentration. An inverse correlation was found between serum phosphorus and plasma 1,25(OH)2D (r = -0.62, P less than 0.005). In addition, a direct correlation was observed between plasma 25(OH)D and 1,25(OH)2D both before (r = 0.66, P less than 0.005) and after (r = 0.74, P less than 0.005) phosphorus administration. Thus, the decrease in 1,25(OH)2D levels with phosphorus therapy suggests a role of serum phosphate in the regulation of this sterol, and hypophosphatemia or phosphorus depletion may change the relationship of substrate [25(OH)D] to product [1,25(OH)2D].     

Differential effects of 1,25-dihydroxy-vitamin D3 and 19-nor-1,25-dihydroxy-vitamin D2 on calcium and phosphorus resorption in bone

1,25-Dihydroxy-vitamin D3 [1,25-(OH)2D3] suppresses the secretion and synthesis of parathyroid hormone (PTH) and has been used in the treatment of secondary hyperparathyroidism. However, 1,25-(OH)2D3 can induce hypercalcemia, which often precludes its use. Therefore, an analog of 1,25-(OH)2D3 that would retain its therapeutic effects but produce minor effects on calcium and phosphorus metabolism could be an ideal tool for the treatment of secondary hyperparathyroidism. It has been shown that 19-nor-1,25-dihydroxy-vitamin D2 [19-nor-1,25-(OH)2D2], an analog of 1,25-(OH)2D3, can suppress PTH levels in uremic rats at doses that do not affect plasma ionized calcium levels. The experiments presented here, using parathyroidectomized rats fed diets deficient in either calcium (0.02%) or phosphorus (0.02%), were performed to compare the effects of 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 on calcium and phosphorus resorption in bone. Parathyroidectomized rats received daily intraperitoneal injections of vehicle, 1,25-(OH)2D3 (100 ng), or 19-nor-1,25-(OH)2D2 (100 or 1000 ng) for 9 d. Plasma calcium and phosphorus levels were monitored during the study, and ionized calcium levels were determined at the end of the study. By 9 d, 1,25-(OH)2D3 (100 ng/d) increased total calcium levels to 12.4+/-0.26 mg/dl, compared with 6.32+/-0.25 mg/dl (P<0.001) in control animals. The same dose of 19-nor-1,25-(OH)2D2 (100 ng/d) was much less potent (9.45+/-0.28 mg/dl, P<0.001). Similar results were seen with ionized calcium levels [19-nor-1,25-(OH)2D2, 3.61+/-0.12 mg/dl; 1,25-(OH)2D3, 5.03+/-0.16 mg/dl; P<0.001]. Ionized calcium levels were also lower in rats receiving the higher dose (1000 ng) of 19-nor-1,25-(OH)2D2 (4.59+/-0.09 mg/dl, P<0.05). Similar results were seen in rats fed the phosphorus-deficient diet. 1,25-(OH)2D3 (100 ng) increased plasma phosphorus levels from 4.30+/-0.39 mg/dl in vehicle-treated rats to 7.43+/-0.26 mg/dl (P<0.001). The same dose of 19-nor-1,25-(OH)2D2 had no effect (5.19+/-0.32 mg/dl), whereas the high dose (1000 ng) increased plasma phosphorus levels (7.31+/-0.24 mg/dl) in a manner similar to that of 1,25-(OH)2D3 (100 ng). Therefore, 19-nor-1,25-(OH)2D2 is approximately 10 times less effective in mobilizing calcium and phosphorus from the skeleton, compared with 1,25-(OH)2D3. With its ability to suppress PTH at noncalcemic doses, 19-nor-1,25-(OH)2D2 is a potential therapeutic tool for the treatment of secondary hyperparathyroidism in chronic renal failure.     

Pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) in normal and uraemic men.

BACKGROUND: The therapeutic equivalence of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) on the suppression of PTH synthesis and secretion has not clearly been established. The aim of the present study was to evaluate the pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) after oral and i.v. administration in healthy volunteers and uraemic patients. METHODS: Six healthy volunteers and 12 uraemic patients were included in the study. With an interval of 2 weeks, 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, 4 microg of 1alpha(OH)D(3) i.v. and 4 microg of 1alpha(OH)D(3) orally were administered. Blood samples for analysis of plasma-Ca(2+), plasma-1,25(OH)(2)D(3), and plasma-PTH were drawn at time 0, 0.25, 0.5, 1, 2, 4, 6, 9, 12, 24, 48, and 72 h. The healthy volunteers were studied in all four protocols and the uraemic patients in either the 1alpha(OH)D(3) (n=6) or the 1,25(OH)(2)D(3) (n=6) protocol. RESULTS: After oral administration of 1,25(OH)(2)D(3) the bioavailability of 1,25(OH)(2)D(3) was 70.6+/-5.8/72.2+/-4.8% in healthy volunteers/uraemic patients (n.s.). After i.v. administration the volume of distribution of 1,25(OH)(2)D(3) was similar, 0.49+/-0.14 vs 0.27+/-0.06 l/kg in healthy volunteers vs uraemic patients (n.s.), while the metabolic clearance rate of 1,25(OH)(2)D(3) was 57% lower in the uraemic patients, 23.5+/-4.34 vs 10.1+/-1.35 ml/min in healthy volunteers vs uraemic patients, respectively (P<0.03). The bioavailability of 1,25(OH)(2)D(3) after i.v. administration of 1alpha(OH)D(3) was 42.4+/-11.0/42.0+/-2.0% in healthy volunteers/uraemic patients (n.s.); and after oral administration of 1alpha(OH)D(3) 42.0+/-2.0/29.8+/-3.1% in healthy volunteers/uraemic patients (n.s.). A small, but significant increase in plasma-Ca(2+) was seen after administration of 1,25(OH)(2)D(3) to the uraemic patients, while no increase was seen after administration of 1alpha(OH)D(3). PTH levels were significantly suppressed in the healthy volunteers 24 h after administration of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, and 4 microg of 1alpha(OH)D(3) orally by 35+/-7, 30+/-8, and 35+/-4%, respectively (all P<0.03). In the uraemic patients, PTH levels were significantly suppressed after administration of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, and 4 microg of 1alpha(OH)D(3) i.v. by 30+/-10, 45+/-7, and 40+/-7%, respectively (all P<0.04). The effect was transitory in the healthy volunteers and lasted for at least 72 h in the uraemic patients. CONCLUSION: The present study found a 57% lower metabolic clearance rate of 1,25(OH)(2)D(3) in uraemic patients, as compared with that of healthy volunteers (P<0.03). The bioavailability of 1,25(OH)(2)D(3) following administration of 1alpha(OH)D(3) i.v. and orally in both healthy volunteers and uraemic patients was markedly lower than after administration of oral 1,25(OH)(2)D(3) (P<0.03). In spite of lower plasma-1,25(OH)(2)D(3) levels after administration of 1alpha(OH)D(3), no significant difference was observed on the suppressive effect of 4 microg i.v. of either 1,25(OH)(2)D(3) or 1alpha(OH)D(3) on the plasma-PTH levels in the uraemic patients. This might suggest the existence of an effect of 1alpha(OH)D(3) on the parathyroid glands which is independent of the plasma-1,25(OH)(2)D(3) levels, that are achieved after oral or i.v. administration of 1alpha(OH)D(3).     

Relevance of vitamin D metabolite concentrations in supporting the diagnosis of primary hyperparathyroidism.

We compared the relationships between 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in patients with primary hyperparathyroidism (PHPT) and 38 volunteer blood donors. There was no significant difference in mean 25(OH)D levels between patients with PHPT (34 +/- 21 nmol/L; n = 21) and the donor samples (41 +/- 19 nmol/L; n = 38). Serum 1,25(OH)2D levels were higher in the patients with PHPT compared with the donors (122 +/- 61 pmol/L vs 56 +/- 41 pmol/L; p less than 0.001). The 95th percentile 1,25(OH)2D value for the donors was exceeded in 65% of the patients with PHPT. There was a significant correlation between serum 1,25(OH)2D versus 25(OH)D in the patients with PHPT (r = 0.50; p less than 0.05) but not in the donors (r = 0.02). We conclude from the distinct elevation in 1,25(OH)2D levels in the majority of our patients with PHPT that the concentration of this parathyroid hormone-dependent hormone can be of critical value in corroborating the diagnosis of PHPT.     

The effects of intraperitoneal calcitriol on calcium and parathyroid hormone

Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.     

Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis

The effect of intravenous 1 alpha(OH)D3 on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1 alpha(OH)D3 under careful control of serum Ca2+. 1 alpha(OH)D3 was given intravenously at doses of up to 4 micrograms three times a week, and blood samples were obtained every week, including 1 week before treatment (basal control). No patients were treated with oral vitamin D metabolites. At the end of the study intact PTH levels were reduced by an average of 67 +/- 6%, and COOH-terminal immunoreactive PTH levels were reduced by 35 +/- 6%. Serum Ca2+ was kept within normal levels, but showed a slight increase from 1.17 to 1.30 mmol/l. An effect of calcium on PTH secretion could not be excluded, but an effect of 1 alpha(OH)D3, independent of serum Ca2+ was also found. This effect may be mediated by 1,25(OH)2D3, assuming a large capacity of the 25-hydroxylase in the liver to convert 1 alpha(OH)D3 to 1,25(OH)2D3. Also, the parathyroid glands may possess receptors for 1 alpha(OH)D3 with an effect similar to that established for the 1,25(OH)2D3 receptors. Thus, although the exact mechanisms of the action of 1 alpha(OH)D3 have not yet been completely clarified, it is concluded that intravenous administration of 1 alpha(OH)D3 may be of benefit in the treatment of secondary hyperparathyroidism of uremia.     

Absence of effect of 24,25-dihydroxycholecalciferol on serum immunoreactive PTH in patients with persistent hyperparathyroidism after renal transplantation

Three hypercalcemic renal transplant recipients with stable, excellent renal function (creatinine clearance 74 +/- 11.8 ml/min) were treated with 60 micrograms 24,25(OH)2D3 by mouth daily for three months. Immunoreactive c-terminal PTH, intact PTH, 1,25(OH)2D3, 25(OH)D3, 24,25(OH)2D3, and serum and 24 h urine calcium, phosphate, magnesium and creatinine were obtained before, at one week, one month and three months of treatment, and at six weeks post-treatment. Significant elevations in serum levels of 24,25(OH)2D3 were induced by therapy (1.32 +/- .16 ng/ml to 30.06 +/- 5.18 ng/ml at one month). Moderate elevations of c-terminal PTH and normal levels of intact PTH remained unchanged throughout the study. Serum calcium remained elevated, serum phosphate and magnesium remained depressed and creatinine clearance and urinary excretion of calcium, phosphate, and magnesium remained unchanged. Furthermore, 1,25(OH)2D3 and 25(OH)D3 remained in the normal range throughout the study. We conclude that 24,25(OH)2D3 did not have a suppressant effect on levels of iPTH in the clinical setting of persistent hyperparathyroidism after successful renal transplantation.     

Effect of cinacalcet on hypercalcemia and bone mineral density in renal transplanted patients with secondary hyperparathyroidism

BACKGROUND: Persistent secondary hyperparathyroidism (SHP) is the most frequent cause of hypercalcemia observed in approximately 10% of renal transplanted (RT) patients 1 year after surgery. Persistent SHP with hypercalcemia is an important factor of bone loss after renal transplantation. This study prospectively evaluates the effects of Cinacalcet therapy on serum calcium (SCa) and parathyroid hormone (PTH) blood levels, and basically on bone mineral density (BMD) in RT patients with persistent hyperparathyroidism. METHODS: Nine RT patients (eight women, one man) with allograft function more than 6 months were included based on total SCa more than 10.5 mg/dL and intact parathyroid hormone (iPTH) concentration more than 65 pg/mL. After inclusion, patients started on a single daily oral dose of 30 mg of Cinacalcet. At inclusion and every study visit blood levels of creatinine, Ca, P, alkaline phosphatase, iPTH 1,25- dihydroxyvitamin D3, and 25-hydroxyvitamin D3 were assessed. Baseline and at the end of study radial BMD were measured. Study follow-up was 12 months. RESULTS: During the study period, SCa decreased from 11.72+/-0.39 to 10.03+/-0.54 mg/dL (P<0.001). iPTH decreased from 308.85+/-120.12 to 214.66+/-53.75 mg/dL (P<0.05). The mean serum creatinine decreased from 1.58+/-0.34 to 1.25+/-0.27 mg/dL (P=0.03) and the mean radial BMD increased from 0.881+/-0.155 to 0.965+/-0.123 gr/cm2 (P<0.05). There were no significant changes in the other parameters assessed. One patient was excluded for gastrointestinal intolerance. CONCLUSIONS: In RT patients with hypercalcemia secondary to persistent SHP, Cinacalcet corrects hypercalcemia and PTH, simultaneously improving BMD.     

Vitamin D metabolites and their binding protein in adult diabetic patients

Vitamin D metabolites and vitamin D-binding protein were measured in the serum of nonketotic Bantu and Caucasian insulin-requiring diabetic subjects from Zaire and Belgium, respectively. In Caucasian diabetics, whether untreated (N = 18) or insulin treated (N = 26), no abnormalities were found. The Bantu diabetics (N = 20) were more insulin-deficient and had a poorer glucose control than the Caucasians. They presented, compared with Bantu controls, a significant decrease in the serum concentrations of 25-hydroxyvitamin D3 (26 +/- 10 vs. 35 +/- 14 micrograms/L, P less than .01), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (38 +/- 15 vs. 58 +/- 17 ng/L, P less than .001), and vitamin D-binding protein (303 +/- 55 vs. 356 +/- 41 mg/L, P less than .001). The decreased concentrations of vitamin D metabolites in the adult Bantu diabetic patients may be partly explained by a concomitant decrease in the concentration of vitamin D-binding protein, possibly due to insulin deficiency. The ratio between the molar concentrations of 1,25-(OH)2D3 and vitamin D-binding protein, used as an index of the free hormonal level, was also decreased, in association with a decreased serum calcium level. In conclusion, no abnormalities in vitamin D metabolism were found in Caucasian insulin-dependent diabetics, whereas low serum 1,25(OH)2D3 concentrations and hypocalcemia were found in poorly controlled Bantu diabetic subjects.     

Effect of Activated Vitamin D on Glucoparameters in HCV Seropositive and Seronegative Patients on Chronic Hemodialysis

Introduction: Many studies support the role of vitamin D in the pathogenesis of both types of diabetes. Pancreatic tissues express the vitamin D receptor (VDR) and vitamin D-binding protein; some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose intolerance, defective insulin secretion, and sensitivity. Epidemiological links have been established between type 2 diabetes mellitus (DM) and hepatitis C virus (HCV) infection. Aim: To explore the possible therapeutic potential of pharmacologic doses of 1-α-hydroxy vitamin D therapy in improving pancreatic β-cell function in HCV seropositive hemodialysis (HD) patients. Patients and methods: Twenty HCV seropositive HD patients and 20 HCV seronegative patients as control group were randomly selected from HD units. 1-α-Hydroxy vitamin D therapy was administrated in the dose ranged from 0.25 to 0.5 μg/day for 3 months. Corrected total serum calcium, phosphorus, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D [25(OH) vitamin D], 1,25-dihydroxy vitamin D, and glucoparameters [fasting blood glucose, glycohemoglobin test (HbA1c%), homeostatic model assessment (HOMA)-insulin resistance, and HOMA-β-cell function% (B%)] were measured under basal conditions and after 3 months of therapy. Results: There was highly significant improvement in the concentrations of fetal bovine serum (FBS), serum insulin, HbA1c%, 25(OH) vitamin D, and HOMA-β-cell function in HCV seropositive and HCV seronegative groups after oral 1-alphacalcidiol therapy (p < 0.001). Positive correlation exists between the percentage increase in serum insulin and that in HOMA-β-cell function versus 25(OH) vitamin D (p < 0.021 and p < 0.027, respectively) in HCV negative group. Conclusion: 1-α-Hydroxy vitamin D oral therapy may improve glycemic control in HCV seropositive and HCV seronegative HD patients.     

Normocalcemic hyperparathyroidism in patients with recurrent kidney stones: a disease entity or vitamin D deficiency?

This retrospective data analysis was undertaken to examine the biochemical differences between renal stone formers with normocalcemic hyperparathyroidism (NHPT) and those with normal parathyroid hormone (PTH) levels. Our goal was to ascertain whether 25-hydroxyvitamin D (25(OH)D) status related to PTH levels in this patient cohort. Our findings among 74 patients with NHPT indicate that stone formers with NHPT had significantly lower 25(OH)D levels compared to 192 controls (p = 0.0001) and that 25(OH)D is positively correlated with 1,25-dihydroxyvitamin D values (R = 0.736, p = 0.015). Sequential measurements (after 3 - 5 years), among 11 patients with NHPT who did not receive vitamin D (VitD) preparations, showed a significant increase in urinary calcium (3.43 ± 1.96 vs. 5.72 ± 3.95, p = 0.0426) without a significant change in PTH levels. VitD supplementation, to 3 patients resulted in significant PTH decrease (11.8 ± 1.8 vs. 9.8 ± 1.3, p = 0.003). Prospective studies are needed to confirm the role of vitamin supplementation in renal stone formers with NHPT.     

The impact of over-the-counter vitamin D supplements on vitamin D and parathyroid hormone levels in chronic kidney disease

BACKGROUND: In addition to the known disturbances in mineral metabolism and vitamin D activation, the majority of patients with chronic kidney disease (CKD) do not have sufficient vitamin D stores. The impact of supplementation with low-dose, nonactive forms of vitamin D (calciferol) on parathyroid hormone (PTH) levels in this population is unknown, however. METHODS: A cross-sectional evaluation of vitamin D levels, intact parathyroid hormone (iPTH) and other laboratory results in 108 stage 3 and stage 4 CKD patients according to their intake of over-the-counter vitamin D. RESULTS: 37 patients took 400 IU of vitamin D daily with supplemental calcium and 71 did not. Compared to subjects who did not take it, patients who were on the supplement had higher 25(OH)D (31 +/- 15 vs. 17 +/- 9) ng/ml, higher 1,25(OH)D (21 +/- 12 vs. 16 +/- 9) pg/ml, lower iPTH (75 +/- 48 vs. 144 +/- 100) pg/ml and were more likely to meet K-DOQI PTH guidelines. However, these subjects were more likely to have oversuppressed iPTH values. The groups did not differ with regard to demographics, glomerular filtration rate and calcium and phosphorus levels. CONCLUSIONS: Vitamin D supplements may be a valuable tool in the prevention and treatment of hyperparathyroidism in patients with stages 3 and 4 CKD. CKD patients who have oversuppressed PTH need to be asked about their vitamin supplement intake.     

Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients

BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (1,25D(3)) to suppress parathyroid hormone (PTH), but dosing of 1,25D(3) is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)2-vitamin D2 (paricalcitol) and the prohormone 1alpha-OH-vitamin D2 (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca x P, while still suppressing PTH. METHODS: We performed a prospective study to assess the acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO4, and PTH were measured over 36 h. RESULTS: Serum phosphorus rose faster, and peaked significantly higher at 36 h following doxercalciferol (2.12 +/- 0.11 mmol/l) than paricalcitol (1.85 +/- 0.07 mmol/l; p = 0.025). Ca x P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 +/- 0.26 vs. 4.54 +/- 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). CONCLUSION: Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca x P.