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      Intravenous Vitamin D Therapy Reduces PTH-(1–84)/Large C Fragments Ratio in Chronic Hemodialysis Patients

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          Abstract

          Background: 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. Methods: 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. Results: 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). Conclusion: 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.

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          The spectrum of bone disease in end-stage renal failure--an evolving disorder.

          We have assessed the bone histology in 259 chronic dialysis patients, all of whom were in the same dialysis program. All patients had bone biopsies with quantitative histomorphometry, intact parathyroid hormone (PTH) measurements, basal and deferoxamine stimulated serum aluminum levels. Results demonstrate the increased incidence of the recently described aplastic bone lesion, particularly in patients treated with peritoneal dialysis (PD). Aluminum-related bone disease is much less common than previously described, perhaps in relation to the declining use of aluminum as a phosphate binder. A different pattern of bone lesions is seen in PD as compared with hemodialysis (HD), with low turnover disorders comprising 66% of the lesions seen in PD and high turnover lesions accounting for 62% of the bone histologic findings in HD. The difference in these patterns may relate to alterations in PTH levels, as mean PTH levels in HD patients were 2-1/2 times the levels found in PD patients (P < 0.0005), while older age, higher prevalence of diabetes and a shorter duration of dialysis may also have contributed to the findings in the PD patients. We suggest that PD, perhaps by maintaining calcium at higher levels, may more effectively suppress the parathyroid gland.
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            Evidence for abnormal calcium homeostasis in patients with adynamic bone disease.

            To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts.
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              Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients.

              Current evidence suggests that administration of 1,25(OH)2D3 to patients with chronic renal insufficiency results in suppression of secondary hyperparathyroidism only if hypercalcemia occurs. However, since the parathyroid glands possess specific receptors for 1,25(OH)2D3 and a calcium binding protein, there is considerable interest in a possible direct effect of 1,25(OH)2D3 on parathyroid hormone (PTH) secretion independent of changes in serum calcium. Recent findings indicate substantial degradation of 1,25(OH)2D3 in the intestine, therefore, it is possible that while oral administration of the vitamin D metabolite increases intestinal calcium absorption, the delivery of 1,25(OH)2D3 to peripheral target organs may be limited. We therefore compared the effects of orally or intravenously administered 1,25(OH)2D3 on the plasma levels of 1,25(OH)2D3 and the effects of these two modes of treatment on PTH secretion. Whereas oral administration of 1,25(OH)2D3 in doses adequate to maintain serum calcium at the upper limits of normal did not alter PTH levels, a marked suppression (70.1 +/- 3.2%) of PTH levels was seen in all 20 patients given intravenous 1,25(OH)2D3. Temporal studies suggested a 20.1 +/- 5.2% decrease in PTH without a significant change in serum calcium with intravenous 1,25(OH)2D3. In five patients the serum calcium was increased by the oral administration of calcium carbonate, the decrement in serum i-PTH was only 25 +/- 6.65% when compared with 73.5 +/- 5.08% (P less than 0.001) obtained by the administration of intravenous 1,25(OH)2D3. Thus, a similar serum calcium achieved by intravenous 1,25(OH)2D3 rather than calcium carbonate has a greater suppressive effect in the release of PTH. These studies indicate that 1,25(OH)2D3 administered intravenously rather than orally may result in a greater delivery of the vitamin D metabolite to peripheral target tissues other than the intestine and allow a greater expression of biological effects of 1,25(OH)2D3 in peripheral tissues. The use of intravenous 1,25(OH)2D3 thus provides a simple and extremely effective way to suppress secondary hyperparathyroidism in dialysis patients.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2004
                November 2004
                17 November 2004
                : 98
                : 3
                : c93-c100
                Affiliations
                aDepartment of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, and bTeraoka Memorial Hospital, Fukuyama, Japan
                Article
                80680 Nephron Clin Pract 2004;98:c93–c100
                10.1159/000080680
                15528944
                67570062-0eea-470b-911e-e141d15de9fb
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 25 November 2003
                : 21 June 2004
                Page count
                Figures: 4, Tables: 2, References: 20, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Vitamin D i.v. therapy,Parathyroid hormone,PTH-(1–84)/large C-PTH fragments ratio

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