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      Calcitriol Regresses Cardiac Hypertrophy and QT Dispersion in Secondary Hyperparathyroidism on Hemodialysis

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          Abstract

          Background: Sudden cardiac death is common in patients on hemodialysis (HD), and its rate is as high as 25% of all cardiac deaths associated with left ventricular hypertrophy (LVH) and secondary hyperparathyroidism. A prolonged QT interval on standard electrocardiography is related to an increase in sudden death in various patient groups. It is also well known that LVH has been noted in uremic patients with high parathyroid hormone levels. Methods: To evaluate the response of intravenous calcitriol treatment on the QT interval and LVH in HD patients with secondary hyperparathyroidism (intact parathyroid hormone, iPTH, >450 ng/ml), echocardiographic, electrocardiographic (ECG), and biochemical assessments were performed over a 15-week period in 25 HD patients before and after intravenous calcitriol treatment. We also evaluated 25 age-, sex-, HD duration-, and BMI-matched HD control patients with secondary hyperparathyroidism. Results: In patients receiving intravenous calcitriol, a significant reduction in iPTH levels (p < 0.05) and alkaline phosphatase levels (p < 0.01) was found without changes in values of serum calcium and ionized Ca<sup>2+</sup>, phosphorus, Na<sup>+</sup>, K<sup>+</sup>, Mg<sup>2+</sup>, hematocrit, blood pressure, or other hemodynamic changes. Echocardiograms showed significant decreases in the thickness of the interventricular septum (p < 0.05), left posterior wall thickness (p < 0.05), and left ventricle mass index (LVMi, p < 0.01). In addition, sequential ECG measurement in patients with calcitriol treatment showed significant reductions in QTc<sub>max</sub> (QT<sub>max</sub> interval corrected for heart rates, p < 0.01) and QTc dispersion (QT dispersion corrected for heart rates, p < 0.01). However, in the control patients, biochemical, hemodynamic, and ECG changes, as well as myocardial structural and functional changes were not seen. Multiple regression analysis in all patients indicated that iPTH and LVMi levels were independent predictors of QTc<sub>max</sub> while the LVMi level was the only independent predictor of QTc dispersion (p < 0.05). Conclusions: Our study showed a significant correlation between LVMi and QT dispersion in HD patients with secondary hyperparathyroidism. Intravenous calcitriol treatment, to be used for the control of secondary hyperparathyroidism, was found to cause regression of myocardial hypertrophy and a reduction in the QTc interval and dispersion, without biochemical and hemodynamic changes. These findings suggest that an active vitamin D metabolite has a cardioprotective action in HD patients.

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          Most cited references 15

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          Activated injectable vitamin D and hemodialysis survival: a historical cohort study.

          Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions.
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            Myocardial fibrosis: functional significance and regulatory factors.

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              Electrocardiographic abnormalities in patients receiving hemodialysis.

              We assessed standard 12-lead and Holter electrocardiographic (ECG) abnormalities in maintenance hemodialysis (HD) patients. Of 221 outpatients receiving HD, 143 (65%) had ECG abnormalities. Rates were higher in male, elderly, hypertensive, and diabetic patients than in female, younger, normotensive, and nondiabetic patients. The prevalence of ECG changes correlated inversely with HD duration. Serial ECGs were compared in 87 patients whose average HD duration was 7.5 +/- 2.5 years. Thirty-four patients (39%) showed normal ECGs throughout, 27 (31%) relatively stable abnormalities, 22 (25%) worsening, and 4 (5%) reversion to normal. Age, hypertension, and diabetes are factors related to abnormal ECG findings. Among the 142 Holter recordings from 72 patients, 70 (97%) were basically in sinus rhythm, and 2 (3%) were in atrial fibrillation. The average frequency of supraventricular premature contractions (SVPCs) was 1597 +/- 9725 per 24 hours, and that of ventricular premature contractions (VPCs), 556 +/- 1415. VPCs were multifocal in 9%, in runs in 25%, and early in 1%. In 29 (40%) of recordings, VPCs appeared mainly during and for several hours after HD. ST-T changes were seen in 43 (60%). In 11, ST depression occurred during and a few hours after HD. Patients receiving HD showed diverse ECG abnormalities. Holter ECGs revealed a high incidence of arrhythmias and ST-T changes, which frequently appeared in relation to HD timing.
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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
                2006
                January 2006
                14 September 2005
                : 102
                : 1
                : c21-c29
                Affiliations
                Division of Nephrology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea
                Article
                88295 Nephron Clin Pract 2006;102:c21–c29
                10.1159/000088295
                16166802
                © 2006 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.

                Page count
                Tables: 6, References: 38, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/88295
                Categories
                Original Paper

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