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      Dietary and Pharmacological Control of Calcium and Phosphate Metabolism in Dialysis Patients

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          Abstract

          Chronic kidney disease-mineral and bone disorder is a new term defining a complex syndrome which underlines the need of a systemic approach to disturbances of calcium and phosphate metabolism in patients with renal failure. In recent years, the availability of new phosphorus binders and the appearance of new selective vitamin D receptor activators and calcimimetics have increased our current armamentarium and have changed previous paradigms. All these drugs can be used in combination, acting in distinct yet complementary pathways, with a resultant improvement in their individual clinical profile and reduction in secondary effects, while enhancing the achievement of clinical guideline targets. On the other hand, we should be aware that treatment costs are increasing and most of our knowledge is opinion-based. In this article, we shall consider rational recommendations on the control of calcium, phosphorus and parathyroid hormone while awaiting new evidence. We shall also briefly review some important related issues such as vascular calcification, adynamic bone disease, osteoporosis and the need of parathyroidectomy. Future guidelines may modify current recommendations, but we believe that the lack of an absolute evidence is not equivalent to the lack of awareness of the important problem which chronic kidney disease-mineral and bone disorder represents.

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          Most cited references137

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          Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

          Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism. Copyright 2004 Massachusetts Medical Society
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            Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.

            Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of phosphorus, it is plausible that higher levels of serum phosphate within the normal range may also be associated with adverse outcomes. We performed a post hoc analysis of data from the Cholesterol And Recurrent Events (CARE) study. Baseline serum phosphate levels were measured in 4127 fasting participants who were randomized to receive pravastatin 40 mg daily or placebo and followed up for a median of 59.7 months. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. During nearly 60 months of follow-up, 375 participants died. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio per 1 mg/dL, 1.27; 95% confidence interval, 1.02 to 1.58). After categorization based on baseline phosphate level ( or =4 mg/dL) and further adjustment, a graded independent relation between phosphate and death was observed (P for trend=0.03). For instance, participants with serum phosphate > or =3.5 mg/dL had an adjusted hazard ratio for death of 1.27 (95% confidence interval, 1.02 to 1.59) compared with those with serum phosphate of <3.5 mg/dL. Higher levels of serum phosphate were also associated with increased risk of new heart failure, myocardial infarction, and the composite of coronary death or nonfatal myocardial infarction, but not the risk of stroke. We found a graded independent relation between higher levels of serum phosphate and the risk of death and cardiovascular events in people with prior myocardial infarction, most of whom had serum phosphate levels within the normal range. Given the ready availability and low cost of serum phosphate assays, this finding may prove clinically useful.
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              New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study.

              L Kauppila (1997)
              The purpose of the present study was to assess the location, severity and progression of radiopaque lumbar aortic calcifications and to evaluate the utility of summary scores of lumbar calcification in a population-based cohort. Lateral lumbar films, obtained in 617 Framingham heart study participants, were analysed for the presence of abdominal aortic wall calcification in the region corresponding to the first through fourth lumbar vertebrae. The severity of the anterior and posterior aortic calcification were graded individually on a 0-3 scale for each lumbar segment and the results were summarized to develop four different composite scores: (1) affected segments score (range 0-4); (2) anterior and posterior affected score (range 0-8); and (3) antero-posterior severity score (range 0-24). The prevalence of aortic calcification was 37% in men and 27% in women at baseline and 86% in both genders at the follow-up exam 25 years later. During the follow-up interval, the mean of the affected segments score increased from 0.7 in men (0.5 in women) to 2.7 (2.8 in women), the mean of the anterior and posterior affected score from 1.2 (0.8 in women) (P = 0.012 for difference between genders) and the mean of the antero-posterior severity score increased from 1.5 (1.3 in women) to 9.3 (10.3 in women). The antero-posterior severity score offered a slight advantage over other composite scores and had the highest inter-rater intra-class correlations. In summary, lumbar aortic calcification can be graded and composite summary scores are reproducible. This technique appears to provide a simple, low cost assessment of subclinical vascular disease.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2009
                May 2009
                18 March 2009
                : 27
                : 4
                : 369-386
                Affiliations
                Fundació Puigvert, Universitat Autònoma de Barcelona, y REDinREN, Instituto de Investigación Carlos III, Barcelona, Spain
                Article
                209250 Blood Purif 2009;27:369–386
                10.1159/000209250
                19295200
                e04fb57c-9262-414f-9fd7-1d3730e1ac4a
                © 2009 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
                Page count
                Tables: 1, References: 196, Pages: 18
                Categories
                Focus: Calcium and Phosphate Control in CKD. Guest Editor: P. Messa, Milan

                Cardiovascular Medicine,Nephrology
                Lanthanum,Vascular calcification,Adynamic bone disease,Secondary hyperparathyroidism,Chronic kidney disease,Vitamin D,Paricalcitol,Calcimimetics,Phosphorus binders,Sevelamer

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