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      Cross-Sectional Analysis of Abnormalities of Mineral Homeostasis, Vitamin D and Parathyroid Hormone in a Cohort of Pre-Dialysis Patients

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          Abstract

          Background: Disturbances in mineral and vitamin D metabolism, which affect parathyroid hormone (PTH) synthesis, are well recognized in patients receiving dialysis. However, it is unclear at what stage of chronic kidney disease (CKD) these abnormalities develop. Methods: The associations between CKD stages 3 and 5, and alterations of calcium, phosphate, vitamin D and PTH concentrations were assessed in 249 patients (mean age 61 years, 66% male) and 79 age- and sex-matched healthy controls. Results: As compared to controls, serum phosphate concentrations were elevated among CKD patients (1.40 vs. 1.11 mmol/l; p < 0.0001). And levels of both 25-hydroxyvitamin D (42.1 vs. 60.4 nmol/l; p < 0.0001) and 1,25-dihydroxyvitamin D (58.2 vs. 119.5 pmol/l; p < 0.0001) were lower among patients with CKD, even among those with only stage 3 CKD and despite 73% of patients receiving vitamin D supplements. The ratio of 1,25-dihydroxy- to 25-hydroxyvitamin D was lower than controls, even among patients with stage 3 CKD (p = 0.0001), and this ratio diminished with advancing renal impairment. Concomitant elevations were observed in intact PTH (13.8 vs. 4.2 pmol/l; p < 0.0001) and whole PTH (7.9 vs. 2.7 pmol/l; p < 0.0001). Conclusion: Impaired conversion of 25-hydroxy- to 1,25-dihydroxyvitamin D is an early feature of renal disease, and progresses as renal function deteriorates.

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          Most cited references 15

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          Vitamin D3 and calcium to prevent hip fractures in the elderly women.

          Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.
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            Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States.

            Recent Kidney Disease Outcomes Quality Initiative guidelines have raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and deficiency in patients with chronic kidney disease (CKD) not yet on dialysis therapy; however, no cross-sectional study across latitudes has been performed to support this assertion. Baseline screening data from a prospective study were used to determine calcidiol levels in subjects with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25 nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L). Two hundred one subjects with a mean age 65 +/- 13 years and calculated glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated. Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with moderate and severe CKD had sufficient levels, respectively. Mean calcidiol levels were less than sufficient levels in all geographic locations tested. Multivariate analysis found log calcidiol level correlated with calcium level (P = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18 patients who had calcidiol levels measured in winter and late summer after confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to 21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). This cross-sectional cohort study found a high prevalence of calcidiol deficiency and insufficiency in patients with moderate and severe CKD not on dialysis therapy regardless of geographic location.
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              A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate.

              In clinical practice, the glomerular filtration rate (GFR) is often estimated from plasma creatinine. Several studies have shown cystatin C (cys C) to be a better parameter for the diagnosis of impaired renal function. No data are available, however, on the performance of cys C in follow-up of patients, compared with creatinine. Also, comparisons of cys C with the Cockcroft and Gault (C&G) formula for estimation of GFR are few. Plasma samples were obtained from 93 consecutive patients seen for GFR determination and from 30 patients with diabetes mellitus type 2, of whom 23 were investigated a second time after 2 years. GFR was determined with [125I]iothalamate. Plasma creatinine was determined enzymatically and the creatinine clearance calculated according to C&G. Cys C was measured with a particle-enhanced immunonephelometric method. GFR correlated with 1/cys C (r = 0.873) as well as with C&G (r = 0.876). The area under the curve (AUC) of the receiver operating curves (ROCs), a measure of diagnostic accuracy, for cys C (0.931) and C&G (0.938) were equal (P = 0.815) and both better than the creatinine AUC (0.848; P = 0.006). Bland and Altman analysis showed that the simple formula GFR = -4.32 + 80.35 x 1/cys C, derived from our data, gave more accurate (P < 0.0001) and more precise (P = 0.024) GFR estimates than obtained with the C&G formula. The day-to-day variation (biological +analytical) for cys C was small (3.1%, SD 2.51%) in diabetic patients. In the follow-up study in diabetic patients, cys C was the parameter which had the best correlation (r = 0.66) with changes in GFR. Cys C shows a high correlation with GFR. With a very simple formula, cys C gives a good estimate of GFR, more accurate and precise than C&G. Because biological variation is low, cys C gives also a good assessment of GFR changes during follow-up. Cys C is the preferred endogenous parameter for GFR.
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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
                2007
                November 2007
                21 September 2007
                : 107
                : 3
                : c109-c116
                Affiliations
                aDepartment of Nephrology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, bRenal Studies Group, Clinical Trial Service Unit, University of Oxford, Oxford, cCentre for Nephrology, Royal Free and University College Medical School, London, dDepartment of Clinical Chemistry, University of Liverpool, Liverpool, eDivision of Medicine, University Hospital Birmingham NHS Trust, Birmingham, UK; fDivision of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, Calif., USA
                Article
                108652 Nephron Clin Pract 2007;107:c109–c116
                10.1159/000108652
                17890873
                © 2007 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
                Figures: 1, Tables: 3, References: 23, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Vitamin D, Calcium, Chronic kidney disease, Parathyroid hormone

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