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      Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients

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          Abstract

          Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH) 2D) from a cohort of incident hemodialysis patients. Vitamin D binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH) 2D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH) 2D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.

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          Vitamin D levels and early mortality among incident hemodialysis patients.

          M. Wolf, A. Shah, O. Gutiérrez … (2007)
          Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality.
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            Vitamin D levels and patient outcome in chronic kidney disease.

            Pietro Ravani, Fabio Malberti, Giovanni Tripepi … (2009)
            Vitamin D deficiency has been linked to cardiovascular disease and early mortality in patients on hemodialysis; however, it is not known if the same association exists at earlier stages of chronic kidney disease. To determine this we enrolled 168 consecutive new referrals to a chronic kidney disease clinic over a 2 year period and followed them for up to 6 years. All patients were clinically stable and had an estimated glomerular filtration rate (eGFR) at stage 2 or less and were without an imminent need for dialysis. Baseline 25-hydroxyvitamin D levels directly and significantly correlated with eGFR. After an average follow-up of 48 months, 48 patients started dialysis and 78 had died. In crude analyses, 25-hydroxyvitamin D predicted both time to death and end-stage renal disease. A dual-event Cox's model confirmed 25-hydroxyvitamin D as an independent predictor of study outcomes when adjusted for age, heart failure, smoking, C-reactive protein, albumin, phosphate, use of converting enzyme inhibitors or angiotensin receptor blockers, and eGFR. Our study shows that plasma 25-hydroxyvitamin D is an independent inverse predictor of disease progression and death in patients with stage 2-5 chronic kidney disease.
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              Vitamin D Insufficiency and Deficiency in Chronic Kidney Disease

              Esther González, Ashutosh Sachdeva, Dana A Oliver … (2004)
              Background: Kidney disease has been identified as a risk factor for vitamin D deficiency in hospitalized patients, and low levels of 25-hydroxyvitamin D have been suggested to be a risk factor for hyperparathyroidism in patients with chronic kidney disease (CKD). However, little is known about the magnitude of vitamin D deficiency in patients with CKD living in the United States. Methods: In this regard, we examined the levels of 25(OH)D in 43 patients with CKD and serum creatinine between 1 and 5 mg/dl (calculated glomerular filtration rate 111–11 ml/min per 1.73 m 2 ) as well as in 103 patients undergoing hemodialysis. Results: In the predialysis patients, we found that 37 of the 43 patients (86%) had suboptimal levels of vitamin D (<30 ng/ml). Regression analysis indicated that there was a negative correlation between 25(OH)D and intact parathyroid hormone (PTH). Alkaline phosphatase showed a similar but less sensitive relationship. Serum albumin levels correlated with 25(OH)D levels. In contrast to findings reported in normal individuals, the levels of calcitriol correlated with those of 25(OH)D in the patients with CKD. In the group undergoing maintenance hemodialyis, we found that 97% of the patients had vitamin D levels in the suboptimal range, and there was no correlation of 25(OH)D levels with either PTH or serum albumin values. These data indicate that vitamin D insufficiency and deficiency are highly prevalent in patients with CKD and may play a role in the development of hyperparathyroidism. The functional significance of low levels of 25(OH)D in patients with stage 5 CKD remains to be determined.
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0323470
                Journal ID (pubmed-jr-id): 5428
                Journal ID (nlm-ta): Kidney Int
                Journal ID (iso-abbrev): Kidney Int.
                Title: Kidney International
                ISSN (Print): 0085-2538
                ISSN (Electronic): 1523-1755
                Publication date Nihms-submitted: 14 February 2012
                Publication date (Electronic): 07 March 2012
                Publication date (Print): July 2012
                Publication date PMC-release: 01 January 2013
                Volume: 82
                Issue: 1
                Pages: 84-89
                Affiliations
                [1 ]Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
                [2 ]Division of Clinical Pathology, Department of Clinical Chemistry, Beth Israel Deaconess Medical Center, Boston, MA
                [3 ]Howard Hughes Medical Institute and Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
                Author notes
                Corresponding Author: Ishir Bhan, MD, MPH, Division of Nephrology, Massachusetts General Hospital, Bullfinch 127, Boston, MA 02114. Tel: 617-724-3934 Fax: 617-726-8481. ibhan@ 123456partners.org
                Article
                Manuscript ID: NIHMS354859
                DOI: 10.1038/ki.2012.19
                PMC ID: 3376220
                PubMed ID: 22398410
                SO-VID: 0c4ce053-6837-4778-86d6-9c6c64292aaa
                History
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: K23 DK081677-03 || DK
                Categories
                Subject: Article

                ScienceOpen disciplines: Nephrology
                Keywords: vitamin d,vitamin d binding protein,mineral bone disease,free hormone hypothesis,vitamin d deficiency,chronic kidney disease,dialysis
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: vitamin d, vitamin d binding protein, mineral bone disease, free hormone hypothesis, vitamin d deficiency, chronic kidney disease, dialysis

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