Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice

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Abstract

Native hypovitaminosis D (n-hVITD) is frequently found from the early stages of chronic kidney disease (CKD) and its prevalence increases with CKD progression. Even if the implications of n-hVITD in chronic kidney disease-mineral bone disorder (CKD-MBD) have been extensively characterized in the literature, there is a lot of debate nowadays about the so called “unconventional effects” of native vitamin D (25(OH)VitD) supplementation in CKD patients. In this review, highlights of the dimension of the problem of n-hVITD in CKD stages 2–5 ND patients will be presented. In addition, it will focus on the “unconventional effects” of 25(OH)VitD supplementation, the clinical impact of n-hVITD and the most significant interventional studies regarding 25(OH)VitD supplementation in CKD stages 2–5 ND.

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Most cited references 62

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Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

Laura Tripkovic, Helen Lambert, Kathryn Hart … (2012)

Background: Currently, there is a lack of clarity in the literature as to whether there is a definitive difference between the effects of vitamins D2 and D3 in the raising of serum 25-hydroxyvitamin D [25(OH)D]. Objective: The objective of this article was to report a systematic review and meta-analysis of randomized controlled trials (RCTs) that have directly compared the effects of vitamin D2 and vitamin D3 on serum 25(OH)D concentrations in humans. Design: The ISI Web of Knowledge (January 1966 to July 2011) database was searched electronically for all relevant studies in adults that directly compared vitamin D3 with vitamin D2. The Cochrane Clinical Trials Registry, International Standard Randomized Controlled Trials Number register, and clinicaltrials.gov were also searched for any unpublished trials. Results: A meta-analysis of RCTs indicated that supplementation with vitamin D3 had a significant and positive effect in the raising of serum 25(OH)D concentrations compared with the effect of vitamin D2 (P = 0.001). When the frequency of dosage administration was compared, there was a significant response for vitamin D3 when given as a bolus dose (P = 0.0002) compared with administration of vitamin D2, but the effect was lost with daily supplementation. Conclusions: This meta-analysis indicates that vitamin D3 is more efficacious at raising serum 25(OH)D concentrations than is vitamin D2, and thus vitamin D3 could potentially become the preferred choice for supplementation. However, additional research is required to examine the metabolic pathways involved in oral and intramuscular administration of vitamin D and the effects across age, sex, and ethnicity, which this review was unable to verify.

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An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

A Nykjaer, D Dragun, D. Walther … (1999)

Steroid hormones may enter cells by diffusion through the plasma membrane. However, we demonstrate here that some steroid hormones are taken up by receptor-mediated endocytosis of steroid-carrier complexes. We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin. Endocytosis is required to preserve 25-(OH) vitamin D3 and to deliver to the cells the precursor for generation of 1,25-(OH)2 vitamin D3, a regulator of the calcium metabolism. Megalin-/- mice are unable to retrieve the steroid from the glomerular filtrate and develop vitamin D deficiency and bone disease.

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Antibacterial effects of vitamin D.

Martin Hewison (2011)

Interaction between vitamin D and the immune system has been recognized for many years, but its relevance to normal human physiology has only become evident in the past 5 years. Studies of innate immune responses to pathogens such as Mycobacterium tuberculosis have shown that pathogen-recognition receptor-mediated activation of localized vitamin D metabolism and signaling is a key event associated with infection. Vitamin D, acting in an intracrine fashion, is able to induce expression of antibacterial proteins and enhance the environment in which they function. The net effect of these actions is to support increased bacterial killing in a variety of cell types. The efficacy of such a response is highly dependent on vitamin D status; in other words, the availability of circulating 25-hydroxyvitamin D for intracrine conversion to active 1,25-dihydroxyvitamin D by the enzyme 25-hydroxyvitamin D-1α-hydroxylase. The potential importance of this mechanism as a determinant of human disease is underlined by increasing awareness of vitamin D insufficiency across the globe. This Review will explore the molecular and cellular systems associated with antibacterial responses to vitamin D in different tissues and possible consequences of such a response for the prevention and treatment of human immune disorders.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 15 August 2019

Publication date Collection: August 2019

Volume: 11

Issue: 8

Electronic Location Identifier: 1918

Affiliations

[1 ]Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

[2 ]Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy

[3 ]Department of Internal Medicine n3, Ternopil State Medical University, 46002 Ternopil, Ukraine

[4 ]Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20122 Milan, Italy

Author notes

[* ]Correspondence: piergiorgio.messa@ 123456unimi.it or piergiorgio.messa@ 123456policlinico.mi.it ; Tel.: +39-025-503-4551; Fax: +39-025-503-4550

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Carlo Alfieri https://orcid.org/0000-0003-3860-5219

Simone Vettoretti https://orcid.org/0000-0002-1040-4952

Mario Cozzolino https://orcid.org/0000-0002-8494-6252

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Publisher ID: nutrients-11-01918

DOI: 10.3390/nu11081918

PMC ID: 6723756

PubMed ID: 31443249

SO-VID: f54e93c7-fb0d-4d23-b67c-7efb6c0213ca

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Native Hypovitaminosis D in CKD Patients: From Experimental Evidence to Clinical Practice

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Research from Ukraine

Most cited references 62

Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis123

An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3.

Antibacterial effects of vitamin D.

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