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The immunoregulatory function of vitamin D: implications in chronic kidney disease

Nature Reviews Nephrology volume 8, pages 403–412 (2012)Cite this article

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Abstract

Cardiovascular and infectious diseases remain the most common causes of death among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Basic science and epidemiological studies indicate that vitamin D has importance not only for cardiovascular health, but also for the immune response. Vitamin D signaling pathways regulate both innate and adaptive immunity, maintaining the associated inflammatory response within physiological limits. Levels of both the inactive as well as active form of vitamin D (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively) are decreased in patients with CKD and ESRD. It is reasonable to hypothesize, therefore, that the immune dysfunction associated with vitamin D deficiency in patients with CKD and ESRD in part explains the misdirected inflammatory response and increased susceptibility to infection seen in this population. Indeed, observational studies show that vitamin D deficiency in patients with ESRD is associated with increased mortality, and treatment with vitamin D is associated with a decreased risk of infection, as well as reduced all-cause mortality. However, whether different vitamin D preparations have differential effects on physiological function and clinical outcomes is still unclear. A proper understanding of the immune regulatory function of vitamin D is important for the development of future therapeutic strategies.

Key Points

  • Vitamin D has functions other than its role in calcium and phosphorus homeostasis

  • Vitamin D regulates both the innate and adaptive immune response

  • Cathelicidin, an antimicrobial peptide, is transcriptionally regulated by vitamin D

  • Patients with chronic kidney disease and end-stage renal disease have decreased levels of both the inactive and active forms of vitamin D

  • Vitamin D deficiency could contribute to the immune dysfunction observed in patients with chronic kidney disease

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Figure 1: Regulation of active (1,25[OH]2D3) and inactive (25OHD3 and 24,25[OH]2D3) forms of vitamin D depends on the actions of FGF23 and PTH.
Figure 2: Effects of vitamin D on innate and adaptive immunity.
Figure 3: Regulation of immune function by vitamin D.

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Acknowledgements

This work is supported in part by NIH grant R01 DK073665-01A1 awarded to D. S. Raj.

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Authors and Affiliations

  1. Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine, 2150 Pennsylvania Avenue NW, 20037, Washington, DC, USA

    Kevin A. Sterling, Parham Eftekhari, Paul L. Kimmel & Dominic S. Raj

  2. Medical Department II, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle (Saale), 06120, Germany

    Matthias Girndt

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All authors contributed equally to discussion of content for the article, researching data to include in the manuscript and writing. K. A. Sterling, P. L. Kimmel and D. S. Raj reviewed and edited the manuscript before submission.

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Sterling, K., Eftekhari, P., Girndt, M. et al. The immunoregulatory function of vitamin D: implications in chronic kidney disease. Nat Rev Nephrol 8, 403–412 (2012). https://doi.org/10.1038/nrneph.2012.93

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