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Editor’s note: This is the first of a two-part series. The second installment, focusing on cause-specific outcomes of hypovitaminosis D, will appear in the July issue. 

Key Points

  • Chronic kidney disease has emerged as a condition associated with a significantly higher prevalence of hypovitaminosis D, possibly because uremia may adversely affect the photoproduction of cholecalciferol in the skin.
  • In addition to the standard list of geographic and demographic characteristics indicative of progressively decreasing 25OHD levels, race-ethnicity—specifically pertaining to darks-skinned individuals—shows a high prevalence of low vitamin D levels.
  • Hypovitaminosis D has also been linked to a higher incidence of end-stage renal disease, implicating vitamin D deficiency in processes related to progressive loss of kidney function.

Nutritional vitamin D deficiency (measured as serum 25OH vitamin D) is very common in both the general population and in patients with all stages of chronic kidney disease (CKD). In the latter group, nutritional vitamin D deficiency is compounded by the deficient 1-alfa hydroxylation of 25OH vitamin D, which results in an often profound deficiency in serum 1,25(OH)2 vitamin D levels.

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Besides the known role of vitamin D in the regulation of bone and mineral homeostasis, it is now clear that this molecule also has pleiotropic roles that affect a variety of physiologic processes such as blood pressure regulation, cell proliferation, and the modulation of inflammation. Epidemiologic studies have been very important in discovering the many roles of vitamin D.

Robust associations between low vitamin D levels and all-cause and cause-specific mortality, cardiovascular disease (CVD), hypertension, cancer incidence, and various metabolic disturbances have indicated the need to better characterize the role of vitamin D and to explore the possible role of vitamin D replacement in the treatment of these abnormalities.

This article reviews studies that describe the incidence and prevalence of hypovitaminosis D in various populations, and the various adverse outcomes that low serum vitamin D has been linked to. In the second part of this article, most of the discussion of the harmful effects of hypovitaminosis D will focus on conditions related to CVD morbidity and mortality due to the significance of these issues in patients with CKD, with additional mention of the effects of low vitamin D levels on malignancies.


Vitamin D deficiency has been originally described to be the cause of rickets, which became common during the industrial revolution as a result of the significantly decreased exposure to sunlight in city dwellers. Clinical observations have been important in uncovering the link between rickets and vitamin D: in 1822 a Polish physician from the University of Wilno named Jedrzej Sniadecki recommended exposure to open air and sunshine for the cure of what was then coined the “English disease”.1

The link between sun exposure and rickets was subsequently corroborated by T.A. Palm in 1890.2 These early observations were followed by the discovery of the structure of vitamin D and its role in the regulation of bone and mineral metabolism. More recently, epidemiologic studies have described the common nature of 
vitamin D deficiency in various populations, and have uncovered associations with various clinical outcomes that were not consistent with the notion that this molecule’s role is limited to the regulation of bone and mineral metabolism.

Observational studies describing associations of vitamin D level with multiple different adverse clinical outcomes in both the general population and in patients with CKD will be discussed, without a detailed description of experimental studies or relevant clinical trial data.

The latter have to be considered essential in complementing epidemiologic data and in testing hypotheses that are based on observational studies, and as such merit a separate detailed description which are beyond the scope of this paper. Throughout this paper, the terms serum vitamin D with serum levels of 25OHD will be used interchangeably.