Furthermore, an expanded data set found a 2.5 times increased risk in sepsis or septic shock between sufficient and deficient vitamin D status.

Another investigation found that patients deficient in 25(OH)D had a 1.85 times increased risk of mortality 30 days after critical care initiation, and the association remained significant at 90 and 365 days after (Crit Care Med 2012;40:63-72). 

Of note, the investigators found that rate of sepsis did not skew the results. Another study found that patients with acute kidney injury, when compared with controls, had reduced 1,25(OH)D and vitamin D binding protein at enrollment. In these patients, 25(OH)D was significantly associated with mortality (Clin Endocrinol (Oxf.) 2013;79:491-498).


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Another group of researchers focused specifically on the active 1,25(OH)D. In their cohort, all patients who entered the critical care unit were insufficient in 25(OH)D, and no significant difference was found between 25(OH)D or PTH with regards to 30 day mortality. Patients with 1,25(OH)D values less than 13.6 pg/mL had significantly reduced survival time (PLoS One 2013;8:e64348).

As PTH levels increased in this cohort, 1,25(OH)D levels tended to decrease. As stated before, increases in PTH normally stimulate increases in 1,25(OH)D, such as in response to calcium deficiency. Dysregulation of this relationship may primarily relate to immune system regulation (J Steroid Biochem Mol Biol 2007;103:316-321).

Vitamin D repletion

A recent meta-analysis analyzed the effects of vitamin D supplementation in CKD and demonstrated that vitamin D supplementation significantly increased 25(OH)D levels and decreased PTH. Hypercalcemia and hyperphosphatemia incidence was low in the study populations (Clin J Am Soc Nephrol 2011;6:50-62).

Clinical outcomes such as mortality or infection were not analyzed in this dataset, but at this time, it does help support the evidence that vitamin D repletion can occur without excessive risk of elevated blood mineral levels.

Patients with chronic kidney disease (CKD) have increased risk for endothelial calcification related to elevated calcium and phosphorus aggregating into these tissues. Repleting vitamin D levels with supplementation carries a risk of simultaneously increasing absorption of these minerals in patients with hypercalcemia or hyperphosphatemia. CKD and dialysis patients suffer increased inflammation and immunologic stress due to disease progression and treatments.

Thus, adequate vitamin D for immunologic regulation is important. The role of the dietitian is thus crucial to help ensure that vitamin D levels can be repleted by supplementation or sun exposure while decreasing oral intake of calcium and phosphorus as necessary. Phosphorus intake is particularly problematic because of phosphorus additives in various foods and greater than 90% absorption rates. Dietary education on these topics may allow for adequate vitamin D therapy without complications.