Impact of Vitamin D Repletion in Hemodialysis Patients
Impact of Vitamin D Repletion in Hemodialysis Patients
Dialysis patients often suffer from defects in their immune system (that part of the body
 which fights infection). Evidence suggests that Vitamin D deficiency may have a negative
 effect on immunity, and many dialysis patients are deficient in Vitamin D. We believe that by
 giving Vitamin D to dialysis patients who are deficient, we may help improve their immune
 system. This study will test that idea.
Innate and adaptive immunity are commonly impaired in patients with end stage renal disease
 (ESRD) on dialysis. The myriad of immune defects in these patients, often attributed to
 uremia, may account for their high risk of bacterial infection and suboptimal responses to
 vaccination. The mechanisms underlying these abnormalities in immune function remain elusive,
 but emerging evidence indicates that 25OH-Vitamin D exerts potent and complex control over
 innate and adaptive immunity. Vitamin D deficiency is common in dialysis patients, and the
 immune effects associated with 25OH-Vit D deficiency overlap with those found in many
 dialysis patients. The kidney is the dominant site of 1-alpha-hydroxylase activity required
 for producing active 1,25OH-Vit D; however, immune cells also express the 1-alpha-hydroxylase
 enzyme. Evidence indicates the effects of Vitamin D on modulating immunity require conversion
 of 25OH-Vit D to 1,25OH-Vit D within the immune cells (rather than via circulating 1,25OH-Vit
 D). As a consequence, total body deficiency of 25OH-Vit D can impact immune function despite
 ongoing therapy with active 1,25OH-Vit D (which most dialysis patients are receiving). Our
 preliminary data confirm the high prevalence of 25OH-Vit D deficiency in dialysis patients
 and show that Th1 T cell alloimmunity is stronger in patients deficient in 25OH-Vit D,
 supporting the hypothesis that Vit D deficiency has important immunological consequences.
 Based on the published literature and our preliminary data, we hypothesize that repletion of
 25OH-Vit D enhances immunity in dialysis patients. To test this hypothesis, we propose a
 randomized controlled trial of oral 25OH-Vit D repletion in this patient population. One
 hundred fifty 25OH-Vit D deficient study subjects will be randomized to either treatment with
 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of
 change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months.
 Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC)
 profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T
 cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to
 toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.
Inclusion Criteria:

 1. Age > 18 years

 2. Chronic hemodialysis treatments for at least 2 consecutive months

 3. 25OH-Vitamin D level < 25 ng/mL (inclusion criteria for randomization)

 Exclusion Criteria:

 1. History of acute renal failure requiring dialysis with potential for renal recovery

 2. History of HIV/AIDS

 3. Inability to provide informed consent