Patients with chronic kidney disease (CKD) are commonly deficient in vitamin D, with low levels of both calcidiol (25 hydroxy vitamin D) and calcitriol (1,25-hydroxy vitamin D). Patients with CKD are also known to have abnormalities in their immune cells, increased susceptibility to infection and increased prevalence of malignancies. In patients without kidney disease, repletion of vitamin D appears to help some immune mediated diseases. Thus it is logical that patients with CKD who are vitamin D deficient may benefit from repletion of vitamin D, in either its native form (cholecalciferol/ergocalciferol) or in the form of calcitriol or its analogues. However, no interventional data demonstrates that repletion positively impacts immune status in CKD patients. To test this hypothesis, a large interventional study will be required. However, prior to conducting this study, several important steps are needed. The present proposal aims to generate the necessary data to appropriately plan and conduct a future multi center interventional study. Specifically, we will examine the following specific aims in a population of CKD stage 3 and 4 subjects from Indiana University Affiliated Nephrology Clinics and determine

1. if abnormalities in immune cells and immune blood tests are related to abnormalities in vitamin D.
2. how reproducible these changes are on repeat testing and
3. if repletion of vitamin D changes these cells and immune blood tests in a small pilot study.

Inclusion Criteria:

• no administration of any form of vitamin D supplement or therapy in the last 60 days except for that in a multi vitamin
• Hgb >10 mg/dl
• able to sign informed consent
• CKD stage 3 (GFR 30-59ml/min) or stage 4 (GFR 15-29ml/min)
• iPTH <70pg/ml for stage 3 or iPTH <110pg/ml for stage 4
• calcidiol levels < or +20ng/ml

Exclusion Criteria:

• initial corrected Calcium >9.7mg/dl
• initial serum Phosphorus >5.0mg/dl
• initial standardized blood pressure of >160/100
• history of significant liver disease or cirrhosis
• anticipated requirement for dialysis in 6 months
• malabsorption, severe chronic diarrhea, or ileostomy
• no calcimimetic or active vitamin D therapy 60 days prior to enrollment