Vitamin D and Arterial Function in Patients With Chronic Kidney Disease

Phase 3

Completed

Brief Summary: The purpose of this study is to determine whether nutritional (cholecalciferol) or active vitamin D (calcitriol) supplementation improves vascular endothelial function in patients with stage IIIB and IV chronic kidney disease with vitamin D insufficiency or deficiency. The investigators hypothesize that the use of calcitriol supplementation will result in improved vascular endothelial function as compared to cholecalciferol supplementation.

Recruitment & Eligibility

Inclusion Criteria

Age ≥ 18 years
Chronic kidney disease stage IIIB or IV by 4 parameter Modified Diet in Renal Diseases Formula (Estimated Glomerular Filtration Rate [GFR] 44-15 ml/min/1.73m2)
Vitamin D (D2 + D3) deficient, defined as serum 25(OH)D level < 30 ng/mL
Corrected serum calcium < 10.2 mg/dL
Serum phosphate < 4.6 mg/dL
Serum albumin > 3.0 g/dL
Body mass index < 40 kg/m2
Ability to give informed consent

Exclusion Criteria

Significant co-morbid conditions that lead the investigator to conclude that life expectancy is less than 1 year
Expected to undergo living related kidney transplant in next 6 months
Pregnant, breastfeeding, or unwilling to use adequate birth control
History of severe liver disease
Nephrotic range proteinuria (> 3.5 gm/day)
Use of active vitamin D analogs within 30 days of randomization

Arm && Interventions

Group	Intervention	Description
Cholecalciferol	Cholecalciferol	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months
Calcitriol	Calcitriol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months

Primary Outcome Measures

Name	Time	Method
Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment.	6 months	EDD will be measured by brachial artery flow-mediated dilation (FMD). The mean change in percent FMD from baseline will be documented.

Secondary Outcome Measures

Name	Time	Method
Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein	6 months	Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation
Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB	6 months	The effect of calcitriol and cholecalciferol supplementation will be evaluated calculating the mean change in total vascular endothelial cell NFkB expression. NFkB expression is given as arbitrary units and represent ratios of endothelial cell protein expression to human umbilical vein endothelial cell (HUVEC) expression in order to account for any variation in the staining procedure.