Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Phase 1

Completed

Brief Summary: The goal of this study is to better understand vitamin D catabolism and how it is affected by CKD and race.

Detailed Description: Specifically, the study team will evaluate the metabolic clearance of 25-hydroxyvitamin D3 in individuals with varying degrees of CKD and among participants who self-report race as Caucasian, African American or African. The long-term goal of this work is to enhance the clinical evaluation and treatment of impaired vitamin D metabolism.

Recruitment & Eligibility

Inclusion Criteria

Age ≥ 18 years
Self-reported race Caucasian, African American, or African
Serum total 25(OH)D 10-50 ng/mL
Estimated GFR:
- 60 mL/min/1.73m2 (N=40) 15-45 mL/min/1.73m2 (N=40) <15 mL/min/1.73m2, treated with hemodialysis (N=40)

Exclusion Criteria

Primary hyperparathyroidism
Gastric bypass
Tuberculosis or sarcoidosis
Current pregnancy
Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)
Use of vitamin D3, or vitamin D2 supplements exceeding a mean daily dose of 400 IU, within 3 months (wash-out allowed)
Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
Serum calcium > 10.1 mg/dL
Hemoglobin < 10 g/dL

Arm && Interventions

Group	Intervention	Description
Study Population	D6-25-hydroxyvitamin D3	D6-25-hydroxyvitamin D3

Primary Outcome Measures

Name	Time	Method
Metabolic Clearance of D6-25(OH)D3	8 weeks	Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.

Secondary Outcome Measures

Name	Time	Method
Terminal Half-life of D6-25(OH)D3	8 weeks	Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
Volume of Distribution of D6-25(OH)D3	8 weeks	Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
AUC of D6-25(OH)D3	8 weeks	AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.