Vitamin D Metabolism in Chronic Kidney Disease Patients

Vitamin D Metabolism in Chronic Kidney Disease Patients With Vitamin D Deficiency Treated With Cholecalciferol

To determine whether or not chronic kidney disease (CKD), stages III-V and ESRD , is associated with altered vitamin D metabolism related to fibroblast growth factor-23 (FGF-23) stimulation of Cyp24 and whether they have resistance to elevations of 25 Hydroxyvitamin D (25(OH)D3) after cholecalciferol supplementation.

To determine if such resistance is related to enhanced catabolism of (25(OH)related to elevated levels of FGF-23.

Study Overview

• Status: Unknown
• Conditions: Vitamin D Metabolism is in Chronic Kidney Disease
• Intervention / Treatment: Drug: 10,000 IU of cholecalciferol for a total of 8 weeks

Detailed Description

1. Patients in the Memphis VA Medical Center with documented vitamin D deficiency, determined by measurements of 25(OH)D3, were recruited for this study. 25(OH)D3 measurements are commonly obtained during routine clinical care in both primary care and nephrology clinics. Patient with a wide range of kidney function, ranging from normal estimated glomerular filtration rate (e GFR) to patients with stage III and V (CKD) (estimated GFR <60 ml/min) were recruited treated with weekly oral administration of 10,000 IU of cholecalciferol for a total of 8 weeks in order to correct the vitamin D deficiency.

2. Data collected:

   Baseline characteristics including demographics, laboratory data obtained at primary care clinic visits, clinical data from the VAMC medical record and medications were obtained at the time of inclusion into the study. Serum concentrations of FGF23, 25(OH)D, 1,25 dihydroxyvitamin D(1,25 (OH)₂D), 24,25 dihydroxyvitamin D(24,25(OH)₂D) ,intact parathyroid hormone (PTH), Calcium, Phosphorous and creatinine and urinary concentrations of calcium, phosphate and creatinine from 24 hr urine collections were obtained at the time of inclusion into the study and after 8 weeks of weekly cholecalciferol therapy. Serum and buffy coats which were recollected from dialysis patient's who agreed to participate, were used to measure mRNA levels of FGF-23, CPY27B1 and Cyp 24 expression.

3. Methods utilized in analyzing and interpreting the data Descriptive statistics will be performed to compare serum and urinary measurements before and after cholecalciferol therapy. Associations between estimated glomerular filtration rate and levels of vitamin D metabolites and FGF23, before and after treatment, will also be evaluated. The mRNA expression of FGF-23, CPY27B1 and Cyp 24 will be measured in a subset of dialysis patients who completed the treatment course and agreed to provide the additional samples.
4. Duration of the project: 1 year.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38194
      • Memphis Veteran Affair Medical center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• age 18-85 years; CKD stage III or V; serum 25(OH)D level ≤ 30ng/ml, and serum PTH levels > 70 pg/ml within the last 6 months, informed Consent.

Exclusion Criteria:

• A history of liver disease, sarcoidosis, intestinal malabsorption;
• requirement of dialysis during the study; serum calcium level >10.5 mg/dl,
• calcium-phosphorus product > 70, or
• calcimimetics, or
• phosphorus binders; or
• medications that could affect vitamin D metabolism or
• history of parathyroidectomy.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: (CKD) stages III-V and non -CKD patients; We recruited patients with wide range of eGFR	Drug: 10,000 IU of cholecalciferol for a total of 8 weeks; Subjects were treated with weekly oral administration of 10,000 IU of cholecalciferol for a total of 8 weeks in order to correct the vitamin D deficiency.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D Metabolism in CKD and ESRD Patients with Vitamin D Deficiency treated with Cholicalciferol	Measuring 25(OH)D, FGF23, 24,25(OH)₂D, and 1,25(OH)₂D , PTH, Calcium, Phosphorus at baseline and after 8 weeks of cholecalciferol in a cohort of patients with CKD and non CKD who were having vitamin D defeciency treated with cholecalciferol for 8 weeks	8 weeks

Collaborators and Investigators

• Sponsor: Memphis VA Medical Center
• Investigators: Principal Investigator: Barry M Wall, MD, Memphis , TN ,VAMC; Principal Investigator: HALA M Alshayeb, MD, UTHSC, UCH

Publications and helpful links

General Publications

• Alshayeb H, Showkat A, Wall BM, Gyamlani GG, David V, Quarles LD. Activation of FGF-23 mediated vitamin D degradative pathways by cholecalciferol. J Clin Endocrinol Metab. 2014 Oct;99(10):E1830-7. doi: 10.1210/jc.2014-1308. Epub 2014 Jun 24.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: February 3, 2012
• First Submitted That Met QC Criteria: February 6, 2012
• First Posted (Estimate): February 7, 2012

Study Record Updates

• Last Update Posted (Estimate): February 14, 2012
• Last Update Submitted That Met QC Criteria: February 13, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: FGF-23, CKD, Cyp24, 24,25(OH)2D, vitamin D metabolism
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 00703; Department of Vetrans Affair (Other Identifier: Department of Vetrans Affairs)