Vitamin D Metabolism in Chronic Kidney Disease Patients
Vitamin D Metabolism in Chronic Kidney Disease Patients
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.
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.
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.