Calcium and Phosphorus Whole-Body Balance and Kinetics in Patients With Moderate Chronic Kidney Disease

Not Applicable

Active, not recruiting

Conditions: Chronic Kidney Diseases
Phosphorus and Calcium Disorders
Chronic Kidney Disease Mineral and Bone Disorder

Brief Summary: This pilot study aims to develop a method for simultaneous whole-body calcium and phosphorus balance and full kinetic modeling of both ions in patients with chronic kidney disease.

Detailed Description: The goal of this project is to produce preliminary data on the effects of the commonly prescribed dietary phosphorus restriction on whole-body Calcium (Ca) and Phosphorus (P) balance and kinetics patients with CKD, to support a larger future clinical study. The specific aims are to determine intestinal Ca and P fractional absorption and 2) Ca and P balance and full kinetics, effect sizes variance estimates in patients with CKD on a low Ca diet with high P diet versus dietary P restriction. The hypothesis is that a high P diet, in the context of a typical low Ca diet, leads to P retention negative Ca balance, and that dietary P restriction modestly reduces P retention but does not negative Ca balance.

The study design is a randomized 2-period cross-over study. All outpatient and inpatient visits place at the Indiana CTSI Clinical Research Center located in IU Health University Hospital in Indianapolis, IN. Subjects will be randomly assigned to controlled diets of either low Ca/high P (LCa/HP) or low (LCa/LP) for a 1-week, outpatient diet equilibration period, followed by 1-week inpatient full balance that includes a 48-hour Ca and P absorption testing protocol. After a 1-3 week washout subjects will crossover to the other diet regimen

Recruitment & Eligibility

Inclusion Criteria

Men or women, ages 30-75 years old, any race or ethnicity
Moderate chronic kidney disease
Female subjects must be postmenopausal (>12 months since last menstrual period), surgically sterile, or confirmed not pregnant by pregnancy test
Must be on stable doses of medications (except those noted in exclusion criteria) for at least 4 weeks prior to the study
Willing to discontinue nutritional supplements (e.g. vitamin D, calcium, multivitamin/minerals, or others) upon enrollment until completion of the study
Adequate vitamin D status defined as serum 25D > 20 ng/mL

Exclusion Criteria

Plans to initiate dialysis within 6 months
Hypercalcemia defined as serum calcium >10.5 mg/dL within past 3 months
Hyperkalemia defined as serum potassium >5.5 mg/dL within past 3 months
Hyperphosphatemia defined as serum phosphate >5.5 mg/dL within past 3 months
Intestinal disease that alters absorption or normal intestinal function including celiac disease, small bowel resection, or bariatric surgery
Serious, uncontrolled underlying systemic disease including diabetes, lupus, hypertension
Pregnant or breastfeeding
Prescribed a phosphate binder medication, calcitriol, vitamin D analogs, calcimimetics, parathyroid hormone analogues, and other medications that may alter Ca and P metabolism within past 30 days

Arm && Interventions

Group	Intervention	Description
Sequence A	Low Phosphorus Diet	High Phos crossover to Low Phos
Sequence B	High Phosphorus Diet	Low Phos crossover to High Phos
Sequence B	Low Phosphorus Diet	Low Phos crossover to High Phos
Sequence A	High Phosphorus Diet	High Phos crossover to Low Phos

Primary Outcome Measures

Name	Time	Method
Fractional Calcium Absorption	48 hours	Determined by kinetic modeling of serum and urine Ca-44 isotope after oral and IV isotope administrations
Fractional Phosphorus Absorption	48 hours	Determined by kinetic modeling of serum and urine P-33 isotope after oral and IV isotope administrations
Calcium Balance	1 week	Determined by analysis of calcium content in complete 24-hour urine and stool collections, subtracted from the diet calcium content consumed. Values can be negative, zero, or positive.
Phosphorus Balance	1 weeks	Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed. Values can be negative, zero, or positive.

Secondary Outcome Measures

Name	Time	Method
Serum Intact Fibroblast Growth Factor 23 (iFGF23)	Day 1-8	Determined by enzyme-linked immunoassay (ELISA). Values for each subject are an average of 6 serial measures taken during the 1 week balance period (between Days 1-8)
Serum Intact Parathyroid Hormone (iPTH)	Day 1-8	Determined by enzyme-linked immunoassay (ELISA). Values for each subject are an average of 6 serial measures taken during the 1 week balance period (between Days 1-8)
Serum 1,25-dihydroxyvitamin D (1,25D)	Day 1	Determined by LC-MS/MS. Values are from Day 1 of the metabolic balance period (following 1 week of acclimation to assigned study diet).