CKD
Conditions
Keywords
phosphorus, phosphate, balance, diet, calcium
Brief summary
The aim of the study is to look at the effects of dietary phosphorus on phosphorous and calcium whole-body balance and kinetics in moderate chronic kidney disease (CKD). N = 14 enrolled subjects will be randomly assigned to a cross-over order of (A) Low P Diet, High P Diet. Each cross-over phase will be 19 days and consist of a 7-day outpatient, controlled diet period, followed by a 5- day inpatient, controlled diet, balance, and kinetic study period, followed by a second 7-day outpatient, controlled diet period.
Detailed description
Chronic kidney disease (CKD) affects approximately 37 million (1 in 7) U.S. adults, most of whom experience mineral and bone disorders (CKD-MBD) that increase risk for cardiovascular events, bone fractures, and death. Dietary and pharmaceutical treatments for CKD-MBD have diverse effects on serum calcium and phosphorus levels, but their effects on the underlying physiological processes of calcium and phosphorus balance are largely unknown. This study aims to determine the effects of a low versus high phosphorus bioaccessibility diet on whole-body calcium and phosphorus balance and kinetics, including measures such as estimated intestinal absorption. This study will be a randomized two-phase cross-over design trial that will include a controlled study diet, a phosphorus isotope as a tracer for kinetic modeling, stool and urine collections, and blood draws. After screening, eligible participants who choose to enroll in the study will be asked to participate in two cross-over sessions, each of approximately 3 weeks (19 days) duration during which time all food will be provided according to the randomized diet intervention assignment. After the first week on the study diet, participants will be asked to stay at the clinical research center when they will be given oral and intravenous doses of phosphorus isotope. Serial blood draws and complete urine and fecal collections will be made for 5 days, then the final week will only include blood draws. Between cross-over sessions, there will be a washout period of 1-3 weeks. Participants will then switch diets and repeat the same study process as the first session. Calcium and phosphorus whole-body balance, intestinal absorption, renal excretion, and movement to and from bone will be determined for both minerals. This project will provide foundational knowledge of calcium and phosphorus physiology in CKD that will support progress towards preventing morbidity and mortality associated with CKD-MBD.
Interventions
OTHERLP then HP
Cross-over order of LP then HP diet. Each cross-over phase will be 19 days and consist of a 7-day outpatient, controlled diet period, followed by a 5-day inpatient, controlled diet, balance, and kinetic study period, followed by a second 7-day outpatient, controlled diet period.
OTHERHP then LP
Cross-over order of HP then LP diet. Each cross-over phase will be 19 days and consist of a 7-day outpatient, controlled diet period, followed by a 5-day inpatient, controlled diet, balance, and kinetic study period, followed by a second 7-day outpatient, controlled diet period.
Sponsors
University of Minnesota
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men or women, ages 30-75 years old, any race or ethnicity * Moderate CKD, defined by KDIGO as eGFR category 3b (30-44 mL/min) or 4 (16-29 mL/min) with albuminuria categories A1-A3 * Serum intact parathyroid hormone above assay normal limit * 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 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 based on National Academy of Medicine (then Institute of Medicine) criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphorus Balance | 5 days | Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed |
| Calcium Balance | 5 days | Determined by analysis of calcium content in complete 24-hour urine and stool collections, subtracted from the diet calcium content consumed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fractional phosphorus absorption | 12 days | Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations |
| Bone phosphorus balance | 12 days | Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations |
| Bone calcium balance | 5 days and 12 days | Determined from the natural stable isotope ratio of 44-Ca to 42-Ca in serum and urine |
| Urine phosphorus | 1 week | Determined from the 24-hour urine collections over 1 week (daily average) |
| Urine calcium | 1 week | Determined from the 24-hour urine collections over 1 week (daily average) |
| Net phosphorus absorption | 1 week | Determined by analysis of phosphorus content in complete stool collections, subtracted from the diet phosphorus content consumed, divided by the diet phosphorus consumed. |
| Net calcium absorption | 1 week | Determined by analysis of calcium content in complete stool collections, subtracted from the diet calcium content consumed, divided by the diet phosphorus consumed |
| Creatinine clearance | 2hours, day 8 | Creatinine clearance will be determined from the 2-hour fasting urine and a mid-point blood sample collected on Day 8. |
| Serum Fibroblast growth factor-23 | Day1, Day8 | Measured in a fasting blood collection on Day 1 and Day 8. |
| Serum Parathyroid hormone | Day1, Day8 | Measured in a fasting blood collection on Day 1 and Day 8. |
| Serum 1,25-dihydroxyvitamin D | Day1, Day8 | Measured in a fasting blood collection on Day 1 and Day 8. |
| Serum phosphate | Day1, Day8 | Measured in a fasting blood collection on Day 1 and Day 8. |
| Serum calcium | Day1, Day8 | Measured in a fasting blood collection on Day 1 and Day 8. |
Countries
United States
Contacts
CONTACTKathleen Hill Gallant, PhD
CONTACTStudy Coordinator
PRINCIPAL_INVESTIGATORKathleen Hill Gallant, PhD
University of Minnesota
Outcome results
None listed