Effects of Dietary Phosphorus on Phosphorus and Calcium Whole-Body Balance and Kinetics in Moderate CKD

Not Applicable

Not yet recruiting

• Conditions: CKD

• Registration Number: NCT06712719
• Lead Sponsor: University of Minnesota

Brief Summary

The aim of the study is to look at the effects of dietary phosphorous on phosphorous and calcium whole-body balance and kinetics in moderate chronic kidney disease (CKD). N = 22 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 21 days and consist of a 7-day outpatient, controlled diet period, followed by a 7- 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, calcium and phosphorus isotopes as tracers 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 three weeks 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 calcium and phosphorus isotopes. Serial blood draws and complete urine and fecal collections will be made for 1 week, 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.

Study Timeline

• Study First Submitted: 2024-11-26
• Study First Submitted QC: 2024-11-26
• Study First Posted: 2024-12-02
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-15
• Study Start: 2025-07-01
• Primary Completion: 2027-05-28
• Study Completion: 2027-05-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 22

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.

Exclusion Criteria

• Plans to initiate dialysis within 6 months
• Hypercalcemia defined as corrected serum calcium >9.8 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, bariatric surgery, or chronic diarrhea/malabsorption
• Serious, uncontrolled underlying systemic disease including diabetes, lupus, hypertension in the opinion of their physician
• Pregnant or breastfeeding
• Prescribed and taken a phosphate binder medication, calcitriol, vitamin D analogs, calcimimetics, PTH analogues, and other medications that may alter Ca and P metabolism within past 4 weeks
• Non-English speaking

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Phosphorus Balance	1 week	Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed
Calcium Balance	1 week	Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed

Secondary Outcome Measures

Name	Time	Method
Fractional phosphorus absorption	2 weeks	Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations
Fractional calcium absorption	2 weeks	Determined by kinetic modeling of serum, urine, and stool Ca-44 isotope; after oral and IV isotope administrations
Bone phosphorus balance	2 weeks	Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations
Bone calcium balance	2 weeks	Determined by kinetic modeling of serum, urine, and stool Ca-44 isotope after oral and IV isotope administrations
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.