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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: CKD
• Intervention / Treatment: Other: LP then HP; Other: HP then LP

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.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kathleen Hill Gallant, PhD; Phone Number: 612-625-5285; Email: hillkm@umn.edu
• Study Contact Backup: Name: Study Coordinator; Email: KidneyNutrition@umn.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
      • Contact: Mary Balmes-Fenwick; Phone Number: 317-948-7772; Email: mbalmes@iu.edu
      • Principal Investigator: Sharon M Moe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CKD patients group 1; assigned to Low P Diet (LP) then High P Diet (HP),	Other: LP 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.
Experimental: CKD patients group 2; assigned to HP, then LP.	Other: HP 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphorus Balance	Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed	5 days
Calcium Balance	Determined by analysis of calcium content in complete 24-hour urine and stool collections, subtracted from the diet calcium content consumed	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine phosphorus	Determined from the 24-hour urine collections over 1 week (daily average)	1 week
Urine calcium	Determined from the 24-hour urine collections over 1 week (daily average)	1 week
Net phosphorus absorption	Determined by analysis of phosphorus content in complete stool collections, subtracted from the diet phosphorus content consumed, divided by the diet phosphorus consumed.	1 week
Net calcium absorption	Determined by analysis of calcium content in complete stool collections, subtracted from the diet calcium content consumed, divided by the diet phosphorus consumed	1 week
Creatinine clearance	Creatinine clearance will be determined from the 2-hour fasting urine and a mid-point blood sample collected on Day 8.	2hours, day 8
Serum Fibroblast growth factor-23	Measured in a fasting blood collection on Day 1 and Day 8.	Day1, Day8
Serum Parathyroid hormone	Measured in a fasting blood collection on Day 1 and Day 8.	Day1, Day8
Serum 1,25-dihydroxyvitamin D	Measured in a fasting blood collection on Day 1 and Day 8.	Day1, Day8
Serum phosphate	Measured in a fasting blood collection on Day 1 and Day 8.	Day1, Day8
Serum calcium	Measured in a fasting blood collection on Day 1 and Day 8.	Day1, Day8
Fractional phosphorus absorption	Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations	12 days
Bone phosphorus balance	Determined by kinetic modeling of serum, urine, and stool P-33 isotope after oral and IV isotope administrations	12 days
Bone calcium balance	Determined from the natural stable isotope ratio of 44-Ca to 42-Ca in serum and urine	5 days and 12 days

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Indiana University
• Investigators: Principal Investigator: Kathleen Hill Gallant, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: November 26, 2024
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: diet; phosphorus; balance; calcium; phosphate
• Other Study ID Numbers: TBD2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No