Effect of Dietary Protein Source on Phosphaturia, PTH and FGF23 in Patients With CKD 3 and 4

This study has been completed.
Sponsor:
Information provided by:
Indiana University
ClinicalTrials.gov Identifier:
NCT00764816
First received: October 1, 2008
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

Phosphorus is a substance in the blood that comes from food and is normally cleared from the body by the kidneys. In patients with kidney disease, excess phosphorus may build up in the body as you eat. This leads to problems with bones and blood vessels over time. In this study, we will compare the blood and urine before and after eating one week of a diet with a protein from plants (soy and grains) and before and after another one week of diet with protein from animals (meat and dairy products). The amount of phosphorus that the kidney puts out in the urine, and the changes in blood hormones in response to the diet will be measured at the beginning and end of each week on the two diets.


Condition Intervention
Chronic Kidney Disease
Other: grain (soy) protein diet
Other: casein (meat) protein diet

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Dietary Protein Source on Phosphaturia, PTH and FGF23 in Patients With CKD 3 and 4

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • To determine if the dietary protein source affects fasting serum and urinary phosphorus excretion in patients with CKD stages 3 and 4. [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine if the protein source affects post prandial changes in serum and urinary phosphorus in patients with CKD stages 3 and 4. [ Time Frame: 6 months from baseline ] [ Designated as safety issue: No ]
  • To determine if changes in plasma FGF23 and PTH correlate with urinary phosphorus excretion in response to different protein sources in patients with CKD stages 3 and 4. [ Time Frame: 6 months from baseline ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: October 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 grain (soy) protein diet:
The patient is to eat a grain (soy) protein diet for 7 days. The food is prepared by a registered dietitian.
Other: grain (soy) protein diet
The patient is to eat a grain (soy) protein diet for 7 days. The food is prepared by a registered dietitian.
Active Comparator: 2 casein (meat) protein diet
The patient is to eat a casein (meat) protein diet for 7 days. The food is prepared by a registered dietitian.
Other: casein (meat) protein diet
The patient is to eat a casein (meat) protein diet for 7 days. The food is prepared by a registered dietitian.

Detailed Description:

Chronic Kidney Disease-Mineral Bone disorder (CKD-MBD) is a constellation of problems related to alterations in mineral and bone homeostasis that occur in CKD stage 3-5D (estimated GFR 60-15 ml/min). The damaged kidney is unable to fully excrete a phosphorus load, leading to a compensatory secondary hyperparathyroidism to attempt to increase urinary phosphorus excretion in order to maintain serum phosphorus in the normal range. Eventually this compensation of elevated PTH becomes pathologic and leads to abnormalities in biochemistries, bone and vascular disease, all of which are associated with morbidity and mortality in patients with CKD. Prevention of these complications is key to improved patient outcomes. Unfortunately, this normal or high normal phosphorus does not reflect the "behind the scenes" appropriate and inappropriate compensation. The use of medication to bind phosphorus from food (phosphate binders) may prevent absorption of phosphorus across the intestine and prevent or change the elevations in PTH and other hormones like FGF23. Thus, either urinary excretion of phosphorus, or changes in hormone may be more appropriate end points to evaluate efficacy of phosphate binders than is serum phosphorus.

In healthy individuals, there is variation throughout the day (diurnal) in serum phosphorus and urine phosphorus excretion, but in dialysis patients, this variability appears to be lost. No data exists for patients with stage 3 and 4 (pre-dialysis) CKD. Intestinal phosphorus absorption is also dependent on bioavailability (amount of free phosphorus available to be absorbed), which differs depending on the protein source, as the phosphorus in grain/soy diets is less bioavailable than that from protein from animal/casein protein source. In our animal model of CKD, these differences in bioavailability impact urinary phosphorus excretion and serum levels of FGF-23, but not PTH. As phosphaturia, PTH, and FGF23 may become important end points for future clinical trials, understanding diurnal variability and the relationship to diet in patients with CKD 3 and 4 with normal serum phosphorus levels is critical. We hypothesize that dietary protein source will affect the hormonal response and diurnal phosphorus homeostasis in advanced CKD. To test this hypothesis, we will examine the following specific aims in a population of CKD stage 3 and 4 subjects from the Indiana University Affiliated Nephrology Clinics and determine

  1. if the dietary protein source affects fasting serum and urinary phosphorus excretion
  2. if the protein source affects post prandial changes in serum and urinary phosphorus in patients
  3. if changes in plasma FGF23 and PTH correlate with urinary phosphorus excretion in response to different protein sources.

We will conduct a cross over study to assess blood and urine after one week of a diet that differs only in the source of the protein (and thus the bioavailability of phosphorus).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age >18 years
  • eGFR 20-45 by modified MDRD equation
  • protein/creatinine ratio <5
  • blood pressure <150/95
  • not taking calcium binder or supplements, vitamin D, or phosphate binders
  • normal serum phosphorus and calcium corrected for albumin and intact PTH <100pg/ml
  • medically stable
  • able to give informed consent and come for all visits

Exclusion Criteria:

  • history of significant liver disease or cirrhosis
  • medically unstable
  • unable to tolerate diets
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00764816

Locations
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Sharon M Moe, MD Indiana University School of Medicine
  More Information

Publications:
Responsible Party: Sharon M. Moe, MD, Indiana University Department of Medicine
ClinicalTrials.gov Identifier: NCT00764816     History of Changes
Other Study ID Numbers: 0807-03
Study First Received: October 1, 2008
Last Updated: June 22, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Chronic kidney disease, stages 3 and 4
phosphaturia
phosphorus
PTH
FGF23
Dietary protein source

Additional relevant MeSH terms:
Kidney Diseases
Hypophosphatemia, Familial
Renal Insufficiency, Chronic
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Hypophosphatemia
Phosphorus Metabolism Disorders
Renal Insufficiency
Caseins
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014