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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00764816
• Other study ID #: 0807-03
• Status: Completed
• Phase: N/A
• First received: October 1, 2008
• Last updated: June 22, 2011
• Start date: October 2008
• Est. completion date: February 2011

Study information

• Verified date: June 2011
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Indiana University School of Medicine	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Moe SM, Zidehsarai MP, Chambers MA, Jackman LA, Radcliffe JS, Trevino LL, Donahue SE, Asplin JR. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011 Feb;6(2):257-64. doi: 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine if the dietary protein source affects fasting serum and urinary phosphorus excretion in patients with CKD stages 3 and 4.		6 months after baseline	No
Secondary	To determine if the protein source affects post prandial changes in serum and urinary phosphorus in patients with CKD stages 3 and 4.		6 months from baseline	No
Secondary	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.		6 months from baseline	No