Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats

Kendal M. Burstad; Dennis P. Cladis; Colby J. Vorland; Meryl E. Wastney; Annabel Biruete; James M. Dominguez; Kalisha D. O'Neill; Neal X. Chen; Sharon M. Moe; Kathleen M. Hill Gallant

doi:10.1002/jbm4.10698

Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats

Kendal M. Burstad, Dennis P. Cladis, Colby J. Vorland, Meryl E. Wastney, Annabel Biruete, James M. Dominguez, Kalisha D. O'Neill, Neal X. Chen, Sharon M. Moe, Kathleen M. Hill Gallant

Food Science and Nutrition

Research output: Contribution to journal › Article › peer-review

Abstract

Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using ³³P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out.

Original language	English (US)
Article number	e10698
Journal	JBMR Plus
Volume	6
Issue number	12
DOIs	https://doi.org/10.1002/jbm4.10698
State	Published - Dec 2022

Bibliographical note

Funding Information:
This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI‐KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co‐PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award.

Funding Information:
This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI-KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co-PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. The authors thank Dr James C Fleet for technical and scientific guidance, especially on the use of the oral gavage absorption test technique; Pamela J Lachcik, MS, for technical training on rat procedures; the wonderful staff of the Purdue University Laboratory Animal Program and the LSA Animal Facility; and Ying Dong, Kaylee Brunsting, Abby Emigh, and Samuel Loebig for their assistance in the completion of this project.

Funding Information:
KMHG has received speaker honoraria from Ardelyx and scientific consulting fees from Tricida. CJV has received honoraria from The Obesity Society and the Alliance for Potato Research and Education. The institution of CJV, Indiana University, has received funds to support his research from National Cattlemen's Beef Association; Alliance for Potato Research and Education; the Gordon and Betty Moore Foundation; and NIH. AB has received research grants from Keryx Pharmaceuticals and honoraria from Amgen. SMM is a scientific consultant for Sanifit, Amgen, and Ardelyx. KMB, DPC, JMD, NXC, KO, and MEW have nothing to disclose.

Publisher Copyright:
© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Keywords

ANIMAL MODELS
DISORDERS OF CALCIUM/PHOSPHATE METABOLISM
NUTRITION
PRECLINICAL STUDIES
PTH/VitD/FGF23

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jbm4.10698

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Burstad, K. M., Cladis, D. P., Vorland, C. J., Wastney, M. E., Biruete, A., Dominguez, J. M., O'Neill, K. D., Chen, N. X., Moe, S. M., & Hill Gallant, K. M. (2022). Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats. JBMR Plus, 6(12), Article e10698. https://doi.org/10.1002/jbm4.10698

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abstract = "Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out.",

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author = "Burstad, {Kendal M.} and Cladis, {Dennis P.} and Vorland, {Colby J.} and Wastney, {Meryl E.} and Annabel Biruete and Dominguez, {James M.} and O'Neill, {Kalisha D.} and Chen, {Neal X.} and Moe, {Sharon M.} and {Hill Gallant}, {Kathleen M.}",

note = "Funding Information: This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI‐KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co‐PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. Funding Information: This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI-KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co-PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. The authors thank Dr James C Fleet for technical and scientific guidance, especially on the use of the oral gavage absorption test technique; Pamela J Lachcik, MS, for technical training on rat procedures; the wonderful staff of the Purdue University Laboratory Animal Program and the LSA Animal Facility; and Ying Dong, Kaylee Brunsting, Abby Emigh, and Samuel Loebig for their assistance in the completion of this project. Funding Information: KMHG has received speaker honoraria from Ardelyx and scientific consulting fees from Tricida. CJV has received honoraria from The Obesity Society and the Alliance for Potato Research and Education. The institution of CJV, Indiana University, has received funds to support his research from National Cattlemen's Beef Association; Alliance for Potato Research and Education; the Gordon and Betty Moore Foundation; and NIH. AB has received research grants from Keryx Pharmaceuticals and honoraria from Amgen. SMM is a scientific consultant for Sanifit, Amgen, and Ardelyx. KMB, DPC, JMD, NXC, KO, and MEW have nothing to disclose. Publisher Copyright: {\textcopyright} 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.",

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AU - Burstad, Kendal M.

AU - Cladis, Dennis P.

AU - Vorland, Colby J.

AU - Wastney, Meryl E.

AU - Biruete, Annabel

AU - Dominguez, James M.

AU - O'Neill, Kalisha D.

AU - Chen, Neal X.

AU - Moe, Sharon M.

AU - Hill Gallant, Kathleen M.

N1 - Funding Information: This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI‐KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co‐PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. Funding Information: This project was funded through the American Society for Bone and Mineral Research (ASBMR) Rising Star Research Award (KMHG) and the National Institutes of Health (NIH), National Institute for Diabetes and Digestive and Kidney Diseases award number K01DK102864 (KMHG). CJV was supported in part by the Gordon and Betty Moore Foundation. AB was supported by Indiana CTSI-KL2. This publication was made possible with support from grant numbers KL2TR002530 (Sheri Robb, PI) and UL1TR002529 (Sarah Wiehe and Sharon Moe, co-PIs) from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. The authors thank Dr James C Fleet for technical and scientific guidance, especially on the use of the oral gavage absorption test technique; Pamela J Lachcik, MS, for technical training on rat procedures; the wonderful staff of the Purdue University Laboratory Animal Program and the LSA Animal Facility; and Ying Dong, Kaylee Brunsting, Abby Emigh, and Samuel Loebig for their assistance in the completion of this project. Funding Information: KMHG has received speaker honoraria from Ardelyx and scientific consulting fees from Tricida. CJV has received honoraria from The Obesity Society and the Alliance for Potato Research and Education. The institution of CJV, Indiana University, has received funds to support his research from National Cattlemen's Beef Association; Alliance for Potato Research and Education; the Gordon and Betty Moore Foundation; and NIH. AB has received research grants from Keryx Pharmaceuticals and honoraria from Amgen. SMM is a scientific consultant for Sanifit, Amgen, and Ardelyx. KMB, DPC, JMD, NXC, KO, and MEW have nothing to disclose. Publisher Copyright: © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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N2 - Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out.

AB - Dietary phosphorus restriction and phosphorus binders are commonly prescribed for patients with chronic kidney disease (CKD). However, occurrences of non-adherence to these interventions are common. As low-phosphorus (LP) diets have been consistently experimentally shown in vitro to increase intestinal phosphorus absorption efficiency, a bout of non-adherence to diet or binders may cause an unintended consequence of enhanced intestinal phosphorus absorption. Thus, we aimed to determine the effect of a single bout of high-phosphorus (HP) intake after acclimation to a LP diet. Male Sprague Dawley rats with 5/6 nephrectomy (n = 36) or sham operation (n = 36) were block-randomized to 1 of 3 diets: LP (0.1% P w/w), HP (1.2%), or LP followed by acute HP (LPHP 0.1% then 1.2%). Phosphorus absorption tests were conducted using 33P radioisotope administrated by oral gavage or intravenously (iv). Although the overall two-way ANCOVA model for intestinal fractional phosphorus absorption was non-significant, exploratory comparisons showed intestinal fractional phosphorus absorption efficiency tended to be higher in rats in the LP compared with HP or LPHP groups. Rats in the HP or LPHP groups had higher plasma phosphorus compared with rats in the LP group, but the LPHP group was not different from the HP group. Gene expression of the major intestinal phosphate transporter, NaPi-2b, was lower in the jejunum of rats in the LPHP group compared with rats in the HP group but not different in the duodenum. These results demonstrate that an acute HP load after acclimation to a LP diet does not lead to enhanced intestinal fractional phosphorus absorption efficiency in 5/6 nephrectomized male rats. These data provide evidence against the notion that dietary phosphorus restriction or binder use adversely increases absorption efficiency after a single instance of dietary or binder non-adherence. However, other adverse consequences of fluctuating dietary phosphorus intake cannot be ruled out.

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KW - DISORDERS OF CALCIUM/PHOSPHATE METABOLISM

KW - NUTRITION

KW - PRECLINICAL STUDIES

KW - PTH/VitD/FGF23

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Acute High Dietary Phosphorus Following Low-Phosphorus Diet Acclimation Does Not Enhance Intestinal Fractional Phosphorus Absorption in Nephrectomized Male Rats

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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