Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Amelia K. Fotheringham; Samantha M. Solon-Biet; Helle Bielefeldt-Ohmann; Domenica A. McCarthy; Aisling C. McMahon; Kari Ruohonen; Isaac Li; Mitchell A. Sullivan; Rani O. Whiddett; Danielle J. Borg; Victoria C. Cogger; William O. Ballard; Nigel Turner; Richard G. Melvin; David Raubenheimer; David G. Le Couteur; Stephen J. Simpson; Josephine M. Forbes

doi:10.1016/j.isci.2021.103308

Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Amelia K. Fotheringham, Samantha M. Solon-Biet, Helle Bielefeldt-Ohmann, Domenica A. McCarthy, Aisling C. McMahon, Kari Ruohonen, Isaac Li, Mitchell A. Sullivan, Rani O. Whiddett, Danielle J. Borg, Victoria C. Cogger, William O. Ballard, Nigel Turner, Richard G. Melvin, David Raubenheimer, David G. Le Couteur, Stephen J. Simpson, Josephine M. Forbes

Biomedical Sciences

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

1 Scopus citations

Abstract

The kidneys balance many byproducts of the metabolism of dietary components. Previous studies examining dietary effects on kidney health are generally of short duration and manipulate a single macronutrient. Here, kidney function and structure were examined in C57BL/6J mice randomized to consume one of a spectrum of macronutrient combinations (protein [5%–60%], carbohydrate [20%–75%], and fat [20%–75%]) from weaning to late-middle age (15 months). Individual and interactive impacts of macronutrients on kidney health were modeled. Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury. Kidney outcomes did not align with cardiometabolic risk factors including glucose intolerance, overweight/obesity, dyslipidemia, and hypertension in mice with chronic low protein consumption. This study highlights that protein intake over a lifespan is an important determinant of kidney function independent of cardiometabolic changes.

Original language	English (US)
Article number	103308
Journal	iScience
Volume	24
Issue number	11
DOIs	https://doi.org/10.1016/j.isci.2021.103308
State	Published - Nov 19 2021

Bibliographical note

Funding Information:
We acknowledge the assistance of the Translational Research Institute flow cytometry core facility department, specifically Dr Yitian Ding and Dr David Sester. We also acknowledge the support of the Translational Research Institute Histology department and the microscopy facility, particularly Mr Adler Ju. We would also like to acknowledge the kind assistance of Carolina Correa and Martin Horan. A.K.F. was supported by an Australian Postgraduate Award and a Frank Clair scholarship . J.M.F. was supported by a National Health and Medical Research Council of Australia (NHMRC) Fellowship ( GNT1102935 ). M.A.S. was supported by a Mater Research McGuckin Early Career Fellowship , the University of Queensland's Amplify Initiative , Mater Foundation , Equity Trustees and the L G McCallam Est , and George Weaber Trusts . This work was also supported by Mater Foundation and a Federal Government Infrastructure Grant awarded to TRI. The original animal study was supported by the an NHMRC Project grant (GNT 571328 ), the Aging and Alzheimers Research Fund of Concord RG Hospital, and the Sydney Medical School Foundation . S.M.S.-B. is supported by an NHMRC Peter Doherty Biomedical Fellowship ( GNT1110098 ).

Publisher Copyright:
© 2021 The Authors

Keywords

Animal physiology
Metabolomics
Physiology
Systems biology

UN SDGs

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

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10.1016/j.isci.2021.103308

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Fotheringham, A. K., Solon-Biet, S. M., Bielefeldt-Ohmann, H., McCarthy, D. A., McMahon, A. C., Ruohonen, K., Li, I., Sullivan, M. A., Whiddett, R. O., Borg, D. J., Cogger, V. C., Ballard, W. O., Turner, N., Melvin, R. G., Raubenheimer, D., Le Couteur, D. G., Simpson, S. J., & Forbes, J. M. (2021). Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure. iScience, 24(11), [103308]. https://doi.org/10.1016/j.isci.2021.103308

Fotheringham, AK, Solon-Biet, SM, Bielefeldt-Ohmann, H, McCarthy, DA, McMahon, AC, Ruohonen, K, Li, I, Sullivan, MA, Whiddett, RO, Borg, DJ, Cogger, VC, Ballard, WO, Turner, N, Melvin, RG, Raubenheimer, D, Le Couteur, DG, Simpson, SJ & Forbes, JM 2021, 'Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure', iScience, vol. 24, no. 11, 103308. https://doi.org/10.1016/j.isci.2021.103308

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abstract = "The kidneys balance many byproducts of the metabolism of dietary components. Previous studies examining dietary effects on kidney health are generally of short duration and manipulate a single macronutrient. Here, kidney function and structure were examined in C57BL/6J mice randomized to consume one of a spectrum of macronutrient combinations (protein [5%–60%], carbohydrate [20%–75%], and fat [20%–75%]) from weaning to late-middle age (15 months). Individual and interactive impacts of macronutrients on kidney health were modeled. Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury. Kidney outcomes did not align with cardiometabolic risk factors including glucose intolerance, overweight/obesity, dyslipidemia, and hypertension in mice with chronic low protein consumption. This study highlights that protein intake over a lifespan is an important determinant of kidney function independent of cardiometabolic changes.",

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author = "Fotheringham, {Amelia K.} and Solon-Biet, {Samantha M.} and Helle Bielefeldt-Ohmann and McCarthy, {Domenica A.} and McMahon, {Aisling C.} and Kari Ruohonen and Isaac Li and Sullivan, {Mitchell A.} and Whiddett, {Rani O.} and Borg, {Danielle J.} and Cogger, {Victoria C.} and Ballard, {William O.} and Nigel Turner and Melvin, {Richard G.} and David Raubenheimer and {Le Couteur}, {David G.} and Simpson, {Stephen J.} and Forbes, {Josephine M.}",

note = "Funding Information: We acknowledge the assistance of the Translational Research Institute flow cytometry core facility department, specifically Dr Yitian Ding and Dr David Sester. We also acknowledge the support of the Translational Research Institute Histology department and the microscopy facility, particularly Mr Adler Ju. We would also like to acknowledge the kind assistance of Carolina Correa and Martin Horan. A.K.F. was supported by an Australian Postgraduate Award and a Frank Clair scholarship . J.M.F. was supported by a National Health and Medical Research Council of Australia (NHMRC) Fellowship ( GNT1102935 ). M.A.S. was supported by a Mater Research McGuckin Early Career Fellowship , the University of Queensland's Amplify Initiative , Mater Foundation , Equity Trustees and the L G McCallam Est , and George Weaber Trusts . This work was also supported by Mater Foundation and a Federal Government Infrastructure Grant awarded to TRI. The original animal study was supported by the an NHMRC Project grant (GNT 571328 ), the Aging and Alzheimers Research Fund of Concord RG Hospital, and the Sydney Medical School Foundation . S.M.S.-B. is supported by an NHMRC Peter Doherty Biomedical Fellowship ( GNT1110098 ). Publisher Copyright: {\textcopyright} 2021 The Authors",

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AU - McMahon, Aisling C.

AU - Ruohonen, Kari

AU - Li, Isaac

AU - Sullivan, Mitchell A.

AU - Whiddett, Rani O.

AU - Borg, Danielle J.

AU - Cogger, Victoria C.

AU - Ballard, William O.

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AU - Melvin, Richard G.

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AU - Simpson, Stephen J.

AU - Forbes, Josephine M.

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N2 - The kidneys balance many byproducts of the metabolism of dietary components. Previous studies examining dietary effects on kidney health are generally of short duration and manipulate a single macronutrient. Here, kidney function and structure were examined in C57BL/6J mice randomized to consume one of a spectrum of macronutrient combinations (protein [5%–60%], carbohydrate [20%–75%], and fat [20%–75%]) from weaning to late-middle age (15 months). Individual and interactive impacts of macronutrients on kidney health were modeled. Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury. Kidney outcomes did not align with cardiometabolic risk factors including glucose intolerance, overweight/obesity, dyslipidemia, and hypertension in mice with chronic low protein consumption. This study highlights that protein intake over a lifespan is an important determinant of kidney function independent of cardiometabolic changes.

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Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Abstract

Bibliographical note

Keywords

UN SDGs

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