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

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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 languageEnglish (US)
Article number103308
Issue number11
StatePublished - 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


  • Animal physiology
  • Metabolomics
  • Physiology
  • Systems biology


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