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
Affiliations
Amelia K. Fotheringham
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
Samantha M. Solon-Biet
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; School of Medical Sciences, University of Sydney, Sydney 2006, NSW, Australia
Helle Bielefeldt-Ohmann
School of Veterinary Science, University of Queensland, Gatton Campus, Gatton 4343, QLD, Australia; School of Chemistry & Molecular Biosciences, University of Queensland, Brisbane 4067, QLD, Australia
Domenica A. McCarthy
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
Aisling C. McMahon
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia; ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
Kari Ruohonen
Animal Nutrition and Health, Cargill, Sandnes, Norway
Isaac Li
Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
Mitchell A. Sullivan
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
Rani O. Whiddett
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia
Danielle J. Borg
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia
Victoria C. Cogger
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia; ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
William O. Ballard
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, NSW, Australia
Nigel Turner
Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales Sydney, NSW 2052, Australia
Richard G. Melvin
Department of Biomedical Sciences, University of Minnesota Medical School, 1035 University Drive, Duluth 55812, MN, USA
David Raubenheimer
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, NSW, Australia
David G. Le Couteur
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; Centre for Education and Research on Aging, and Aging and Alzheimer's Institute, Concord Hospital, Sydney 2139, NSW, Australia; ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney 2139, NSW, Australia
Stephen J. Simpson
Charles Perkins Centre, University of Sydney, Sydney 2006, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, NSW, Australia
Josephine M. Forbes
Glycation and Diabetes Complications Group, Mater Research Institute-The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4072, QLD, Australia; Faculty of Medicine, University of Queensland, Brisbane 4067, QLD, Australia; Department of Medicine, University of Melbourne, Heidelberg, VIC 3084, Australia; Corresponding author
Summary: 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.
