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A high protein diet at the upper end of the Acceptable Macronutrient Distribution Range (AMDR) leads to kidney glomerular damage in normal female Sprague-Dawley rats

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dc.contributor.supervisor Aukema, Harold (Human Nutritional Sciences) en
dc.contributor.author Wakefield, Andrew
dc.date.accessioned 2007-09-18T12:40:58Z
dc.date.available 2007-09-18T12:40:58Z
dc.date.issued 2007-09-18T12:40:58Z
dc.identifier.uri http://hdl.handle.net/1993/2834
dc.description.abstract In setting the AMDR for protein at 10-35% of daily energy, the Institute of Medicine acknowledged a lack of data regarding the safety of long-term intakes. The current study assessed the impact of chronic (17 months) protein consumption at the upper end of the AMDR on renal function, histology, and inflammation. Using plant and animal whole protein sources, female Sprague-Dawley rats (70 days old; n=8-11 at 4, 8, 12, or 17 mo.) were randomized to either a normal (NP; 15% of energy) or high protein (HP; 35% of energy) diet. Egg albumen and skim milk replaced carbohydrates in the HP diet. Diets were balanced for energy, fat, vitamins and minerals, and offered ad libitum. Renal function was analyzed by creatinine clearance and urinary protein levels. Glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis were assessed on kidney sections. Kidney disease progression was determined by the measurement of transforming growth factor beta-1 (TGF-β1) and renal inflammation by the measurement of chemokines monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation normal T-cell expressed and secreted (RANTES). Rats consuming the HP compared to NP diet had ~17% higher kidney weights (P<0.0001) and ~4.8 times higher proteinuria (P<0.0001). There was a trend towards higher creatinine clearance with HP (P=0.055). Consistent with this, HP compared to NP rats had ~22% larger glomeruli (P<0.0001) and ~33% more glomerulosclerosis (P=0.0003). The HP diet had no significant effect on tubulointerstitial fibrosis and renal TGF-β1 levels and did not result in higher renal levels of MCP-1 and RANTES. In fact, per mg renal protein, HP rats had ~16% lower MCP-1 (P<0.0001) and ~34% lower levels of RANTES (P<0.0001) than NP. The absence of an increase in cytokine levels may be a reflection of the moderate changes in renal pathology observed in rats offered HP diets. These data in normal female rats suggest that protein intakes at the upper end of the AMDR are detrimental to kidney health in the long-term. While modest, this may have implications for individuals whose kidney function is compromised, especially given the prevalence of those unaware of their kidney disease within North America. en
dc.format.extent 2292632 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject High Protein Diet en
dc.subject Acceptable Macronutrient Distribution Range en
dc.subject Renal Hypertrophy en
dc.subject Glomerular Damage en
dc.title A high protein diet at the upper end of the Acceptable Macronutrient Distribution Range (AMDR) leads to kidney glomerular damage in normal female Sprague-Dawley rats en
dc.type info:eu-repo/semantics/masterThesis
dc.degree.discipline Human Nutritional Sciences en
dc.contributor.examiningcommittee House, James (Animal Science) Smyth, Donald (Internal Medicine/Pharmacology) en
dc.degree.level Master of Science (M.Sc.) en
dc.description.note October 2007 en


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