A diet with 35 % of energy from protein leads to kidney damage in female Sprague–Dawley rats

• Published in: British journal of nutrition Vol. 106; no. 5; pp. 656 - 663
• Main Authors: Wakefield, Andrew P., House, James D., Ogborn, Malcolm R., Weiler, Hope A., Aukema, Harold M.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 14.09.2011; CABI Pub
• Subjects: adverse effects; animal models; Animals; Biological and medical sciences; Body Weight; Chemokine CCL2; Chemokine CCL2 - physiology; chemokines; creatinine; Diet; Dietary Proteins; Dietary Proteins - adverse effects; energy; etiology; Feeding. Feeding behavior; Female; fibrosis; Fundamental and applied biological sciences. Psychology; Homocysteine; Homocysteine - physiology; humans; hypertrophy; Kidney Diseases; Kidney Diseases - etiology; Kidney Diseases - physiopathology; Kidney Function Tests; Kidneys; Metabolism and Metabolic Studies; Nutrition research; Organ Size; physiology; physiopathology; Proteins; Rats; Rats, Sprague-Dawley; Receptors, CCR2; Receptors, CCR2 - physiology; Renal function; Rodents; Swine; Transforming Growth Factor beta1; Transforming Growth Factor beta1 - physiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; weight loss; Renal hypertrophy; High-protein diet; Kidney; Glomerular damage; Animal model; Rat; Rodentia; Supplemented diet; Protein; Feeding; Vertebrata; Mammalia; Urinary system; Animal; Female; Lesion; Hypertrophy
• ISSN: 0007-1145; 1475-2662; 1475-2662
• DOI: 10.1017/S0007114511000730

High-protein (HP) diets for weight loss remain popular despite questions surrounding overall safety. In a recent study using the pig model, we showed that long-term intakes from whole proteins at 35 % energy (en %) cause moderate renal histological damage. To examine whether this observation may be species specific or more generalisable, the effect of this diet in rats was examined. Using plant and animal whole proteins, 70-d-old female Sprague–Dawley rats were randomised to either a normal-protein (NP; 15 en %) or a HP (35 en %) diet for 4, 8, 12 and 17 months. Renal function was assessed by creatinine clearance and urinary protein levels, and pathology was assessed by examination of glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis. Rats consuming the HP diet had 17 % higher kidney weights (P < 0·0001), three times higher proteinuria (P < 0·0001) and 27 % higher creatinine clearance (P = 0·0012) compared with those consuming the NP diet. Consistent with this, HP-fed rats had larger glomeruli (P < 0·0001) and more glomerulosclerosis (P = 0·0003) compared with NP-fed rats. The HP diet also resulted in altered levels of free monocyte chemoattractant protein-1 (P < 0·0001). The histological changes are consistent with those observed in the pig model. In contrast to the pig model, the elevated proteinuria and creatinine clearance observed in the rat model are also usually observed with HP consumption in human subjects. These results indicate that the rat is a useful model for HP effects on the kidney and, along with previous results using the pig model, suggest that long-term intake of high levels of protein may be detrimental to renal health.