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

Br J Nutr. 2011 Sep;106(5):656-63. doi: 10.1017/S0007114511000730. Epub 2011 May 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Chemokine CCL2 / physiology
  • Dietary Proteins / adverse effects*
  • Female
  • Homocysteine / physiology
  • Kidney Diseases / etiology*
  • Kidney Diseases / physiopathology
  • Kidney Function Tests
  • Organ Size
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CCR2 / physiology
  • Transforming Growth Factor beta1 / physiology


  • Ccr2 protein, rat
  • Chemokine CCL2
  • Dietary Proteins
  • Receptors, CCR2
  • Transforming Growth Factor beta1
  • Homocysteine