Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB243

Poster Communications

The Effect of Dietary Amino Acids on Chronic Kidney Disease Progression in Rats

S. Pillai1, G. Pellegrini2, F. Verrey1

1. Institute of Physiology, University of Zurich, Zurich, Zurich, Switzerland. 2. Laboratory for Animal Model Pathology (LAMP), Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland.

Chronic Kidney Disease (CKD) affects over 10% of the population (1). However, the mechanisms by which proteins/amino acids cause an increase in the Glomerular Filtration Rate (GFR) and kidney function deterioration are not well understood. Our study aims to unravel the differential impact of specific dietary amino acids/groups of amino acids on the progression of CKD. We used the well-established 5/6th Nephrectomy (5/6th Nx) model to induce CKD. 5/6th Nx Wistar Han rats were randomly divided 4 weeks after surgery, into groups receiving either the control diet (18% protein, n=10) or one of different diets, in each case containing 8% protein supplemented with a 10% mix of free amino acids (AAs): Essential- (EAAs n=15), Non-Essential- (NEAAs n=10), Branched Chain- (BCAAs n=14), Aromatic- (AAAs n=10), or all AAs in the same proportion as in the protein mix (8+10 n=18). Also, we had a group that was fed a diet of 18% protein, supplemented with 1.82% L-arginine (n=10). Both GFR and RPF were measured in free moving animals: GFR transcutaneously using FITC-sinistrin, and RPF using radiolabelled para-aminohippurate (PAH). We found that none of the modified diets caused any decrease in body weight, food and water consumption in the different groups up to 9 weeks after surgery. However, the pace of RPF and GFR alteration was diet-dependent. Animals receiving AAAs and EAAs showed the slowest progression, whereas the most dramatic reduction was in the case of animals on the BCAA diet (from 1.5 +/-0.1 ml/min/100g BW to 0.55 +/- 0.033 ml/min/100g BW, p<0.05, values expressed as means ± S.E.M., compared by ANOVA with Tukey post test). We also tested GFR changes in animals who were on the different diets but did not undergo 5/6th Nx and therefore, had no CKD. They showed no change in GFR 9 weeks after mock surgery (1.42 +/- 0.11 and 1.42 +/- 0.13 ml/min/100g BW). The kidneys of the BCAAs-receiving 5/6th Nx rats also showed the strongest increase in smooth muscle actin (2-fold) and collagen (more than 3-fold) mRNA expression, as expected for a higher level of inflammation and fibrosis compared to animals on the control diet. Towards deciphering the mechanisms underlying these differential effects of the various amino acid diets on CKD progression, we tested the activity of signalling pathways, specifically changes in phospho and total Stat3, Akt and S6k levels. No changes were observed at the phospho/total kidney protein level in such cases (using Western blots, repeated 3 times) for the diet groups. We found that different amino acid diets given for 5 weeks exert no impact on healthy kidneys, but they suggest that in CKD, high levels of dietary BCAAs exert a deleterious effect on progression, whereas high levels of AAAs surprisingly display a protective effect.

Where applicable, experiments conform with Society ethical requirements