The Effect Of Dietary Amino Acids On Chronic Kidney Disease Progression in Rats

Abstract

Chronic kidney disease (CKD) affects over 10% of the population (Troidle, 2014) and is on the rise. An increase in the protein intake, one of the characteristics of a western‐type diet, is thought to have a detrimental effect by increasing the Renal Plasma Flow (RPF), inducing hyperfiltration and increasing acid load. In addition to these, the source of the protein i.e. animal or vegetal (Goraya and Wesson, 2016) and consequently its amino acid content, might also play a role in the progression of the disease. The actual mechanisms by which these proteins / amino acids lead to increased Glomerular Filtration Rate (GFR) and to kidney function deterioration is not well understood.In our experiments, we address the question of which amino acids, or groups of amino acids, might affect the progression of renal disease.To address this question, we utilized the well‐established 5/6th Nephrectomy (5/6th Nx) model. 5/6th Nx Wistar Han rats were randomly divided into groups, receiving either the control diet (18% protein), or one of different diets, in each case containing 8% protein supplemented with 10% amino acid (aa) mix (Essential aas, Non‐essential aas, Branched chain aas or all aas in the same proportion as in the protein mix). Both GFR and RPF were measured in free moving animals, GFR transcutaneously using FITC‐sinistrin, and RPF by using radiolabelled para‐aminohippurate (PAH). None of the modified diets caused any decrease in body weight, food or water consumption in the different groups. However, the pace of RPF and GFR alteration was diet‐dependent, with the slowest change in animals receiving the EAA diet, and the most dramatic one in the animals on BCAAs. The kidney of these BCAA receiving rats also showed the strongest increase in smooth muscle actin and collagen mRNA expression in their kidney, as expected for a higher level of inflammation and fibrosis. The SMA levels were increased 2‐fold and the collagen levels were increased more than 3‐fold compared to animals on the control diet. Taken together, these results suggest that high levels of BCAAs contained in the diet have a deleterious effect on the progression of CKD.Support or Funding InformationThis research/project was supported by the NCCR Kidney. CH funded by the Swiss National Science Foundation