Dietary Amino Acids Affect the Rate of Chronic Kidney Disease Progression in Rats

Abstract

The population affected by CKD continues to increase but the mechanisms by which proteins/amino acids lead to an increase in the Glomerular Filtration Rate (GFR) and kidney function deterioration are not well understood. Our study aims to unravel the differential impact that specific groups of amino acids might have on the progression of Chronic Kidney Disease. We utilized the well‐established 5/6th Nephrectomy (5/6th Nx) model to induce CKD. 5/6th Nx Wistar Han rats were randomly divided into groups receiving either the control diet (18% casein protein, n=10) or one of different diets, in each case containing 8% protein supplemented with 10% of a mix of free amino acids (AAs): Essential‐ (EAAs), Non‐Essential‐(NEAAs), Branched Chain‐ (BCAAs), Aromatic‐ (AAAs), or all AAs in the same proportion as in the protein mix (8+10). In addition to this, we also had a group that was fed a diet containing 18% protein supplemented with 1.82% L‐arginine. Both GFR and RPF were measured in free moving animals, GFR transcutaneously using FITC‐sinistrin, and RPF by using radiolabelled para‐aminohippurate (PAH).Our results show 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 case of the animals on the BCAA diet (from 1.5 +/−0.1 ml/min/100g BW to 0.55 +/− 0.033 ml/min/100g BW). 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. These animals showed no decrease 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 and collagen mRNA expression, as expected for a higher level of inflammation and fibrosis. The SMA protein levels were increased 2‐fold and the collagen levels more than 3‐fold compared to animals on control diet. Towards deciphering the mechanisms underlying these differential effects of the various amino acids diets on CKD progression, we are testing the activity of various signalling pathways, specifically changes in phospho‐ and total Stat3, Akt and S6k levels. No changes were observed at the protein level (using Western blots, repeated 3 times) for the various diet groups. Taken together, our results show that different amino acid diets given for 9 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.Support or Funding InformationThis study is supported by the Swiss National Centre of Competence in Research (NCCR), Kidney Control of Homeostasis (Kidney. CH)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.