A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease

Christophe Barba,Laetitia Koppe,Bérengère Benoit,Claudie Pinteur,Christophe O Soulage,Griet Glorieux,Emilie Bres,Stéphanie Chanon,Cécile Picard,Sandra Pesenti,Aurélie Vieille-Marchiset,Denis Fouque

doi:10.1038/s41598-021-98718-x

Abstract

Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition.

Highlights

Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear
In order to study in CKD mice, the specific effects of reducing dietary intake of three aromatic amino acids on uremic toxins production and renal function, we designed and constructed an amino acid-defined normoproteic diet (NPD) modeled on a 14% protein diet used as standard (AO4 diet)
We investigated two additional diets: a LPD with a global decrease in amino acids content, in which 5% of calories were derived from amino acids through a uniform reduction of every amino acid in the NPD diet; and a low aromatic amino-acid diet (LA-AAD) in which all aromatic amino acids were reduced by two-thirds to match the levels of the LPD, while all other amino acids were kept at the level of the NPD

Summary

Introduction

Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition. In the CKD area, recent publications suggest that plant based diet improve renal o utcomes[16,17]

Objectives

Methods

Results

Conclusion