Oxidative Storm Induced by Tryptophan Metabolites: Missing Link between Atherosclerosis and Chronic Kidney Disease.

Iwona Kwiatkowska,Justyna M Hermanowicz,Dariusz Pawlak,Michal Mysliwiec,Kamil Karolczak

doi:10.1155/2020/6656033

Abstract

Chronic kidney disease (CKD) occurrence is rising all over the world. Its presence is associated with an increased risk of premature death from cardiovascular disease (CVD). Several explanations of this link have been put forward. It is known that in renal failure, an array of metabolites cannot be excreted, and they accumulate in the organism. Among them, some are metabolites of tryptophan (TRP), such as indoxyl sulfate and kynurenine. Scientists have become interested in them in the context of inducing vascular damage in the course of chronic kidney impairment. Experimental evidence suggests the involvement of TRP metabolites in the progression of chronic kidney disease and atherosclerosis separately and point to oxidative stress generation as one of the main mechanisms that is responsible for worsening those states. Since it is known that blood levels of those metabolites increase significantly in renal failure and that they generate reactive oxygen species (ROS), which lead to endothelial injury, it is reasonable to suspect that products of TRP metabolism are the missing link in frequently occurring atherosclerosis in CKD patients. This review focuses on reports that shed a light on TRP metabolites as contributing factors to vascular damage in the progression of impaired kidney function.

Highlights

Chronic kidney disease (CKD) is one of the most commonly occurring diseases in the world, with more than 850 million people afflicted [1]
This review focuses on the link between renal impairment and atherosclerosis and on oxidative stress as a contributing factor to the development of these diseases separately and as a link between these two comorbid conditions
Since it is known that atherosclerosis develops often in patients suffering from CKD, it is logical to suspect TRP metabolites as agents that by accumulating in kidney failure lead to vascular impairment

Summary

Introduction

Chronic kidney disease (CKD) is one of the most commonly occurring diseases in the world, with more than 850 million people afflicted [1]. Accumulated KYN metabolites, via the ability to induce/potentiate oxidative stress, show a negative or toxic effect on many cellular processes, which may lead to cell damage, an increased rate of apoptosis, or triggering the inflammatory processes that reflect a disturbance of homeostasis of various organs and systems [98, 111, 112, 118, 119].

Results

Conclusion