Polyphenols and Their Metabolites in Renal Diseases: An Overview

Abstract

Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.

Keywords: acute kidney injury; chronic kidney disease; diabetic nephropathy; drug-induced nephrotoxicity; metabolites; polyphenols; renal cancer; renal diseases.

Figure 1

The journey of dietary polyphenols in the human body. Some polyphenols are absorbed in the small intestine, after deglycosylation. There and at the liver, phenolic compounds undergo phase I and II metabolism. From the liver, they are redirected to the small intestine, through biliary secretion and then absorbed into the systemic circulation. Parent polyphenols and metabolites that are not absorbed upstream reach the colon and undergo microbiota metabolism before entering the bloodstream. Polyphenol metabolites in circulation reach target organs and tissues, where they exert their biological activity and are ultimately excreted in the urine. (Figure created in the Mind the Graph platform, available at www.mindthegraph.com, accessed on 23 October 2021).

Figure 2

Selection of physiologically relevant polyphenol metabolites for kidney protection. We collected available data from both the literature on dietary and supplementation intervention studies as well as from two polyphenol databases, Phyto Hub and Phenol-Explorer. These data allowed the identification of the most nutritionally relevant circulating polyphenol metabolites previously detected and quantified in human urine. We then estimated the maximum urinary concentrations in µM. After exclusion of phenolic metabolites that are known to be also generated from endogenous sources, as well as those identified in human urine in concentrations < 1 µM, this approach led us to a selection of 34 polyphenol metabolites.