Effects of Maqui Supplementation on Gut Microbiota, Inflammation, and Oxidative Stress in Patients With Chronic Kidney Disease

Overview

Chronic kidney disease (CKD) is a highly prevalent condition in Chile and worldwide and is associated with a substantial burden of morbidity, particularly cardiovascular morbidity. In the early stages of CKD, treatment aims to preserve kidney function and slow the progression of associated complications. Several conditions have been reported in association with CKD, including impaired antioxidant capacity, inflammation, and alterations in the gut microbiota (GM), which contribute, among other complications, to the loss of kidney function and cardiovascular damage. In the search for therapeutic approaches to modulate CKD-related complications, there is growing interest in complementary non-pharmacological interventions, including nutritional strategies within the "Food as Medicine" concept. In this context, maqui remains largely unexplored in CKD. Maqui contains phenolic compounds with bioactive properties and strong antioxidant activity, which have also been associated with anticancer, antimicrobial, and anti-inflammatory effects, as well as inhibition of enzymes involved in metabolic syndrome, making this fruit of particular interest for human health. To date, no studies have evaluated the therapeutic potential of maqui in relation to oxidative stress, inflammation, gut microbiota, and CKD progression, or whether these biomarkers and the response to maqui supplementation differ according to biological sex. To evaluate the effects of maqui supplementation in men and women on the modulation of gut microbiota, inflammatory parameters, and oxidative stress in patients with stage 3 and 4 chronic kidney disease. A longitudinal, randomized, double-blind clinical trial will be conducted in patients with CKD recruited from healthcare centers in the Metropolitan Region of Santiago, Chile. Participants will receive either a dietary supplement containing dried maqui extract in powder form, equivalent to 200 mg of Delphinol, or placebo for three months. At baseline and after three months of intervention, gut microbiota composition, uremic toxins, inflammatory and oxidative stress markers (plasma antioxidant capacity, urinary polyphenols, IL-6, high-sensitivity C-reactive protein \[hs-CRP\], NGAL, and uremic toxins), parameters of CKD progression, and anthropometric and dietary parameters will be assessed.

This is a three-month, randomized, double-blind, placebo-controlled pilot clinical trial designed to evaluate the effects of maqui supplementation in adults with stage 3-4 chronic kidney disease (CKD). The study focuses on biological pathways involved in CKD progression, particularly systemic inflammation, oxidative stress, gut microbiota alterations, and the generation of gut-derived uremic toxins. An exploratory component of the study will examine whether baseline characteristics and responses to the intervention differ according to biological sex. Participants will be randomly assigned to receive either a powdered maqui supplement, providing an amount equivalent to 200 mg of Delphinol, or a maltodextrin placebo once daily for three months. Randomization will be balanced by sex and age and conducted independently from the research team. Study products will be identified using alphanumeric codes to maintain blinding of participants and the clinical and research teams throughout the intervention. Clinical and biological assessments will be performed at baseline and after three months of supplementation. Blood and urine samples will be collected to characterize kidney function, systemic inflammation, oxidative status, and other biochemical parameters related to CKD progression. Stool samples will be collected at the same time points to evaluate gut microbiota composition and gut-derived uremic toxins. Gut microbiota will be characterized through sequencing of the V4 region of the 16S rRNA gene. The study will also assess anthropometric and body composition parameters, blood pressure, and dietary intake. Dietary intake will be evaluated using three-day food records, which will also be used to estimate the Dietary Inflammatory Index. Participants will receive monthly follow-up by a nutritionist during the intervention to assess adherence and identify relevant changes in dietary intake or other factors that could influence the response to supplementation. The study is intended to provide preliminary clinical and biological evidence regarding the potential effects of maqui supplementation in CKD and to generate data for the design of a larger clinical trial. Given the pilot nature of the study, analyses according to biological sex will be considered exploratory.