Marcia Ribeiro

Chronic kidney disease (CKD) is characterized by systemic metabolic disturbances and oxidative stress. Nutritional interventions using bioactive compounds such as sulforaphane (SFN) may represent a promising adjuvant strategy to attenuate these alterations. This study evaluated the effects of SFN supplementation on the untargeted metabolomic profile of non-dialysis CKD patients. A randomized, placebo-controlled clinical trial was conducted in 14 patients with CKD stages 3–5 who received either 400 µg per day of SFN or placebo for 30 days. Serum samples were analyzed using proton nuclear magnetic resonance (¹H NMR) spectroscopy to identify metabolomic alterations and their correlations with markers of oxidative stress, inflammation, and gene expression. SFN supplementation tended to reduce 2-hydroxyisovalerate and glycerol levels, metabolites associated with insulin resistance and oxidative stress, and attenuated methanol elevation. Correlations were identified between heme oxygenase-1 (HO-1) and several amino acids, and between NRF2 and glycerol, suggesting an interplay between amino acid metabolism and antioxidant defense. Overall, SFN modulated the metabolomic profile of CKD patients, particularly metabolites related to mitochondrial function, lipid metabolism, and oxidative balance. These findings demonstrate that NMR-based metabolomics is a powerful non-invasive approach for elucidating the molecular effects of nutritional therapies in CKD and support SFN as a potential nutraceutical strategy in renal care.

Background and Objectives: Chronic kidney disease (CKD) is closely associated with gut dysbiosis, and sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, may help to mitigate this condition. Methods: These are secondary exploratory analyses from a previous study that included 16 patients with CKD (stages 3 to 5). The patients were divided into two groups: the Sulforaphane (SFN) group (400 mcg/day of SFN) and the placebo group, both of which received treatment for four weeks. Fecal DNA extraction was performed, and amplicon sequencing was conducted on an Illumina MiSeq V3 platform. The sequence data were analyzed using the QIIME 2 software package. Plasma uremic toxin concentrations (indoxyl sulfate, IS, and p-cresyl sulfate, pCS) were measured by HPLC with fluorescence detection. Results: No significant differences were observed in the gut microbiota alpha microbial richness and diversity after supplementation. However, supplementation with SFN altered the taxonomic composition and resulted in changes to the complexity of the microbial network. A distinct set of Amplicon Sequence Variants (ASVs) was observed post-supplementation with SFN, dominated by genera such as Megamonas, Sphingobium, Clostridia, and Hungatella, indicating a treatment-specific microbial signature. The placebo group showed significant increases in IS and pCS, whereas the SFN group presented non-significant changes. Conclusions: SFN supplementation for one month did not significantly alter microbial diversity or uremic toxin levels in non-dialysis CKD patients; however, it led to changes in microbial composition and network complexity, suggesting a modulatory effect on specific microbial interactions.

Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: This randomized, double-blind, placebo-controlled trial involved HD patients allocated to receive either royal jelly plus green propolis EPP-AF^® (100 mg RJ + 500 mg GP) or placebo capsules daily for 2 months. Before and after the intervention period, the biochemical parameters, inflammatory cytokines, and uremic toxins were measured. Results: A total of 38 HD patients completed the 2-month supplementation study, with 19 patients in each group. After 2 months, the treated group showed a significant reduction in plasma levels of IL-6 (0.78 to 0.63 pg/mL, p = 0.008) and total cholesterol (138.60 to 111.85 mg/dL, p = 0.03), whereas no changes were observed in the placebo group. Uremic toxins did not change after intervention. Conclusion: Apitherapy with RJ + GP EPP-AF^® extract significantly reduced plasma IL-6 and total cholesterol in HD patients. This supplementation shows promise as a non-pharmacological strategy to reduce cardiovascular risk markers in this population.

Chronic inflammation plays a central role in the progression and complications of chronic kidney disease (CKD). The nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway has emerged as a crucial mediator of the inflammatory response in CKD. This cross-sectional study evaluated the expression of NLRP3 in patients with CKD undergoing different treatments. Blood samples were collected from 32 non-dialysis (ND) patients [63 (11.2) years, estimated glomerular filtration rate, 43.5 (22.0) mL/min, BMI, 29.5 (10.0) kg/m²)], 50 hemodialysis (HD) patients [48.5 (16.5) years, 60.5 (50) months on HD, BMI, 24.2 (4.9) kg/m²)], and 8 peritoneal dialysis (PD) patients [56.5 (8.5) years, 40.5 (41.2) months on PD, BMI, 28.8 (2.6) kg/m²)]. The mRNA expression level of NLRP3 was measured using real-time PCR. The cytokines and the malondialdehyde (MDA) levels were also assessed. The results indicated that the mRNA level of NLRP3 was significantly elevated in patients undergoing HD (1.23, IQR = 0.95) compared with that in non-dialysis patients (0.79, IQR = 0.35) and in patients undergoing PD (0.77, IQR = 0.38) after adjusting for confounding variables, including age, sex, BMI, and dialysis duration. Furthermore, the MDA levels were significantly higher in HD patients. NLRP3 is upregulated in HD patients, and the results suggested that the inflammasome may be associated with oxidative stress in patients with CKD.

In physiological situations involving cell damage, molecules derived from mitochondria or bacteria are produced. These molecules are known as N-formyl peptides and are detected by formyl peptide receptors (FPRs), which stimulate immune cells to migrate to the specific site of injury or infection. Despite their initially beneficial effects on health, N-formyl peptides also contribute to the development or exacerbation of chronic non-communicable diseases. Therefore, understanding the metabolic pathways related to the involvement of N-formyl peptides and FPRs may increase our ability to regulate immune responses and precisely target FPRs with personalized strategies, offering a promising approach for the treatment of specific diseases. In this way, bioactive compounds in food may influence N-formyl peptides, interacting with the receptors either competitively or by inhibiting them, which affects the inflammatory response and oxidative reactions of cells. This review examines the pathways associated with forming N-formyl peptides, the activation of FPRs, and the roles of bioactive compounds in regulating N-formyl peptides.

Genetic predisposition accounts for less than 20% of the global disease burden, highlighting the substantial role of environmental factors in health outcomes. In chronic kidney disease (CKD), a growing global prevalence, understanding the interplay between genes and the environment is crucial. Emerging research in the exposome and genome underscores how environmental exposures interact with genetic variants to influence the development and progression of CKD. The term “exposome” encompasses a variety of factors, including personal behaviors like smoking, a sedentary lifestyle, and making specific dietary choices (such as consuming ultra-processed foods, sugar, or fat). It also includes broader determinants such as pesticides, air, water, and soil pollution, nanoplastics, global warming, stressful life events, and socioeconomic status. Research on the exposome significantly increases our understanding of toxicological processes and individual variations in susceptibility to environmental stressors. This narrative review aims to explore the exposome associated with CKD, highlight key environmental exposures in its development, and discuss potential preventive and therapeutic strategies informed by these exposure-related factors.

Purpose of review This narrative review investigates how urolithins produced by the gut microbiota can regulate transcription factors (such as NRF2, NF-kB, and PPAR-γ) associated with senescence, inflammation, and imbalanced redox status. It also discusses the potential benefits of urolithins for patients with chronic diseases, including cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease. Recent Findings Studies have shown that urolithins have many health benefits, including anti-inflammatory, antioxidant, antimicrobial, and anti-atherosclerotic effects. They are also linked to improved mitochondrial function and imbalanced redox associated with activating the Nrf2/ARE pathway. Summary Urolithins are metabolites produced by gut microbiota from ellagic acid and ellagitannins, polyphenols primarily found in nuts and fruits, including pomegranates and berries like raspberries, cloudberries, and blackberries.

Gut dysbiosis, characterized by an imbalance in the gut microbiota, has emerged as a potential factor influencing CKD progression. This condition plays a crucial role in the gut-kidney axis, where changes in microbial composition can contribute to systemic inflammation and uremic toxin production and ultimately exacerbate kidney damage. Understanding the dynamics of the gut-kidney axis provides new insights into potential therapeutic strategies to mitigate CKD progression. Diet is the primary driver of gut microbiota composition. Therefore, an approach emphasizing healthy nutritional patterns is recommended for improving overall health, cardiovascular disease, and profoundly altered metabolic patterns in patients with CKD. Dietary modifications have been explored as therapeutic strategies targeting the microbiome to improve outcomes in CKD. An emerging therapeutic target is the production of dysmetabolites by the gut microbiota, which may help alleviate uremic and cardiovascular toxicity. In addition, future research should broaden the scope to include other microorganisms, such as fungi, archaea, and viruses. This expanded focus will enable a more comprehensive understanding of the gut-kidney axis and pave the way for more personalized and effective treatment strategies for patients with CKD. This review explores the role of lifestyle, particularly diet, in kidney health; highlights new gut microbiome therapies; and identifies research opportunities in CKD.