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Abstract: PO2045

Mitochondrial Dysfunction and Uremic Toxins from Gut Microbiota in CKD Patients: Is There a Link?

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Mafra, Denise, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Paiva, Bruna, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Reis, Drielly Vargas, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Teixeira, Karla thais Resende, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Moreira, Laís Gouveia, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Capistrano, Estelina Serrano de Marins, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Cardozo, Ludmila Fmf, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
  • Nakao, Lia S., Universidade Federal do Parana, Curitiba, PR, Brazil
  • Brito, Jessyca Sousa de, Federal University Fluminense, Rio de Janeiro, RJ, Brazil
Background

Dysbiosis in patients with chronic kidney disease (CKD) is associated with increased production of uremic toxins, such as indoxyl sulfate (IS), p-cresyl sulfate (p-CS) and indole-3-acetic acid (IAA), which are linked to oxidative stress and may be related to mitochondrial dysfunction with alterations in peroxisome proliferator activated gamma receptor coactivator 1 alpha (PGC-1α), respiratory nuclear factor 1 (NRF-1) and mitochondrial transcription factor (TFAM). The aim of this study was to verify possible associations between metabolites produced by gut microbiota and genes related to mitochondrial function (PGC-1α, NRF-1, TFAM) in CKD patients.

Methods

This was a cross-sectional, observational study, involving 46 patients with CKD: 20 patients on hemodialysis (HD) (12 men, 44.2 ± 8.9 years) and 26 non-dialysis patients (8 men, 57.6 ± 6.2 years, GFR 25.0 ± 13.0mL/min), selected by non-probabilistic sampling of convenience. Plasma levels of IS, p-CS and IAA were assessed by high-performance liquid chromatography (HPLC). The analysis of the gene expression of PGC1-α, NRF-1 and TFAM were performed by real time Polymerase Chain Reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). For statistical analysis, software R, version 3.5.0 (R Core Team, Vienna, Austria) was used and the results were expressed as mean ± standard deviation, with a significance level of p <0.05.

Results

As expected, the levels of uremic toxins were higher in HD patients than in non-dialysis patients [IS: 31.1 ± 14.3 mg/L vs 2.9 ± 1.7 mg/L (p <0.001); p-CS: 53.4 ± 34.6 mg/L vs 14.6 ± 10.8 mg/L (p <0.001); IAA: 2560.1 ± 1379.6 ug/L vs 1050.4 ± 984.8 ug/L)]. There was no significant difference in the mitochondrial parameters TFAM and PGC1a between the groups of patients. In the HD group was observed a positive linear correlation between TFAM and NRF1 (r = 0.978, p <0.001); as well as between PGC1a and NRF1 (r = 0.8, p = 0.006). However, in both groups there was no correlation between mitochondrial genes and uremic toxins.

Conclusion

The uremic toxins levels were significantly higher in HD patients; however, we did not find any correlations with the parameters of mitochondrial function analyzed.

Funding

  • Government Support - Non-U.S.