A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis

Abstract

Introduction: Indoxyl sulfate (IS) and p‐cresyl sulfate (p‐CS) are albumin‐bound uremic toxins that are difficult to remove by hemodialysis (HD). Human serum albumin (HSA) carries several compounds, including fatty acids that can bind to site II of HSA and represent competing ligands for uremic toxins. The aim of this study was to investigate the association between fatty acids and uremic toxin plasma levels in patients undergoing HD. Methods: Thirty‐three HD patients (51.5% male, 54.9 ± 10.2 years old, 44.63 ± 28.4 months on HD, albumin level of 3.8 ± 0.3 g/dL) were evaluated. The erythrocyte fatty acid content (saturated fatty acid [SFA], monounsaturated fatty acid [MUFA], and polyunsaturated fatty acid [PUFA]) was measured by gas chromatography, and total IS and p‐CS plasma levels were measured by reversed‐phase high‐performance liquid chromatography. Findings: The mean percentages of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) + DHA and gamma‐linolenic (GLA) acid in the erythrocyte membrane were 1.35% ± 0.74%, 1.85% ± 0.79%, and 0.33% ± 0.26%, respectively. The mean levels of IS and p‐CS were 19.4 ± 11.9 mg/dL and 101.5 ± 57.2 mg/dL, respectively. There was no significant association between SFA and MUFA and IS and p‐CS; however, a negative correlation was found between p‐CS and specific PUFAs, and the association between GLA and p‐CS levels was retained after adjusting for potential confounding variables (β = −0.49, P = 0.007). Discussion: Polyunsaturated fatty acids may contribute to the decrease in p‐CS uremic toxin plasma levels in patients with chronic kidney disease undergoing HD.

Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis

“…Taking this fact into consideration, Kemp et al demonstrated a negative correlation between p-CS plasma levels and specific polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic (GLA) in patients with CKD on HD. This result suggests that PUFAs could contribute to reduce uremic toxin plasma levels in patients with CKD undergoing HD [51].…”

Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais

“…Além disso, os AGPIs de hemácias do nosso estudo diferem dos resultados anteriores. 48 , 55 , 57 Isto pode ser devido à falta de padronização da análise de AG circulante. Os AG das hemácias são expressos em percentagens do AG total, o que significa que os níveis de AG dependem dos AG analisados pelo método.…”

“…Traditional cardiovascular risk factors do not reflect the full complexity of the atherosclerotic disease, so much so that emerging cardiovascular risk factors have gained emphasis in the literature, 18 , 45 - 48 and the effects of PUFA on CVD are beyond these factors. 18 Among the various non-traditional risk factors, it has been shown that sdLDL-c is a better predictor of CAD risk than LDL-c. 1 The current study found that RBC n-6 PUFA and n-6/n-3 ratio were positively associated with smaller average LDL particle size and higher levels of sdLDL-c.…”

“…In addition, RBC PUFA in our study differs from previous results. 48 , 55 , 57 This may be due to a lack of standardization of circulating FA analysis. RBC FA are expressed in percentages of total FA, meaning that the FA levels depend on FA analyzed by the method.…”

Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular

“…Essa endotoxemia metabólica leva a um estresse oxidativo, e à produção de lipídios aterogênicos, LDL oxidado (LDLox) e fosfolipídios oxidados – que levam à resposta inflamatória do complexo CD36-TLR4-TLR6. 35 , 36 Ainda, o consumo elevado de AGSs aumenta os níveis de lipídios, de LDL minimamente modificada e de LDLox, que ativam a via inflamatória CD14-TLR4-MD2. 35 O consumo elevado de AGSs também pode alterar a composição lipídica do HDL e a capacidade de efluxo do colesterol, diminuindo sua função e aumentando o risco cardiovascular.…”