Xenobióticos y toxinas urémicas en la enfermedad renal crónicaAcumulación y efectos del bisfenol A y S. Uso de probióticos para la prevención de la acumulación de toxinas de origen intestinal.

  1. Ruiz Priego, Alberto
Supervised by:
  1. Emilio González Parra Director
  2. Sebastián Mas Fontao Director

Defence university: Universidad Autónoma de Madrid

Fecha de defensa: 12 February 2021

  1. Antonio Dueñas Laita Chair
  2. Concepción Peiró Vallejo Secretary
  3. Marta Ruiz Ortega Committee member
  4. J.A. Herrero Calvo Committee member
  5. David Martínez Hernández Committee member

Type: Thesis


Chronic Kidney Disease (CKD) is a multifactorial disease. There are several factors that contribute to the progression of this pathology, such as uremic toxins, which may be increased in CKD patients as a consequence, for example, of intestinal dysbiosis. On the other hand, there are ubiquitous environmental molecules that can be toxic to CKD patients, especially to those in more advanced stages. Among these molecules, bisphenol A (BPA) stands out, which accumulates in the body of these patients due to its renal elimination. Currently, the industry has alternatives to this molecule, such as bisphenol S (BPS), which, despite being structurally similar to BPA, is more heat stable. However, studies of the possible effects of BPS in humans are scarce, especially in CKD. In vitro and in vivo studies on exposure to BPA confirm that this molecule is capable of accelerating the progression of kidney disease through increased oxidative stress and blocking autophagic flow, thus favoring key processes in the progression of the disease such as inflammation and renal fibrosis, all the mechanisms feeding back each other. Once known BPA toxicity, we decided to evaluate whether BPS was capable of producing similar effects. In vitro tests showed that, at equivalent concentrations, BPS does not produce cytotoxic effects or increases in oxidative or inflammatory stress in epithelial cells of the human renal proximal tubule. On the other hand, the effect of hemodialysis on plasma concentrations of BPA and BPS in patients with CKD was studied in two crossover design studies, one acute (1 week) and the other chronic (3 months), using different dialyzers according to their membranes: polysulfone (contains BPA and BPS) and polynephron (without BPA, but with BPS), where after the estimated period in each trial the patients changed dialyzer to evaluate the effects of each. The plasma levels of BPA and BPS in the CKD patients were higher than those of the healthy population, and the levels of BPS were lower than those of BPA in both groups. In relation to the acute and chronic tests, no differences were observed in the concentrations of BPA and BPS depending on the dialyser, although the polysulfone dialyzers showed a greater accumulation of BPA when comparing the two studies, unlike the concentrations of BPS that were remained stable in both studies and dialyzers, indicating a time-dependent accumulation of BPA in the body of patients with the polysulfone dialyser.