Bisphenol S is a haemodialysis-associated xenobiotic that is less toxic than bisphenol A.

BACKGROUND: Bisphenol S (BPS) is a structural analogue of bisphenol A (BPA) that is found in the environment. BPS may accumulate in anuric patients due to decreased urinary excretion. The toxicity and health effects of BPS are poorly characterized. METHODS: A cross-over study was performed using polynephron (PN) or polysulphone (PS) dialysers for a short (1 week each, 14 patients) or long (3 months each, 20 patients) period on each dialyser. Plasma BPA, BPS and hippuric acid were assessed by SRM mass spectrometry (SRM-MS). The biological significance of the BPS concentrations found was explored in cultured kidney tubular cells. RESULTS: In haemodiafiltration (HDF) patients, plasma BPS was 10-fold higher than in healthy subjects (0.53 ± 0.52 versus 0.05 ± 0.01 ng/mL; P = 0.0015), while BPA levels were 35-fold higher (13.23 ± 14.65 versus 0.37 ± 0.12 ng/mL; P = 0.007). Plasma hippuric acid decreased after an HDF session, while BPS and BPA did not. After 3 months of HDF with the same membranes, the BPS concentration was 1.01 ± 0.87 ng/mL for PN users and 0.62 ± 0.21 ng/mL for PS users (P non-statistically significant). In vitro, BPS and BPA leaked from dialysers containing them. In cultured tubular cells, no biological impact (cytotoxicity, inflammatory and oxidative stress gene expression) was observed for BPS up to 200 µM, while BPA was toxic at concentrations ≥100 µM. CONCLUSIONS: BPS may be released from dialysis membranes, and dialysis patients display high BPS concentrations. However, BPS concentrations are lower than BPA concentrations and no BPS toxicity was observed at concentrations found in patient plasma.

Influence of dialysis membrane composition on plasma bisphenol A levels during online hemodiafiltration.

INTRODUCTION: Bisphenol A (BPA) is an ubiquitous environmental toxin that is also found in dialyzers. Online hemodiafiltration (OL-HDF) more efficiently clears high molecular weight molecules, and this may improve BPA clearance. However, the BPA contents of dialysis membranes may be a source of BPA loading during OL-HDF. METHODS: A prospective study assessed plasma BPA levels in OL-HDF patients using BPA-free (polynephron) or BPA-containing (polysulfone) dialyzers in a crossover design with two arms, after a run-in OL-HDF period of at least 6 months with the same membrane: 31 patients on polynephron at baseline were switched to polysulfone membranes for 3 months (polynephron-to-polysulfone) and 29 patients on polysulfone were switched to polynephron for 3 months (polysulfone-to-polynephron). RESULTS: After a run-in OL-HDF period of at least 6 months with the same membrane, baseline pre-dialysis BPA was lower in patients on polynephron (8.79±7.97 ng/ml) than in those on polysulfone (23.42±20.38 ng/mL, p<0.01), but still higher than in healthy controls (<2 ng/mL). After 3 months of polynephron-to-polysulfone switch, BPA was unchanged (8.98±7.88 to 11.14±15.98 ng/mL, ns) while it decreased on the polysulfone-to-polynephron group (23.42±20.38 to 11.41±12.38 ng/mL, p<0.01). CONCLUSION: OL-HDF for 3 months with BPA-free dialyzer membranes was associated to a significant decrease in predialysis BPA levels when compared to baseline BPA levels while on a BPA-containing membrane.

Bisphenol A is an exogenous toxin that promotes mitochondrial injury and death in tubular cells.

BACKGROUND: Uremic toxins that accumulate in chronic kidney disease (CKD) contribute to CKD complications, such as CKD progression. Bisphenol A (BPA) is a ubiquitous environmental toxin, structurally related with p-cresol, that accumulates in CKD. Our aim was to characterize the nephrotoxic potential of BPA. Specifically, we addressed BPA toxicity over energy-demanding proximal tubular cells. METHODS: Cell death and oxidative stress were evaluated by flow cytometry and confocal microscopy in HK-2 human proximal tubular epithelial cells. Functional assays tested ATP, intracellular Ca2+ , mitochondrial function (tetramethylrhodamine methyl [TMRM]), oxygen consumption, Nrf2-binding, MitoSOX, and NADPH oxidase activity. Gene expression was assessed by qRT-PCR. RESULTS: Following acute exposure (24 hours), proximal tubular cell viability was decreased by BPA concentrations ≥50 µM while a seven-day exposure resulted in a progressive loss of cell viability at a nanomolar range. Within 24 hours, BPA promoted mitochondrial dysfunction leading to energy depletion and increased mitochondrial and cytoplasmic oxidative stress and apoptosis in a concentration-dependent manner. An antioxidant response was observed manifested by nuclear Nrf2 translocation and increased expression of the Nrf2 target genes Heme oxygenase 1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO-1). CONCLUSIONS: This study demonstrates for the first time that BPA causes mitochondrial injury, oxidative stress and apoptotic death in tubular cells. These results characterize BPA as an exogenous toxin that, similar to uremic toxins, may contribute to CKD progression.

Bisphenol (A) uremic toxin to take into account in the Renal disease in Hemodialysis / Bisfenol (A) una toxina a tener en cuenta en el enfermo renal en hemodiálisis

Abstract Introduction: Most uremic toxins are by-products of protein metabolism by action of intestinal flora. The metabolism of aromatic amino acids originates phenolic type residues. The most studied is p-cresol that is associated with renal function and vascular damage. Bisphenol A (BPA) is an exogenous molecule with characteristics similar to these aromatic uremic toxins. BPA is an estrogenic endocrine disruptor, found in tin cans, plastic bottles, epoxy resins and in some dialyzers. This molecule accumulates in patients who have impaired renal function. Observational studies have shown that exposure of BPA is linked to renal and cardiovascular injury, among many others in humans, and in animal studies a causal link has been described. Kidneys with normal renal function rapidly excrete BPA, but insufficient excretion in patients with CKD results in accumulation of BPA in the body.

Resumen Muchas toxinas urémicas son originadas como consecuencia del catabolismo proteico por la flora intestinal. El metabolismo de aminoácidos aromáticos origina residuos de tipo fenólico. De estas toxinas, la más estudiada es el p-cresol, que se asocia a la función renal y daño vascular. El Bisfenol A (BPA) es una molécula exógena de características semejantes a estas toxinas urémicas aromáticas. El BPA es un disruptor endocrino estrogénico que se encuentra en latas de conserva, botellas de plástico, resinas epoxi y en algunos dializadores. Esta molécula se acumula en pacientes que tienen deteriorada la función renal. Estudios observacionales han demostrado que una exposición a BPA está vinculada, entre otras muchas, a lesión renal y cardiovascular en los seres humanos; en estudios en animales se ha descrito un vínculo causal. Los riñones con función renal normal excretan rápidamente BPA, pero una excreción insuficiente en pacientes con ERC da lugar a la acumulación del BPA en el organismo.