**6. Conclusion**

with sterile water at body temperature. Previous studies had already shown that different polysulfone membranes leach varying amounts of BPA [31–37]. Obviously, this is also true for polysulfone membranes from the same manufacturer, indicating variations in different polysulfone lots or different extraction processes during fiber spinning. Additionally, a different amount of BPA is eluted from low-flux polysulfone membranes compared with highflux polysulfone membranes. This difference, higher in HF membranes, may be attributed to a higher polymer content; usually less permeable low-flux membranes have a tighter wall structure compared with high-flux membranes. Since BPA is not a starting material of polyethersulfone membranes, the very small amounts of BPA eluted from this dialyzer most likely originate, in some cases, from the polycarbonate housing. Moreover, Krieter in his study also found that no differences in BPA levels were determined between the blood and dialysate compartments. This was because the unbound BPA can easily pass the dialysis membrane and equilibrate during recirculation. In vitro experiment suggests that dialyzers differing in elutable BPA used during chronic hemodialysis would have an impact on plasma BPA levels. Recently, Bosch-Panadero et al. [38] performed a cross-over study to evaluate the impact of the dialyzer choice (BPA-free versus BPA-containing) on serum and intracellular BPA levels and on inflammation and oxidative stress markers in a group of 69 prevalent patients on hemodialysis. The main finding of this study was that the choice of dialyzer in terms of BPA content impacts on acute (after a single dialysis session) and chronic (after 3 months of continuous use of the same type of dialyzer) changes in serum BPA levels. This reinforces the hypothesis of Krieter et al. that dialyzer BPA content may contribute to BPA burden in patients on hemodialysis. The expression of oxidative stress markers was significantly higher after 3 months of hemodialysis with BPA-containing membranes with respect to BPA-free dialyzers. Three months of hemodialysis with BPA-containing membranes increased significantly circulating C-reactive protein (CRP) and IL-6 with respect to BPA-free dialyzers. These patients are more sensitive to BPA accumulation and potential toxicity due to the loss of the physiologic BPA excretion mechanisms in urine. In this same work, authors indicated that the serum BPA levels were 35-fold higher in patients on hemodialysis than in healthy controls confirming that serum BPA levels increased with decreasing renal function and are highest in individuals on hemodialysis. A particular group of hemodialysis patients are those with diabetes. Recently, in a cross-over study, values of serum BPA have been measured in a group of 47 patients in which 12 had

diabetes [39]. All patients were treated with low-flux polysulfone dialyzers.

small number of subject investigated.

84 Bisphenol A Exposure and Health Risks

those without diabetes. This difference disappeared for postdialysis measurement.

In this study, postdialysis serum levels of BPA were significantly higher than predialysis levels. Additionally, diabetic patients showed higher predialytic BPA levels compared with

Unfortunately, no association was found between serum BPA levels and age, body mass index, dialytic vintage, blood pressure, and other medical parameters, probably due to the

Up to now, we analyzed the dialyzer contribution to BPA in the blood of hemodialyzed patients, but recently, Bacle et al. [40] evaluated the potential exposure to BPA via the entire process of BPA is an estrogenic endocrine disruptor molecule with phenolic structure, used in the synthesis of polycarbonate plastics and epoxy resins. Exposition in the human population occurs mainly through the diet, in particular from food and beverages.

BPA could migrate into food from food and beverage containers with internal epoxy resin coatings and from products made of polycarbonate plastic such as tableware, food containers, and water bottles. BPA exposure results from either the release of unpolymerized monomers or the slow decay of polymer bonds in polycarbonate, leading to monomer release into foods and liquids. Starting from this information, data analysis coming from several large studies in various countries shows that the majority of the population examined have detectable levels of BPA conjugates in the urine. Indeed, in view of the rapid conjugation and elimination half-time of BPA, these levels reflect the exposure of the past hours just before the sample collection.

On the contrary, in patients with limited or absent kidney function, BPA may accumulate in the serum. The BPA accumulation in these subjects accounts from diet and medical device containing BPA, that is, extracted from the device by hydrophobic components present in the blood. Repeated loading of BPA during hemodialysis with BPA-containing membranes may aggravate the problem due to migration of BPA from dialyzers to the blood of patients and its inefficient removal due to the high protein-bound fraction of plasma BPA.

Some recent studies on the chronic use of BPA-free dialyzers indicate decrease of BPA serum levels in dialyzed patients reflecting a potential beneficial effect on inflammation and oxidative stress.

Furthermore, additional BPA contamination sources come from water and medical devices used to produce the dialysate fluid involved in hemodialysis treatment.

It is also advised that attention should be taken to avoid BPA cross contamination during medical devices production, with particular consideration to hemodialyzers. The possibility to replace BPA in these products should be assessed as well as the toxicological profile of the alternative materials. This issue could be a criterion for the purchase of medical devices commonly used in hemodialysis.

In conclusion, patients on hemodialysis have higher levels of serum and intracellular BPA with respect to healthy controls and the choice of dialysis membrane impacts on these levels. Dialyzers with BPA-containing membranes increase serum BPA levels. Studies indicate an increase of BPA serum concentration after a single dialysis session, confirming that hemodialysis does not compensate lack of urine BPA excretion.

Use of BPA-containing dialysis membranes further adds to the BPA burden of patients on hemodialysis. In contrast, it would be advisable the chronic use of BPA-free dialyzers to decrease BPA serum levels and related clinical effects.
