Endocrine disrupting chemicals (EDCs) were defined as "an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects". These compounds are mainly eliminated by the renal route. However, patients with end-stage kidney disease treated by dialysis (ESKDD) can no longer eliminate these EDCs efficiently. Furthermore, EDCs exposure could occur via leaching from medical devices used in dialysis therapy. As a result, ESKDD patients are overexposed to EDCs. The aims of this study were to summarize EDCs exposure of ESKDD patients and to evaluate the factors at the origin of this exposure. To handle these objectives, we performed a literature review. An electronic search on PubMed, Embase and Web of science databases was performed. Twenty-six studies were finally included. The EDCs reported in these studies were Bisphenol A (BPA), Bisphenol S (BPS), Bisphenol B (BPB), Nonylphenol, Di(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP), and Butylbenzyl phthalate (BBP). Regarding the environment of dialysis patients, BPA, BPB, BPS, DEHP, DBP and nonylphenol have been found. Environmental exposure affects EDCs blood levels in ESKDD patients who are overexposed to BPA, BPS, BPB and DEHP. For ESKDD patients, dialyzers with housing in polycarbonate and fibers in polysulfone seem to overexpose them to BPA. Regarding dialysis therapy, peritoneal dialysis seems to decrease patient exposure vs hemodialysis therapy, and hemodiafiltration therapy seems to reduce this exposure vs hemodialysis therapy. Regarding DEHP, levels tend to increase during dialysis and when DEHP plasticizer is used in PVC devices. Finally, in the European Union a regulation on medical devices was adopted on 5 April 2017 and has been applied recently. This regulation will regulate EDCs in medical devices and thereby contribute to reconsideration of their conceptions and, finally, to reduction of ESKDD patients' exposure.

The health safety conditions governing the practice of online hemodiafiltration (OL-HDF) do not yet incorporate the risks related to the presence of endocrine disruptors such as bisphenol A (BPA). The aim of this study was to assess, for the first time, the exposure to BPA but also to its chlorinated derivatives (ClxBPA) (100 times more estrogenic than BPA) during OL-HDF. We demonstrated that BPA is transmitted by the different medical devices used in OL-HDF: ultrafilters, dialysis concentrate cartridges (and not only dialyzers, as previously described). Moreover, BPA has been found in dialysis water as well as in ultrapure dialysate and replacement fluid due to contamination of water coming from municipal network. Indeed, due to contaminations provided by both ultrafilters and water, high levels of BPA were determined in the infused replacement fluid (1033 ng.L⁻¹) from the beginning of the session. Thus, our results demonstrate that dialysis water must be considered as an important exposure source to endocrine disruptors, especially since other micropollutants such as ClxBPA have also been detected in dialysis fluids. While assessment of the impact of this exposure remains to be done, these new findings should be taken into account to assess exposure risks in end-stage renal disease patients.

The use of medium cut-off (MCO) polyarylethersulfone and polyvinylpyrrolidone blend membrane is an emerging mode in hemodialysis. Recent studies have shown that MCO membranes exhibit a middle high molecular weight uremic toxin clearance superior to standard high flux hemodialysis. We conducted a systematic literature review and meta-analysis of randomized controlled trials to investigate whether MCO membranes efficiently increase the reduction ratio of middle molecules, and to explore the potential clinical applications of MCO membranes. We selected articles that compared beta 2-microglobulin (β2M), kappa free light chain (κFLC), lambda free light chain (λFLC), interleukin-6 (IL-6), and albumin levels among patients undergoing hemodialysis. Five randomized studies with 328 patients were included. The meta-analysis demonstrated a significantly higher reduction ratio of serum β2M (p < 0.0001), κFLC (p < 0.0001), and λFLC (p = 0.02) in the MCO group. No significant difference was found in serum IL-6 levels after hemodialysis. Albumin loss was observed in the MCO group (p = 0.04). In conclusion, this meta-analysis study demonstrated the MCO membranes’ superior ability to clear β2M, κFLC, and λFLC. Serum albumin loss is an issue and should be monitored. Further studies are expected to identify whether MCO membranes could significantly improve clinical outcomes and overall survival.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Haemodialysis (HD) with medium cut-off (MCO) dialyzer allows efficient depuration of middleweight uraemic toxins, with albumin loss similar to that observed with post-dilution online haemodiafiltration (HDF) [ 1, 2]. We recently conducted a randomized, open-label, crossover study [ 3] that included 40 patients assigned to receive either 3 months of MCO-HD followed by 3 months of high-flux HD (HF-HD) or vice versa. After 3 months of MCO-HD, we observed a significant decrease in serum levels of albumin, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1-25(OH)₂D]. Both 25(OH)D and 1-25(OH)₂D circulate bound at 85–90% to vitamin D–binding protein (VDBP) and at 10% to albumin. VDBP, a 52-kDa glycoprotein synthetized predominantly by the liver, has many important functions, including not only transport of vitamin D metabolites, but also control of bone metabolism, binding of fatty acids and modulation of inflammatory response [ 4]. Alpha-1 acid glycoprotein (AGP), another 41-kDa glycoprotein synthesized by the liver, is a major member of the positive acute-phase protein family with immunomodulatory properties and an important role in the binding of drugs and steroid hormones [ 5].