Bisphenol A in Chronic Kidney Disease

Abstract

The estrogenic endocrine-disrupting substance bisphenol A (BPA) is extensively used as a starting material for a variety of consumer plastic products including dialyzer materials. The present study was performed to explore plasma BPA levels in patients with impaired renal function and to investigate if dialyzers differing in elutable BPA influence plasma levels in patients on maintenance hemodialysis. In vitro BPA was eluted from high-flux polyethersulfone (PUREMA H, referred as PUR-H), high-flux polysulfone (referred as HF-PSu), and low-flux polysulfone (referred as LF-PSu) dialyzers by recirculation with water for 180 min. In a cross-sectional clinical study, plasma BPA levels of outpatients with different stages of chronic kidney disease (CKD) from four different centers were determined. Furthermore, in a prospective, randomized, and crossover setting, 18 maintenance dialysis patients were subjected successively to 4 weeks of thrice-weekly hemodialysis with each LF-PSu, HF-PSu, and PUR-H. In addition, the fractions of protein-bound and free BPA were determined in a subset of dialysis patients. The mass of BPA eluted from the blood compartments in vitro under aqueous conditions varied for the three dialyzers being very low for PUR-H (6.2 ± 2.5 ng; P < 0.001), intermediate for HF-PSu (48.1 ± 7.7 ng), and highest for LF-PSu (140.8 ± 38.7 ng; P < 0.01). In 152 prevalent patients with CKD enrolled in the cross-sectional trial, plasma BPA started to rise after stage 3. Maintenance hemodialysis patients had more than six times higher BPA concentrations than patients with CKD stage 5 not yet on dialysis (10.0 ± 6.6 vs. 1.6 ± 1.8 ng/mL; P < 0.001). The BPA concentrations highly and inversely correlated with renal function. In the randomized controlled study, the plasma BPA concentrations were highly elevated compared with healthy controls (range 9.1 ± 4.5-12.0 ± 6.0 ng/mL vs. ≤0.2 ± 0.1 ng/mL; P < 0.001), but no change of the plasma levels was observed during hemodialysis with any of the three dialyzers in the course of a single treatment and over a period of 4 weeks. The protein-bound fraction of plasma BPA in the dialysis patients was 74 ± 5%. Renal function and, most likely, the total quantity of ingested BPA are essential parameters affecting plasma BPA concentrations. Dialyzers are one additional source of BPA, but differences in the elutable BPA content are not associated with a significant effect on BPA plasma levels in Western European maintenance dialysis patients. Due to high protein binding, the removal of BPA by hemodialysis is limited.

The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood

“…17 We have found high serum BPA levels in patients on hemodialysis compared with patients with normal renal function, which is consistent with prior observations that serum BPA rises when the GFR falls below 60 ml/min. 21 In this regard, our data support the concept that patients on hemodialysis represent a high-risk population for BPA overload, which may require special regulatory status with regards to BPA-containing medical devices. BPA may migrate from dialyzers to the blood of patients on hemodialysis.…”

Bisphenol A in Chronic Kidney Disease

“…Krieter et al [33] also reported release of BPA from three diferent high and low lux dialyzers with diferent surface area (from 1.3 to 1.7 m 2 ) and with polycarbonate housing. BPAfree sterile water was circulated through the blood and dialysate compartments at 37°C, and BPA was measured by ELISA method.…”

“…By contrast, increased serum BPA with decreasing renal function and higher levels in hemodialysis was observed in diferent studies, suggesting that BPA may accumulate in CKD [31][32][33].…”

“…Additionally, the fractions of protein-bound and free plasma BPA in the maintenance of dialysis patients are 74 ± 5 and 26 ± 5%, respectively [33]. Moreover, a tissue/blood partition coeicient of 1.4 for nonadipose tissues and 3.3 for fat tissues further compromises the dialyzability of BPA [36], implying a concentration gradient highly in favor of driving BPA from dialysate to patient's blood.…”

“…However, Krieter et al [33] showed that considerable amounts of BPA were eluted from dialyzers with polysulfone membranes in 180 min of simulating (in vitro) dialysis conditions with sterile water at body temperature. Previous studies had already shown that diferent polysulfone membranes leach varying amounts of BPA [31][32][33][34][35][36][37]. Obviously, this is also true for polysulfone membranes from the same manufacturer, indicating variations in diferent polysulfone lots or diferent extraction processes during iber spinning.…”