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.

In this retrospective study, patients with thrombophilia had a significantly higher risk of early transplant failure. These data point toward a potential contribution of thrombophilia to transplant loss, a hypothesis that needs further study.

A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.

Spectrofluorimetry, flow microcalorimetry, and differential scanning microcalorimetry (DSMC) were used to study the conformation, binding function, and ligand loading of uremic albumin obtained from the blood plasma of 2 end-stage renal disease (ESRD) patients before and after charcoal plasma treatment at different pH values (3.0-9.0). The spectrofluorimetric patterns of conformational N-F transition at low pH (4.2-3.5) are practically identical for both samples of uremic human serum albumin (HSA) and control HSA from healthy donors. After the charcoal treatment at pH 3.0 and 4.0, the enthalpies of complexing on uremic HSA with bromsulfalein and sodium dodecylsulfate approach that of donor HSA. The binding affinity of uremic HSA for sodium octanoate, phenol red, and salicylic acid following low pH charcoal treatment even exceed those of donor HSA. At the same time the charcoal treatment of uremic plasma at neutral and alkaline pH does not notably improve the binding characteristics of isolated HSA. Adsorption at low pH values completely restores the tryptophan fluorescence spectrum position of uremic albumin and improves the thermodynamic characteristics of its melting process. Using DSMC data, it can nevertheless be concluded that some conformational changes or a certain amount of high-affinity bound endogenous ligands still remain after low pH uremic HSA purification. The latter conclusion requires additional improvements of adsorption treatment of uremic plasma.

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