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Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes. [ABSTRACT FROM AUTHOR]

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

[Display omitted] • Two-dimensional borocarbonitrides (BCN) nanosheets with B and N heteroatoms co-doping proved to be promising as adsorbents for blood purification. • The as-fabricated B-PES microspheres delivered considerable adsorption capacities on creatinine, uric acid and bilirubin. • In simulated perfusion, B-PES microspheres showed outstanding toxin removal efficiency experiments even at a high perfusion rate. • The used B-PES microspheres can be rapidly regenerated and recycled by fast-drying through photothermal effect. Adsorbents, which can be used to directly eliminate uremic toxins from blood, are decisive for hemoperfusion that maintains human renal function. However, developing adsorbents with large adsorption capacity, excellent chemical stability, high hemocompatibility and good cyclicity for toxins is still challenging. Herein, we proposed a type of two-dimensional (2D) carbon materials-borocarbonitrides (BCN) nanosheets as a novel uremic toxin adsorbent for blood perfusion. Theoretical analysis firstly confirmed the stronger binding capacity of BCN layer towards small molecular toxins than that of graphene. To make it applicable for practical perfusion, BCN nanosheets engineered sulfonated polyether sulfone (SPES) microspheres (B-PES) are thus constructed. Through static adsorption, the B-PES-4 achieves effective toxin adsorption capacities of 26, 40 and 197 mg g−1 on creatinine, uric acid and bilirubin respectively, which are 550%, 508% and 1756% outperforming pure SPES microspheres. In addition, simulated perfusion experiments demonstrate a good toxin removal efficiency for the microspheres, for example, over 80% of bilirubin is removed at a high perfusion rate of 20 mL min−1. Moreover, the B-PES microspheres neither induce hemolysis and immunoreaction in the blood nor affect cell viability. As a proof of concept, the photothermal property of BCN nanosheets is innovatively exploited for fast-drying and efficient recycling of the used B-PES microspheres. These features, together with the reusability, blood and cell compatibility, make the platform highly promising for clinical blood purification and artificial kidney application. [ABSTRACT FROM AUTHOR]

In hemofiltration (HF) and hemodiafiltration (HDF), removal of medium and high-molecular-weight solutes is greatly enhanced by convective mechanisms as compared with simple diffusion; increasing convective flows may allow greater removal rates of these solutes. Use of “predilution” (pre-H[D]F) may allow higher ultrafiltration rates than the “postdilution” mode (post-H[D]F); yet, the dilution of plasma water may have unpredictable effects on “endogenous” water convection. We have applied a mathematical analysis to evaluate and compare endogenous water convective flow rates in pre-H(D)F vs. post-H(D)F. Endogenous plasma water recovered in ultrafiltrate was calculated according to patient (hematocrit, total protein level) and session parameters (blood flow, ultrafiltration rate, programmed weight loss), in absolute terms and as a fraction of endogenous plasma water delivery to the filter. Maximally efficient post-H(D)F was modelled according to a preset postfilter hematocrit or filtration fraction. Nomograms were constructed expressing endogenous water convective fluxes in relation to parameters of interest (ultrafiltration rate, blood flow, hematocrit) with both post-H(D)F and pre-H(D)F, and “efficiency” of pre-H(D)F vs. post-H(D)F (as the ratio of endogenous water convective flow rate with the 2 techniques) as a function of the ultrafiltration/reinfusion rate. In post-H(D)F, the model predicts maximal ultrafiltration rates within the limits of a preset hemoconcentration at the filter outlet; additionally, the model allows to calculate ultrafiltration/reinfusion quantities to be set in pre-H(D)F to equal and overcome maximal convective efficiency of post-H(D)F. This “equivalence” ultrafiltration rate may greatly vary according to patient's hematocrit and blood flow, so that the ultrafiltrate-reinfusate volume available in the system dictates, in any patient, which mode of reinfusion may attain higher “endogenous” convective flow rates. Pre-H(D)F may allow higher fractional and absolute “endogenous” convective flow rates as compared with post-H(D)F, provided that adequate amounts of reinfusate are available. For lower reinfusate volumes than “equivalence” values, post-H(D)F remains a better option. [ABSTRACT FROM AUTHOR]

Uremic toxin removal based on diffusion and/or convection allows eliminating solutes with negative metabolic impact. Uremic solutes can be classified as small and water-soluble compounds, larger “middle” molecules, or protein bound solutes. The question arises whether more removal of each of these solute classes affects patient survival. Kt/V of urea is currently used as a surrogate for small water-soluble solute removal. There is ample evidence that Kt/V and survival are correlated, but the threshold Kt/V remains a matter of debate. Probably, the actually proposed threshold of 1.2 is too low. This impact of Kt/V is in contradiction with the low toxicity of urea and points to a role for other water-soluble solutes, e.g., potassium. More removal of middle molecules results in a lower morbidity and also in a lower mortality. In addition, a relationship has been demonstrated between the use of membranes with large pore size and a decrease of inflammatory status, by itself an important factor related to mortality. One of the problems is that large pore membranes are at the same time more biocompatible and reflect more dialysate impurities, compared to many small pore membranes, whereas they also reflect more dialysate impurities. It remains uncertain which one of these factors, if any, has a predominant effect. Recent studies point to a separate effect of pore size but await confirmation. Protein bound toxins inhibit several biochemical functions. Their removal pattern is totally different from that of classical markers such as urea. In analogy with drugs, it is essentially the free unbound fraction that exerts biological action; this free fraction is inversely related to serum albumin, another inflammatory marker related to survival. In a final section of this presentation, attention will be drawn to the relationship in uremic patients between inflammation, malnutrition, cardiovascular disease, and mortality, and some of the potential culprits are... [ABSTRACT FROM AUTHOR]

In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)