Personalized Management of Sodium and Volume Imbalance in Hemodialysis to Mitigate High Costs of Hospitalization.

The primary objective of hemodialysis (HD) is lowering concentrations of organic uremic toxins that accumulate in blood in end-stage kidney disease (ESKD) and redress imbalances of inorganic compounds in particular sodium and water. Removal by ultrafiltration of excess fluid that has accumulated during the dialysis-free interval is a vital aspect of each HD session. Most HD patients are volume overloaded, with ∼25% of patients having severe (>2.5 L) fluid overload (FO). The potentially serious complications of FO contribute to the high cardiovascular morbidity and mortality observed in the HD population. Weekly cycles imposed by the schedule of HD treatments create a deleterious and unphysiological "tide phenomenon" marked by sodium-volume overload (loading) and depletion (unloading). Fluid overload-related hospitalizations are frequent and costly, with average cost estimates of $ 6,372 per episode, amounting to some $ 266 million total costs over a 2-year period in a US dialysis population. Various strategies (e.g., dry weight management or use of fluids with different sodium concentrations) have been attempted to rectify FO in HD patients but have met with limited success largely due to imprecise and cumbersome, or costly, approaches. In recent years, conductivity-based technologies have been refined to actively restore sodium and fluid imbalance and maintain the predialysis plasma sodium set point (plasma tonicity) of each patient. By automatically controlling the dialysate-plasma sodium gradient based on the specific patient needs throughout a session, an individualized sodium dialysate prescription can be delivered. Maintaining precise sodium mass balance helps better control of blood pressure, reduces FO, and thus tends to prevent hospitalization for congestive heart failure. We present the case for personalized salt and fluid management via a machine-integrated sodium management tool. Results from proof-of-principle clinical trials indicate that the tool enables individualized sodium-fluid volume control during each HD session. Its application in routine clinical practice has the potential to mitigate the substantial economic burden of hospitalizations attributed to volume overload complications in HD. Additionally, such a tool would contribute toward reduced symptomology and dialysis-induced multiorgan damage in HD patients and to improving their treatment perception and quality of life which matters most to patients.

Membrane requirements for high-flux and convective therapies.

Worldwide, high-flux dialysis (HF-HD) has now surpassed low-flux dialysis (LF-HD) as the predominant treatment modality, recognition that removal of larger uremic retention solutes is desirable for the treatment of patients with end-stage chronic kidney disease (CKD). An even more advanced form of HF-HD in terms of removal of a broad spectrum of uremic toxins is on-line hemodiafiltration (HDF), involving convective transport mechanisms for solute removal. With the modality reaching considerable technical maturity over the last two decades, on-line HDF is now recognized for its clinical efficiency and effectiveness, versatility and safety. Such has been the success of on-line HDF that, in Europe, more patients are treated with on-line HDF than even peritoneal dialysis. Fabrication of high-flux membranes for convective therapies is more than a matter of simply making the membrane 'more open' or of increasing the membrane pore size which is not the only determinant for achieving higher convection. While convective transport of larger uremic retention solutes primarily demands membranes with high hydraulic permeability and sieving capabilities, the making of a modern dialysis membrane involves several other considerations that culminate in the delivery of an effective and safe therapy. In this communication I outline the essential membrane requirements and principles for solute removal by convection, as well of meeting additional features related to the therapy. The basic principles of the membrane manufacturing processes by which desired membrane morphology is derived for the separation phenomena involved in dialysis are further described. An awareness of this enables one to appreciate that, depending on the individual constituents and variations of the manufacturing processes, fabrication of all high-flux membranes entails achieving a balance between the ideal or desired criteria for blood purification. Dialysis membranes for convective therapies, even from the same base polymer, exhibit significant differences in their morphology and thus in their ability to facilitate convection.

Hemodialyzer: from macro-design to membrane nanostructure; the case of the FX-class of hemodialyzers.

Very few innovations have characterized the different components of the hemodialyzers in the past 20 years. Most improvements have concerned membrane biocompatibility. In this article, we focus our attention on the most recent advances in hemodialyzer components from the macro design of the unit to the nanostructure of the membrane. For this purpose, we took as an example the FX class of hemodialyzers (FMC, Bad Homburg, Germany). The studied devices were chosen as an example representing some of the most recent hemodialyzers and are well suited to describe technical innovations occurring in the field of dialyzer technology. In vitro and in vivo studies were performed to characterize hemodynamic parameters of three models (1.4-1, 8, and 2.2 m2) and to determine membrane permeability, sieving coefficients, and solute clearances. The units were characterized by a relatively high resistance of the blood and dialysate compartments, leading to an increased internal filtration if compared with similar hemodialyzers of other series. Nevertheless, the flow distribution in both compartments was homogeneous and well balanced. This effect was obtained by the improved blood and dialysate ports design, the increased packing density of the fibers and a reduction of the inner diameter of the fibers from 200 to 180 microm. At the same time, the sieving coefficients for middle-large solutes such as beta2 microglobulin and insulin were higher than those observed in standard high flux dialysers. The same effect was noted for the clearance values of these solutes. This was observed in the absence of significant albumin leakage. These results were obtained thanks to a new nano-controlled spinning technology applied to the fiber. The innermost layer of the membrane is in fact characterized by a homogeneous porosity, with increased number of pores of large dimension but a sharp cutoff of the membrane excluding albumin losses. In conclusion, new technologies and new diagnostic tools today allow for improvement in hemodialyzer design from its macro-components to its nano-structure. The application of nanotechnology to hemodialysis will probably contribute to further developments in hemodialyzer manufacturing.