Micro-computed tomography for the quantification of blocked fibers in hemodialyzers

A novel technique based on micro-CT scanning is developed to quantify coagulation in fibers of hemodialyzers. This objectivation is needed to allow accurate assessment of thrombogenicity of dialyzers used during hemodialysis, for example when comparing different strategies to avoid coagulation and/or fiber blocking. The protocol allowed imaging at a resolution of 25 mu m, making it possible to count the open, non-coagulated fibers in a non-invasive way. In 3 fresh, non-used FX600 hemodialyzers, patent fiber counts were extremely consistent (10748 +/- 2). To illustrate the potential of this technique, different dialysis parameters currently used as surrogates for fiber blocking were evaluated during 20 hemodialysis sessions. After dialysis, the FX600 dialyzers were visually scored for clotting, dried and subsequently weighed and scanned. The number of patent fibers (10003 [ 8763,10330], range 534-10692) did not correlate with any of the recorded surrogate parameters. Micro-CT scanning is a feasible, objective, non-invasive, accurate and reproducible tool for quantification of the degree of fiber blocking in a hemodialyzer after use, making it a potential gold standard for use in studies on fiber blocking during renal replacement therapies

Silver-based Microbial Check Valve for Spacecraft Potable Water Systems

As human space exploration increases, the development of a more efficient potable water treatment system suited for spacecraft becomes crucial. This Waste-management Education Research Consortium (WERC) challenge was designed to explore the viability of microbial control through the utilization of silver ions as a biocide for possible integration into the Tranquility Node 3 water purification system aboard the International Space Station (ISS). Current systems using iodine risk causing hyperthyroidism from overexposure; however, silver can be safely ingested without this side effect. After researching silver delivery methods including electrochemical ion production, controlled release, or a combination of the two, our team decided to design a controlled release system capable of meeting the constraints listed in the problem statement. By using a membrane similar to those within dialysis devices a system was designed to deliver silver ions to a stream of water that requires arguably no power and is exceptionally lightweight. While the silver delivery system fulfilled the constraints of the WERC problem statement, our team also examined the use of resins like those contained in the current Microbial Check Valve (MCV). Resin substitutes capable of selective silver sorption are recommended as replacements for those within the current MCV to prevent backwards microbial diffusion through the system. Multiple designs will be presented in this paper. First, our membrane-controlled release silver delivery system (SDS) is presented to specifically address the WERC Task 1 deliverables. Second, a proposed upgrade to the ISS water system is described that replaces the ion exchange resin beds with silver-selective media prevent microbial contamination of water in the potable water system of the spacecraft. Given the extreme lightweight nature of the SDS, nil power requirement, and minor modification to the existing system, Hogs In Space has delivered a highly effective method to deliver and control silver based on the WERC Task 1 requirements

Where and when to inject low molecular weight heparin in hemodiafiltration? : a cross over randomised trial

Background and Objective : Low molecular weight heparins (LMWHs) are small enough to pass large pore dialysis membranes. Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration. The aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration. Study Design, Setting, Patients : In 13 chronic hemodiafiltration patients, 3 approaches of injection were compared in a randomised cross over trial: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0), ii) 5 min after the start at the inlet line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa activity, thrombin generation, visual clotting score and reduction ratios of urea and beta2microglobulin were measured. Results : Anti-Xa activity was lower with IN0 compared with IN5 and OUT0, and also more thrombin generation was observed with IN0. No differences were observed in visual clotting scores and no clinically relevant differences were observed in solute reduction ratio. An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation. Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin. Conclusions : Injection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended. Additionally, we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy

Design and modeling of a portable hemodialysis system

Research to improve artificial renal replacement therapies is varied across the many different parts of a hemodialysis system. Work largely focuses on developing a better dialyzer - the component that is directly responsible for removing wastes from the blood - but less study is devoted to the entire hemodialysis system. This work seeks to improve hemodialysis in two ways: by proposing a new renal replacement therapy that does not rely on traditional hemodialysis components, and by investigating the feasibility of adapting current hemodialysis practices to a portable format. While an alternative renal replacement therapy may be the best solution to today's dialysis problems, this work further focuses on reducing hemodialysis to a portable format through systematic engineering design. In that process, a detailed system model is made in Simulink that can account for the large number of inputs of such a system - the blood flow rate, dialyzer size, treatment time, etc. - allowing for detailed exploration of the design space. Once the model is completed, it is verified through in vitro experiments carried out with porcine blood. Additionally, the model is verified against published human hemodialysis data. After model verification, hemodialysis concepts are generated that allow for maximum portability under different patient conditions.M.S.Committee Chair: Rosen, David; Committee Member: Ku, David; Committee Member: Paredis, Chri

Estimation of dialysis treatment efficiency by means of system identification

When treating patients suffering from renal failure with hemodialysis, an obvious point of interest is the actual blood cleaning efficiency of the dialyzer (artificial kidney). This efficiency is called clearance or dialysance. The method currently used for estimating clearance is based on doing a step-change on the process. Due to the nature of the process, this method is slow and has a relatively large output spread. This master thesis investigates a new method of finding clearance by means of system identification. The dialyzer is modelled as a discrete-time system, and perturbed by use of a pseudo-binary random sequence. The input/output-data is then fed into an optimal Kalman filter for parameter estimation. The gain and offset of the identified system is directly related to the dialyzer clearance of the treatment. The method shows promising results, usually converging to good parameters within 15 minutes, and then tracking changes continuously for the rest of the treatment. It also provides better accuracy, with a considerable reduction in spread compared to the old method. Main obstacles stem from variable time-delays in the system and measurement offsets

Radionuclide method for evaluating the performance of hemodialysis in vivo

Radionuclide method for evaluating the performance of hemodialysis in vivo.BackgroundSpecifications of dialyzer performance are generally based on in vitro measurements. There is, however, a shortage of data on dialyzer performance in vivo. The aim of this study was to use continuous measurement of technetium-99m-diethyltriaminepentaacetic acid (Tc-99m-DTPA) blood concentration as a means of continuously monitoring dialyzer function in vivo in patients undergoing routine hemodialysis.MethodsThe study population comprised 15 patients (45 to 80 years old; 13 males). Tc-99m-DTPA was administered intravenously 90 minutes before obtaining a blood sample and starting dialysis. Blood Tc-99m-DTPA activity was continuously monitored by passing the line carrying blood from the patient to the dialyzer close to a scintillation probe mounted in a shielded housing. At the end of hemodialysis, lasting 180 to 300 minutes, chromium-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) was given intravenously and a blood sample taken 90 minutes later. Baseline dialyzer blood flow (Qb) and dialysate flow (Qd) were 250 to 350mL/min and 500mL/min, respectively. The rate constant, α, of the decrease in blood Tc-99m-DTPA activity was used as the measure of moment-to-moment dialyzer function. Pre- and postdialysis extracellular fluid volumes were calculated from the blood Tc-99m-DTPA and Cr-51-EDTA concentrations (VDTPA and VEDTA) before and after dialysis. Tc-99m-DTPA clearance was measured as the product of α and VDTPA. Dialyzer urea clearance was calculated from pre- and postdialysis urea nitrogen concentrations and the time of dialysis. The effects of brief changes in Qb and Qd on dialyzer function were assessed from the associated changes in α.ResultsThe Tc-99m-DTPA clearance profile was biexponential, becoming monoexponential about 1 hour after starting hemodialysis, with α remaining constant for as long as dialysis continued in five patients in whom Qb and Qd were left unaltered. Mean (SEM) plasma Tc-99m-DTPA clearance averaged over the entire period of dialysis in all 15 patients was 110 (3.1)mL/min. It correlated with urea clearance (r = 0.71) (P < 0.01) which was 225 (9.5)mL/min based on a total body water of 2.5 that of VDTPA and 212 (13)mL/min scaled to 40 L/1.73m2. Extracellular fluid volume decreased by 1.73 (0.74) l over dialysis, which was comparable to the change in weight [1.48 (0.57) kg]. The extraction fraction of Tc-99m-DTPA across the artificial kidney, directly measured from afferent and efferent blood samples under baseline Qb and Qd, was 0.5 (0.013). Average extraction fraction indirectly estimated from Tc-99m-DTPA blood clearance and Qb was 0.54 (0.019). These two measurements of extraction fraction correlated with each other under conditions of varying Qb and Qd (r = 0.74) (N = 27) (P < 0.001). Changes in α resulting from changes in Qb and Qd were similar to changes predicted from computerized modeling. The ratio of mass transfer coefficients of urea and Tc-99m-DTPA with respect to the dialyzer, calculated as if they were permeability-surface area products, was 3.3, similar to the ratio, obtained from the literature, in continuous capillary endothelium.ConclusionTc-99m-DTPA is a useful agent for continuously monitoring dialyzer function in vivo and provides a platform for the use of other radio-pharmaceuticals of different molecular sizes that could be used in an analogous fashion

Mathematical modeling of mass transfer in a hollow fiber dialyzer

A mathematical model describing the flow characteristics and mass transfer has been developed for the hollow fiber dialyzer in countercurrent dialysis. The theoretical expressions are developed from a typical Graetz problem for the stream side, and a first order differential equation for the dialyzate side. The solution of the dimensionless concentration profile is obtained as a summation of orthogonal eigenfunctions in closed form, which are given as product of an exponential function and a confluent hypergeometric function. The analytical solution of the model has been examined by adjusting system parameters, like Sherwood number, Peclet number and the geometry of the system. As expected, at higher Peclet number the bulk concentration in the stream outlet decreases, where as at higher Sherwood number and higher L/R ratio the bulk concentration increases. This can be used to optimize dialyzer performance

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates

Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate flow rates. The dialyzer mass transfer-area coefficient (KoA) for urea is an important determinant of urea removal during hemodialysis and is considered to be constant for a given dialyzer. We determined urea clearance for 22 different models of commercial hollow fiber dialyzers (N = ~5/model, total N = 107) in vitro at 37°C for three countercurrent blood (Qb) and dialysate (Qd) flow rate combinations. A standard bicarbonate dialysis solution was used in both the blood and dialysate flow pathways, and clearances were calculated from urea concentrations in the input and output flows on both the blood and dialysate sides. Urea KoA values, calculated from the mean of the blood and dialysate side clearances, varied between 520 and 1230ml/min depending on the dialyzer model, but the effect of blood and dialysate flow rate on urea KoA was similar for each. Urea KoA did not change (690 ± 160 vs. 680 ± 140 ml/min, P = NS) when Qb increased from 306 ± 7 to 459 ± 10ml/min at a nominal Qd of 500ml/min. When Qd increased from 504 ± 6 to 819 ± 8ml/min at a nominal Qb of 450ml/min, however, urea KoA increased (P < 0.001) by 14 ± 7% (range 3 to 33%, depending on the dialyzer model) to 780 ± 150ml/min. These data demonstrate that increasing nominal Qd from 500 to 800ml/min alters the mass transfer characteristics of hollow fiber hemodialyzers and results in a larger increase in urea clearance than predicted assuming a constant KoA

Preliminary Development of The Dialysis-Membrane-based Passive Biocide Delivery System for Spacecraft Water Recovery Units

The purpose of this investigation is to explore the capabilities of a dialysis-membrane-based system for the in-line dosing of silver ions to treated water in spacecraft water recovery units. The spacecraft environmental control and life support system community (ECLSS) are interested in adopting silver ions as a biocide in future spacecraft water recovery processes since silver ions are effective biocide at concentrations that humans can safely consume. The system has been designed following the configuration of the Water Processor Assembly (WPA) aboard the International Space Station. In this configuration, silver ions have to be added at the last step in the WPA to inhibit the growth of microorganisms in the product water. The dialysis-membrane-based system has to supply silver ions into the potable water at concentrations ranging from 200 to 400 parts per billion during the entire water processing time. The silver ion delivery system has been prototyped by repurposing dialysis membranes used for the separation/purification of low molecular weight solutes. Consequently, the low molecular weight cutoff of the dialysis membrane controls the silver ion release from a concentrated silver ion reservoir and does not require any power. Both computational and experimental studies were conducted to examine the performance of the silver ion delivery and the feasibility of integrating this technology in future spacecraft water recovery units. The preliminary results from this investigation show that the dialysis-membrane-based passive biocide delivery system can supply sufficient silver ions to a stream of deionized water. Nevertheless, the outflow might require dilution, and the membrane may need to undergo preconditioning for optimal performance, especially for reuse