An analytical solution to solute transport in continuous arterio-venous hemodiafiltration (CAVHD) (original) (raw)
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Hemodiafiltration: Technical and Medical Insights
Bioengineering
Despite the significant medical and technical improvements in the field of dialytic renal replacement modalities, morbidity and mortality are excessively high among patients with end-stage kidney disease, and most interventional studies yielded disappointing results. Hemodiafiltration, a dialysis method that was implemented in clinics many years ago and that combines the two main principles of hemodialysis and hemofiltration—diffusion and convection—has had a positive impact on mortality rates, especially when delivered in a high-volume mode as a surrogate for a high convective dose. The achievement of high substitution volumes during dialysis treatments does not only depend on patient characteristics but also on the dialyzer (membrane) and the adequately equipped hemodiafiltration machine. The present review article summarizes the technical aspects of online hemodiafiltration and discusses present and ongoing clinical studies with regards to hard clinical and patient-reported outco...
American Journal of Kidney Diseases, 1999
Clearances of several solutes (urea, creatinine, phosphate, urates,  2 -microglobulin [ 2 -M]) were measured during venovenous continuous renal replacement therapy (CRRT) at various ultrafiltration (Q UF ; 0 to 2 L/h) and dialysate flow rates (Q D ; 0 to 2.5 L/h). Preset Multiflow-60 and Multiflow-100 hollow-fiber dialysers (M-60 and M-100; Hospal-Gambro, St-Leonard, Canada) were compared (five patients for each type). First, we evaluated the impact of predilution on convective clearances: a progressive decrease in patient clearances, similar for both filters, was observed, reaching a maximum of 15%, 18%, and 19% for urea, urates, and creatinine, respectively, with predilution at a Q UF of 2 L/h. Second, we compared convective and diffusive clearances. Because effluent to plasma ratio (E/P) remained at 1 for small solutes (urea, creatinine, phosphate, urates) during convection, clearances were equal to the effluent rate for both dialyzers. However, we observed greater diffusive clearances for small molecules with M-100 than with M-60 at a Q D of 1.5 to 2.5 L/h, the difference being more significant as molecular weight increased. For  2 -M, diffusive clearance was very low and rapidly reached a plateau of 8 and 12 mL/min for M-60 and M-100, respectively, at a Q D greater than 1.5 L/h. Convective clearances for  2 -M increased nonlinearly up to 20 ؎ 2 mL/min at a progressively greater Q UF (from 0.5 to 2 L/h) for both M-60 and M-100. This nonlinear increase was attributed to an increase of almost 40% in E/P for  2 -M from a Q UF of 0.5 to 2 L/h. Third, the interaction between convection and diffusion was assessed by measuring solute clearances at a fixed Q UF (1 and 2 L/h) and variable Q D (0.5 to 2.5 L/h). For small molecules, no significant interaction between convection and diffusion was noticed with M-100, whereas only a small interaction was noticed with M-60. However, for  2 -M, the addition of diffusion (Q D , 0.5 to 2.
Finite Element Analysis of Fluid and Solute Transport in Hemodiafiltration Membranes
Fluid and solute transport in hemodiafilter hollow fibers occurs through a non-trivial interaction of convection and diffusion, modulated by a number of factors that include the non-Newtonian behavior of blood, the density and viscosity dependence of blood on the local hematocrit and protein concentration, the Fahraeus-Lindquist effect on hematocrit, the osmotic effects of protein and partially reflected solutes, and the development of non-constant concentration polarization in the boundary layer along the membrane. Previous models of this process have included lumped-compartment models, models with numerous axially distributed lumped compartments, and one-dimensional axially-dependent models based on ordinary differential equations. Although the latter have provided much insight into the dynamics within and around the hollow fibers, they rely on a number of simplifying assumptions and employ approximations for boundary effects. A higher dimensional multiphysics model of partial differential equations could more completely model the physics involved in hemodiafiltration, greatly reducing the need for simplifying assumptions and potentially generating more accurate results. A two-dimensional axisymmetric FEMLAB model was developed that included the hollow fiber, its interior blood path and exterior dialysis fluid path 10 cm in length. The membrane itself was modeled as an isotropic porous material of 50 µM in thickness having a hydraulic and diffusive permeability equal to that of the Rhône-Polenc AN69 membrane using the Brinkman and convectiondiffusion application modes that included effects of osmotic pressure for protein and solutes on fluid flux. We recently validated the performance of this membrane component of the model against theoretical and experimental data (submitted for publication). The blood path included non-Newtonian blood flow (Carreau model) corrected for local hematocrit and protein concentration, including the Fahraeus-Lindquist effect. The dialysis path was modeled using the Navier-Stokes equations. Separate convection-diffusion modes were used for protein and a small diffusible solute, with inclusion of the effect for a non-unity Staverman reflection coefficient on membrane transport. The model was solved on a quadrilateral mesh using the nonlinear solver. The model can be used to simulate the dynamics of blood flow, fluid flux and solute flux in a hollow fiber under variable conditions during hemodialysis and hemofiltration. The model has to date been validated for hemofiltration fluid flux against experimental data, and is currently being validated for solute flux against experimental data during hemofiltration and hemodialysis.
Crit Care, 2006
Introduction The best modality, for continuous renal replacement therapy (CRRT) is currently uncertain and it is poorly understood how transport of different solutes, whether convective or diffusive, changes over time. Methods We conducted a prospective cross over study in a cohort of critically ill patients, comparing small (urea and creatinine) and middle (β 2 microglobulin) molecular weight solute clearance, filter lifespan and membrane performance over a period of 72 hours, during 15 continuous veno-venous dialysis (CVVHD) and 15 continuous veno-venous hemofiltration (CVVH)sessions. Both modalities were administered based on a prescription of 35 ml/kg/h and using polyacrylonitrile filters. Results Median filter lifespan was significantly longer during CVVHD (37 hours, interquartile range (IQR) 19.5 to 72.5) than CVVH (19 hours, IQR 12.5 to 28) (p = 0.03). Median urea time weighted average (TWA) clearances were not significantly different during CVVH (31.6 ml/minute, IQR 23.2 to 38.9) and CVVHD (35.7 ml/minute, IQR 30.1 to 41.5) (p = 0.213). Similar results were found for creatinine: 38.1 ml/minute, IQR 28.5 to 39, and 35.6 ml/minute, IQR 26 to 43 (p = 0.917), respectively. Median β 2 m TWA clearance was higher during convective (16.3 ml/minute, IQR 10.9 to 23) than diffusive (6.27 ml/minute, IQR 1.6 to 14.9) therapy; nonetheless this difference did not reach statistical significance (p = 0.055). Median TWA adsorptive clearance of β 2 m appeared to have scarce impact on overall solute removal (0.012 ml/minute, IQR-0.09 to 0.1, during hemofiltration versus-0.016 ml/minute, IQR-0.08 to 0.1 during dialysis; p = 0.79). Analysis of clearance modification over time did not show significant modifications of urea, creatinine and β 2 m clearance in the first 48 hours during both treatments. In the CVVHD group, the only significant difference was found for β 2 m between 72 hours and baseline clearance. Conclusion Polyacrylonitrile filters during continuous hemofiltration and continuous hemodialysis delivered at 35 ml/ kg/h are comparable in little and middle size solute removal. CVVHD appears to warrant longer CRRT sessions. The capacity of both modalities for removing such molecules is maintained up to 48 hours. β 2 m = β 2 microglobulin; ARF = acute renal failure; CRRT = continuous renal replacement therapy; CVVH = continuous veno-venous hemofiltration; CVVHD = continuous veno-venous dialysis; IQR = interquartile range; TWA = time weighted average; UF = ultrafiltration.
Ultrafiltration and Backfiltration during Hemodialysis
Artificial Organs, 1995
Ultrafiltration is the pressure-driven process by which hemodialysis removes excess fluid from renal failure patients. Despite substantial improvements in hemodialysis technology, three significant problems related to ultrafiltration remain: ultrafiltration volume control, ultrafiltration rate control, and hackfiltration. Ultrafiltration volume control is complicated by the effects of plasma protein adsorption, hematocrit, and coagulation parameters on membrane performance. Furthermore, previously developed equations relating the ultrafiltration rate and the transmembrane pressure are not applicable to high-flux dialyzers, high blood flow rates, and erythropoietin therapy. Regulation of the ultrafiltration rate to avoid hypotension, cramps and other intradialytic com-plications is complicated by inaccurate estimates of dry weight and patient-to-patient differences in vascular refilling rates. Continuous monitoring of circulating blood volume during hemodialysis may enable a better understanding of the role of blood volume in triggering intradialytic symptoms and allow determination of optimal ultrafiltration rate profiles for hemodialysis. Backfiltration can occur as a direct result of ultrafiltration control and results in transport of bacterial products from dialysate to blood. By examining these problems from an engineering perspective, the authors hope to clarify what can and cannot be prevented by understanding and manipulating the fluid dynamics of ultrafiltration.
Online clearance measurement in high-efficiency hemodiafiltration
Kidney International, 2007
The measurement of ionic dialysance by conductivity variation is an established method in diffusive hemodialysis. To extend the validity of this method for use in highly convective therapies, such as online hemodiafiltration, we derived a new model for the measurement of ionic dialysance. This method was validated in a study involving 12 patients on pre-and postdilution online hemodiafiltration under various conditions. Clinically, there was a very good agreement between the dialysance determined by conductivity variation and blood side urea clearance. Neither the dilution modes nor the flow rate of the substitution fluid was found to significantly influence this agreement. Our results show that ionic dialysance can be easily and precisely measured by conductivity variation, and this provides an excellent surrogate for urea clearance even in highly convective therapies.
Application of a Standard Method to Characterize Clearance Blood Flow Relationships in Hemodialysis
Artificial Organs, 1995
The effectiveness of solute removal of a hemodialyzer may be judged by the ability of the device to remove solutes over the clinical range of blood flow rates. The expression of solule removal characteristics of hemodialyzers at standard or specific blood flow rates is important for clinical use and comparison. The solute removal at a specific blood flow rate is derived mathematically, usually by the fitting of a curve to the blood flow solute removal characteristics established experimentally over a range of blood flow rates. The commonly used methods of obtaining such a relationship are discussed and a new method of curve fitting is described. This method is derived from the mathematical theory defining the overall dialyzer mass transport relationship which governs the clearance blood flow relationship in any dialyzer. The derived relationship between the blood flow rate and the clearance has been validated using data generated for a commercially produced hemodialyzer.