Zhongping Huang

Innovation in the Treatment of Uremia: Proceedings from the Cleveland Clinic Workshop: Blood–Membrane Interactions During Dialysis

In extracorporeal renal replacement therapies, the dialyzer is not only the site at which solute removal occurs but also the extracorporeal circuit component having the largest surface area exposed to blood. Therefore, it is not surprising that interactions between blood components and the dialyzer membrane influence the dialysis procedure in several ways. Based on engineering principles, fluid flow along a surface such as membrane results in the development of a boundary layer which can influence solute removal. Furthermore, the exposure of blood to any extracorporeal artificial surface results in the activation of several pathways within the body, including those involving coagulation and complement activation. One of the byproducts of this generalized activation process is protein adsorption to the membrane surface, another phenomenon which can have a significant impact on solute removal. In this article, a detailed review of the ways in which blood–membrane interactions influence solute removal during hemodialysis and related therapies is provided. The influences of secondary membrane formation and boundary layer/concentration polarization effects on solute removal are specifically discussed. Furthermore, the importance of adsorption as a specific removal mechanism for low‐molecular weight proteins by highly permeable synthetic membranes is highlighted.

Effect of Flow Baffles on the Dialysate Flow Distribution of Hollow-Fiber Hemodialyzers: A Nonintrusive Experimental Study Using MRI

We used an innovative, nonintrusive MRI technique called the two-dimensional (2D) Phase-Contrast (2DPC) velocity-imaging technique to investigate the effect of flow baffles on the dialysate-side flow distribution in two different hollow-fiber hemodialyzers (A and B); each with flow rates between 200 and 1000 mL/min (3.33 x 10(-6) and 1.67 x 10(-5) m3/s). Our experimental results show that (1) the dialysate-side flow distribution was nonuniform with channeling flow occurred at the peripheral cross section of these hollow-fiber hemodialyzers, and (2) the existing designs of flow baffles failed to promote uniform dialysate-side flow distribution for all flow rates studies.

Evaluation of Nano-porous Alumina Membranes for Hemodialysis Application

Globally, kidney failure has consistently been a major health problem. The number of patients suffering from kidney failure is radically increasing. Some studies forecast an exponential growth in the number of kidney failure patients during the coming years. This emphasizes the importance of hemodialysis (HD) membranes. Current dialysis membranes (cellulose based and synthetic polymer membranes) have irregular pore shapes and sizes, nonuniform pore distribution and limited reusable capability, which leads to low efficiency of toxin removal. New alumina membranes with uniform, controllable and well-structured nanoscale pores, channeled pores aligned perpendicular to the membrane plane, high porosity, high thermal and chemical resistance, and better mechanical properties are certainly preferable to currently used membranes. Determination of transport properties of alumina membranes will assist in the development of the alumina membranes for enhancing hemodialysis. Experiments were performed to evaluate hydraulic permeability, solute diffusive permeability, sieving coefficient, and clearance of four solutes (urea, creatinine, Vancomycin, and inulin) for alumina membrane. Based on comparison of these values against those of polyethersulfone (PES) membranes, transport performance of alumina membrane was determined. Hydraulic conductivity of the alumina membrane was approximately twice that of the PES membrane and inulin sieving coefficient for alumina membrane is approximately 21% higher than that for PES membrane. Alumina membrane has higher solute clearances and no albumin leakage, which makes it an effective replacement for current dialysis membranes.

Operational characteristics of continuous renal replacement modalities used for critically ill patients with acute kidney injury

Renal replacement therapy (RRT) is required in a significant percentage of patients developing acute kidney injury (AKI) in an intensive care unit (ICU) setting. One of the foremost objectives of continuous renal replacement therapy (CRRT) is the removal of excess fluid and blood solutes that are retained as a consequence of decreased or absent glomerular filtration. Because prescription of CRRT requires goals to be set with regard to the rate and extent of both solute and fluid removal, a thorough understanding of the mechanisms by which solute and fluid removal occurs during CRRT is necessary. The following provides an overview of solute and water transfer during CRRT and this information is placed in the appropriate clinical context with a discussion of recent clinical trials assessing the relationship between CRRT dose and patient survival. Moreover, the differences between solute removal in CRRT and other dialysis modalities, especially sustained low-efficiency dialysis (SLED) and extended daily dialysis (EDD), along with the potential clinical implications are discussed.

Nanoporous Alumina Membranes for Enhancing Hemodialysis

The nonuniformity of pore size and pore distribution of the current hemodialysis membrane results in low efficiency of uremic solute removal as well as the loss of albumin. By using nanotechnology, an anodic alumina membrane (ceramic membrane) with selforganized nanopore structure was produced. The objective of this study was to fabricate nanoporous alumina membranes and investigate the correlation between various anodization conditions and the pore characteristics in order to find its potential application in artificial kidney/hemodialysis. An aluminum thin film was oxidized in two electrolytes consisting of 3% and 5% sulfuric acid and 2.7% oxalic acid. The applied voltages were 12.5, 15, 17.5, and 20 V for sulfuric acid and 20, 30, 40, and 50 V for oxalic acid. Pore size and porosity were determined by analyzing Scanning Electron Microscopy (SEM) images and hydraulic conductivity was measured. Results show that pore size increased linearly with voltage. Acid concentration affected pore formation but not pore size and pore distribution. Hydraulic conductivity of the ceramic membrane was higher than that of the polymer dialysis membrane. The optimal formation conditions for self-organized nanopore structure of the ceramic membrane were 12.5– 17.5 V in 3‐5% sulfuric acid at 0°C . Under these conditions, ceramic membranes with pores size of 10 nm diameter can be produced. In conclusion, we used anodic alumina technology to reliably produce in quantity ceramic membranes with a pore diameter of 10– 50 nm. Because of more uniform pore size, high porosity, high hydraulic conductivity, and resistance to high temperature, the ceramic membrane has the potential application as a hemodialysis membrane. DOI: 10.1115/1.2360949

A Numerical and Experimental Study of Mass Transfer in the Artificial Kidney

To develop a more efficient and optimal artificial kidney, many experimental approaches have been used to study mass transfer inside, outside, and cross hollow fiber membranes with different kinds of membranes, solutes, and flow rates as parameters. However, these experimental approaches are expensive and time consuming. Numerical calculation and computer simulation is an effective way to study mass transfer in the artificial kidney, which can save substantial time and reduce experimental cost. This paper presents a new model to simulate mass transfer in artificial kidney by coupling together shell-side, lumen-side, and transmembrane flows. Darcys equations were employed to simulate shell-side flow, Navier-Stokes equations were employed to simulate lumen-side flow, and Kedem-Katchalsky equations were used to compute transmembrane flow. Numerical results agreed well with experimental results within 10% error. Numerical results showed the nonuniform distribution of flow and solute concentration in shell-side flow due to the entry/exit effect and Darcy permeability. In the shell side, the axial velocity in the periphery is higher than that in the center. This numerical model presented a clear insight view of mass transfer in an artificial kidney and may be used to help design an optimal artificial kidney and its operation conditions to improve hemodialysis.

Ultrafiltration rate as a dose surrogate in pre-dilution hemofiltration.

For critically ill patients treated with continuous hemofiltration (HF), doses recently shown to improve survival can usually be achieved only in the pre-dilution mode. However, use of the pre-dilution mode results in reduced treatment efficiency, relative to post-dilution at the same ultrafiltration rate (Qf) and blood flow rate (Qb). The objective of this study is to determine the effect of Qf on removal parameters for solutes over a wide molecular weight spectrum in pre-dilution HF. Experiments were performed in an isovolemic, plasma-based pre-dilution system with Qb=200 ml/min. Removal parameters were measured for a 1.2 m2 polysulfone hemofilter (HF1200, Minntech) at Qf values of 20, 40, and 60 ml/min, corresponding to 17, 34 and 51 ml/h/kg for a 70 kg patient (N=3 hemofilters for each Qf). Clearance of urea and creatinine (small solute surrogates) was derived from plasma and ultrafiltrate concentrations at 30, 60, 120, 180, and 240 min while clearance of vancomycin and inulin (middle molecule surrogates) was estimated from changes in plasma concentrations over time. In addition, the sieving coefficient (SC) of vancomycin and inulin was measured at the same time points and at baseline (T=0 min). Our findings indicate pre-dilution had a predictable effect on clearance for each solute, as clearance increased linearly with Qf. Sieving coefficient values were not significantly influenced by either Qf or time and the equivalence of SC values in the middle molecule range suggest attenuation of secondary membrane effects. These data indicate filter performance can largely be preserved despite high Qf values by use of pre-dilution. Moreover, Qf appears to be a reasonable dose surrogate in pre-dilution HF.

Effects of high blood flow and high pre-dilution replacement fluid rates on small solute clearances in hemofiltration.

Background/Aims: In pre-dilution hemofiltration (HF), solute clearance is less than the HF rate. While the amount of this loss is predictable, it has not been validated in high-volume HF associated with high blood flow rates. Methods: Using isovolemic pre-dilution HF, we studied small solute clearances using combinations of blood flow (Q_B; 150, 250, 350, 450 ml/min) and replacement fluid (RF) flow (Q_RF; 2, 4, 6 l/h) to determine clearance losses we entitled ‘measured efficiency’ (E_M). E_M was compared to predicted efficiency (E_P) = (Q_B/Q_B + Q_RF). Results: Pre-dilution produced E_M values of 61–93%. Increases in Q_B for any Q_RF and decreases in Q_RF for any Q_B increased E_M over a wide range of Q_B and Q_RF. E_P was equivalent to E_M. Conclusion: In high-volume pre-dilution HF, E_P can be used to determine E_M across a broad range of Q_B and Q_RF values. Higher Q_RF requires higher Q_B to minimize the attenuating effects of pre-dilution on clearance.

Determinants of Small Solute Clearance in Hemodialysis

Recent outcome trials in chronic dialysis patients raise concerns about the relationship between delivered urea Kt/V and survival. Nevertheless, measurement of delivered small solute clearance remains the most common approach to quantify therapy. The purpose of this review is to provide an overview of the numerous factors influencing small solute clearance during hemodialysis. Although the focus of the review is on the manner in which dialyzer characteristics influence small solute clearances, factors related to other aspects of the extracorporeal circuit and to the patient will also be discussed.

Convective renal replacement therapies for acute renal failure and end-stage renal disease.

Although hemodialysis remains the primary treatment modality for the management of patients with end‐stage renal disease (ESRD), its clearance of relatively large‐sized uremic toxins is limited due to its primarily diffusive nature. Moreover, recent studies suggesting conventional, diffusion‐based therapies may be limited in their ability to influence outcome in ESRD patients indicate the need for alternative chronic dialysis approaches, an example of which is convective therapies. In an analogous manner, a reassessment of the dialytic management of critically ill patients with acute renal failure (ARF) has also occurred recently based on clinical evidence that high‐dose continuous hemofiltration improves survival. These recent clinical results suggest the utilization of convective therapies in both ARF and ESRD will increase in the future. This article provides a review of convective therapies, with an initial discussion of the determinants of convective solute removal. This is followed by a comprehensive overview of the manner in which hemofiltration and hemodiafiltration are applied clinically.