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.

Background: Significant progress has been made in the field of renal replacement therapy for critically ill patients with acute renal failure (ARF) over the past few years. This review highlights these developments. Methods: Recent studies assessing the clinical utility of the RIFLE classification system for the diagnosis of ARF were reviewed. Clinical outcome studies evaluating the effect of continuous renal replacement therapy (CRRT) dose and timing of initiation were assessed. The final review topic was the effect of dialysis modality on the recovery of renal function in ARF patients. Conclusions: Based on recent clinical studies, the increasing use of the RIFLE criteria is justified, as this approach appears to be a robust method for both the diagnosis of and prognostication in ARF. A large randomized trial involving convective CRRT supports the commonly used prescription of 35 ml/ kg/h in clinical practice. Moreover, numerous recent outcome studies, also largely involving convective CRRT, provide a clinical rationale for the increasingly common clinical practice of earlier initiation. Finally, several recent studies suggest CRRT, relative to conventional hemodialysis, results in a greater rate of renal recovery in ARF patients.

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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.

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