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Conventional extracorporeal dialysis relies on diffusion down concentration gradients for the removal of undesirable solutes from the blood. Removal of a solute by diffusion depends on its size; this gives rise to the familiar observation that small solutes such as urea are removed by dialysis more readily than larger solutes such as creatinine and uric acid. The work of Teschan et al.(1) on isolation of toxic substances from uremic blood suggests that these large molecular weight solutes contribute to uremic symptomatology. In addition, with diffusion, the rate of solute removal falls exponentially with time following a first order decay curve. As a result dialysis efficiency is low at low plasma solute concentrations. The limit approached by techniques to improve dialysis efficiency for a solute is the rate of free diffusion in water for the solute in question, and for large toxic solutes such as glutethimide and kanamycin, this maximum rate of removal may be too slow for clinical success.With these limitations for conventional dialysis in mind the present study was undertaken to evaluate a familiar process (2-5) heretofore unexploited as a means to remove toxic solutes, namely ultrafiltration. Such a process would have the advantage of removing solutes small enough to pass through the ultrafilter in proportion to their plasma concentration rather than their concentration gradient, as with diffusion. With the driving force being a pressure gradient rather than a concentration gradient there would not be a sharp a reduction in solute removal at low plasma concentrations as seen with diffusion. In addition the rate of solute removal would be proportional to the applied pressure gradient and this could be adjusted to meet the needs of the clinical situation. MATERIALSA new series of membranes composed of the precipitated polyelectrolytes sodium polystyrene sulfonate and polyvinylbenzyltriemnthyl ammonium chloride in stoichiometric proportions was selected for evaluation. These new membranes, henceforth designated by the trade name Diaflo, can be synthesized in such a way as to provide a family of membranes with a net neutral charge and a wide range of permeabilities to water when a pressure gradient is applied. Figure 1 shows a diagrammatic sketch of the membrane which in itself is only 1-2 mils thick and quite fragile. For greater strength it has been cast on a stout backing of highly porous polyester felt. The overall thickness of membrane and backing is 6-10 mils. Essentially all properties of discrimination and resistance to water flow reside in the membrane skin. EXPERIMENTAL STUDIES AND RESULTSDiaflo membranes were initally studied from the standpoint of traditional diffusive transport in order to see if a significant contribution from diffusion would be present in their subsequent evaluation with ultrafiltration. Figure 2 is a photograph of the Leonard-Bluemle batch dialyzer (6) . A membrane disc is clamped between 2 hemichambers by a metal coupler. Each chamber is stirred at constant temperature by a magne...

A B S T R A C T Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate.No renal medullary gradient for salicylate was demonstrable during both hydropenic and hydrated states. In contrast, both free and conjugated APAP concentrations rose sharply in the inner medulla during hydropenia, reaching a mean maximal value at the papillary tip exceeding 10 times the cortical concentration (P < 0.001), a distribution similar to that of urea. Salicylate had no effect on the APAP gradient, but hydration markedly reduced both the APAP and urea gradients in the medulla. The data indicate that APAP

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