Search for optimizing dialysis therapy. I. Acute effects of hemodiafiltration with a highly permeable membrane and a large dose of convection and diffusion.

Based on the concept that an optimisation of dialysis therapy might be achieved by increasing the removal of small metabolic substances as well as low molecular weight proteins, hemodialfiltration (HDF) was modified. In 9 ESRD patients, HDF was performed acutely for 4 h, where 60 liters of substitution fluid were infused per patient. Two polysulphone F60 membranes in line were used as hemodialfilters. As compared to conventional hemodialysis (HD), performed with a cuprophane dialyser, HDF resulted in higher extraction indices for small solutes assessed by HPLC. Due to the large amount of convection applied, HDF was followed by significant decreases of low molecular weight proteins ranging from 9.5 kdaltons (iPTH, p less than 0.01) to 17 kdaltons (myoglobin, p less than 0.01). Analysis of the protein pattern of the serum revealed a nonlinear function in the decrease of plasma proteins after HDF. It is concluded that even though the detoxification efficacy of the described HDF method is by far superior to conventional HD in quality and quantity, the efficacy is still far from that of excretory renal function. Thus, to further improve efficacy with respect to the catabolic renal function for low molecular weight proteins, membranes for HDF or hemofiltration barriers but should surpass the sieving properties of the glomerulus in the low molecular protein range.

Sodium pump inhibitor in the serum of patients with essential hypertension and its partial purification from hemofiltrate.

A 3-fold higher concentration of "endogenous digitalis" is found in the serum of patients with essential hypertension than in the serum of normotensives, whose concentration was determined in 22 normotensive probands by an receptor assay using isolated (Na+ + K+)-ATPase as 76.3 +/- 9.3 nM ouabain equivalents. Since the concentration of "endogenous digitalis" was 7-19 fold higher in 2 patients, who had become uremic due to a malignant hypertension and since their serum levels fell 3-fold by hemodialysis, the hemofiltrate was used for partial purification of the substance. This was possible by hydrophobic chromatography on Amberlite XAD-2, octadecyl-coated silica gel, anion exchange chromatography and affinity chromatography on membrane-bound (Na+ + K+)-ATPase. The partially purified substance behaved like the material described by Cloix et al. (1985) Biochem. Biophys. Res. Commun. 131:1234-1240 and competed with digoxin for digoxin antibodies. Ascorbic acid isolated on the search for an inhibitor of (Na+ + K+)-ATPase from beef brain inhibited [3H]ouabain binding due to a decrease of the ouabain binding sites by a reduction of a group within the ATP binding site of the enzyme. Unsaturated fatty acids claimed to be "endogenous digitalis (Tamura et al. [1985] J. Biol. Chem. 260:9672-9677)" also lowered the capacity of the cardiac glycoside binding site but did not compete with ouabain.