Study by means of high-performance liquid chromatography of solutes that decrease theophylline/protein binding in the serum of uremic patients.

Substantial changes in protein binding of drugs occur during the progression of renal insufficiency. Protein-bound uremic solutes play a role in the inhibition of drug protein binding. We previously demonstrated that hippuric acid in uremic ultrafiltrate was an inhibitor of the theophylline protein binding.

Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins: role of purines.

End-stage renal disease is associated with a defect in immunologic functions. Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains factors that suppress calcitriol synthesis and its biological actions. In the present study, the effect of UUF on basal and calcitriol-induced membrane bound CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was evaluated.

P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes.

In the end-stage renal disease patient, certain uremic compounds could influence the cellular accumulation of aluminum (Al). In this study, we examined the effect of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased cellular Al uptake and aspartate aminotransferase release and decreased cell growth when Tf-Al, not Al citrate, was added to culture media.

HPLC fractions of human uremic plasma inhibit the RBC membrane calcium pump.

We have reported that uremic plasma filtrates (UF) inhibit the red blood cell (RBC) membrane calcium pump. The inhibitor was dialyzable, smaller than 3,000 molecular weight, heat-stable, and protease-resistant. In the present study, we used reverse-phase preparative HPLC, analytical HPLC, and Sephadex G-25 elution to identify inhibitory fractions.

Disturbed host defense in peritoneal cavity during CAPD: characterization of responsible factors in dwell fluid.

In this study, the factors in overnight dwell fluid (8 to 10 hr dwell) depressing granulocyte (GC) NAD(P)H-oxidase dependent radical species production are characterized. At present, most studies have essentially focused on fresh, unspent dialysate and on peritoneal macrophages. The response to Staphylococcus aureus (Staph A) was dose-dependently depressed for both GC CO2 production (from 91.

Middle molecules: toxicity and removal by hemodialysis and related strategies.

Renal failure results in the retention of metabolites which may arbitrarily be grouped according to their molecular weight: low (< 300 daltons molecular weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in respect to the relative importance of these groups varies. Initially it was thought that small molecules were important.

Mechanisms of uremic inhibition of phagocyte reactive species production: characterization of the role of p-cresol.

It is generally recognized that the uremic syndrome results in a depression of immune function, but the uremic solutes responsible remain largely unidentified. In this study, the effect of 18 known uremic retention solutes, including urea and creatinine, on hexose monophosphate shunt (HMS)-dependent glucose-1-C14 utilization (G1C-U), chemiluminescence production (CL-P) and flow cytometric parameters (FCP) of respiratory burst and phagocytosis were evaluated in granulocytes and/or monocytes. Among the compounds studied, only p-cresol depressed whole blood respiratory burst reactivity (G1C-U, CL-P) dose dependently at concentrations currently encountered in end-stage renal disease (ESRD) (P < 0.

Uraemic toxic retention solutes depress polymorphonuclear response to phagocytosis.

Previous studies from our laboratory have demonstrated that the activity of the hexose monophosphate shunt (HMS) pathway in phagocytosis-related respiratory burst is disturbed in end-stage renal disease. To determine whether uraemic solute retention is responsible for this defect the HMS-path was evaluated by measurements of glucose-1-C14 utilization and determination of 14CO2 production in polymorphonuclear cells (PMNLs), suspended in normal plasma or uraemic biological fluids. Normal PMNLs, while suspended in normal or uraemic plasma, were stimulated with either latex, zymosan or Staph.