The production of platelet-activating factor during hemodialysis.

Regenerated cellulosic membranes (CU) induced the aggregation of plasma-free human neutrophils when recirculated in a dynamic model of dialysis without the patient on the circuit. Neutrophil aggregation was linked to the production of PAF by these cells. In the absence of detectable PAF production, no neutrophil aggregation occurred, as observed during recirculation with polymethylmethacrylate (PMMA) membranes. With polycarbonate (PC), PAF production and aggregation of neutrophils were both almost half the values with CU. PAF production was studied in ten hemodialysis (HD) patients tested twice with CU and once with PC and PMMA membranes. PAF was extracted in the venous blood during filling of the dialyser for 9/20 of patients with CU (3.1 +/- 2.9 ng/ml, mean +/- 1 S.D.) a membrane that induced marked leukopenia (greater than 50% of basal values at 15 min), C3a des Arg generation (greater than 500% at 5 min), and plasma levels of the elastase-alpha 1-proteinase inhibitor complex (greater than 500% at the end of HD). Membranes such as PC and PMMA showing intermediate or low potential to induce leukopenia and C3a des Arg generation, respectively, did not trigger the production and release of PAF in detectable amounts at any interval. However, with PMMA, plasma neutrophil elastase was significantly higher than baseline at the end of dialysis. These levels were not significantly different (p less than 0.05) from those observed with CU and PC membranes.

In vitro complement-independent activation of human neutrophils by hemodialysis membranes: role of the net electric charge.

Polymethylmethacrylate (PMMA) membranes with different net electric charges and percentage water contents (anionic 71%, neutral 70%, cationic 75%) were evaluated for their ability to stimulate plasma-free human polymorphonuclear neutrophils (PMN), and compared for potency to cuprophan (Cu), already described as being a potent trigger of PMN. The release of lysozyme, beta-glucuronidase, lactic dehydrogenase (LDH), and the generation of a platelet aggregating activity were studied in the supernatants from plasma-free human PMN incubated with different membranes. The PMN intracellular content of neutrophil cationic proteins (NCP), elastase, and cathepsin G were also studied by immunofluorescence using specific antisera on smears of PMN before and after incubation with each membrane. Only cationic, but not anionic or neutral PMMA induced a marked release of lysozyme (range 20-25% of the sonicated control, assumed as 100%), and beta-glucuronidase (40-43%), and marked depletion of the intracellular content of NCP, elastase, and cathepsin G, suggesting a degranulation process. Platelet aggregating activity was generated and referred to the release of platelet activating factor (PAF) only in the supernatants from PMN incubated with cationic, but not with anionic, or neutral PMMA membranes. These results indicate that modification of the net electric charge can per se turn PMMA, commonly recognized as inert, into a material with marked PMN activating effects, comparable to those of Cu, a highly reactive polymer.

[Use of slowly resorbing mesh in the repair of kidney rupture due to rejection]. / Uso di rete a riassorbimento lento nel recupero di reni rotti per rigetto.

Personal experience about the use of Vicryl mesh in a case of kidney rupture following rejection is presented. The stopping of bleeding and recovery of diuresis were obtained almost immediately after intervention.

[Role of tumor necrosis factor in hemodiafiltration]. / Ruolo del tumor necrosis factor in emodiafiltrazione.

The Authors review the mechanisms involved in the production of cytokines during substitutive extracorporeal treatment with particular reference to microbial contamination and possibility of backfiltration of bacterial constituents more likely to occur with high permeability membranes. Recent and on-going studies from our laboratory support the contention that patients treated with high permeability membranes may be chronically stimulated. Use of "ultrapure" solution indeed brings about a marked reduction in predialytic plasma levels of tumor necrosis factor (TNF) in regard to what observed when standard solutions are adopted.

Circulating immune complexes in nephritis.

Serum samples from 115 patients with various kidney disease were studied by means of precipitation in 3.5% polyethylene-glycol (the PEG test) and by inhibition of agglutination of IgG-coated polystyrene particles induced by C1q, two tests developed for the detection of circulating immune complexes. Positive results were found in acute glomerulonephritis, particularly in its early stages, and also in chronic forms of glomerulonephritis: membranous, focal sclerosing, mesangiocapillary and focal glomerulonephritis. High levels of circulating immune complexes were found in lupus nephritis. In most cases the test results showed a good correlation with the clinical course of the diseases.

Production of cytokines in hemodialysis.

Tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1 beta) are cytokines primarily produced by monocytes/macrophages when stimulated by endotoxin, complement-derived anaphylatoxins and the specific antigen. In the present study, the plasma levels of TNF-alpha and IL-1 beta were evaluated before and after hemodialysis with cuprophane membrane (in 9 patients) and hemodiafiltration (in 9 patients) using three high-permeability membranes such as polymethylmethacrylate, polyacrylonitrile (AN-69) and polysulfone. In vitro spontaneous production of TNF-alpha and IL-1 beta was evaluated in the supernatants from short-term cultured monocytes obtained before and after treatment. The predialytic levels of TNF-alpha and IL-1 beta were significantly higher (p less than 0.05) in the uremic population than in 21 healthy subjects taken as controls. The analysis of the uremic population regarding the mode of therapy indicated that in hemodialysis the predialytic plasma levels of TNF-alpha and IL-1 beta did not significantly differ from those of healthy subjects. In contrast, in hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, the predialytic plasma levels of both cytokines were significantly (p less than 0.05) increased. No significant variation in plasma levels of both cytokines was observed after hemodialysis with cuprophane membranes. Hemodiafiltration with polymethylmethacrylate and AN-69, but not with polysulfone, brought about a consistent reduction in plasma levels of both cytokines. Detectable amounts of TNF-alpha and IL-1 beta were spontaneously produced by peripheral-blood monocytes 6 h after the end of hemodialysis but not of hemodiafiltration. These studies suggest a possible role of TNF-alpha and IL-1 beta in the biocompatibility of different extracorporeal treatments.

Leukocyte behaviour in chronic uraemic patients undergoing regular dialysis.

A review of the literature is followed by the presentation of data obtained during a study of white blood cell kinetics in patients undergoing regular dialysis treatment. It was found that contact between white blood cells and the dialyzer results in a very prompt 'neutropenia-neutrophilia' stage and the deposition of billions of white blood cells on the membranes at the end of each treatment. A comparison of intradialytic leukocyte behaviour and the mean baseline white blood cell values was made in a total of 49 patients subdivided in four groups: 1. patients using coil and parallel flow dialyzers; 2. patients using dialyzers of different surface area; 3. patients of different dialytic age; 4. patients employing monoused or re-usable filters. No differences were noted in groups 1 and 4. In contrast, employing large dialyzers and the increasing dialytic age led to a variety of white blood cell patterns. Contrary to the information in the literature on leukocyte adhesion, it was observed that the cell deposits on the membranes and on the bubble trap filters, while predominantly composed of neutrophils, also contained monocytes and lymphocytes in proportions similar to those of the normal differential blood count.

[Semeiotic significance of the clinical use of methods of determining serum immunocomplexes in human glomerulonephritis]. / Significato semeiotico dell'utilizzazione clinica delle metodiche di dosaggio di immunocomplessi sierici nelle glomerulonefriti umane.

The application of tests for the determination of serum immune complexes in nephrology has supplied fresh pathogenetic and symptomatological information. An account is given of results obtained in primary and secondary glomerulonephritis using four methods; the solid-phase Clq test, the polyethylene glycol precipitation test, the immunofluorescence on polymorphonucleates tests, and the solid-phase conglutinins test (with anti-IgA antibodies). The results take on a symptomatological meaning in many classes of human glomerulonephritis, both in the differentiation of primary forms and those secondary to systemic diseases, and in prognosis. A critical review is made of the data obtained in a personal series in the light of a long-term follow-up. The limits and specificity of each test are also discussed.