Septicemia in dialysis patients: incidence, risk factors, and prognosis.
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BACKGROUND: Infection is second to cardiovascular disease as a cause of death in patients with end-stage renal disease (ESRD), and septicemia causes a majority of these infectious deaths. To identify patients at high risk and to characterize modifiable risk factors for septicemia, we examined the incidence, risk factors, and prognosis for septicemia in a large, representative group of U.S. dialysis patients. METHODS: We conducted a longitudinal cohort study of incident ESRD patients in the case-mix study of the U.S. Renal Data System with seven years of follow-up from hospitalization and death records. Poisson regression was used to examine independent risk factors for hospital-managed septicemia. Cox proportional hazards analysis was used to assess the independent effect of septicemia on all-cause mortality and on death from septicemia. Separate analyses were performed for patients on peritoneal dialysis (PD) and hemodialysis (HD). RESULTS: Over seven years of follow-up, 11.7% of 4005 HD patients and 9.4% of 913 PD patients had at least one episode of septicemia. Older age and diabetes were independent risk factors for septicemia in all patients. Among HD patients, low serum albumin, temporary vascular access, and dialyzer reuse were also associated with increased risk. Among PD patients, white race and having no health insurance at dialysis initiation were also risk factors. Patients with septicemia had twice the risk of death from any cause and a fivefold to ninefold increased risk of death from septicemia. CONCLUSIONS: Septicemia, which carries a marked increased risk of death, occurs frequently in patients on PD as well as HD. Early referral to a nephrologist, improving nutrition, and avoiding temporary vascular access may decrease the incidence of septicemia. Further study of how race, insurance status, and dialyzer reuse can contribute to the risk of septicemia among ESRD patients is indicated. (+info)
Activation of the kallikrein-kinin system in hemodialysis: role of membrane electronegativity, blood dilution, and pH.
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BACKGROUND: The kallikrein-kinin system activation by contact with a negatively charged surface has been promulgated to be responsible for hypersensitivity reactions. However, to explain the low frequency and heterogeneity of hypersensitivity reactions, we hypothesized that not only the electronegativity of the membrane, but also other physicochemical parameters could influence the activation of the contact phase system of plasma assessed by the measurement of kallikrein activity and bradykinin concentration. METHODS: Plasma kallikrein activity using chromogenic substrate (S2302) and plasma bradykinin concentration (enzyme immuno assay) were measured during the perfusion of human plasma (2.5 ml/min) through minidialyzers mounted with six different membranes [polyacrylonitrile (PAN) from Asahi (PANDX) and from Hospal (AN69), polymethylmethacrylate (PMMA) from Toray, cellulose triacetate (CT) from Baxter, cuprophane (CUP) from Akzo and polysulfone (PS) from Fresenius]. RESULTS: A direct relationship was shown between the electronegativity of the membrane assessed by its zeta potential and the activation of plasma during the first five minutes of plasma circulation. With the AN69 membrane, the detection of a kallikrein activity in diluted plasma but not in undiluted samples confirmed the importance of a protease-antiprotease imbalance leading to bradykinin release during the first five minutes of dialysis. With PAN membranes, the use of citrated versus heparinized plasma and the use of various rinsing solutions clearly show a dramatic effect of pH on the kallikrein activity and the bradykinin concentration measured in plasma. Finally, increasing the zeta potential of the membrane leads to a significant increase of plasma kallikrein activity and bradykinin concentration. CONCLUSIONS: Our in vitro experimental approach evidences the importance of the control of these physicochemical factors to decrease the activation of the contact system. (+info)
Effect of permeability on indices of haemodialysis membrane biocompatibility.
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BACKGROUND: Increases in plasma anaphylatoxins frequently are used as an index of haemodialysis membrane biocompatibility; however, their plasma levels may be influenced by the loss of anaphylatoxins into the dialysate compartment. METHODS: We compared the generation and compartmental distribution of anaphylatoxins, C3a and C5a, in a high flux and a low flux polysulfone membrane dialyser when whole human blood was recirculated through an in vitro haemodialysis circuit. RESULTS: Plasma C3a levels in high flux polysulfone (2.31 +/- 0.81 microg/ml) and low flux polysulfone (3.02 +/- 0.98 microg/ml) dialysers were comparable after 120 min (P = NS). In contrast, dialysate C3a in high flux polysulfone (0.65 +/- 0.31 microg/ml) accounted for 37.5 +/- 7.0% of the total detected (plasma + dialysate) C3a mass in the dialysers, while dialysate C3a in low flux polysulfone dialysers (0.01 +/- 0.01 microg/ml) accounted for only 0.3 +/- 0.3% of the total mass (P < 0.05; high flux vs low flux). Anaphylatoxin C5a was undetectable in the dialysate compartment of either dialyser examined. CONCLUSIONS: Our results indicate that anaphylatoxins readily traverse certain high flux dialysis membranes; consequently, plasma C3a levels may not accurately reflect the C3-activating potential of these membranes. (+info)
Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress".
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Influence of hemodialysis membrane type on pentosidine plasma level, a marker of "carbonyl stress." BACKGROUND: The accumulation of advanced glycation end products (AGEs) in uremia has been ascribed to the retention of carbonyl precursors of AGEs. Pentosidine plasma level has been identified as a surrogate marker of carbonyl precursors ("carbonyl stress"). The influence of hemodialysis (HD) membrane type and residual diuresis on carbonyl stress has not been studied. METHODS: We measured protein-linked and free plasma pentosidine (a surrogate marker of carbonyl stress) by high-performance liquid chromatography in patients on HD with low-flux cellulose (N = 29), high-flux polysulfone (PS; N = 57), polymethylmethacrylate (PMMA) (N = 25), and AN69 (N = 15). RESULTS: Both protein-linked and free pentosidine were similar on low-flux cellulose, high-flux PMMA, and AN69, but were lower (P < 0.01) on high-flux PS. Pentosidine levels were virtually identical on Fresenius and Asahi PS in Japanese and Belgian patients. By multivariate analysis, only the type of HD membrane and residual diuresis proved to be independent determinants (P < 0.001) of pentosidine levels. During a single HD session, the clearance of free pentosidine was similar with all membranes. In three patients who were switched from AN69 to PS, the protein-linked pentosidine level dropped to the control level after resumption of the AN69 membrane. CONCLUSIONS: Both HD membrane type and residual diuresis are independent determinants of pentosidine plasma level, which is a marker of carbonyl stress. (+info)
Tissue engineering of a bioartificial renal tubule assist device: in vitro transport and metabolic characteristics.
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BACKGROUND: Current renal substitution therapy for acute or chronic renal failure with hemodialysis or hemofiltration is life sustaining, but continues to have unacceptably high morbidity and mortality rates. This therapy is not complete renal replacement therapy because it does not provide active transport nor metabolic and endocrinologic functions of the kidney, which are located predominantly in the tubular elements of the kidney. METHODS: To optimize renal substitution therapy, a bioartificial renal tubule assist device (RAD) was developed and tested in vitro for a variety of differentiated tubular functions. High-flux hollow-fiber hemofiltration cartridges with membrane surface areas of 97 cm2 or 0. 4 m2 were used as tubular scaffolds. Porcine renal proximal tubule cells were seeded into the intraluminal spaces of the hollow fibers, which were pretreated with a synthetic extracellular matrix protein. Attached cells were expanded in the cartridge as a bioreactor system to produce confluent monolayers containing up to 1.5 x 109 cells (3. 5 x 105 cells/cm2). Near confluency was achieved along the entire membrane surface, with recovery rates for perfused inulin exceeding 97 and 95% in the smaller and larger units, respectively, compared with less than 60% recovery in noncell units. RESULTS: A single-pass perfusion system was used to assess transport characteristics of the RADs. Vectorial fluid transport from intraluminal space to antiluminal space was demonstrated and was significantly increased with the addition of albumin to the antiluminal side and inhibited by the addition of ouabain, a specific inhibitor of Na+,K+-ATPase. Other transport activities were also observed in these devices and included active bicarbonate transport, which was decreased with acetazolamide, a carbonic anhydrase inhibitor, active glucose transport, which was suppressed with phlorizin, a specific inhibitor of the sodium-dependent glucose transporters, and para-aminohippurate (PAH) secretion, which was diminished with the anion transport inhibitor probenecid. A variety of differentiated metabolic functions was also demonstrated in the RAD. Intraluminal glutathione breakdown and its constituent amino acid uptake were suppressed with the irreversible inhibitor of gamma-glutamyl transpeptidase acivicin; ammonia production was present and incremented with declines in perfusion pH. Finally, endocrinological activity with conversion of 25-hydroxy(OH)-vitamin D3 to 1,25-(OH)2 vitD3 was demonstrated in the RAD. This conversion activity was up-regulated with parathyroid hormone and down-regulated with increasing inorganic phosphate levels, which are well-defined physiological regulators of this process in vivo. CONCLUSIONS: These results clearly demonstrate the successful tissue engineering of a bioartificial RAD that possesses critical differentiated transport, and improves metabolic and endocrinological functions of the kidney. This device, when placed in series with conventional hemofiltration therapy, may provide incremental renal replacement support and potentially may decrease the high morbidity and mortality rates observed in patients with renal failure. (+info)
Experimental studies on environmental contamination with infected blood during haemodialysis.
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To assess the relative importance of different postulated modes of spread of hepatitis B in dialysis units, blood charged with various tracer organisms was used in simulated haemodialysis runs in four laboratories, and the resulting contamination of equipment and environment was measured semi-quantitatively. Some airborne spread of the tracer organism occurred when tubing containing contaminated blood was needled as the "patient" went on and came off the dialyser. Virtually no small airborne particles could be demonstrated however in simulated emergencies in which a blood line was disconnected, or even when bottles of blood were dropped on to a hard floor from a height of 2 metres. Bacillus globigii spores from contaminated blood leaked in small numbers into the dialysing fluid through apparently intact coils. T3 phage, with a particle size of the same order as hepatitis B virus, passed in small quantities through the membrane of a Kiil dialyser from blood to dialysing fluid and also in the reverse direction when added to the header tank. A number of other dialysers were also permeable to phage. Visual assessment of the appropriate moment for inserting the venous line into the "patient" at the onset of dialysis was shown to be unreliable, as the displaced fluid from the end of the venous line was already contaminated before it contained visible red blood cells. Considerable contamination of exposed surfaces and of the buttons on the proportionating unit cabinet occurred. Minor visible splashing of blood was a common-place of the laboratory experiments and was shown to be also a common event during routine haemodialysis in two of the dialysis units taking part in the studies. (+info)
Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane.
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BACKGROUND: The efficiency of dialysis membranes is generally evaluated by assessing their capacity to remove small, water-soluble and non-protein-bound reference markers such as urea or creatinine. However, recent data suggest that protein-bound and/or lipophilic substances might be responsible for biochemical alterations characterizing the uraemic syndrome. METHODS: In the present study, the total concentrations of four uraemic retention compounds (indoxyl sulphate, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) and p-cresol) and of tryptophan, the only protein-bound amino acid and a precursor of indoxyl sulphate, were compared with those of urea and creatinine in pre- and post-dialysis serum and in dialysate of 10 patients; two high-flux (HF) membranes (cellulose triacetate (CTA) and polysulphone (PS)) and a low-flux polysulphone (LFPS) membrane were compared in a crossover design, using HPLC. RESULTS: Except for hippuric acid (67.3+/-17.5% decrease), major differences were found in the percentage removal of the classical uraemic markers on one hand (creatinine 66.6+/-7.0% and urea 75.5+/-5.8% decrease) and the studied protein-bound and/or lipophilic substances on the other (indoxyl sulphate, 35.4+/-15.3% and p-cresol 29.0+/-14.2% decrease; tryptophan, 27.5+/-40.3%, and CMPF, 22.4+/-17.5% increase; P<0.01 vs urea and creatinine in all cases). Hippuric acid removal was more pronounced than that of the remaining protein-bound compounds (P<0. 01). After correction for haemoconcentration, per cent increase of tryptophan and CMPF was less substantial, while per cent negative changes for the remaining compounds became more important. There was a correlation between creatinine and urea per cent removal at min 240 (r=0.51, P<0.01), but all the other compounds showed no significant correlation with either of these two. The three membranes were similar regarding the changes of total solute concentrations from the start to the end of dialysis. CONCLUSIONS: Urea and creatinine are far more efficiently removed than the other compounds under study, except for hippuric acid. There are no striking differences between the HF membranes. Moreover, compared with the LF membrane these HF membranes do not appear to be superior in removing the studied compounds. (+info)
Adequacy of dialysis reduces the doses of recombinant erythropoietin independently from the use of biocompatible membranes in haemodialysis patients.
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BACKGROUND: The effect of the adequacy of dialysis on the response to recombinant human erythropoietin (rHuEpo) therapy is still incompletely understood because of many confounding factors such as iron deficiency, biocompatibility of dialysis membranes, and dialysis modality that can interfere. METHODS: We investigated the relationship between Kt/V and the weekly dose of rHuEpo in 68 stable haemodialysis (HD) patients (age 65+/-15 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-343 months (median 67 months). Inclusion criteria were HD for at least 6 months, subcutaneous rHuEpo for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/ml, and haematocrit (Hct) level targeted to 35% for at least 3 months. Exclusion criteria included HBsAg and HIV positivity, need for blood transfusions or evidence of blood loss in the 3 months before the study, and acute or chronic infections. Hct and haemoglobin (Hb) levels were evaluated weekly for 4 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly dose of rHuEpo were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for the whole group of patients were: Hct 35 +/- 1.2%, Hb 12.1 +/- 0.6 g/dl, TSAT 29 +/- 10%, serum ferritin 204 +/- 98 ng/ml, sAlb 4.1 +/- 0.3 g/dl, Kt/V 1.33 +/-0.19, PCRn 1.11+/- 0.28 g/kg/day, weekly dose of rHuEpo 123 +/- 76 U/kg. Hct did not correlate with Kt/V, whereas rHuEpo dose and Kt/V were inversely correlated (r = -0.49; P < 0.0001). Multiple regression analysis with rHuEpo as dependent variable confirmed Kt/V as the only significant variable (P < 0.002). Division of the patients into two groups according to Kt/V (group A, Kt/V < or = 1.2; group B, Kt/V > or = 1.4), showed no differences in Hct levels between the two groups, while weekly rHuEpo dose was significantly lower in group B than in group A (group B, 86 +/- 33 U/kg; group A, 183 +/- 95 U/kg, P < 0.0001). CONCLUSIONS: In iron-replete HD patients treated with rHuEpo in the maintenance phase, Kt/V exerts a significant sparing effect on rHuEpo requirement independent of the use of biocompatible synthetic membranes. By optimizing rHuEpo responsiveness, an adequate dialysis treatment can contribute to the reduction of the costs of rHuEpo therapy. (+info)