Induction of interleukin-1 during hemodialysis.
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Biomedical subjects
Publications and source records attributed to J L Poignet.
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The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus-seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients.
The generation of compounds such as interleukin 1 (IL-1), tumor necrosis factor alpha (TNF alpha), and the possible encounter of circulating cells with endotoxin (LPS) have been demonstrated during hemodialysis. All these factors are able to induce the production of IL-6 by human monocytes. Anaphylatoxins can be generated following complement activation by cellulosic membrane dialysis. C5a is known to potentiate the LPS-induced production of IL-1 and TNF alpha, and we established that recombinant human C5a was able to act synergistically with LPS in the induction of IL-6 by human monocytes. We investigated whether IL-6 could be detected in the serum of long-term hemodialyzed and uremic patients. Using the very sensitive 7TD1 cell line bioassay, we demonstrated that circulating IL-6 activity was present in the serum of all 14 tested patients, whereas it was occasionally present in normal sera. The presence of serum IL-6 was confirmed using an anti-IL-6 antibody and a specific ELISA (109 +/- 36 pg/ml). Most patients had a reproducible level of IL-6 activity throughout a period of 10 days. The dialysis session did not significantly modify these levels and patients had similar serum IL-6 activity at the start, during or the at end of the dialysis session. The different parameters of the dialysis session (i.e. standard or filtrated dialyzates, complement-activating or nonactivating membranes) did not significantly influence the levels of IL-6. Elevated levels of IL-6 were also observed in uremic patients compared to normal donors, although significantly lower than in hemodialyzed patients (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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Adverse reactions, such as skin flush and pruritus, have been observed among hemodialyzed (HD) patients. A potential relationship between hemodialysis and allergic phenomena prompted us to investigate some allergologic parameters. Total IgE, specific IgE antiethylene oxide and anti-isocyanate toluene diisocyanate, and in vitro spontaneous histamine release (SHR) were measured in 105 long-term stable HD patients. Thirty-two of the patients had occasionally developed skin flush reactions and/or pruritus during dialysis sessions. Blood samples were taken at the start of dialysis, sera were kept frozen until assay, and in vitro SHR was performed on washed leukocytes at 37 degrees C for 40 minutes. A high (range, 20% to 80%) and reproducible in vitro SHR was observed among 24% of patients. No correlation was found between SHR and the type of dialysis membrane used (copolymer of acrylonitrile-methallyl-sodium sulfonate, cuprophan, and polysulfone). High SHR (i.e., greater than 20%) was observed mainly among patients with detectable antiethylene oxide IgE antibodies (p less than 0.001). High levels of IgE (greater than 300 ng/ml), specific IgE antibodies, and a high in vitro SHR were all observed concomitantly in 26% of the patients with skin flush reactions and/or pruritus, whereas all three of these parameters together were present in only 3% of the symptom-free patients. To our knowledge, this is the first time that a high in vitro SHR has been described among HD patients, and putative correlations with in vivo phenomena are discussed.
Effects of metabolic acidosis were compared between bicarbonate dialysis (BCD) and acetate-free biofiltration (AFB). Three stable dialysis patients (1M, 2F, mean age 30 yrs) were selected for the study because their bicarbonate (BC) pre-dialysis plasma concentration were always under 16 mmol/l while they were on 33 mmol/l-BCD thrice weekly for 12 months. They were switched to a 6 months period of AFB. Pre- and post-dialysis BC plasma concentration, other blood chemical parameters and mass removal (total collection of used dialysate) of urea (U), creatinine (Cr), uric acid (UA), and phosphate (P) were measured during the last week of each period, including 3 dialysis sessions. Mean calorie and protein intake were 29.4 KCal/kg.d and 1.5 g/Kg.d (BCD period) and 38.2 Kcal/Kg.d and 1.5 g/Kg.d (AFB period) respectively. BC plasma concentration (Mean +/- SE, mmol/l) at the pre and post-dialysis in AFB were significantly higher than those in BCD (16.6 +/- 0.7 vs 20.8 +/- 0.6; p less than 0.001, 22.7 +/- 0.8 vs 25.8 +/- 0.8; P less than 0.02). Pre- and post-dialysis U plasma concentration (Mean +/- SE, mmol/l) in AFB were significantly lower than those in BCD (34.3 +/- 2.51 vs 20.8 +/- 0.59, 10.5 +/- 1.32 vs 7.5 +/- 0.92; P less than 0.001). Pre-dialysis P plasma concentration (Mean +/- SE, mmol/l) in AFB was significantly lower than that in BCD (1.85 +/- 0.09 vs 1.50 +/- 0.15; P less than 0.01). Cr, UA and P mass removal in BCD and AFB were not significantly different. However, U mass removal in AFB was significantly lower than that in BCD.(ABSTRACT TRUNCATED AT 250 WORDS)
A retrospective study of 40 patients with chronic renal failure who underwent haemodialysis for more than 10 years (mean: 153 months) showed that 18 patients (45 p. 100) had arthralgia in the shoulders, hands, wrists and knees, 13 (32 p. 100) had carpal tunnel syndrome requiring surgery, and 20 (50 p. 100) were found to have bone cavities in the humeral head, external supra-acetabular region, carpus and patella. Aluminium overload was present in 47 p. 100 of the patients, and amyloid deposits were found in 10 of the 12 patient operated upon for carpal tunnel syndrome. This study confirms the frequency in patients under long-term haemodialysis of an articular pathological entity consisting of arthralgia, carpal tunnel syndrome, juxta-articular bone cavities and amyloid deposits which are now known to be made of beta 2-microglobulin. The initial lesion seems to affect the synovial membrane; it appears to be facilitated by age and is often associated with aluminium overload. The mechanism(s) responsible for amyloid deposits remain (s) to be elucidated.
We have used a new analytical micromethod to study the pharmacokinetics of desferrioxamine and its aluminium chelates in patients with chronic renal failure on haemodialysis. Desferrioxamine (Desferal, CIBA, Basle) was given by 1-h infusion just after the haemodialysis at 20, 40, 80 mg/kg body wt. and during the first and the last hour of the haemodialysis at 40 mg/kg. The concentrations of desferrioxamine during infusions showed a linear increase with increasing doses. The maximum concentrations and the AUC obtained when desferrioxamine was infused during the haemodialysis were not statistically different but slightly lower than those obtained in post dialysis administration. This result indicates that the loss of desferrioxamine by transfer in the dialysate is quite moderate within 1 h. During the interdialysis period, there was a decrease of plasma desferrioxamine concentrations with a mean half-life of 18.7 +/- 5.2 h and an increase in plasma concentrations of aluminium desferrioxamine chelate. In vitro studies show that a lengthy contact between desferrioxamine and plasma is necessary for complete chelation of A1 already present in plasma. During the following dialysis session, there was an important decrease of desferrioxamine and of its iron and aluminium chelates in blood plasma representing their transfer to the dialysis fluid.
Serum carboxyterminal parathyroid hormone (PTH) concentration (homologous measurement of the 53-84 fragment and heterologous bovine measurement) has been measured and correlated with both clinical and radiological findings of secondary hyperparathyroidism (HPT), studied quantitatively according to a score published in literature, in 95 patients with chronic renal failure on maintenance hemodialysis. Mean serum PTH concentration (53.84) is statistically higher in patients with severe clinical and radiological evaluation of HPT than in patients with moderate or slight manifestations of HPT (M +/- DS: 515.8 +/- 243.7 pg/ml VS 271.3 +/- 166.1 pg/ml p less than 0.001). However, even with high serum concentration, serum PTH level does not allow to predict HPT severity, suggesting a retention of PTH fragments in serum without biologic activity probably.
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In six anuric haemodialysed patients, aluminium and iron mass transfer were determined 48 hours after 40 and 80mg/kg body weight desferrioxamine intravenous infusion. All patients were aluminium overloaded (mean +/- SEM: 2.91 +/- 1.05 mumol/g wet tissue bone) and two had high plasma ferritin. Haemodialysis and haemofiltration were performed using a highly permeable membrane. The adequate dose of desferrioxamine for aluminium removal is 40mg/kg, since aluminium mass transfer induced by haemodialysis and haemofiltration (47.4 and 40 mumol/session) are not significantly different from that obtained with 80mg/kg. Iron removal is dose related in high plasma ferritin concentration patients: 50 and 100 mumol/session with haemodialysis and 29 and 175 mumol/session with haemofiltration after 40 and 80mg/kg body weight respectively.
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From January 1973 to March 1983, 108 IDD patients with a mean age of 46 years were accepted to the dialysis program of the Hôpital de la Pitié. Since January 1973, 67 patients have been treated by hemodialysis. Since August 1978, 38 patients have been treated by CAPD. Three patients have been treated by intermittent peritoneal dialysis. Although diabetic patients remain at a higher risk compared to patients of the same age group, very encouraging results are observed including a 75% survival rate at three years among hemodialyzed patients less than 50 years old. Since 1978, CAPD, when home dialysis was possible, was selected as a first choice treatment. Some severe peritoneal complications still jeopardize the advantages of this method. Diabetics with ESRD, even in the older age group, should not be excluded from treatment. They should be offered within an integrated program all dialysis methods and transplantation.
In the last eight years 100 insulin dependent diabetics (IDD) have been dialysed at the Hôpital de la Pitié. Since August 1978 31 have been started on continuous ambulatory peritoneal dialysis (CAPD). Cumulative duration of treatment was 336 patient months, with an average time of 10.8 months. The actuarial technique success rate was 82 per cent at one year and 65 per cent at 18 months. Causes of drop out were seven deaths and six transfers to haemodialysis. The peritonitis rate was one episode every year. For some IDD patients and within the period of observation, CAPD offers a unique opportunity to be dialysed at home with excellent clinical and biological results.
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Kinetics of phosphate removal, based on hourly collection of used dialysate or filtrate and hourly changes of phosphate plasma concentration, were studied in hemodialysis (QB 300; QD 500 ml/min), hemodiafiltration (QB 300; QD 500; QSF 25 ml/min), and hemofiltration (QB 250; QSF 70 ml/min) for six 5-hour sessions in each mode of therapy. Whatever the pretreatment phosphate concentration (1.5-2.0 mmol/L range), and whatever the treatment modality used, final plasma phosphate concentration was in the narrow range of 0.8-0.9 mmol/L, and about 50% of the total mass transfer occurred during the first 2 hours. At the third hour, a steady state is reached, suggesting that removal of phosphate is limited by the rate of phosphate transfer from body compartments to extracellular fluid, which was on the average about 362 mumol/kg.hr. Consequently, total phosphate mass transfer accounts only for 20 to 28 mmol per session. Control of pretreatment phosphatemia in the range of 1.5 to 2.0 mmol/L depends on daily phosphate binder prescription, calcitriol supplementation, and control of metabolic acidosis; one cannot rely on intermittent phosphate removal during the dialysis session.