In the present in vitro study we investigated filtration and adsorption of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) during predilution and postdilution hemofiltration with polysulfone, polyacrylonitrile, polyamide and cellulose triacetate membranes. The median sieving coefficient (SC) for all membranes was 0.0 for TNF-α, below 0.15 for IL-6 and below 0.15 for IL-8 during postdilution hemofiltration. Differences in SC between filtration modes were less than 0.05. Maximal differences in SC between membranes were 0.11 for IL-6, 0.0 for TNF-α, and 0.11 for IL-8. The progressive decrease in cytokine concentrations was identical between the two filtration modes and most pronounced with the polyacrylonitrile membrane (reduction 77% for IL-6, 39% for TNF-α and 95% for IL-8 after 4 h of hemofiltration). The relative contribution of adsorption to the reduction in cytokines was 100% for TNF-α for all membranes, between 53 (cellulose triacetate) and 83% (polyacrylonitrile) for IL-6, and for IL-8 between 0 (polysulfone) and 100% (polyacrylonitrile). In conclusion, the reduction in TNF-α, IL-6 and IL-8 was most impressive with the polyacrylonitrile membrane after 4 h of hemofiltration and was largely due to adsorption. Adsorption of TNF-α, IL-6 and IL-8 was also seen with the other membranes. None of the membranes filtered TNF-α. Sieving of IL-6 and IL-8 was low for all membranes with only marginal differences between membranes or between filtration modes.
The effects of daily administration of 250-2,000 mg furosemide (F) were studied in patients on hemodialysis who still had residual renal function. In a short study, 10 patients (endogenous creatinine clearance 0.6-5.3 ml/min/1.73 m2) used 1,000 mg F twice daily during 7 days, and in a long-term study 13 patients (endogenous creatinine clearance 0.7-6.8 ml/min/1.73 m2) were treated during 1 year with 250-1,000 mg F orally each day. In the short study, we observed an increase in the 24-hour volume excretion with a median of 109% (p < 0.005). Urinary sodium excretion increased 210%, chloride 346% and potassium 65% when compared with the control period. In the long-term study, a marked initial rise in diuresis and electrolyte excretion was found. However, during a 1-year follow-up, a gradual decrease in response with time was found caused by progression of renal disease. There were no signs of ototoxicity. Side effects were bollous dermatosis on the limbs after exposure to sunlight during the summer (3 patients). We conclude that high-dose F is effective in patients on hemodialysis with residual urinary production. However, in the long term, the diuretic effects diminish because of progression of the underlying renal disease.
Renal function contributes markedly to the adequacy of continuous ambulatory peritoneal dialysis (CAPD). The best way to measure it in clinical practice has not been established. Ten stable CAPD patients with residual renal function were investigated to compare the GFR measured as inulin clearance (Cli) with the creatinine clearance (Clc), the urea clearance (Clu), and with 0.5(Clc + Clu). Thereafter, an analysis of whether the administration of cimetidine could improve the accuracy of these clearances was performed. Two clearance periods (CP) of 24 h were investigated. During CP-2, patients received 400 mg cimetidine twice daily, for a total dose of 1200 mg. Two h before the urine and dialysate collection period, inulin was administered iv. Calculations were done for each CP for Cli, Clc, Clu, Clc-Cli, the Clc/Cli ratio, and the tubular secretion of creatinine (TSc). No differences between CP-1 and CP-2 were present for urinary excretion of volume and solutes, and clearance rates of inulin and urea. The median TSc decreased from 0.71 mumol/min (range, -0.24 to 5.90) in CP-1 to 0.30 mumol/min (range, -0.18 to 0.64) in CP-2 (P < 0.05). Therefore, the median ratio of Clc/Cli decreased from 1.23 (range, 0.87 to 2.20) in CP-1 to 1.11 (range, 0.95 to 1.51) in CP-2 (P < 0.05). The median overestimation of the Cli in CP-1 by the Clc was 0.90 mL/min (range, -0.28 to 3.80) and by the 0.5(Clc + Clu) was 0.30 (range, -0.67 to 1.52). The median overestimation of Cli during cimetidine treatment in CP-2 was 0.43 mL/min (range, -0.21 to 1.20). The range, in differences between Cli and Clc, in CP-2 was smaller than that between Cli and 0.5(Clc + Clu) in CP-1. The difference between the clearance rate of inulin and creatinine or the combined clearance rate of urea and creatinine was not influenced by the magnitude of the average GFR. It can be concluded that the administration of cimetidine improved the accuracy of measuring the GFR with the Clc in CAPD patients.
Small solutes clearances cannot be increased by furosemide. Increasing the instilled volume of dialysis fluid and the number of exchanges both affect solute clearance. Studies are necessary on long-term effects of manipulation of the peritoneal membrane with nitroprusside.
These results confirm the increased platelet turnover in patients with chronic renal failure. Moreover this study shows that the kidney does not seem to play a major role in the overall Tpo production in the body.
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