[Cyclosporin A in the therapy of nephrotic syndrome]. / Ciclosporin A in der Therapie des nephrotischen Syndroms.

The altered permeability of the glomerular capillaries for plasma proteins in nephrotic syndrome (NS) appears as a consequence of immunological or autoimmunological processes. Increasing knowledge concerning the action of cytokines on the permeability of the vascular barrier, and the possibility to suppress their production with ciclosporin A (CsA), especially of the cytokine interleukin-2, made its therapeutic use for the treatment of NS reasonable. On the basis of clinical data the following conclusions are made with respect to the relevancy of CsA for the treatment of NS: 1. CsA affects the NS of histological different glomerular diseases. 2. CsA acts better in steroid-sensitive or steroid-dependent NS than in steroid-resistant NS. 3. The response to CsA is higher in NS due to minimal change nephropathy (MCN) than in NS due to focal glomerular sclerosis (FSGS). 4. CsA seems to influence some of steroid-resistant NS due to FSGS, membranous glomerulonephritis (MGN) and IgA nephropathy (IgAN). 5. As with steroids, a relapse of NS due to CsA withdrawal and in consequence a dependency may appear with a higher risk for side effects during long-term treatment.

Elimination of vancomycin during hemofiltration.

The study was designed to establish guidelines for vancomycin treatment of patients with acute renal failure undergoing hemofiltration. During 27 hemofiltration treatments in four anuric patients requiring daily consecutive hemofiltration therapy, plasma levels and elimination rates of vancomycin were measured. Regression analysis of the initial vancomycin concentration versus the total amount of vancomycin eliminated showed a clear linear relationship (r = 0.91), thus permitting prediction of the total elimination via hemofiltration by measurement of the initial plasma concentration. Applying these calculations the dosage in patients undergoing hemofiltration can be determined by monitoring the initial plasma concentration. The findings also indicate that hemofiltration is an effective method for treatment of vancomycin intoxication.

Early detection of amatoxins in human mushroom poisoning.

Amatoxins were detected radioimmunologically as early as 90-120 min after ingestion in the gastric fluid and urine of a 15-year-old boy who tried to commit suicide by ingestion of wild mushrooms. This early detection of amatoxins in the urine is proof of rapid absorption from the intestinal tract and subsequent excretion by the kidneys in man.

Efficacy of membrane filtration, influence on hemostasis, immunoglobulins and inflammation mediators during daily plasma exchanges.

Plasma exchange (PE) by membrane filtration was performed with the following hollow fibers: cellulose-diacetate (Plasmaflo 01, Plasmaflo 02, Asahi, Japan), polypropylene (Plasmaflux, Fresenius, FRG) and polymethylmethacrylate (Plasmax, Toray, Japan). The elimination-coefficient (EC) for certain plasma proteins was calculated. With all hollow fibers no correlation between the EC for about ten plasma proteins with a molecular weight of 54.000 dalton up to 2.400.000 dalton. The mean EC-values for the fibers studied were: 0.32 (Plasmaflo 01), 0.52 (Plasmaflo 02), 0.52 (Plasmaflux) and 0.58 (Plasmax). Membrane filtration performed with the single needle technique using either Plasmaflo 02 or Plasmaflux resulted in a significantly lower efficiency with mean EC-values of 0.33 and 0.32 respectively. After three or four days of PE treatment using three liters of 3% human albumin solution as replacement fluid several alterations in parameters of hemostasis were altered: Antithrombin III levels dropped to 35% of normal value after each plasma exchange but increased to normal range within 24 hours during the observed period of four consecutive PE, Fibrinogen concentration dropped permanently to a preexchange value of 40% of the initial concentration after three plasma exchanges. A 40-50% decrease was also observed for prothrombin, plasminogen and alpha-2-macroglobulin after plasma exchange. A decrease in the platelet count ranging from 5 to 25% after each plasma exchange was observed but returned to the initial level before the next treatment. The concentrations of IgG IgA and IgM decreased to less than 20% of preexchange values and C 3 and C 4 to 20-30: of preexchange values after three plasma exchanges.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrashort hemodiafiltration: efficiency and hemodynamic tolerance.

During hemodiafiltration, solutes are removed simultaneously by diffusion and convection. Increase of the fraction removed by diffusion, by using large surface area hemodiafilters, allows a further reduction of treatment time by hemodiafiltration. To assess the efficiency and biochemical safety of ultrashort treatment (mean duration 3 X 105 +/- 14 min/week) six patients (age 22-64) have been observed for six months. There were no differences in the clinical state or in the biochemical parameters compared to those found during the preceding hemodialysis period (3 X 240 min/week). In a second study, hemodynamic measurements in six individual patients aged 34-72 have been compared during a 90 min ultrashort hemodiafiltration (90 min) and during a 240 min hemodialysis. Circulatory stability was maintained during hemodiafiltration despite a rate of fluid removal that was 2.5 times that which occurred during hemodialysis. During both techniques there was a reduction of stroke volume and an adequate norepinephrine-induced rise of peripheral resistance. Plasma levels of vasopressin did not change during treatment. There were no differences in the frequency and quality of premature ventricular beats between the two treatments. The data from the two studies suggests that ultrashort hemodiafiltration (3 X 1.5-2 hr/week) provides biochemical safety as well as hemodynamic stability.

Influence of middle molecules on the anemia of uremic patients.

To evaluate their toxicity at the cellular level, middle molecules from uremic serum were incubated with erythrocytes from healthy subjects and the activity of the enzyme Delta-aminolevulinic acid dehydrase (D-ALA-D) and peroxidative hemolysis were investigated. Uremic middle molecules caused a significant decrease of the D-ALA-D activity of normal erythrocytes which was not due to differences in the concentrations of Pb, Cd or Zn. The decreased enzyme activity could be restored by adding reduced glutathione (GSH; 5 mmol/L) together with the middle molecules to the assay system. Uremic middle molecules caused a significant increase of peroxidative hemolysis in normal erythrocytes. Uremic middle molecules contribute to the anemia of uremic patients by impeding hemoglobin synthesis and by increasing peroxidative hemolysis, possibly by affecting SH-groups. H2O2-producing compounds should be avoided in uremic patients.

Hemodiafiltration: a new alternative to hemofiltration and conventional hemodialysis.

A new dialysis method, termed hemodiafiltration, is proposed. The procedure consists of the combination of hemofiltration and conventional hemodialysis using high flux membranes with a transmembrane pressure (TMP) of 300--500 mmHg and a dialysate flow of 900 ml/min. Due to the combination of convective mass transfer and diffusion, the clearance values of both small and larger molecules are significantly higher than during hemofiltration or hemodialysis alone with the same membranes. The removal of excess water is better tolerated than during hemodialysis. With this new method, six patients have been successfully treated for six months (three times per week, three hours per treatment) without side effects. Thus hemodiafiltration appears to be the method of choice to shorten dialysis time.

Simultaneous hemofiltration/hemodialysis: an effective alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients.

Hemofiltration and hemodialysis were performed simultaneously with the Polyacrylnitrile membrane in a single pass dialyzate flow system. Due to the combination of convective mass transfer and diffusion, the clearances of both small and large molecules were significantly higher than during hemofiltration or hemodialysis alone. The removal of excess water was better tolerated than during hemodialysis. Six patients have been treated by this technique for 6 months 3 X 3 hr/week without side effects, and the new procedure appears to be the method of choice to shorten dialysis time.