Changing emphasis in modern hemodialysis therapies: cost-effectiveness of delivering higher doses of dialysis.

This paper describes the clinical experience of a therapy concept involving advanced functions of a new dialysis machine system (5008 Therapy System, Fresenius Medical Care, Bad Homburg Germany) that is able to provide adequate Kt/V for patients, while consuming lower amounts of dialysate, water and energy during the treatment. The novel 'AutoFlow' function of this therapy system adjusts automatically the dialysate flow rate according to the effective blood flow rate of the individual patient without compromising the dose of dialysis the patient receives. The new therapy system of Fresenius Medical Care enables a more widespread application of advanced convective treatment modalities in a more affordable manner.

Tolerability and efficacy of multidose epoetin beta (Reco-Pen) for subcutaneous administration in patients with anemia due to renal failure.

AIMS: To assess the tolerability, safety and efficacy of the epoetin beta multidose cartridge formulation, self-administered subcutaneously via a pen device (Reco-Pen), in adult patients with renal anemia. METHODS: Patients receiving maintenance epoetin therapy were switched to the subcutaneous (SC) multidose formulation of epoetin beta (NeoRecormon). The frequency of adverse events, local tolerability, and changes in blood pressure and laboratory variables were recorded. Hematologic parameters, transfusion requirements and epoetin beta dosage were also assessed. RESULTS: A total of 406 patients were entered in the intention-to-treat analysis. Mean treatment duration was 82.3 days. Fifty patients (12.3%) withdrew from the study; 14 (3.4%) discontinued because of adverse events. Treatment was well tolerated, with adverse events considered probably related to treatment in only 5 cases, and 1 case of local intolerability. There were no clinically significant changes in blood pressure or laboratory variables, and no changes in hematologic parameters or transfusion requirements. Unexpectedly, the epoetin beta dose was reduced by almost one-third in patients previously maintained on SC epoetin. CONCLUSION: SC administration of this multidose epoetin beta formulation with the Reco-Pen device was well tolerated and effective. It is possible that the improved capacity to individualize dose may have contributed to the considerable reduction in SC epoetin beta dosage requirement.

High-dose torasemide, given once daily intravenously for one week, in patients with advanced chronic renal failure.

Effects, both acute and after repeated dosing of 200 mg of intravenous torasemide in comparison to baseline values on placebo, were investigated with respect to 24 h fractional volume excretion and electrolyte excretion, signs of peripheral edema and changes in body weight in the present open uncontrolled multicenter study. Fourty-four patients with advanced chronic renal failure (mean creatinine clearance 8.9 +/- 9.6 ml/min, range 1.1-63.7 ml/min) were enrolled after they had given their informed consent. The increase vs placebo in the primary efficacy variable 24 h fractional volume excretion was statistically significant both acutely (p = 0.0001) and after repeated daily injections (p = 0.0012). The acute changes of the means of fractional volume excretion (from 14.32% to 21.07%) and of absolute 24 h urinary volume (from 1303 ml to 2124 ml) were as expected from earlier data. In addition to the acute results our study showed that after seven days of daily injections there was still a considerable diuretic effect (mean fractional volume excretion: 18.10%, absolute 24 h urinary volume: 1664 ml). Our data support earlier results in that the change in fractional potassium excretion was considerably smaller than that of sodium of chloride excretion. However, this effect which was more pronounced after acute administration of torasemide seems to vanish after repeated dosing. After repeated dosing there was only a minor change in calcium excretion and there was no alteration in phosphate excretion, neither acutely nor with repeated dosing. Along with the enhanced diuresis there was a relevant reduction in body weight and a clinical significant improvement preexisting signs of peripheral edema. Torasemide was found to be also efficacious in patients on hemodialysis (with residual diuresis of > or = 300 ml): after the first i.v. dose of 200 mg torasemide the mean fractional volume excretion was increased from 16.22% at baseline by 3.42% to 18.99% (in absolute 24 h urinary volume from 1044 ml at baseline by 563 ml to 1607 ml). In parallel, the mean fractional sodium excretion was increased from 8.67% at baseline by 2.99% to 11.14% (in absolute 24 h urinary sodium excretion from 83.3 mmol at baseline by 51.2 mmol to 128.0 mmol). There was no serious adverse events related to the administration of torasemide. Torasemide appears to be a good choice for the treatment of patients with renal failure.

Comparison of efficacy and tolerance of different oral doses of torasemide and furosemide in patients with advanced chronic renal failure.

In a double-blind, randomised group comparative study the efficacy of daily oral administration of 100 mg and 200 mg torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) were compared with that of 250 mg furosemide over 2 weeks in patients with advanced chronic renal failure, who had been pretreated with a maintenance therapy of 500 mg furosemide per day. Of the 19 patients 7 had been allocated strictly at random to 100 mg torasemide, 6 to 200 mg torasemide and 6 patients to 250 mg furosemide. The volume excretion after administration of 200 mg torasemide was significantly higher than after administration of 250 mg furosemide and non-significantly higher than after 100 mg torasemide. In comparison with baseline values under pretreatment with 500 mg furosemide there was a slight reduction of fluid and sodium excretion in the 100 mg torasemide group and a clear reduction in the 250 mg furosemide group. In contrast, in the 200 mg torasemide group excretion of fluid and sodium increased. The tolerance was good in all 3 groups.

[Ascites as a complication of hepatic storage of hydroxyethyl starch in long-term dialysis]. / Ascites als Komplikation hepatischer Speicherung von Hydroxyethylstärke (HES) bei Langzeitdialyse.

Three adult dialysis patients developed ascites after having received repeatedly the plasma substitute hydroxyethyl starch (HES 40/0.5). In two cases (total dose 180, and 330 g HES, respectively) the ascites was reversible after discontinuation of the HES administration. In the third case (total dose 915 g HES) the ascites could be controlled only by implantation of a Denver shunt. In this latter case it was shown by histological, electron microscopical, and biochemical findings that the ascites was caused by hepatic sinusoidal obstruction due to an extreme storage of HES in the sinusoidal lining cells. Additional storage was detected in hepatocytes, bile duct epithelia, endothelial cells, and fibroblasts in the portal tracts. Biochemically HES was found in liver tissue at a concentration of 4% (w/w). Although in renal impairment plasma clearance of HES is not significantly different from normal individuals, long-term administration of HES must be regarded inadvisable because of tissue storage which apparently is especially significant in this condition.

[The influence of intraoperative autotransfusion (IAT) on plasmaproteins in patients with posttraumatic intraabdominal bleeding or hemorrhage during vascular surgery (author's transl)]. / Plasmaproteine unter dem Einfluss maschineller intraoperativer Autotransfusion (IAT) bei gefässchirurgischer und traumatischer intraabdomineller Blutung.

In 29 patients (12 vascular and 17 trauma cases) the effect of intraabdominal bleeding and surgical management under intraoperative autotransfusion on several plasmaproteins was examined. The following parameters were monitored immediately before and after autotransfusion as well as 24, 48, 72 hours and one week later, in the thawed serum: 1. albumen and the carrier proteins prealbumen, transferrin, retinol-binding protein, 2. acute phase reactants: c-reactive protein coeruloplasmin, haptoglobin, 3. fractions of complement: C1q, C3c, C5 and C 3-activator, 4. serum-cholinesterase. With usual treatment by infusion of electrolyte solutions during operation and the following days, and further applicated blood transfusion, plasma and fresh frozen plasma by clinical needs, while the immediate blood loss during operation was replaced by autotransfusion, there was no change in preoperative dates. Only at the 3rd day the typical picture of catabolic situation of the postoperative period was observed in vascular cases and not at all in trauma cases. Thus the changes were closely related to the preexisting disease or state of shock, without further detoriation by intraoperative autotransfusion. 7 days later a sometimes overshooting normalization of the parameters was observed. Only cholinesterase remained extremely low, especially in vascular cases.

Evaluation of essential amino acids and keto acids in uremic patients on low-protein diet.

The effectiveness of a mixture of five analogues of essential amino acids and the remaining four essential amino acids as compared to a preceeding treatment period of the nine essential amino acids was evaluated in 16 chronic uremic patients fed a low-protein diet. During amino acid analogues supplementation, there was a tendency for blood urea nitrogen to fall whereas creatinine did not change. Serum phosphate decreased in most patients, whereas serum calcium rose in some subjects. Protein metabolism, as judged by serum transferrin, Clq, C3c, total complement activity, was improved. Furthermore, the concentrations of prealbumin and retinol-binding protein, which are elevated in uremia, showed a further increase that might favor a vitamin A intoxication.

[Intraoperative autotransfusion and haemolysis (author's transl)]. / Erste Erfahrungen mit der maschinellen intraoperativen Autotransfusion. Die Haemolyse.

In 29 patients (12 vascular and 17 trauma cases) receiving autotransfusion the effects of haemolysis caused by the Bentley ATS-system were examined. The following parameters were monitored: 1. Overall haemolysis rate and fractions in serum and urine, --2. Total and direct bilirubin in all patients with or without preexisting icterus, --3. Plasma-proteins: Albumen, haptoglobin, haemopexin, transferrin and C3-activator. --In both groups extremely high rates of free haemoglobin in serum were found in some cases. The peak of haemoglobinuria was observed several hours after the autotransfusion or at the end of the operation. The different plasma proteins showed increased activity to cope with haemolysis within the first 24 h. After one week they still showed overshooting levels in some cases which permitted conclusions concerning the extent of the reactions. The transformation of free haemoglobin in bilirubin has to be strongly suspected. The changes of the parameters were not in relation to the volume of autotransfusion. No irreversible complications due to haemolysis caused by the autotransfusion systems were observed.

[On the use of concentrated haptoglobin in the treatment of a haemolytic transfusion accident of the ABO-system (author's transl)]. / Uber die Anwendung von Haptoglobinkonzentrat in der Behandlung eines ABO-bedingten haemolytischen Transfusionszwischenfalls.

The clinical course and the treatment of a case of severe haemolytic ABO-incompatibility are described. In addition to the routine therapy 3 times 2000 units of haptoglobinconcentrate were given since it is known according to the literature to metabolize free haemoglobin. The clinical result seems to confirm the beneficial effect. The course remained free of complications and the hospital stay was not prolonged. Further clinical experience is needed to confirm the effectiveness of the treatment with haptoglobin in cases with severe haemolysis.

[The pros and cons of haemoperfusion (author's transl)]. / Hämoperfusion -- Pro und Kontra.

6 patients with severe self-poisoning were treated by charcoal-haemoperfusion in our centre up to now. In four of them (all suffering from sleeping drug overdosage) the treatment was successful. Two patients with intoxications by agrochemicals died in spite of haemoperfusion. Side effects of haemoperfusion were drops of blood pressure and platelet count, depletion of immune bodies, and adsorption of remedies. Up to now, the indication for haemoperfusion has to consider these secondary actions of encapsulated charcoal as inevitable.

[Lysozyme and beta2-microglobulin in cerebrospinal fluids from healthy children and in children with diseases of the central nervous system (author's transl)]. / Lysozym und beta2-Mikroglobulin im Liquor gesunder Kinder und bei Kindern mit Erkrankungen des Zentralnervensystems

Lysozyme is absent from normal cerebrospinal fluid (C.S.F.) and in C.S.F. from children with viral meningitis. Appreciable amounts of lysozyme were noted in C.S.F. from children with bacterial meningitis (0.23 +/- 0.14 mg/100 ml) and cerebral convulsions (0-0.82 mg/100 ml). The C.S.F.-lysozyme content is a sensitive indicator for bacterial meningitis and important in the differential diagnosis between viral and bacterial meningitis. The beta2-microglobulin content of C.S.F. in healthy children was 0.11 +/- 0.05 mg/100 ml; in children with viral meningitis 0.20 +/- 0.06 mg/100 ml and in children with bacterial meningitis 0.44 +/- 0.17 mg/100 ml. Children with cerebral convulsions had also a rise in C.S.F. beta2-microglobulin.

Hemodynamics and myocardial electrolyte (k+/na+) metabolism early in hemorrhagic shock during asphyxia.

In tests on guinea pig hearts in situ asphyxia tolerance was found to be increased early in hemorragic shock four times control value. These results are suggestive of an energy saving mechanism in shock whereby the heart is not damaged out metabolically relieved. Myocardial analyses showed that, owing to shock-related cardiac relief, under a simultaneous asphyctic stress the intracellular potassium stock decreases later and markedly less.

[Nutrition problems in kidney diseases]. / Ernährungsprobleme bei Nierenerkrankungen

The practice of dietetic therapy is unusual today for patients suffering from renal failure without hypertension and reduction of glomerular filtration rate. Specific treatment is needed, however, for arterial hypertension, uremia, calculus and uralith disease. Experiments in rats showed, that a lot of uremic symptoms following poorly functioning kidneys are partly at least caused by disturbances in amino acid metabolism. Uremia patients with dysfunctioning plasma protein metabolism (transferrin, complement, cholinesterase, prealbumin and retinolbinding protein) need oral, respectively parenteral substitution of essential amino acids. This substitution is very important under catabolic stress conditions in uremic syndrome with and without vividialysis treatment.

[Haemoperfusion with activated charcoal and ion exchanger in phalloidin intoxicated rats (author's transl)]. / Hämoperfusion mit Aktivkohle und Ionenaustauscher bei phalloidin-vergifteten Ratten

Amberlite-XAD-4 and activated charcoal haemoperfusion permit a considerable increase in 14C-methyl-phalloin elimination in vitro which surpasses the effect of haemodialysis treatment. However, in the in-vivo experiment using phalloidin intoxicated rats (1.5 or 2.0 mg/kg i.v.) prolongation of the survival period could not be attained 0y haemoperfusion.

Suitability of non-glucose-carbohydrates for parenteral nutrition.

Postoperative parenteral nutrition can only be optimally effective if the characteristics of post-traumatic metabolism are taken into account. Two main possibilities are discussed for the carbohydrate component of parenteral nutrition during this phase: glucose with high doses of insulin or non-glucose carbohydrates (sugar substitutes) possibly in a suitable combination with glucose. The risks as well as the technical and organisational problems involved in the use of them are discussed and the authors prefer the second of the two alternatives. Possible side effects of non-glucose carbohydrates are pointed out and it is shown how these can be avoided by observing dose guidelines. So far a combination of frucose : glucose : xylitol in a ratio of 2 : 1 :1 with a total dose of 0.50 g/kg/hour has been studied most thoroughly. This combination normalises the fat metabolism and improves glucose tolerance without requiring exogenous insulin. Experiences with this combination as well as individual non-glucose carbohydrates on operated patients have been given continuously for up to 7 days and in some cases even for several weeks. No side effects, no deviations from a steady state and no abnormal changes of the laboratory values occurred. The authors are of the opinion that non glucose carbohydrates are necessary if the facilities for frequent blood sugar controls are not available.

[Importance of postoperative parenteral feeding--measured by low and high-molecular plasma proteins]. / Bedeutung der postoperativen parenteralen Ernährung--gemessen an nieder- und hochmolekularen Plasmaproteinen

By continuous parenteral administration of carbohydrates, combined with essential amino acids and L-histidine, a significant improvement in urea nitrogen and plasma protein metabolism could be obtained in 24 patients during the first ten days after abdominal surgery. A comparable control group of 15 patients who received only water, electrolytes and vitamins in the postoperative phase showed significantly worse results. The observation that under the influence of parental nutrition the beginning azotemia and the deficit of immunoglobulins especially of the complement components improved more quickly after the stress of surgery seems to be an important clinical aspect. At the same time it became evident that adequate parenteral nutrition can have a significant effect on the postoperative behaviour of some plasma proteins (retinol-binding protein, albumin,transferrin, prealbumin).

Long-term effects of essential amino acids supplementation in patients on regular dialysis treatment.

18 patients on RDT receiving a high caloric diet with daily protein intake of 1 g/kg body wt demonstrated a decreased serum concentration of total protein, albumin, transferrin and several components of the complement system (except C4). Long-term administration (60 weeks) of essential amino acids (EAA) and histidine at the end of each hemodialysis improved the serum concentrations of the investigated proteins, whereas the serum concentration of inorganic phosphorus decreased slightly. Interruption of the EAA therapy for 16 weeks in the 13 patients studied resulted in a decrease of transferrin and various factors of the complement system.