[End stage of chronic kidney disease and metabolic acidosis]. / Konecné stadium chronického onemocnení ledvin a metabolická acidóza.

Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR < 0.3 ml/s/1.73 m2 or, alternatively, to 19% in patients with GFR 0.25-0.3 ml/s/1.73 m2. Notwithstanding the primary cause of the renal disease, declining GFR is associated with compensatory increase in ammoniac production in residual nephrons. This is an adaptive mechanism aimed at maintaining sufficient elimination of acids despite reduced volume of functional tissue. However, an increased ammoniac production simultaneously becomes a stimulus for activation of the complement via an alternative route and is thus one of the factors contributing, through this induced inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of ß2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative effect on patient survival. Alkali substitution from a dialysis solution is the main pillar of metabolic acidosis management in patients on hemo- as well as peritoneal dialysis. Available technologies allow individualization of the treatment and this should be observed.

Negative association between plasma levels of adiponectin and polychlorinated biphenyl 153 in obese women under non-energy-restrictive regime.

The aim of this study was to reveal whether accumulation of the persistent organic pollutants (POPs), especially polychlorinated biphenyl (2,2',4,4',5,5'-hexachlorobiphenyl, PCB 153), affects plasma levels of adiponectin in obese patients. The study was designed as a longitudinal intervention trial with a control group, where 27 obese women (body mass index (BMI)>30 kg/m(2); age 21-74 years) were studied before (OB) and after (OB-LCD) a 3-month low-calorie-diet intervention (LCD; 5 MJ daily). As the control group, 9 female volunteers without LCD intervention were used (C; BMI=19-25 kg/m(2); age 21-64 years). Plasma levels of PCB 153 were measured by high-resolution gas chromatography with electron capture detection; total adiponectin and insulin plasma levels were quantified by immunoassays; and adiponectin multimeric complexes were quantified by immunoblotting. Plasma levels of total adiponectin, high and medium molecular weight multimers significantly negatively correlated with plasma levels of PCB 153 in OB, but not in C or in OB-LCD, whereas the LCD intervention lowered BMI by 3.3+/-3.0 kg/m(2). Our results may suggest suppression of adiponectin by PCB 153 in obese women under non-energy-restrictive regime, which may contribute to the known association of PCB 153 and other POPs with type 2 diabetes.

[Specific aspects of peritoneal dialysis in diabetic patients]. / Specifické aspekty peritoneální dialýzy u diabetiku.

Together with hemodialysis and renal transplantation, peritoneal dialysis is an established method of renal replacement therapy. While evolving in parallel with hemodialysis worldwide, it was not until 1990 that peritoneal dialysis, as we know it today, was introduced to this country when high-quality disposables also became available. In the early 1990s, after adequately increasing the throughput of our dialysis and transplant centers, renal replacement therapy became available to all patients requiring it, that is, also to those with diabetes and other patients with comorbidities in this country. The mortality rates of dialysis-dependent patients with diabetes and chronic renal failure are significantly higher compared with those of dialysis patients without diabetes. This holds true both for hemodialysis and peritoneal dialysis. The survival rates of dialysis patients (with and without diabetes) over the first years of dialysis treatment are higher for those on peritoneal dialysis compared with hemodialysis, presumably because residual renal function is maintained longer with peritoneal dialysis. Peritoneal dialysis in patients with diabetes is usually associated with a higher incidence of peritonitis, but not its complications. This is not the case in our unit where the incidence of peritonitis does not differ significantly between patients with diabetes (1 : 38.9 months) and those without it (1 : 51.4 months). However, peritonitis incidence in our center is kept at levels much lower than accepted by the European guidelines (1 : 24) and those developed by the International Society of Peritoneal Dialysis (1 : 18), and than is usual in current clinical practice. Peritoneal dialysis patients and, in particular, those with diabetes, are likely to benefit from the use of modern peritoneal dialysis solutions containing the glucose polymer icodextrin or amino acids as the osmotic agent instead of glucose, or dialysis solutions with a reduced content of glucose degradation products. Such solutions have been shown to feature improved biocompatibility parameters and lower systemic metabolic load. Some observational non-randomized trials have reported improved survival and a lower incidence of peritonitis in patients both with and without diabetes treated with these modern dialysis solutions. Randomized trials are warranted to confirm these findings.

[Icodextrine peritoneal dialysis solution in clinical practice]. / Icodextrinový peritoneální dialyzacní roztok v klinické praxi.

Icodextrin, a glucose polymer, is an alternative osmotic agent to glucose in peritoneal dialysis solutions. Icodextrin generates ultrafiltration through colloid osmosis and is thus effective even during long-term (e.g., nighttime) dwells and in cases of high peritoneal permeability, where it prevents dialysate reabsorption into the systemic circulation. Ultrafiltration is maintained even in the presence of peritonitis. The incidence of bacterial peritonitis is not different when using icodextrin- or glucose-based solutions. Some time ago, icodextrin use was implicated in an increased incidence of sterile peritonitis. This was due to contamination of some batches of the solution by peptidoglycan present in the cell wall of G+ bacteria. Using exact isotope methods, treatment with icodextrin-based solution has been shown to improve the hydration status of peritoneal dialysis patients, suggesting a potential for improved blood pressure control. Icodextrin-based dialysis is associated with a reduction of left ventricular mass. Given the methodological flaws of trials conducted to date, the acute hemodynamic effects of icodextrin cannot be conclusively interpreted. Inclusion of icodextrin-based solution instead of the glucose-based one into the prescription of peritoneal dialysis decreases the metabolic load with glucose potentially having a beneficial effect on hyperlipidemia, hyperinsulinemia and hyperleptinemia, with improved glycemic control in patients with diabetes as an additional benefit. Function of the peritoneum as a dialysis membrane is stable during icodextrin-based treatment, possibly longer compared with glucose-based solutions. Data derived from a large-scale registry have shown lower mortality oficodextrin-treated patients; this, however, needs to be confirmed by prospective randomized controlled trials.

[Hemodialysis in the treatment of chronic kidney failure. Present status]. / Hemodialýza v lécbe chronického selhání ledvin. Soucasný stav.

In advanced countries haemodialysis treatment is available to all patients with chronic renal failure who need it. At present nephrologists must resolve the problem when it is possible to with-hold long-term haemodialysis treatment, or withdraw it because it no longer leads to prolongation of a good quality life. The results of long-term dialysis treatment depend on the correct timing of its initiation and the quality of nephrological care provided already a long time before the development of renal failure. The morbidity, mortality and quality of life of the patients are influenced in a fundamental way by the quality of provided haemodialysis. An important factor is the dose of dialysis treatment evaluated according to index Kt/Vurea reflecting the urea elimination and obviously also the elimination of other low molecular weight substances. Although prospective controlled trials did not prove so far a favourable effect of haemodialysis membranes permeable for larger molecules ("high-flux" membranes) on the patients' fate, the possible toxic effect of so-called middle molecule substances and peptides with a low molecular weight is assumed. Data suggesting improvement of the quality of life of patients having daily haemodialyses call for further investigations. A still unresolved problem of contemporary haemodialysis systems remains inadequate biocompatibility which leads to reactions associated with possible acute and long-term damage of dialyzed patients.

Fibrinolysis in chronic renal failure, dialysis and renal transplantation.

The best known function of the fibrinolytic system is its ability to dissolve blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion from plasminogen through the action of activators, the most important of which is tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally related to the development of atherosclerosis and associated thrombotic complications, as well as with the development of venous and arterial thrombosis. A chronic decrease in renal function leads to hypofibrinolysis due primarily to low levels of tPA. Hypofibrinolysis is present both in patients treated by long-term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely raises the plasma levels of tPA, primarily as a result of the bioincompatibility of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis solution dwell time is associated with an increase in PAI-I levels in the abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients. In transplant patients, the main abnormality is also hypofibrinolysis which, however, unlike the situation with the other methods of renal replacement therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma levels of PAI-I in transplant patients is played by steroid- and cyclosporine-based immunosuppression, most likely by metabolic disorders such as insulin resistance or dyslipoproteinemia, and by genetic factors. Animal experiments with chronic rejection have shown abnormalities in local fibrinolysis in the graft, particularly increased PAI-I expression. Fibrinolysis defects may contribute to an early and frequent development of atherosclerosis in patients with chronic renal failure, to chronic dysfunction of the renal transplant, or to peritoneal fibrosis and peritoneal catheter obstruction in patients on peritoneal dialysis. The exact role of hypofibrinolysis in the development of these complications, and the potential for modulating it, warrant further research.

[Effect of a dialysis solution with icodextrin on ultrafiltration and selected metabolic parameters in patients treated with peritoneal dialysis]. / Vliv podání dialyzacního roztoku s icodextrinem na ultrafiltraci a vybrané metabolické parametry nemocných lécených peritoneální dialýzou.

BACKGROUND: To date, peritoneal dialysis has been performed almost exclusively using dialysis solutions containing glucose as the osmotic agent. Use of these solutions is fraught with problems regarding adequate fluid removal from the body and is also associated with undesirable metabolic effects; hence the search for alternative osmotic agents. A dialysis solution with the glucose polymer icodextrin generates ultrafiltration on the principle of colloidal osmosis. The aim of the study was to establish the effect of icodextrin-base dialysis solution on the magnitude of ultrafiltration and evaluate selected metabolic parameters of patients treated by ambulatory peritoneal dialysis. METHODS AND RESULTS: A total of 9 patients whose glucose-based solution was replaced by an icodextrin-based solution during the night-time exchange were evaluated. A control group of 9 patients used glucose-solution during all exchanges. Night-time bag ultrafiltration, blood pressure, and the serum levels of lipids, insulin, leptin, maltose, and amylase were determined before icodextrin administration (time 0), at one-month intervals (time 1, 2, 3), and one month after study completion (time 4). In icodextrin-treated patients, ultrafiltration rose from 246.5 +/- 60.5 ml (mean +/- SEM) at time 0 to 593.1 +/- 87.4 ml; p < 0.01, at time 1, to 547 +/- 67 ml; p < 0.05, at time 2, and to 586.7 +/- 58.8 ml; p < 0.01, at time 3, the icodextrin administration led to a rise in maltose from 0.02 +/- 0.01 g/l at time 0 to 0.1 +/- 0.1 g/l; p < 0.01, at time 1, to 1.0 +/- 0.09 g/l; p < 0.01, at time 2, and to 1.1 +/- 0.09 g/l; p < 0.01, at time 3, with a fall to zero values at time 4 (NS). Icodextrin administration was followed by a decrease in leptinemia from 34.6 +/- 17.2 ng/ml at time 0 to 21.7 +/- 8.9 ng/ml; p < 0.05, at time 1, to 21.4 +/- 9.5 ng/ml; p < 0.05, at time 2, and to 15.9 +/- 24.1 ng/ml; p < 0.05 at time 4. Insulin and lipid levels were not affected. There was no change in the above parameters in the control group. Icodextrin-treated patients reduced their antihypertensive medication, but not statistically significantly. CONCLUSION: Icodextrin administration significantly increase ultrafiltration thus providing for effective control of hydration status without the need for high-level glucose-based dialysis solutions. The use of a glucose polymer-based dialysis solution is associated with a significant yet reversible rise in serum maltose. The decrease in leptin may signal a reduction in body weight after replacing glucose in dialysis solutions with icodextrin, or enhanced rates of leptin elimination as a result of ultrafiltration-induced convective transport.

[The role of cytokines in peritoneal dialysis]. / Uloha cytokinu pri peritoneální dialýze.

Peritoneal dialysis is a method of renal replacement therapy which has been increasingly in use worldwide and, in recent years, also in our country. A factor limiting long-term use of peritoneal dialysis is the maintenance of the function of the peritoneum as a dialysis membrane. Impairment of the anatomical and functional integrity of the peritoneal membrane may be due to severe or recurrent peritonitis but, also, in patients without a history of peritoneal infection, presumably as a result of contact between the peritoneum and a bioincompatible dialysis solution. When investigating the structural and functional changes in the peritoneal membrane, considerable attention was given to cytokines. The main source of cytokines in the peritoneal cavity are macrophages, mesothelial cells, and fibroblasts. In peritoneal dialysis, cytokines play a role both in defense against the development of peritoneal infection and in the course of peritoneal infection. By virtue of their biological effects, cytokines may affect the permeability of the peritoneal membrane and, consequently, the efficacy of peritoneal dialysis. In addition, cytokines are released on contact of the peritoneum with the dialysis solution and may thus be made use of in biocompatibility studies. Changes of cytokine levels can be studied--when performing peritoneal dialysis in clinical practice--in the dialysis solution drained from the peritoneal cavity, in tissue cultures, and in animal experiments. The effects of cytokines are modified by the action of their soluble receptors and antagonists. Future studies are warranted to clarify the role of cytokine antagonists and their soluble receptors.

[Renal anemia and the effect of long-term dialysis]. / Renální anémie a úcinnost dlouhodobé dialýzy.

Renal anaemia causes in patients with chronic renal failure numerous serious problems which can be favourably influenced by improvement of the anaemia. There is a number of known factors which cause deterioration of anaemia and make its treatment more difficult. For a long time it was not clear that these negatively acting factors included also insufficiently effective dialysis treatment. The authors of the submitted paper evaluate the relationship between anaemia and the effectiveness of dialysis based on new data reported in the literature and their own results. From this evaluation ensues that inadequate haemodialysis, assessed from the percentage reduction of urea in blood, is associated with a reduced response to recombinant human erythropoietin which is the basic remedy of renal anaemia. If the inadequate intensity of haemodialysis is increased, anaemia improves substantially. In patients on continuous ambulatory peritoneal dialysis (CAPD) there is a direct relationship between the effectiveness of blood purification expressed by the index KT/Vurea, i.e. the indicator of urea elimination, and the severity of anaemia. In patients treated by CAPD there is a significant association between the haematocrit and KT/Vurea supplied by the peritoneum as well as the kidneys. KT/Vurea supplied by the patient's own kidneys is from the aspect of anaemia more significant. Some facts regarding the relationship between anaemia and the effectiveness of dialysis treatment remain obscure so far. This however does not influence the fact that based on data available at present, effective dialysis must be included among basic prerequisites of effective treatment of renal anaemia in dialyzed patients.

The anemia in continuous ambulatory peritoneal dialysis patients is related to Kt/V index.

Anemia in chronic renal failure causes a number of serious problems to the patient. As a result, it is imperative to make use of all rational options to alleviate it. The present study addresses the question, the answer to which is not yet known, whether or not the degree of anemia depends on the efficacy of continuous ambulatory peritoneal dialysis (CAPD) and, if so, what the importance of peritoneal clearance and residual renal function is. A significant correlation between the hematocrit (Hct) and the total weekly Kt/V index (tKt/V) (r = 0.61, p<0.01), total weekly creatinine clearance (tCLCR) (r = 0.50, p<0.05), and residual glomerular filtration rate (r = 0.43, p<0.05) was demonstrated in a group of 22 CAPD patients. Stepwise regression analysis showed that of all the variables monitored, Hct depends exclusively on tKt/V (p<0.01, r2 = 0.37). The value of Hct in a group of patients with a tKt/V <2.3 (n = 15) was 28.9+/-1.2% (arithmetic mean +/- SEM) while in a group with a tKt/V > or =2.3 (n = 7), it was 35.1+/-1.9% (p<0.01). On dividing tKt/V and tCLCR into their peritoneal and renal components, a significant correlation between Hct and renal Kt/V (r = 0.47, p<0.05) was found; stepwise regression analysis identified renal Kt/V (p<0.01) and peritoneal Kt/V (p<0.05), with R2 = 0.38 as major variables with an effect on Hct. The authors conclude the efficacy of blood purification is another factor affecting renal anemia in CAPD patients. The relationship between anemia and blood purification is best expressed using the Kt/V index. The Kt/V provided by one's own kidneys seems to be of greater importance for anemia than the Kt/V provided by peritoneal dialysis. The results provide the basis for prospective interventional studies.

Tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1) in patients treated with continuous ambulatory peritoneal dialysis.

AIM: To establish whether the values of two key enzymes of fibrinolysis, tissue-type plasminogen activator (tPA) and its inhibitor (PAI-1), differ between patients treated with continuous ambulatory peritoneal dialysis (CAPD) and healthy volunteers and whether plasma and dialysate tPA and PAI-1 values vary during one exchange of dialysis solution. METHODS: A total of 11 patients with chronic renal failure, treated with CAPD during the peritoneal equilibration test (in addition with blood sampling at time 0), and a control group of 11 healthy volunteers were examined. To identify the factors involved in the changes in tPA and PAI-1, 9 CAPD patients were subsequently monitored, in a crossover manner, during dialysis with solutions of 1.36 and 3.86% dextrose and off dialysis. RESULTS: Compared with healthy individuals, CAPD-treated patients showed a significantly lower tPA activity (0.39 vs. 0.81 IU/ml, p < 0.05). Changes in plasma fibrinolysis during one exchange of dialysis solution were characterized mainly by a decrease in PAI-1 concentrations and activities caused by the circadian rhythm of fibrinolysis. To explain, in the crossover part of the study, the values of plasma PAI-1 antigen at time 0 (07.00 h) and at time 2 (09.00 h) were 9.4 versus 6.5 ng/ml with the 1.36% solution (p < 0.05), 8.2 versus 4.9 with the 3.86% solution (p < 0.05), and 14.1 versus 9.1 ng/ml off dialysis (p < 0.01). Compared to baseline (0 ng/ml with 1.36 as well as 3.86% solutions), the levels of PAI-1 antigen in dialysis solution rose, apparently due to local production in the peritoneal cavity, to 0.5 ng/ml (p < 0.05) with the 1.36% solution, to 0.7 (p < 0.05) with the 3.86% solution after a 2-hour dwell time, and to 1.6 (p < 0.05) and 1.3 ng/ml (p < 0.05) after a 4-hour dwell time, respectively. Hence, the different dextrose levels in the dialysis solutions had no effect on the monitored parameters of fibrinolysis. CONCLUSION: The lower activity of plasma tPA, and the increase in PAI-1 levels in dialysis solutions may contribute to the development of thromboses in CAPD patients and to fibrin formation on the peritoneal surface with consequences such as peritoneal fibrosis.

[The effect of dialysis solutions containing amino acids on the nutritional status of patients treated with continuous ambulatory peritoneal dialysis]. / Vliv dialyzacního roztoku s obsahem aminokyselin na nutricní stav nemocných lécených kontinuální ambulantní peritoneální dialýzou (CAPD).

BACKGROUND: In the patient population which is subjected to haemodialysis or peritoneal dialysis is a high prevalence of protein-energy malnutrition which independently on the causal factor causes a deterioration of their prognosis. To influence protein nutrition in patients on peritoneal dialysis Nutrineal was developed, i.e., a dialysis solution using as an osmotic agent a 1.1% amino acid mixture instead of glucose used as a rule. The objective of the present study was to evaluate the effect of its administration on some nutritional indicators in patients treated by continuous ambulatory peritoneal dialysis (CAPD) and to assess its tolerance. METHODS AND RESULTS: The authors investigated eight patients aged 45.5 years (29-78 years, median, minimal and maximal value), treated for 19.9 (5-42) months by CAPD. For a period of four weeks Nutrineal was administered once a day instead of glucose based solution to patients without diseases complicating nutrition, with a serum albumin concentration (ALB) below 35 (20-34) g/l. Before treatment and after its termination an anthropometric examination was made, the rate of protein catabolism was examined (PCR), plasma concentrations of total proteins were assessed, as well as ALB, transferrin (TRF) and 14 free amino acids substituted by the dialysis solution. For statistical comparison the paired Wilcoxon test was used. As compared with the baseline value of 0.83 g/kg/24 h after treatment a significant increase of PCR was recorded--to 0.96 g/kg/24 h (p < 0.05) as well as a significant increase of the urea concentration from 18.4 (10.9-34.8) mmol/l to 26.7 (19.6-33) mmol/l (p < 0.05). The value of phosphorus declined significantly from 2.25 (1.6-2.6) to 1.9 (0.9-2.5) mmol/l (p < 0.05). No significant difference was recorded in the anthropometric findings and in concentrations of total proteins, ALB, TRF and amino acids. CONCLUSIONS: Four weeks administration of a solution with amino acids raised significantly the PCR which may be indirect evidence of an anabolic effect and it reduced plasma phosphates which participate in uraemic toxicity. The solution was well tolerated by the patients. Final evaluation of the values of the solution containing amino acids calls for long-term and controlled studies.

Hemocompatibility in hemodialysis and erythropoietin therapy.

Two studies designed to investigate the effect of recombinant human erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on hemocompatibility were conducted. Study 1, whose main aim was to establish whether treatment with rHuEPO enhances coagulation activation during dialysis, included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3% and then during therapy at a HCT of 29.3%. The plasma concentrations of the thrombin-antithrombin III complex were not higher during rHuEPO therapy than before it when performing hemodialysis with a Cuprophan membrane. No significant difference was demonstrated either in the values of activated clotting times (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma C5a concentrations (ELISA) established during dialysis sessions before and during rHuEPO therapy. In Study 2, which focused primarily on the question of whether or not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8 patients on chronic dialysis were examined both before therapy at a mean HCT value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the examinations made during rHuEPO and before rHuEPO therapy; however, statistically significant differences were found between dialysis sessions involving Cuprophan and AN69HF membranes. No significant difference between examination before and during rHuEPO was demonstrated in activated clotting time nor thrombocyte and white blood cell counts in this study either. The authors conclude that rHuEPO therapy does not enhance coagulation activation during hemodialysis, does not have an effect on thrombocyte activation, and does not influence complement activation and changes in white blood cell counts.

[The effect of erythropoietin on fibrinolysis in hemodialyzed patients]. / Vliv erytropoetinu na fibrinolýzu u hemodialyzovaných nemocných.

BACKGROUND: According to some data treatment with human recombinant erythropoietin (EPO) in dialyzed patients leads to a more frequent occurrence of thromboses. One of the possible causes could be reduced fibrinolysis. The objective of the present study was to assess the effect of EPO in dialyzed patients on two key enzymes of fibrinolysis, i.e. the tissue activator of plasminogen (t-PA) and the inhibitor of the plasminogen activator (PAI-1). METHODS AND RESULTS: In eight patients dialyzed for prolonged periods examined under otherwise equal conditions before EPO treatment (haematocrit 22.9%--median value) and after 9.5 weeks of EPO treatment (Recormon, s.c.) when a haematocrit of 30% was achieved, activities (chromogenic substrates) and antigens (ELISA of t-PA and PAI) were assessed. All examinations were made before and after venous occlusion. Between examinations made before treatment and during EPO treatment no significant difference was found in the t-Pa activities assessed before venous occlusion (before EPO 0.9 IU/ml--during EPO 0.6, not significant Wilcoxon's paired test) nor after venous occlusion (3.2-3.8, n.s.). PAI activities before venous occlusion (10.9 U/ml-18.3, n.s.) and after venous occlusion (9.7-11.5, n.s.) did not differ significantly either, when comparing values before and in the course of EPO treatment. Similarly as in the case of activities in antigens t-PA and PAI no difference was found before and during EPO. CONCLUSIONS: No effect of EPO on the investigated indicators of fibrinolysis was found. The results of the presented investigation are at variance with the idea that EPO reduces fibrinolysis in dialyzed patients and thus contributes to the development of thrombotic complications.

[Continuous ambulatory peritoneal dialysis--an effective method of treatment in chronic renal failure]. / Kontinuální ambulantní peritoneální dialýza--úcinná metoda lécení chronického selhání ledvin.

The authors evaluate the results of treatment of continuous ambulatory peritoneal dialysis (CAPD) in seven patient with chronic renal failure during a 12-month period. The baseline examination was made one month before CAPD was started, one day before insertion of a Tenckhoff catheter and then after 1, 3, 6 and 12 months of treatment. The highest assessed mean serum urea concentrations during treatment were 19.8 +/- 2.3 mmol/l (arithmetic mean +/- SE of the mean), creatinine 815.1 +/- 43.1 mmol/l. The haematocrit improved significantly due to CAPD. From the mean value of 22.5 +/- 1.7% recorded one month before treatment it increased to 32.8 +/- 2.5% after 12 months of therapy. In five patients CAPD made it possible to discontinue and in two to reduce antihypertensive medication. During the investigation period the authors did not detect a drop of total protein and albumin in serum. Serum cholesterol increased significantly during treatment. Peritonitis was recorded four times during the total period of 70 months of treatment, i.e. on average one episode during 17.5 months of treatment. Based on their results the authors conclude that CAPD is at present one of the very effective methods of treatment of chronic renal failure. The incidence of peritonitis was already during the first year when treatment was initiated comparable with the results in departments where it is commonly used and after further experience it declined to one episode per 38.8 months of treatment. The method deserves wider application than hitherto.

[Hypofibrinolysis after venous occlusion in patients treated with long-term hemodialysis]. / Hypofibrinolýza po zilní okluzi u nemocných lécených dlouhodobou hemodialýzou.

BACKGROUND: Haemodialysis patients with chronic renal failure suffer not only from thromboses of the vascular access but frequently also from atherosclerosis with thrombotic complications. Knowledge of the etiopathogenesis of thrombotic complications in haemodialysis patients are incomplete. The aim of the present study was to evaluate fibrinolysis at the level of plasminogen activation under conditions of a dynamic test, using methods which reflect sensitively and specifically the activity of the tissue-type plasminogen activator (t-PA) and the activity of the inhibitor of the tissue-type plasminogen activator (PAI-1). METHODS AND RESULTS: The group of examined subjects was formed by 16 patients (9 men and 7 women, mean age 42 years, range 26-63) who suffered from chronic renal failure (causes: 9x chronic glomerulonephritis, 6x interstitial nephritis, 1x polycystic kidneys) treated by long-term haemodialysis on average for 52 (20-110) months; the control group of 11 healthy volunteers was very close as regards age distribution. t-PA and PAI-1 were examined after stimulation by venous occlusion (VO). In healthy subjects VO significantly raises the t-PA activity (first value before, second after VO: t-PA 0.81-2.19 IU/ml, p < 0.01), specific t-PA activity (0.19-0.31 IU/ng, p < 0.05) and t-PA/PAI (0.06-0.24 IU/U, p < 0.01, decreases PAI activity (11.80-10.98 U/ml, p < 0.05) and specific PAI activity (0.52-0.40 U/ng, p < 0.01). In the group of haemodialysis patients VO did not change significantly the t-PA activity (p = NS), the specific t-PA activity (p = NS), nor the ratio of t-PA/PAI (p = NS); the PAI declined significantly (13.78-10.65 U/ml, p < 0.05), similarly as the specific PAI activity (0.97-0.65 U/ng, p < 0.01). From comparison of the results of fibrinolysis from healthy and dialysis subjects ensues that the response to VO in dialysis patients differs from that in healthy subjects. CONCLUSIONS: Dialysis patients have impaired fibrinolysis manifested by a lacking rise of activity of the plasminogen tissue activator after stimulation by venous occlusion. The small rise of t-PA activity after venous occlusion can contribute to the development of thrombotic complications in haemodialyzed patients.

[The effect of erythropoietin therapy on biocompatibility in hemodialysis]. / Vliv lécby erytropoetinem na biokompatibilitu pri hemodialýze.

In order to evaluate the treatment with erythropoietin (EPO) on selected indicators of biocompatibility the authors examined 8 patients dialyzed for prolonged periods before treatment (HTK = 0.23, median), during EPO treatment (Recormon, administered by the s.c. route, HTK = 0.28) in the course of 4-hour haemodialysis on dialyzers with a Cuprophan membrane. The examination before and during treatment was made under equal conditions. Heparinization was also equal despite the fact that during EPO in four patients the residual blood volume in the dialyzer was increased. Comparison of the results before treatment and during EPO treatment did not reveal at any of the collection times (before dialysis, during the 15th, 10th, 60th and 235th minute of the procedure significant differences in the number of leucocytes, plasma concentrations of the C5a complement component, number of thrombocytes and activated coagulation times. Plasma concentrations of the thrombin-antithrombin III complex were in EPO during the 60th minute of haemodialysis significantly lower (p < 0.05) than before EPO. The authors conclude that EPO treatment does not have a significant effect on changes in the number of leucocytes in blood during haemodialysis nor on the activation of complement by an alternative way. EPO does not lead to a greater activation of the coagulation system during haemodialysis; the lower concentration of the thrombin-antithrombin III complex suggests the opposite. Explanation of this finding, similarly as detection of the cause of the increased residual blood volume in some patients, calls for further investigation.