Concentration of Lp(a) and other apolipoproteins in predialysis, hemodialysis, chronic ambulatory peritoneal dialysis and post-transplant patients.

Serum levels of lipids, lipoprotein(a) Lp(a) and other apolipoproteins were determined in 47 predialysis patients, 40 hemodialysis (HD) patients, 39 chronic ambulatory peritoneal dialysis (CAPD) patients, 11 patients after kidney transplantation and 47 healthy subjects as reference group. The predialysis, HD, and CAPD patients had disturbances in the concentration of serum triglyceride (TG), high density lipoprotein (HDL)-cholesterol, apolipoprotein AI (apoAI), total apoCIII, apoCIII present in the particles without apoB (apoCIII non B), and Lp(a) and HDL-cholesterol, low density lipoprotein (LDL)-cholesterol/HDL-cholesterol, HDL-cholesterol/apoAI, apoAI/apoB, and apoAI/apoCIII ratios. Predialysis patients had significantly lower concentrations of HDL-cholesterol and total apoE levels than CAPD patients and total apoE level than HD patients. Moreover, both HD and CAPD patients had significantly increased levels of apoB containing apoE (apoB:E) and apoB containing apoCIII (apoB:CIII). The concentrations of serum TG, total cholesterol, LDL-cholesterol, apoB, Lp(a) in CAPD patients were statistically higher than in HD patients. The patients after transplantation demonstrated normalization of lipid and lipoprotein parameters and lipoprotein ratios except serum levels of TG, total apoCIII, apoCIII non B and the apoAI/apoCIII ratio. We concluded that abnormal lipid and lipoprotein concentrations in patients with uremia may be the cause of their high risk of atherosclerosis, but posttransplant patients exhibited improved levels of serum lipids, Lp(a) and other lipoprotein parameters and lipoprotein composition, which could be an index of decreased atherogenic status.

Lipoprotein profiles at different stages of chronic renal insufficiency.

BACKGROUND: Lipoprotein abnormalities characteristic of renal dyslipoproteinemia are significantly associated with different stages of chronic renal insufficiency. The renal dyslipoproteinemia may contribute not only to accelerated development of atherosclerosis but also to progression of human chronic renal insufficiency. METHODS: The purpose of the studies was to estimate the lipid and lipoprotein profiles in 52 not dialysed patients with various renal insufficiency advancement. Basing on creatinine level the patients were divided into 3 groups. CR1-A--serum creatinine 2-5 mg/dL (n = 16), CR1-B--serum creatinine 5-10 mg/dL (n = 19), CR1-C--serum creatinine > 10 mg/dL (n = 17). RESULTS: In CR1-A and CR1-B dyslipoproteinemia was found at different stages of renal insufficiency which was manifested by the significant increase of TG, TC, LDL-C, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and significant decrease of HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in comparison with controls. We also observed decreased TG, TC, LDL-C, apo AI, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and unchanged HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in cm-c in comparison to CR1-A. The decrease of the lipoprotein parameters in CR1-C might result from malnutrition (statistically decreased albumin level) and metabolism disturbances connected with the renal insufficiency advancement. Negative correlation between IG, HDL-C levels (r = -0.43, p < 0.001) and TG, IIDL-C/apoAI (r = -0.56; p < 0.001) were found, which confirmed the abnormal composition of HDL molecules and indicated a high risk of atherosclerosis. CONCLUSION: Our results may indicate that of atherosclerosis in CR1 patients is connected with dyslipoproteinemia and disturbances in HDL molecular composition and with different stages of chronic renal insufficiency.

Lipid and lipoprotein ratios as risk factors of atherosclerosis in patients with chronic renal insufficiency (CRI).

The serum levels of lipids, apolipoproteins and lipoprotein ratios in 19 healthy persons and 20 patients with uraemia not dialyzed were determined. Based on creatinine level the patients were divided into two groups: L (serum creatinine 2-5 mg/dl) and H (serum creatinine 5-10 mg/dl). Dyslipoproteinaemia in uraemic patients is already manifested in the early stages of the disease through its abnormal apolipoproteins rather than lipid profile and it suggests a high risk of atherosclerosis.

Subcutaneous r-HuEPO therapy in CAPD patients: dose determination and clinical experience.

We present our results on the efficacy and safety of low dose r-HuEPO given subcutaneously in the treatment of anaemia in CAPD. We have studied 10 stable patients (5 males, 5 females) on CAPD. In our study subcutaneous r-HuEPO was administered twice a week for 6 months. Mean initial dose of r-HuEPO was 67.3+/-21.7 U/kg/week, and maintenance dose was 35.8+/-12.1 U/kg/week. The target Hb concentration was 10-12 g/dl. All patients responded to r-HuEPO. During treatment significant increases of haemoglobin concentration (p<0.05), haematocrit (p<0.05), red cell count (p<0.05) and reticulocyte count (p<0.05) were observed. We found no significant changes in total white cell or platelet counts. Long-term r-HuEPO treatment did not influence significantly plasma levels of electrolytes (Na, K, Ca), urea and creatinine. We found no significant changes in ultrafiltration volumes. In the present study the mean systolic and diastolic blood pressures did not change. Liver function tests were normal at the beginning and at the end of the study. r-HuEPO treatment was associated with a decrease of ferritin (455+/-90 vs. 224+/-83 microg/l. Oral or intravenous iron substitution became necessary in 6 patients. Side effects in our study were minimal; one patient had myalgia after the first seven doses but this disappeared as treatment was continued. Two patients reported pain (mild) at the injection site. In the present study, the correction of anaemia was accompanied by a substantial improvement in the quality of life, mainly in capacity for work, household and social activities.

Effect of dialysis membranes on lipoprotein profile of serum in haemodialysed patients.

The subjects of the studies were 31 haemodialysed (HD) patients with chronic renal insufficiency (CRI). In this group of patients the lipoprotein profile was determined and 8 patients were selected for further studies. During the study the patients were treated with cuprophane membranes for 6 months. For the next 6 months the same patients were treated using polysulfone dialysers, and for further 6 months HD with polysulfone dialysers was continued. Patients' sera were tested after every 6 months of treatment. The delta values were calculated as 6-month HD with polysulfone minus 6-month HD with cuprophane (deltaI) and 12-month HD with polysulfone minus 6-month HD with polysulfone (deltaII). We concluded that after long-term HD with low flux polysulfone treatment the lipoprotein profiles improved, but the mechanism of the process is not clear.

Serial cytokine changes in peritoneal effluent and plasma during peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD).

OBJECTIVE AND DESIGN: Secretion of IL-2 and sIL-2R in the peritoneal dialysis fluid and in the peripheral blood during peritonitis with reference to the process of IL-6 and IL-8 release were investigated. SUBJECTS: 17 patients with end-stage renal disease, treated with continuous ambulatory peritoneal dialysis. METHODS: ELISA method using commercial kits, Genzyme Corp Boston and DAKO. RESULTS: Markedly increased IL-6 (mean; 2895 +/- 1360 pg/ml) and IL-8 concentration (1459 +/- 966 pg/ml) in drain dialysate fluid at the onset of peritonitis, started to drop rapidly in the successive samples after antibiotics had been administered. Statistically significant increase of IL-2 (197 +/- 92 pg/ml) and sIL-2R (287 +/- 79 pg/ml) was observed 16 h later and kept increasing until reaching the peak after 24 h. CONCLUSION: Secretion of IL-6 and IL-8 pro-inflammatory cytokines which are mainly synthesized in mesothelium cells is followed by the activation of lymphocytes, their infiltration and the production of T lymphocyte derived IL-2 and sIL-2R.

Influence of some immune factors on the IL-6 and soluble IL-2 receptors in haemodialysed patients.

In respect to the immune deficiency state of long-term haemodialysed patients, both cytokines and their receptor disturbances have been taken into consideration. The purpose of our study was to evaluate the effect of uraemic and haemodialysis factors on the interleukin-6 and interleukin-2 soluble receptor levels and the reactivity after influenza vaccination. We have found that IL-6 and IL-2 receptor levels were statistically significantly elevated (98.8 +/- 39 pg/ml and 1557 +/- 544 U/ml, respectively) in serum of haemodialysed patients. The fact that increased immune complexes statistically correlated with soluble IL-2 receptor levels (p < 0.01) was very interesting for us. In order to study the immunological response after vaccination, 10 patients have been investigated after influenza vaccination. Plasma samples were collected before, as well as 1 and 4 weeks after vaccine administration. Antibody titres measured by haemagglutinin inhibition showed decreased antibody levels in haemodialysed patients. We conclude that the interleukin disturbance and the elevated interleukin-2 receptor levels together with the presence of circulating immune complexes can influence in some way the immune response of haemodialysed patients.

Influence of intraperitoneal vancomycin on peritoneal dialysis efficiency. A clinical study.

Peritonitis is a major complication of intermittent peritoneal dialysis (IPD); over 70% of the infections are caused by Gram-positive bacteria. Vancomycin (V) is the antibiotic of choice in the treatment of peritonitis caused by G(+). The influence of vancomycin on peritoneal transport in IPD patients has not been described before. We have investigated the effect of intraperitoneal vancomycin on dialysis efficiency in 8 IPD patients using dialysis solutions containing either lactate or acetate. The following parameters were measured: net ultrafiltration (UF), concentration ratios (D/P) of urea, creatinine, potassium, peritoneal clearances (ml/min) of urea, creatinine, potassium, mass transfer of sodium (MTNa), sodium sieving index (SCNa). It has been found that vancomycin significantly decreases D/P urea (p < 0.05) and creatinine (p < 0.05). We found also a significant decrease of mean clearance of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not change significantly. There was no significant change in UF, MTNa, and SCNa. Our preliminary data suggest that vancomycin decreases the permeability of peritoneum for certain low molecules in IPD patients which may have a negative impact on dialysis efficiency.

Plasma lipoproteins in patients with chronic renal failure (CRF).

The clinical picture in chronic renal failure (CRF) shows great variability depending on age, sex, aetiology of disease, grades of renal injury and type of treatment. Significant increases of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and and apo B concentrations, significant decreases of high-density lipoprotein cholesterol (HDL-chol) levels and apo A and apo AI concentrations, and no significant changes in total cholesterol (TC) have been shown in CRF patients. Significant increases of TC/HDL-chol, LDL-chol/HDL-chol, apo B/apo AI and apo B/LDL-chol ratios were also demonstrated. That indicates a high risk of atherosclerosis even when total cholesterol levels are in the normal range. There were highly significant and positive correlations between TC/HDL-chol and LDL-chol/HDL-chol ratios, apo B and LDL-chol concentrations as well as between the apo B/apo AI and LDL-chol/HDL-chol ratios.

[Expression of platelet activation markers--selectin P and glycoprotein CD63 during hemodialysis]. / Ekspresja markerów aktywacji plytek krwi--selektyny p oraz glikoproteiny CD63 w czasie hemodializy.

The bleeding tendency is a common feature of chronic uremia. Abnormalities of platelet function play a role in the pathogenesis of this disorder. A direct contact between platelets and an artificial dialysis membrane results in strong activation of thrombolysis. The aim of our study was to investigate platelets activation in vivo during haemodialysis. We used monoclonal antibodies specific against platelet activation markers--selectin P (CD62) and glycoprotein CD63. The expression of those antigens was analyzed by flow cytometry. Blood samples were obtained from 20 long-term haemodialysed patients with end-stage renal disease. After 15 minutes of haemodialysis the expression of CD62 and CD63 was significantly higher (p < 0.001) as compared CD63 glycoprotein. Our results show that haemodialysis has a significant influence on platelet activation and can favour co-existence of the bleeding tendency and the prothrombotic status in long-term hemodialyzed patients.

Influence of indobufen on occlusion of arteriovenous fistulas and some platelet activity in intermittent peritoneal dialysis patients.

Thrombotic complications constitute a significant problem connected with maintaining arteriovenous fistulas (A-V) for a long time. It has been established that platelets play an important role in the development of thrombosis in high flow systems. Aspirin and dipyridamole do not decrease the frequency of shunt thrombosis. Some of the more recently synthetised antiplatelet drugs (i.e. indobufen, 2-p-oxo-isoindolinyl-phenyl-butyric acid) could be promising in the prevention of such complications. The study group consisted of 40 patients in the terminal stage of renal failure treated with intermittent peritoneal dialysis (IPD). The A-V fistulas were formed by the same surgeon anesthetist team and this allowed for the elimination of technical errors. All patients were divided into two groups. Group I received indobufen at the dose of 2 x 100 mg/24 h orally. Group II received no antiplatelet treatment. The therapy started 24 h before A-V formation. The treatment was continued for 3 weeks. The following tests of platelet function were performed before indobufen therapy, after 9 h and 3 weeks of treatment: ADP and adrenaline induced platelet aggregation, platelet circulating aggregates, MDA level, platelet factor 3 and 4 and bleeding time. During indobufen treatment only a significant decrease in ADP induced aggregation was observed. No prolongation of the bleeding time was noted. No case of fistula thrombosis in indobufen group was observed. This complication, however, appeared in 3 patients (15%) of the control group (without antiplatelet therapy).

[The effect of indobufen on platelet function and dialyzer regeneration in patients on hemodialysis]. / Wplyw indobufenu na czynnosc krwinek plytkowych i regeneracje dializatorów u chorych hemodializowanych.

In 16 patients on chronic haemodialysis treatment the platelet activation and function were studied during 2 weeks antiplatelet therapy with indobufen. Followings tests were made: platelet count, platelet aggregation, platelet factor 3 and 4. Indobufen inhibited platelet function, mainly release of platelet factor 4 and improved dialyser regeneration.

Influence of intraperitoneal gentamicin on peritoneal transport in IPD patients.

We have investigated the effect of intraperitoneal gentamicin on dialysis efficiency in 10 intermittent peritoneal dialysis (IPD) patients. The following parameters were measured: net ultrafiltration (UF); concentration ratios (D/P) of urea, creatinine, potassium; peritoneal clearances (ml/min) of urea, creatinine, potassium; mass transfer of sodium (MTNa); sodium sieving index (SCNa). It has been found that gentamicin significantly decreased D/P urea (p < 0.056) and D/P creatinine (p < 0.05). We found also a significant decrease of mean clearances of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not significantly change. There was no significant change in UF, MTNa and SCNa. Our preliminary data suggest that gentamicin decreases the permeability of the peritoneum for certain low molecules in IPD patients, which may have a negative impact on dialysis efficiency.

[The response to the hepatitis B virus vaccine in patients undergoing hemodialysis and peritoneal dialysis--personal experience]. / Odpowiedz na szczepienie szczepionka przeciw wirusowemu zapaleniu watroby typu B chorych hemodializowanych i dializowanych otrzewnowo-doswiadczenia wlasne.

In 55 hemodialyzed and 15 patients on CAPD the presence of hepatitis B and C markers was estimated before the beginning of the vaccination series against hepatitis B with Engerix B vaccine. The initial anti-H Bs antibody titres was also estimated in these patients. The patients without H Bs Ag who have the anti-Hbs titres below 10 IU/I were qualified for this vaccination. The vaccination was needed by 40% of hemodialyzed patients H Bs(-) and 93% patients on CAPD. After completing the half year lasting series of vaccinations, the serological answer in vaccinated patients was estimated. The protective antibody titres above 10 IU/I was produced by 62.5% of patients on hemodialysis and 64.4% of patients on CAPD. The presence of anti-HCV antibodies had insignificant influence on the ability of producing the protective antibody titres in vaccinated patients.

The effect of subcutaneous recombinant human erythropoietin (r-Hu EPO) in CAPD patients with renal anaemia.

Several factors may contribute to the pathogenesis of uraemic anaemia but there is general agreement that inadequate secretion of erythropoietin is the main cause. Recombinant human erythropoietin (r-Hu EPO) is today widely used in the treatment of patients with renal anaemia. Initial studies were conducted on patients receiving haemodialysis (HD) using intravenous dosing, and number of reports have confirmed the efficacy and safety of the hormone. However, there is still limited information on the use of r-Hu EPO in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The cost of this treatment was initially very high. The optimal way of administration of the drug and optimal dosage is still under discussion. More studies are needed to optimize treatment from a clinical as well as an economic point of view. We therefore present our result on the efficacy and safety of low dose r-Hu EPO given subcutaneously in th treatment of anemia in CAPD patients.

[Evaluation of platelet function during treatment with recombinant human erythropoietin (r-HuEPO) in patients hemodialyzed and dialyzed peritoneally]. / Ocena funkcji plytek w czasie leczenia rekombinowana ludzka erytropoetyna (r-HuEPO) u chorych hemodializowanych (HD) i dializowanych otrzewnowo (PDO).

In eight patients with terminal renal insufficiency treated with repeated haemodialyses (group I) and six patients treated with intermittent peritoneal dialysis (group II), the effect was studied of treatment with r-HuEPO on the platelet count and activity. In the studied patients the following was determined: platelet count, ADP-induced aggregation, circulating aggregates, and the third (PF3) and fourth (PF4) platelet factors. The studies were performed before the introduction of r-HuEPO and during the treatment--after achieving of haematocrit increase in the patients to 30%. No significant increase was observed of platelet count or activity. In none of the studied patients the development of thrombotic complications was observed with haematocrit increase to 30%. In both studied groups during the treatment with r-HuEPO a significant increase was found of haemoglobin concentration, red blood cell count, and haematocrit value in relation to the values before starting the treatment.

[Successful pregnancy outcome in a patient with acute renal failure superimposed on chronic renal failure treated with repeated hemodialysis]. / Pomyslinie zakonczona ciaza u pacjentki z ostra, nalozona na przewlekla niewydolnosc nerek, leczonej powtarzanymi hemodializami.

A case is presented of successful pregnancy in a patient with acute renal failure superimposed on chronic controlled renal failure. The cause which led to development of acute renal failure were severe water-electrolyte equilibrium disturbances due to diarrhoea. Appropriately conducted conservative treatment in the period of oliguria, and early institution of treatment with repeated haemodialysis (taking into account the minimal fluctuations of body fluids, and adequate heparinization) were decisive for successful outcome of pregnancy in this patient.

The effect of pilocarpine on electrodermal resistance in chronic hemodialyzed patients.

Electric resistance of forearm skin was examined in 40 hemodialyzed (HD) patients under resting conditions and after subjecting the skin to the action of a 10% pilocarpine gel. The results were compared with a control group of a 100 healthy volunteers. An increased skin resistance was observed before dialysis and then a significant post-dialysis fall to the normal level followed. The response to the applied pharmacological stimulus in the HD group was similar to that in the control group. The results suggest that the rise in skin resistance in patients with renal failure and the so-called uremic dry skin, are not connected with the dysfunction of the glands themselves but rather with their insufficient stimulation.