No impact of hyperkalaemia with renin-angiotensin system blockades in maintenance haemodialysis patients.

BACKGROUND: Renin-angiotensin system (RAS) blockades, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well accepted for the cardiorenal-protective benefits added to antihypertensive effects in chronic kidney diseases (CKD), but associated with an increased risk of hyperkalaemia. However, few studies have investigated the effect of RAS blockades on serum potassium in dialysis patients. METHODS: Hyperkalaemia associated with RAS blockades by ACEI and/or ARB was evaluated in 69 patients on maintenance haemodialysis, who underwent a three-period crossover study in four groups (no exposure to RAS blockades, ACEI or ARB alone and ACEI plus ARB treatments), lasting one month in each period. RESULTS: Sixty-two patients completed this prospective 3-month study, and no one stopped the study because of the development of hyperkalaemia and/or complications. Mean serum K was similar among the four periods (no exposure, 5.54+/-0.67 mmol/l; ACEI alone, 5.54+/-0.75 mmol/l; ARB alone, 5.50+/-0.66 mmol/l; ACEI+ARB combination, 5.42+/-0.66 mmol/l) and was also equal when compared between the two groups with and without exposure to RAS blockades (5.48+/-0.68 vs 5.54+/-0.67 mmol/l, P=NS). The incidence of severe hyperkalaemic episodes (>6.0 mmol/l) upon monthly predialysis serum K determination was 25.8% with no exposure to RAS blockades, 29.8% for ACEI alone, 19.6% for ARB alone and 17.7% for ACEI+ARB combination without statistically significant differences among the four periods (P=NS). Among covariables, the degree of Kt/V, intakes of other medications interfering with potassium homeostasis and diabetes mellitus did not result in any significant hyperkalaemic changes during the 3-month study period except anuric patients compared with non-anuric patients (5.58+/-0.69 vs 5.19+/-0.65 mmol/l, P<0.001). CONCLUSION: Neither monotherapy (ACEI or ARB) nor combination therapy (ACEI plus ARB) is associated with the additional risk of hyperkalaemia in patients on maintenance haemodialysis. However, those patients with anuria on RAS blockades warrant the cautious monitoring of serum K to prevent hyperkalaemia.     

Pentraxin 3 is elevated in haemodialysis patients and is associated with cardiovascular disease.

BACKGROUND: Pentraxins are mediators of inflammation as well as markers of the acute-phase reaction. While elevation of C-reactive protein (CRP) in patients with renal failure and its association with cardiovascular disease is well described, there are no data on pentraxin 3 (PTX3) in this population. METHODS: Plasma was obtained from 44 chronic haemodialysis (HD) patients, 35 peritoneal dialysis (PD) patients, 39 patients with chronic renal failure (CRF) not on dialysis therapy and 14 age-matched normal subjects. PTX3 production in whole blood was also investigated in samples taken before and during HD. RESULTS: PTX3 plasma levels were significantly higher in HD patients (5.8 +/- 0.6 ng/ml) compared with the other three groups. There were no significant differences between PD patients (1.5 +/- 0.4 ng/ml), CRF patients (1.5 +/- 0.4 ng/ml) and normal subjects (0.76 +/- 0.2 ng/ml). In dialysis patients, PTX3 levels correlated significantly with time on renal replacement therapy (RRT) and with weekly erythropoietin dose. PTX3 levels were significantly higher in patients with coronary artery disease and peripheral artery disease compared with those without. During a single HD session, PTX3 production was higher in whole blood samples taken after 3 h HD compared with samples taken before HD. CONCLUSIONS: PTX3 levels are markedly elevated in HD patients. The increase in PTX3 production in whole blood after HD indicates that the HD procedure itself contributes to elevated PTX3 levels in HD patients. The association between PTX3 and cardiovascular morbidity suggests a possible connection of PTX3 with atherosclerosis and cardiovascular disease in HD patients.     

Determinants of progressive vascular calcification in haemodialysis patients.

BACKGROUND: We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS: We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS: Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION: Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.     

Laparoscopic cholecystectomy in haemodialysis patients

Objective : To study the effect and safety of laparoscopic cholecystectomy in haemodialysis patients. Method : From May 1994 to December 1998, the clinical progress of nine haemodialysis patients who underwent laparoscopic cholecystectomy were reviewed. Results : Eight patients recovered very well from surgery, while one patient had a mild complication of a collection of seroma represented by ultrasound in the gallbladder region. Conclusions : Perioperative management is important when performing laparoscopic cholecystectomy in patients on haemodialysis. Those patients on well‐managed haemodialysis will tolerate laparoscopic cholecystectomy.      

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

Vitamin A and zinc status in patients on maintenance haemodialysis

BACKGROUND: The objective of this study was to assess the vitamin A and zinc serum levels in patients undergoing haemodialysis (HD) in the city of Recife, in the north-eastern region of Brazil. METHODS: The study comprised 55 patients and 28 healthy controls. The retinol and zinc serum concentrations were analysed by using high-performance liquid chromatography (HPLC) and atomic absorption spectrophotometry, respectively. RESULTS: The mean retinol serum concentration in patients (2.50 +/- 0.86 micromol/L) was significantly greater (P < 0.001) than that found in controls (1.26 +/- 0.86 micromol/L). The retinol serum levels in the patients were as follows: 47.3% of the patients had elevated levels (>/= 2.24 and < 3.50 micromol/L); 16.4% of the patients had serum levels >/= 3.50 micromol/L, which indicated hypervitaminosis; and 9.1% of the patients had serum levels below the normal range (<1.05 micromol/L), a rate that among the controls was 42.9% (P < 0.01). In regard to zinc, the serum levels found in the patients (10.59 +/- 3.12 micromol/L) were similar to those found in the controls (11.43 +/- 2.82 micromol/L) (P > 0.05). Although 49.1% of the patients and 35.7% of the controls were classified as deficient in zinc, this difference was not statistically significant (P > 0.05). RESULTS: The results identified a high prevalence of zinc deficiency in the groups studied, and point to a trend towards more elevated retinol serum levels in patients undergoing dialysis as compared with those in healthy controls.     

Safety of low-dose spironolactone administration in chronic haemodialysis patients.

BACKGROUND: Prevention of cardiovascular diseases is essential in chronic haemodialysis patients. Recently, low-dose spironolactone has been shown to decrease cardiovascular mortality in patients with severe heart failure. However, since haemodialysis patients are prone to hyperkalaemia, a known side effect of spironolactone, this treatment is not used in this population. We performed a study to assess whether low-dose spironolactone (3 x 25 mg/week) could be administered without inducing hyperkalaemia in haemodialysis patients. METHODS: The study design included a 2-week baseline period, followed by a 4-week treatment period in which doses of spironolactone were started at 12.5 mg three times/week for 2 weeks, then increased to 25 mg three times/week, and followed by a 2-week wash-out period. Fourteen patients receiving low-dose spironolactone after each dialysis were compared with 21 haemodialysis patients (control group). RESULTS: Low-dose spironolactone did not change mean serum potassium (4.9 +/- 0.7 vs 4.9 +/- 0.3 mmol/l: control). The mean plasma canrenone level induced by administration of spironolactone 25 mg three times/week in the 14 treated patients was 13 +/- 5.3 ng/ml. Serum aldosterone was not significantly modified by the administration of spironolactone in these patients [before, median 0.35; interquartile range (IQR) 0.11-2.83 nmol/l vs after, median 0.22; IQR 0.12-0.60 nmol/l, NS]. Dietary potassium intake and the use of ion-exchange resin, angiotensin-converting enzyme inhibitors and beta-blockers were similar for the two groups throughout the study. CONCLUSION: This non-randomized and non-blinded study shows that administration of 25 mg spironolactone thrice weekly is not associated with an increased frequency of hyperkalaemia in haemodialysis patients when they are carefully monitored. More studies are required, however, before concluding that spironolactone administration is safe in the chronic haemodialysis population.     

Oral activated charcoal suppresses hyperphosphataemia in haemodialysis patients

Aim: Hyperphosphataemia is almost inevitable in end stage renal disease (ESRD) patients and is associated with increased morbidity and mortality. In this study we examined whether oral activated charcoal (oAC) reduces serum phosphate level in haemodialysis patients. Methods: This was an open‐label, prospective, uncontrolled study. One hundred and thirty‐five haemodialysis patients were included in this study, with cessation of treatment with any phosphate binders during a 2 week washout period. Patients with serum phosphate levels greater than 5.5 mg/dL during the washout period were included for treatment with oAC. oAC was started at a dose of 600 mg three times per day with meals and was administered for 24 weeks. oAC dose was titrated up during the 24 week period to achieve phosphate control (3.5–5.5 mg/dL). A second 2 week washout period followed the end of oAC treatment. Results: In the 114 patients who successfully completed the trial, the mean dose of activated charcoal was 3190 ± 806 mg/day. oAC reduced mean phosphate levels to below 5.5 mg/dL, with mean decreases of 2.60 ± 0.11 mg/dL (P < 0.01) and 103 (90.4%) of the patients reached the phosphate target. After the second washout period the phosphate levels increased to 7.50 ± 1.03 mg/dL (P < 0.01). Serum intact parathyroid hormone (iPTH) levels declined from 338.75 ± 147.77 pg/mL to 276.51 ± 127.82 pg/mL (P < 0.05) during the study. oAC had no influence on serum prealbumin, total cholesterol, triglycerides, serum ferritin, haemoglobin or platelet levels and the levels of 1,25‐dihydroxyvitamin D were stable during the study. Conclusion: In this open‐label uncontrolled study, oAC effectively controls hyperphosphataemia and hyperparathyroidism in haemodialysis patients. The safety and efficacy of oAC needs to be assessed in a randomized controlled trial.     

Quality of sleep and health-related quality of life in haemodialysis patients.

BACKGROUND: Sleep complaints are common in haemodialysis patients. In the general population, insomnia impacts negatively on health-related quality of life (HRQoL). The objective of this study was to examine the association between quality of sleep and HRQoL in haemodialysis patients independent of known predictors of HRQoL. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) and HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF-36) in 89 haemodialysis patients. RESULTS: Sixty-three (71%) subjects were 'poor sleepers' (global PSQI >5). The SF-36 mental component summary (MCS) and physical component summary (PCS) correlated inversely with the global PSQI score (MCS, r = -0.28, P < 0.01; PCS, r = -0.45, P < 0.01). The PCS score also correlated with age (r = -0.24, P = 0.02), haemoglobin (r = 0.21, P = 0.048) and comorbidity (r = -0.40, P < 0.01), and mean PCS was lower in depressed subjects (26.2 vs 35.9, P = 0.02). Subjects with global PSQI >5 had a higher prevalence of depression, lower haemoglobin and lower HRQoL in all SF-36 domains. The global PSQI score was a significant independent predictor of the MCS and PCS after controlling for age, sex, haemoglobin, serum albumin, comorbidity and depression in multivariate analysis. CONCLUSIONS: Poor sleep is common in dialysis patients and is associated with lower HRQoL. We hypothesize that end-stage renal disease directly influences quality of sleep, which in turn impacts on HRQoL.     

Glucose-added dialysis fluid prevents asymptomatic hypoglycaemia in regular haemodialysis.

BACKGROUND: Hypoglycaemia (HG) has been demonstrated during chronic haemodialysis (HD). These events may become more frequent with the current use of glucose-free bicarbonate dialysis solution, the standard formula in most dialysis facilities in the last decade. On the other hand, HG-related symptoms are unusual among patients during or just after dialysis sessions. The aim of this study was to evaluate the occurrence of HG in diabetic (DM) and non-diabetic (NDM) end-stage renal failure patients during HD using dialytic solution without and with glucose. METHODS: Forty-two chronic renal failure patients-21 DM and 21 NDM-randomly selected among the 97 in our dialysis unit were submitted to an HD session with glucose-free bicarbonate solution (phase 1). Serum glucose was measured at 30, 60, 150 and 240 min. In eight patients (four DM and four NDM) glucose was also measured in fluid leaving the dialyser at 30, 60 and 150 min. After a week, all procedures were repeated in the same patients, this time with a 90 mg/dl glucose-added bicarbonate solution (phase 2). We compared the glucose levels and the number of symptomatic and asymptomatic HG events in each group in phases 1 and 2, using bivariate analysis methods with confidence limit of 0.95%. RESULTS: Data were expressed as mean+/-SD. No patient presented any clinical evidence of HG. For all patients, the mean plasma glucose level (mg/dl) was significantly higher in phase 2 than in phase 1 (138.2+/-96.3 vs 120.7+/-75.9; P=0.0392). This occurred in DM (171.1+/-104.5 vs 132.5+/-71.0; P=0.0067), but not in NDM (101.3+/-19.4 vs 95.2+/-21.2; P=0.06). With glucose-free HD solution, 10 patients (five DM, five NDM) presented 18 measures of glycaemia under 70 mg/dl, and with glucose-added solution, only one (DM) presented two measures under 70 mg/dl-P=0.0045 (number of patients); P=0.0003 (number of HG measures). Among DM patients, values for HG measures in phase 1 (49.1+/-16.2 mg/dl) were significantly lower than in phase 2 (65.0+/-1.4 mg/dl)-P=0.0139. For all patients, glucose was lost in HD fluid leaving the dialyser at lower values in phase 2 (5.2+/-2.9 g/h) than in phase 1 (16.7+/-10.9 g/h)-P<0.0001. CONCLUSIONS: Asymptomatic HG was frequent during HD when glucose-free dialysis solution was used. Glucose was lost in dialytic fluid leaving the dialyser in significantly lower amounts when using glucose-added solution than glucose-free solution. Glucose-added dialysis solution at 90 mg/dl significantly reduced the number and severity of HG episodes and although it caused higher mean glycaemia in DM patients during HD, its use seems advisable in all patients.     

Influence of ANF on the cardiovascular response to volume expansion in haemodialysis patients

Plasma ANF concentration in uraemic patients is very sensitiveto changes in extracellular volume. It is unknown, however,if the release of this vasoactive hormone has a compensatoryrole in the haemodynamic response to extracellular volume expansionin these patients. We investigated the effect of isolated ultrafiltrationfollowed by isovolumic re-expansion by saline in seven haemodialysispatients. The experiment was repeated on two occasions and theUF rate as well as the rate of volume re-expansion in the twostudies were accurately matched. During the phase of volumere-expansion, we infused either ANF (0.83 µg/mm) or aplacebo, in random order and cross-over. Central venous pressure,arterial pressure, haematocrit, and plasma ANF concentrationwere measured in baseline conditions, after ultrafiltration,and 0, 15, and 30 mm after isovolumic re-expansion. In the control experiment (placebo), isolated ultrafiltrationcaused a marked reduction in central venous pressure and inarterial pressure and a pronounced haematocrit increase. Thesechanges were reversed by volume re-expansion. In the activeexperiment, during the phase of volume re-expansion ANF infusiondoubled plasma ANF concentration as compared to control experimentbut it did not affect the ongoing haemodynamic response northe haematocrit changes. Doubling of plasma ANF concentration has no influence on thehaemodynamic and microcirculatory adaptations to acute volumeexpansion in haemodialysis patients. The data indicate thatit is unlikely that raised plasma ANF concentration has a majorrole in the cardiovascular response to acute extracellular volumeexpansion in these patients.     

The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.

BACKGROUND: Hyperkalaemia is common in patients with advanced renal disease. In this double-blind, randomized, three-sequence, crossover study, we compared the effect of three dialysate bicarbonate concentrations ([HCO3-]) on the kinetics of serum potassium (K+) reduction during a conventional haemodialysis (HD) session in chronic HD patients. METHODS: We studied eight stable HD patients. The choice of dialysate [HCO3-] followed a previously assigned treatment protocol and the [HCO3-] used were low bicarbonate (LB; 27 mmol/l), standard bicarbonate (SB; 35 mmol/l) and high bicarbonate (HB; 39 mmol/l). Polysulphone dialysers and automated machines provided blood flow rates of 300 ml/min and dialysis flow rates of 500 ml/min for each HD session. Blood samples were drawn at 0 (baseline), 15, 30, 60 and 240 min from the arterial extracorporeal line to assess blood gases and serum electrolytes. In three of the eight patients, we measured serum K+ 1 h post-dialysis as well as K+ removal by the dialysis. The same procedures were followed until the completion of the three arms of the study, with a 1 week interval between each experimental arm. RESULTS: Serum K+ decreased from 5.4+/-0.26 (baseline) to 4.96+/-0.20, 4.90+/-0.19, 4.68+/-0.13 and 4.24+/-0.15 mmol/l at 15, 30, 60 and 240 min, respectively, with LB; from 5.38+/-0.21 to 5.01+/-0.23, 4.70+/-0.25, 4.3+/-0.15 and 3.8+/-0.19 mmol/l, respectively, with SB; and from 5.45+/-0.25 to 4.79+/-0.17, 4.48+/-0.17, 3.86+/-0.16 and 3.34+/-0.11 mmol/l, respectively, with HB (P<0.05 for high vs standard and low [HCO3-] at 60 and 240 min). The decrease in serum K+ correlated with the rise in serum [HCO3-] in all but LB (P<0.05). Potassium rebound was 3.9+/-10.2%, 5.2+/-6.6% and 8.9+/-4.9% for LB, SB and HB dialysates, respectively (P=NS), while total K+ removal (mmol/dialysis) was 116.4+/-21.6 for LB, 73.2+/-12.8 for SB and 80.9+/-15.4 for HB (P=NS). CONCLUSIONS: High dialysate [HCO3-] was associated with a faster decrease in serum K+. Our results strongly suggest that this reduction was due to the enhanced shifting of K+ from the extracellular to the intracellular fluid compartment rather than its removal by dialysis. This finding could have an impact for those patients with life-threatening pre-HD hyperkalaemia.     

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.     

A registry of haemodialysis patients and the progress of haemodialysis services in Lithuania.

Background. Until 1990, haemodialysis (HD) in Lithuania wasunderdeveloped, but after independence, development of HD started.Until 1996, no precise data about HD patients in Lithuania wereavailable. In order to create a registry of HD, we started tocollect data about dialysis services and HD patients in 1996.Every collection of data was followed by distribution and discussionof the results within the nephrological community. This studydescribes the changes of Lithuanian HD between 1996–2002. Methods. Between 1996 till 2002 all HD centres in Lithuaniawere annually visited and data were collected about all HD patients(response rate of 100%). The evaluation of the results duringour observational study was made according to the European BestPractice Guidelines. During annual conferences for nephrologists,the guidelines and data of our HD registry were presented. Results. There was an increase in the number of HD stations(from 25 p.m.p. to 75 p.m.p., P<0.001), in HD patients (from60 p.m.p. to 237 p.m.p., P<0.001) and in the incidence ofnew HD patients (from 54.3 p.m.p. to 103 p.m.p., P<0.01).The mean age of HD patients increased from 47.2±16.1years in 1996 to 56.0±14.9 in 2002 (P<0.001). Themain underlying cause of ESRD was chronic glomerulonephritis,but its rate decreased from 54.5% in 1996 to 27.5% in 2002 (P<0.001).The percentage of diabetics increased from 7.1% to 16.4%, P<0.05,and in hypertensive nephropathy from 3.1% to 10.9%, P<0.05.We observed improvement of the quality of HD in Lithuania duringthese 5 years. The percentage of patients on bicarbonate HDincreased from 7.1% in 1996 to 100% in 2002 (P<0.001). Thepercentage of patients receiving more than 12 h HD/week increasedfrom 30.8% in 1996 to 53.5% in 2002 (P<0.001). The mean Kt/Vin 1999 was 0.81±0.53, but it increased in 2002 to 1.22±0.27,P<0.001. In 2002, 84.6% of all HD patients were examinedfor HB_sAg, 82.3% for anti–HCV, 31.2% for anti-HB_s and57.1% for anti-HB_c. The percentage of patients receiving phosphatebinders increased from 65.2% in 1996 to 84.4% in 1997 and 90.5%in 2002. Serum parathyroid hormone (PTH) levels were measuredin 27.3% of HD patients in 1999 but in 85.2% of patients in2002. The mean haemoglobin (Hb) concentration increased from92±15.4 g/l to 105±14.7 g/l; the percentage ofpatients with Hb>100 g/l increased from 27.5% to 64% in 2001.The percentage of HD patients receiving epoetin was 94.6% in2001 as compared with 78% in 1997. There was a marked increasein the use of intravenous iron (from 7.5% patients in 1997 to70.8% in 2000). The mean weekly dose of Epo was lower in HDpatients receiving intravenous iron than in patients receivingoral iron. Conclusions. Over the period of 1996–2002 the HD servicessignificantly expanded in Lithuania. The introduction of EuropeanBest Practice Guidelines and the establishment of a HD registrywith feedback of the results stimulated the significant progressin the quality of HD and in the management of the patients.     

IL-1beta, TNF-alpha and IL-6 release from monocytes in haemodialysis patients in relation to dialytic age.

BACKGROUND: It has been suggested that changes in immune response to infectious agents in patients on haemodialysis might be due to impaired monocyte function; uraemic and haemodialysed patients overproduce proinflammatory cytokines, such as interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). METHODS: We quantitated the cytokines released into the plasma and into the supernatants of 24-h cultured purified monocytes, under basal conditions and after stimulation by lipopolysaccharide from Escherichia coli, in 15 healthy subjects (CON), 20 uraemic patients who had not yet started dialysis (CRF) and 60 haemodialysed patients (HD), who were divided into three groups of 20 patients corresponding to short-, medium- and long-term dialysis. RESULTS: Monocytes from HD patients spontaneously secreted significantly higher levels of cytokines than those from controls and uraemic patients who had not yet started dialysis. After stimulation with lipopolysaccharide (LPS), cytokine levels in culture supernatants of cells from HD patients were significantly lower than those from controls and uraemic patients. Moreover, levels of cytokines in monocyte supernatants and plasma from short-, medium- and long-term haemodialysed patients decreased progressively with dialytic age. Monocytes from haemodialysed patients tended to be constitutively active, but their ability to secrete proinflammatory cytokines was inversely correlated with dialytic age. CONCLUSIONS: These results indicate that prolonged treatment with dialysis can be considered a form of chronic stress that causes the progressive activation of monocytes, which ultimately leads to monocyte exhaustion and dysfunction.     

Influence of haemodialysis and left ventricular failure on peripheral A(2A) adenosine receptor expression.

BACKGROUND: Haemodialysis (HD) sometimes accelerates left ventricular failure (LVF). As adenosine (ADO) is strongly implicated in cardiovascular functions, particularly via A(2A) receptor activation and as changes of peripheral A(2A) receptors mirror changes occurring in the cardiovascular system, we examined the influence of HD and LVF on both ADO plasma concentration and the expression of A(2A) receptors (i.e. Bmax, K(D) and mRNA amount) of peripheral blood mononuclear cells. METHODS: This cross-sectional study included 61 chronic renal failure (CRF) patients: 41 without LVF (24 haemodialysed and 17 undialysed) and 20 with LVF (9 haemodialysed and 11 undialysed). Ten LVF patients without CRF and 10 healthy subjects were also examined. RESULTS: (i) Bmax values of CRF patients without LVF were significantly decreased in undialysed patients compared with haemodialysed patients, and compared with controls (69 +/- 25 vs 98 +/- 33 vs 180 +/- 60 fmol/mg of protein, P < 0.05). Bmax values of CRF patients with LVF were lower in undialysed patients than in haemodialysed patients (60 +/- 27 vs 101 +/- 27 fmol/mg of protein, P < 0.05). Bmax values of LVF patients without CRF were lower than in controls (51 +/- 19 vs 180 +/- 60 fmol/mg of protein). (ii) A(2A) mRNA expression was increased in haemodialysed patients compared with controls (20.2 +/- 0.75 vs 17.6 +/- 1.3, P < 0.05). (iii) ADO plasma levels were high in haemodialysed patients and further increased during the HD sessions. CONCLUSION: The number of A(2A) receptors was decreased by CRF with or without LVF. However, this decrease was less important in haemodialysed patients. The changes in peripheral A(2A) receptor expression suggest a significant inflammatory response to HD and heart or kidney failure. Whether these changes do reflect alterations in cardiomyocytes needs further investigation.     

Association of interferon-gamma +874A polymorphism with reduced long-term inflammatory response in haemodialysis patients.

BACKGROUND: We have studied the effects of interferon (IFN)-gamma allelic variations on expression levels of pro- and anti-inflammatory cytokines and on long-term inflammatory status in haemodialysis patients. METHODS: Genotyping was performed in 123 patients for single nucleotide polymorphisms in the first intron of the IFN-gamma gene (+874 T/A). They were prospectively followed for 2 years. Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR technique) and serum C-reactive protein (CRP) concentrations were compared in patient groups with different IFN-gamma genotypes. Serum CRP was evaluated every month and inflammatory state was defined as percent of abnormal values (above 5 mg/l) over total determinations. Of the total, 102 patients survived and completed 24+/-1 monthly CRP determinations. The IFN-gamma +/-874 A/A, 'low-producer' genotype was associated with decreased (P<0.05) mRNA levels of IFN-gamma and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation (37+/-6%) than the +/-874 A/T and T/T, 'intermediate and high-producer' genotypes (59+/-6%, and 60+/-5%, respectively). The mRNA levels of tumor necrosis factor-alpha, IL-10 and of transforming growth factor-beta1 were not different in the three groups of patients. Pooled analysis in deceased (10+/-3 monthly CRP determinations) and survived patients confirmed the results obtained in the patients who completed the follow-up period. CONCLUSIONS: The 'low-producer' IFN-gamma +874 A/A genotype was associated with a preventive effect on long-term CRP elevation in haemodialysis patients possibly mediated by decreased gene expression of IFN-gamma and IL-6.