A new 'online' method to measure increased exhaled isoprene in end-stage renal failure.

BACKGROUND: Isoprene is the most abundant hydrocarbon present in breath, and recent reports indicate that breath concentrations increase following haemodialysis. The purpose of this study was to establish whether selected ion flow tube mass spectrometry (SIFT-MS), a newly established technique in breath analysis, may be used to quantify breath isoprene in haemodialysis patients in the clinical setting. SIFT-MS is compared and contrasted with the established gas chromatography mass spectrometric technique for this purpose. METHODS: Three consecutive exhalations from 19 haemodialysis patients (12 males, seven females) undergoing a morning dialysis shift were analysed just prior to commencing treatment. Within 5 min of completing their usual dialysis regimen, using polysulphone membranes, the breath of each patient was analysed again. Additional contemporary samples were obtained from 17 normal controls. Breath isoprene was quantified using SIFT-MS, a method previously validated quantitatively using neat isoprene. RESULTS: Successful measurements of breath isoprene were obtained for each subject within 2 min, with minimum disruption to a busy dialysis environment. The coefficient of variation of triplicate measurements of breath isoprene was <10%. Prior to dialysis, the mean (+/-SD) breath isoprene concentration (138+/-63 parts per billion (ppb)) was significantly greater than for normal controls (89+/-36 ppb; P=0.016). Immediately following treatment, breath isoprene increased significantly to 184+/-95 ppb (P=0.023). CONCLUSIONS: SIFT-MS permits the accurate and rapid measurement of breath isoprene in haemodialysis patients in the clinical setting. The previously reported increase in breath isoprene following dialysis treatment is confirmed. SIFT-MS is the ideal analytical tool to investigate this phenomenon further.     

The effect of high-flux hemodialysis on renal anemia

BACKGROUND: Anemia is an important predictor of mortality and morbidity in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Erythropoietin (EPO) is an expensive drug, which increases the cost of therapy. In addition, anemia persists in 20-30% of cases despite EPO treatment. In this study, which depended on the idea that the clearance of moderate and high molecular weight erythropoiesis inhibitors leads to an improvement in terms of anemia, we aimed to investigate the effect of high-flux dialysis on anemia and EPO requirement in patients undergoing HD. METHODS: The study included 48 patients with ESRD on chronic HD treatment who could not reach the target hemoglobin (Hb) level, despite treatment with at least 200 IU/kg/week subcutaneous EPO. Patients were randomized into two groups and HD was performed with polysulphone low-flux dialyzer (Fresenius F6 HPS) or polysulphone high-flux dialyzer (Fresenius F60) for 6 months. RESULTS: Although the EPO doses were significantly lower (p<0.001) in the high-flux dialysis group, Hb levels showed a significant increase (p<0.001). In the low-flux dialysis group, Hb levels showed no significant increase, despite the steady increase in EPO doses. In the high-flux group, the reduction of beta2-microglobulin (b2-MG) and phosphorus levels during dialysis was significantly higher when compared to the low-flux group (p<0.001). During the follow-up period, while b2-MG levels decreased significantly in the high-flux group (p<0.05), there was an increase in the low-flux group (p<0.05). Kt/V(urea) values showed no significant difference throughout the study. CONCLUSIONS: Our results suggest that high-flux dialysis use is effective and this can be an alternative method in terms of controlling renal anemia and reducing the cost of therapy. These beneficial effects of high-flux dialysis are probably mediated by the improved clearance of moderate and high molecular weight toxins.     

Myeloperoxidase serves as a marker of oxidative stress during single haemodialysis session using two different biocompatible dialysis membranes.

BACKGROUND: There is increased oxidative stress in patients undergoing haemodialysis (HD); however, little is known of how different dialysis membranes contribute to the oxidative stress induced by the dialysis procedure per se. We therefore studied the influence of two different dialysis membranes on oxidative stress during HD. METHODS: Eight patients undergoing HD three times per week were enrolled in this cross-controlled study. Patients sequentially received HD using polysulphone (PS) and regenerated cellulose (RC) dialysis membranes for 1 week each. Blood samples were collected in the last section of each hollow fibre 0, 15, 120 and 240 min after starting HD. We determined superoxide anion production derived from neutrophils, superoxide dismutase (SOD) and glutathione peroxidase (GPx) derived from washed red cells, plasma myeloperoxidase (MPO), plasma thiobarbituric acid-reactive substances (TBARS), plasma advanced oxidation protein products (AOPP) and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: Leukocyte numbers, including neutrophils, lymphocytes and monocytes, decreased significantly after 15 min of dialysis, more so with RC than with PS membrane. For both membranes, superoxide anion production transiently increased during the first 15 min whereas the post-dialysis production was decreased. Plasma MPO levels persistently increased during dialysis with the two membranes. Moreover, the increase was more marked with RC than with PS membrane. AOPP and 8-OHdG levels increased progressively when using RC membranes. There were no significant differences in SOD, GPx, TBARS, AOPP and 8-OHdG levels between the two membranes. CONCLUSIONS: The biocompatibility of the dialyser affects oxidative stress production during a single dialysis session. The measurement of MPO may serve as a reliable marker of the degree of oxidative stress induced using dialysis membranes of different biocompatibilities.     

Dialysis filter type determines the acute effect of haemodialysis on endothelial function and oxidative stress.

BACKGROUND: Endothelial function of large arteries is impaired in chronic haemodialysis patients and oxidative stress due to the dialysis procedure has been suggested as a causal factor. However, it is not clear whether different types of dialysis membranes affect endothelial function differently. Therefore we determined endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery as well as markers of oxidative stress immediately before and after haemodialysis (HD) with either a cellulosic cuprophane or a synthetic polysulphone dialyser in a blinded, randomized, cross-over study. METHODS: Twelve haemodialysis patients (age 55+/-3 years, time on dialysis 20+/-2 months, mean fluid change -1782+/-21 ml, systolic/diastolic blood pressure 139/75 mmHg) were included. Using a multi-gate-pulsed Doppler system (echo-tracking device) brachial artery FMD and nitroglycerine-induced, endothelium-independent vasodilatation (NMD) were measured. Patients were randomized to HD with either a polysulphone or a cuprophane membrane and were crossed over to the other filter. Investigators were blinded to the type of membrane used. Serum concentrations of oxidized LDL (oxLDL) and alpha-tocopherol as markers of oxidative stress were measured before and after each dialysis session. RESULTS: Data are given as mean+/-SEM. Treatment with polysulphone filter HD did not significantly affect FMD (baseline 9.3+/-2.0% vs after HD 9.6+/-1.8%). After dialysis with a cuprophane membrane FMD decreased from 9.4+/-2.1 to 7.4+/-1.8% (P<0.05). NMD was not significantly affected by HD irrespective of the membrane material used. Serum levels of oxLDL were not changed by either treatment; however, alpha-tocopherol concentrations fell significantly after dialysis with the cuprophane filter (baseline 18.0+/-2.3 after HD 16.6+/-1.3 micro g/ml, P<0.05), while alpha-tocopherol levels remained unchanged when the polysulphone membrane was used. CONCLUSIONS: The type of dialysis filter membrane determines the acute effect of haemodialysis on arterial endothelial function. Differences in biocompatibility and oxidative stress may account for the observed differential effects, since the decrease of FMD after dialysis with a cellulosic cuprophane membrane-but not with a synthetic polysulphone membrane-was associated with a reduction in serum vitamin E.     

Effects of different dialysis modalities on cardiac autonomic dysfunctions in end-stage renal disease patients: one year prospective study

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end-stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long-term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one-year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 +/- 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG-Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.     

Muscle ubiquitin m-rNA levels in patients with end-stage renal disease on maintenance hemodialysis

BACKGROUND: Loss of lean body mass is frequently reported in patients with end-stage renal disease (ES-RD). Inadequate nutrient intake, superimposed illnesses, endocrine disorders, uremia and acidosis are some of the potential causes of muscle depletion. Previous reports on experimental models show that lean body mass depletion results from enhancement of muscle tissue protein catabolism, mainly associated with activation of ATP-ubiquitin-dependent proteolysis. Little is known, however, about the affects on this proteolytic system in ESRD patients on maintenance hemodialysis (HD). The present study was designed to investigate the expression of ubiquitin mRNAs in skeletal muscle of patients with ESRD on maintenance HD. METHODS: Biopsies from the rectus abdominis muscle were obtained from eight ESRD patients and from six control subjects undergoing surgery for benign disease. Ubiquitin mRNA levels were measured by Northern blotting analysis. RESULTS: Patients with ESRD had mild metabolic acidosis, as a result of chronic intermittent HD. There were no significant differences between HD patients and controls with regard to the 1.2kb polyubiquitin mRNA species (332.9+/-139 vs 324.2+/-60; ns), but the levels of the 2.4 kb mRNA species were significantly lower in HD patients than in controls (1687+/-542 vs 2529.9+/-325, p=0.01). No correlation was observed between ubiquitin mRNA levels and nutritional parameters and degree of acidosis. CONCLUSIONS: The present study found that the ubiquitin mRNA levels were not increased in the muscle of stable, mildly acidotic hemodialysis patients.     

Peritoneal dialysis in diabetic patients

Diabetes mellitus is the fastest growing cause of end-stage renal disease (ESRD) and has become the leading cause of such ESRD worldwide. In the United States, between 1984 and 1997, the proportion of new patients starting renal replacement therapies whose ESRD was caused by diabetes increased from 27% to 44.4%. Canada saw an increase from 16.5% in 1984 to 28.9% in 1997, and many European countries had similar increases. Among the modes of renal replacement, many clinicians have favored continuous ambulatory peritoneal dialysis (CAPD) for the treatment of diabetic ESRD for several reasons. Many studies have compared clinical outcomes in diabetic patients undergoing CAPD, and nondiabetic patients undergoing CAPD, or diabetic patients undergoing peritoneal dialysis (PD) and those undergoing hemodialysis (HD). However, only a small number of diabetic dialysis patients have been followed up for more than 5 years, largely because of the presence of several comorbid conditions at the start of dialysis and the coexistence of far-advanced target-organ damage at dialysis initiation and its progression during the course of dialysis. Diabetic patients undergoing PD and HD probably have similar survival, and those undergoing CAPD have lower survival and technique success rates than nondiabetic patients of comparable age. This article reviews the literature and our experience with diabetic patients undergoing PD and compares clinical outcomes in diabetic patients undergoing PD and HD.     

Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin

BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.     

Volatile alkanes and increased concentrations of isoprene in exhaled air during hemodialysis.

In this study we examined breath volatile hydrocarbon concentrations in exhaled air of hemodialysis patients. We assessed both C(2)-C(5) alkanes - among them ethane and pentane the production of which in man is essentially due to the action free radicals exert on polyunsaturated fatty acids - and isoprene, an unsaturated hydrocarbon the biosynthesis and biological effects of which are the subject of controversy and mounting interest. Twenty patients were studied. Evaluation was performed intrapatient in the breath of patients with chronic renal failure, before and after dialysis (20 patients) and, in the same cases, during hemodialytic treatment (10 patients). Breath concentrations of these volatile hydrocarbons, determined before dialysis, were not different from those of normal subjects. Dialysis did not modify the levels of the C(2)-C(5) saturated hydrocarbons ethane, propane, butane and pentane. Instead, there was a marked increase in isoprene in all patients (basal values rose by a mean of 270%). Since isoprene was not present in the fluids or filters used for dialysis and there were only traces in the ambient air, the isoprene must have been produced endogenously during hemodialysis. As no situation has previously been reported to increase endogenous production of isoprene in humans, patients in hemodialysis offer a unique opportunity to investigate in depth the medical, biological and toxicological aspects of isoprene.     

Survival analysis of pediatric dialysis patients in Taiwan

Aim: The long‐term survival of Taiwanese children with end‐stage renal disease (ESRD) has not been reported before. This study aimed to determine the long‐term survival, mortality hazards and causes of death in paediatric patients receiving dialysis. Methods: Paediatric patients (aged 19 years and younger) with incident ESRD who were reported to the Taiwan Renal Registry from 1995 to 2004 were included. A total of 319 haemodialysis (HD) and 156 peritoneal dialysis (PD) patients formed the database. After stratification by dialysis modality, multivariate Cox proportional‐hazards model was constructed with age, sex and co‐morbidity as predictive variables. Results: The annual paediatric ESRD incidence rate was 8.12 per million of age‐related populations. The overall 1‐, 5‐, and 10‐year survival rates for PD patients were 98.1%, 88.0% and 68.4%, respectively, and were 96.9%, 87.3% and 78.5% for HD patients. The survival analysis showed no significant difference between HD and PD (P = 0.4878). Using ‘15–19 years’ as a reference group, the relative risk (RR) of the youngest group (0–4 years) was 6.60 (95% CI: 2.50–17.38) for HD, and 5.03 (95% CI: 1.23–20.67) for PD. The death rate was 24.66 per 1000 dialysis patient‐years. The three major causes of death were infection (23.4%), cardiovascular disease (13.0%) and cerebrovascular disease (10.4%). Hemorrhagic stroke (87.5%) was the main type of foetal cerebrovascular accident. Conclusion: We conclude that there was no significant difference of paediatric ESRD patient survival between HD and PD treatment in Taiwan. The older paediatric ESRD patients had better survival than younger patients.     

Acute effect of haemodialysis on arterial stiffness: membrane bioincompatibility?

BACKGROUND: Repetitive endothelial damage from dialysis membrane incompatibility is a probable cause of accelerated atherosclerosis in haemodialysis patients. Consequently pulse wave velocity (PWV), a measure of arterial stiffness, was utilized as a surrogate marker of vascular dysfunction during dialysis with two commonly used synthetic dialysers. METHODS: PWV was monitored before, during and after haemodialysis using both polysulphone and polyamide membranes. PWV, an arterial stiffness measure, was calculated from the carotid to the femoral (C-F) and also to the radial (C-R) artery. In a further group, PWV was monitored while polysulphone and polyamide membranes were perfused with blood without dialysate. RESULTS: Mean aortic (C-F) PWV was lower during dialysis with the polyamide membrane, being 14 and 16% less following 75 and 135 min of dialysis (P<0.05) in 24 patients. Because intradialytic intravascular volume changes alter PWV, a subgroup analysis in 11 patients where dialysis fluid removal during both periods was minimal (<1 kg) was performed, and a persistent and significant increase in aortic PWV was detected with the polysulphone kidney being maximal (40%) at 75 min (P<0.01). This increase was negatively correlated with pre-dialysis PWV (P<0.01). In contrast, the polyamide dialyser did not change PWV. An increase in C-R PWV was also noted with the polysulphone membrane (P<0.05). In the nine patients where membranes were perfused with blood without dialysate, aortic PWV was again significantly increased by the polysulphone (P<0.01), but not the polyamide dialyser. CONCLUSIONS: Haemodialysis with polysulphone but not polyamide membranes acutely alters aortic 'stiffness', an effect postulated to be due to membrane bioincompatibility. However, factors including age, time on dialysis and underlying vascular disease, were also found to impact on these acute dialysis-induced changes to vascular function. Since these acute changes disappear post-dialysis, their long-term consequences are uncertain.     

Malnutrition-inflammation-atherosclerosis (MIA) syndrome components in hemodialysis and peritoneal dialysis patients

BACKGROUND: Malnutrition, inflammation, and atherosclerosis (MIA syndrome) are common in end-stage renal disease (ESRD) patients. Each component of MIA syndrome is the predictor of outcomes in ESRD patients. In this cross-sectional study, we aimed to compare both dialysis modalities for MIA syndrome components. MATERIAL AND METHODS: Thirty hemodialysis (HD) (mean age 44 +/- 11 years, 14 male and 16 female, mean time on dialysis: 31.0 +/- 19.0 months) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (41 +/- 9 years, 12 male and 18 female, mean time on dialysis: 25.5 +/- 21.5 months) were included. In order to determine malnutrition in ESRD patients, serum albumin level and anthropometric measurements were used. For inflammation, serum C-reactive protein level, erythrocyte sedimentation rate, and fibrinogen levels were measured. Mean-carotid artery intima media thickness (m-CIMT), presence of carotid plaque and serum homocysteine level were used to determine atherosclerosis. RESULTS: Five CAPD patients (16%) and one HD patient (3%) was hypoalbuminemic. HD and CAPD groups were similar for inflammation. Mean-CIMT and serum homocysteine level were higher in HD patients than CAPD patients. There was a positive correlation between homocysteine and m-CIMT. CONCLUSION: Before choosing renal replacement therapy, malnutrition, inflammation, and atherosclerosis parameters must be investigated in ESRD patients. Hemodialysis seems to be more advantageous for malnutrition components than CAPD. Both dialysis modalities seem to be similar for inflammation, and CAPD modality has superiority for atherosclerosis. Before choosing the type of renal replacement therapy, assessment of MIA syndrome components could be useful for individualization of the decision on which dialytic modality is appropriate in ESRD patients.     

Oxidative stress during dialysis: effect on free radical scavenging enzyme (FRSE) activities and glutathione (GSH) concentration in granulocytes

Background. Living cells are protected by free radical scavenging enzymes against oxygen radical-mediated damage. It has been suggested that granulocytes are activated on the surface of dialyser membranes, resulting in the generation of free radicals. We have recently reported a lack of plasma lipid peroxidation and unchanged glutathione peroxidase (GSH-Px) as well as glutathione reductase (GSSG-R) activities in red blood cells of haemodialysis patients. However, because mature red cells are free of DNA and RNA, free radical scavenging enzymes (FRSE) cannot be regulated on the gene level in response to an acute oxidative stress. In contrast to erythrocytes, granulocytes are nucleated cells and FRSE protein concentrations can therefore be modulated. Methods. GSH-Px, GSSG-R, superoxide dismutase (SOD) activities and total glutathione (GSH) were determined spectrophotometrically using a Cobas Fara semi-automatic analyser in granulocytes of 31 healthy blood donors and in 28 patients with chronic renal failure (CRF) for more than 6 months before as well as immediately after a single dialysis treatment. Patients were treated either by haemodialysis (n=17) using low-flux polysulphone membranes or by haemofiltration (n=11) using high-flux polysulphone membranes. Results. Compared to healthy controls, SOD and GSSG-R activities were increased in granulocytes of HD and HF patients, GSH and GSH-Px were decreased before a single treatment. After dialysis SOD and GSH-PX activities were significantly induced by both HD and HF whereas GSSG-R activities and GSH were decreased. Conclusions. These results show that the enzymatic defence against oxygen radicals can be induced in granulocytes of patients undergoing regular dialysis treatment, whereas the non-enzymatic defence is compromised as shown by decreased GSH concentrations, both suggesting increased oxidative stress.     

Effects of late referral to a nephrologist in patients with chronic renal failure

BACKGROUND: We lack information about the role of late diagnosis of end-stage renal disease (ESRD), late nephrological referral and its impact on biochemical variables and first hospitalization in East Anatolia, Turkey. METHODS AND RESULTS: For a total of 101 ESRD patients, dialysis was initiated between January 1998 and December 2002 at the Yuzuncu Yil University Hospital. Early referral (ER) and late referral (LR) were defined as the time of first referral or admission to a nephrologist greater or less than 12 weeks, respectively, before initiation of haemodialysis (HD). RESULTS: The need for urgent dialysis was less among the early referral cases compared with the late referral cases (P = 0.03). Patients with LR started dialysis with lower levels of haemoglobin (8.6 vs 9.5 g/dL, P < 0.05) bicarbonate (16 vs 12 mEq/lt, P < 0.03) and albumin (2.9 vs 3.29 mg/dL, P < 0.02) and with higher serum levels of blood urea nitrogen (173 vs 95 mg/dL, P < 0.001), creatinine (10 vs 7.9 mg/dL, P < 0.001) and potassium (5.3 vs 4.8, P < 0.04). Hospitalization duration beginning at dialysis was significantly longer in the LR group (27.3 +/- 24) compared with the ER group (13.4 +/- 7.5, P < 0.001). When the groups were compared in terms of distance between the patients home and hospital, there were significantly more patients living far away from hospital (i.e. >100 km) in the LR group compared with the ER (P < 0.0001) group. CONCLUSION: Early referral to a nephrology unit and/or early diagnosis of ESRD results in better biochemical variables, shorter first hospitalization length and a higher percentage of elective construction of AVF and the availability to start with an alternative dialysis modality (i.e. CAPD).     

Effects of Different Dialysis Modalities on Cardiac Autonomic Dysfunctions in End‐Stage Renal Disease Patients: One Year Prospective Study

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end‐stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long‐term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one‐year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 ± 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG‐Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.     

The red blood cell deformability in patients suffering from end stage renal failure on hemodialysis or continuous ambulatory peritoneal dialysis

Anemia is the main problem for patients suffering from end stage renal disease (ESRD). This study aimed to determine whether the index of rigidity (IR), that shows red blood cells (RBCs) deformability and the possible IR disturbances can provide an explanation about the cause of anemia, in patients undergoing maintenance hemodialysis (HD) or on peritoneal dialysis. The IR was determined in 39 hemodialyzed patients, who were already in dialysis for a period of time ranging from 16 to 120 months (mean+/-SD=41.8 +/-24.1) (Group A). Furthermore, the IR was measured in 32 patients on continuous ambulatory peritoneal dialysis (CAPD), who were in CAPD for a period of time ranging from 6 to 60 months (mean+/-SD = 10.7+/-9.9) (Group B). Finally, the IR was determined in 17 normal individuals (group C). The RBCs IR was measured twice in group A (before and after the end of a hemodialysis session) and once in groups B and C. The IR was determined by hemorrheometry (method of filtration), using special equipment. In group A the IR was increased in comparison to the control group (C) (17.9+/-6.2 vs. 10.2+/-1.8, p<0.0001). This increase was even higher in the measurement at the end of the hemodialysis session (paired t-test, p < 0.0001). The RBCs IR in CAPD patients was significantly lower than that of HD patients (12+/-3.8 vs. 17.9+/-6.2, p<0.0001) and was not statistically different from the control group (12+/-3.8 vs. 10.2+/-1.8, p=0.068). It is concluded from the study that: 1) in HD patients occur disturbances in the deformability of the RBCs, that are worsened by the hemodialysis session; 2) the index of rigidity of RBCs is significantly higher in the HD patients than in CAPD patients; 3) in patients on CAPD, the disturbance of deformability of the RBCs was less in comparison to the control group, which however does not reach the statistically significant levels.     

Elimination and clearance of pamidronate by haemodialysis

Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.     

Interleukin-6 is an independent predictor of mortality in patients starting dialysis treatment.

BACKGROUND: The mortality rate is high among end-stage renal disease (ESRD) patients, and recent evidence suggests that this may be linked to inflammation. The activity of interleukin-6 (IL-6) and its soluble receptor (sIL-6R) are markedly up-regulated in ESRD patients, and plasma IL-6 levels predict outcome in haemodialysis (HD) patients. However, it has not been established whether elevated plasma IL-6 also predicts outcome in ESRD patients treated by peritoneal dialysis (PD), and how it relates to the data on HD patients. The predictive power of sIL-6R levels on outcome is also unknown in this patient population. METHODS: To determine whether or not plasma IL-6 and sIL-6R predict patient survival, we studied 173 ESRD patients (62% males, 53+/-1 years of age) near the initiation of dialysis treatment (99 PD, 74 HD patients). The patients were followed for a mean period of 3.1+/-0.1 years (range 0.1-7.1 years) and were stratified at the start of dialysis treatment according to age, gender, presence of cardiovascular disease, malnutrition (determined by subjective global assessment), diabetes mellitus, and IL-6 and sIL-6R plasma levels. RESULTS: A significantly different (P<0.0001) mortality rate was observed in different groups when patients were divided into quartiles according to IL-6 levels. Furthermore, the same differences were observed, less notably however, for sIL-6R (P<0.05). When patients were stratified according to IL-6 quartiles and analysed separately according to the different initial treatment groups, a similar profile of survival was observed for PD (P<0.01) and HD (P<0.05) patients. In a Cox proportional hazard model adjusting for the impact of age, malnutrition, diabetes mellitus and male gender, log IL-6 values were independently associated with poor outcome (P<0.05). CONCLUSIONS: The present study demonstrates that the strong predictive value of elevated IL-6 levels for poor outcome in ESRD patients is similar in both HD and PD patients starting treatment.