Maintenance Hemodialysis Treatment Research Articles

Comparison of survival between diabetic and non-diabetic patients on maintenance hemodialysis: A single-centre experience

We analyzed survival rates of 144 prevalent patients on maintenance hemodialysis from 1998 to 2003 at the Department of Nephrology and Dialysis, Rijeka University Hospital, Rijeka, Croatia, and evaluated risk factors predicting their survival. Included were only end-stage renal disease (ESRD) patients on maintenance hemodialysis treatment dialysed more than 6 months before entering the study and who were clinically stable. The patients were randomised in two groups according to the presence or absence of diabetic nephropathy as the cause of ESRD and followed-up. The patient's death as outcome measure was recorded. The survival rates were estimated by the Kaplan–Meier method. The major causes of death were cardiovascular disease in 40 (60.6%) patients. An acute myocardial infarction in 15 (22.7%) patients was the major single cause of death. We found a significantly lower survival of diabetic patients than non-diabetic patients ( P = 0.0013). The most important predictors of death among diabetic patients on maintenance hemodialysis were hyperglycaemia ( P < 0.001), ischemic heart disease ( P = 0.004), hypercholesterolemia ( P = 0.013), and low delivered dialysis dose ( P = 0.013). The survival of diabetic patients undergoing hemodialysis was much worse than survival of non-diabetic patients. The cardiovascular disease remained the major cause of death in both groups. Early detection of pre-existing cardiovascular risk factors and diseases, and treatment of infections leading to sepsis, are of great importance, as they may influence the survival rates. Intensive management of diabetic patients is essential.

Progressive resistance training during hemodialysis: Rationale and method of a randomized‐controlled trial

Skeletal muscle wasting in patients receiving maintenance hemodialysis (HD) has been well documented. The rationale for prescribing progressive resistance training (PRT) in this cohort in an attempt to reverse this catabolism and induce a wide spectrum of physiological, functional, and psychological health-related adaptations is extremely strong. Unfortunately, the barriers to exercise adoption in this cohort are many, which may explain the persisting sedentariness of this population and the lack of widespread clinical programs such as are now commonplace in cardiac rehabilitation and pulmonary rehabilitation units. Current health care practices for HD patients do not address the negative health issues of inactivity and muscle wasting. Therefore, we conducted the first randomized-controlled trial to prescribe PRT during maintenance HD treatment. The purpose of this paper is to present the rationale and methodology that we utilized for implementing intradialytic PRT in a conventional outpatient HD clinic. Potential areas for modification of PRT regimens in this setting are also presented.

Aggravation of Anemia by Helico Bacter Pylori Infection in Maintenance Hemodialysis Patients

To elucidate whether and how in patients on maintenance hemodialysis (HD), infection of H. pylori intensifies the anemia, a cross-sectional study that was conducted on 39 patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis treatment who had various upper gastrointestinal complaints consisting of epigastric pain, epigastric burning, postprandial fullness, early satiety, bloating and belching. Mean ages of patients were 46(±18) years. The dialysis duration was 30±(35) months (median: 18 months). Mean±SD of hemoglobin and hematocrit level of all patients were 9±2 g/dl and 28±6. The value of serum helicobacter pylori (H. Pylori) specific IgG antibody titers of all patients was 7.6 (±9.9)u/ml (median:2 u/ml). In this study non significant difference of H. Pylori-IgG antibody level between males and females or diabetic and non-diabetic hemodialysis patients were seen, and a significant inverse correlation of H. Pylori-IgG antibody level with serum hemoglobin and hematocrit in male hemodialysis patients and a significant inverse correlation of H. Pylori-IgG antibody level with serum iron were found. Also non significant correlation of serum H. Pylori-IgG antibody level with Hgb, Hct and serum iron in all patients, female, non diabetics and diabetic HD groups were found. In hemodialysis patients an inverse correlation between H. pylori infection with hemoglobin and hematocrit level as well as with serum iron, implies more attention to H. pylori infection in these patients and aggravation of anemia with H. pylori infection needs aggressive treatment of H. pylori infection in these patients. © Asian Network for Scientific Information, 2006.

Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions

Oxidative modification of low-density lipoprotein (LDL) and its deleterious effect on endothelium is implicated in the pathogenesis of atherosclerosis. Endothelium responds to such an insult by upregulating the synthesis of heme oxygenase-1 (HO-1) and ferritin. Endothelial cell damage and dysfunction have been observed in patients with chronic kidney disease (CKD) on maintenance hemodialysis (HD). We studied the effect of low-molecular-weight components of uremic plasma on LDL oxidation and LDL-oxidation-provoked endothelial cell reactions, such as the induction of cytotoxicity and the upregulation of cell-protective HO-1 and ferritin. Plasma ultrafiltrate (molecular weight<5000 Da) from CKD patients on HD or when treated conservatively exhibited a pronounced inhibition on heme-mediated oxidative modification of LDL. Endothelial cell cytotoxicity provoked by LDL oxidation was also attenuated by plasma ultrafiltrate from CKD patients. During HD treatment, a dramatic drop occurred in the retardation of oxidative reactions, and a loss of endothelial cytoprotection exerted by plasma ultrafiltrate was noted. The upregulation of HO-1 and ferritin in response to oxidative stress of LDL was blunted by uremic plasma ultrafiltrate that was released by the end of HD. The decreased antioxidant capacity of ultrafiltrate after HD occurred as a consequence of the intradialytic removal of L-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-beta-D-glucuronide, p-cresol, and phenol. Intradialytic removal of L-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-beta-D-glucuronide, p-cresol, and phenol increases the risk of LDL oxidation and subsequent endothelial cell damage, which underlines the importance of activation of cytoprotective HO-1 and ferritin in endothelium.

Association of Serum Homocysteine with Anemia in Maintenance Hemodialysis Patients

To investigate the relationship between homocysteine level and anemia in maintenanc e hemodialysis patients, a cross-sectional study that was conducted on patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis treatment. The study was carried out on 39 (F=15 M=24) stable hemodialysis HD patients. Mean ages of patients were 46±18 years. The length of the time patients had been on hemodialysis was 30±35 months (median: 18 months). The value of serum homocysteine of all patients was 5±2 µmol/L (median : 4.5 µmol/L). Mean±SD of hemoglobin and hematocrit level of al l patients were 9±2 g/dl (median : 9 g/dl), and 28±6% median: 29% respectively. In this study, we assessed for the first time the positive relation of serum homocysteine with anemia in patients on maintenanc e hemodialysis. In addition, in male HD patients a significant positive correlation of serum homocysteine with serum ferritin and a significant inverse correlation of serum homocysteine with serum total iron binding capacity (TIBC) were seen. It is possible that the high levels of serum homocysteine in some conditions may increases the micro inflammatory state of uremia in hemodialysis patients and had a role in intensification of anemia. In the meantime more research needs to confirm our conclusion.

Strong Inverse Association of Serum Parathormone with Plasma HCO3 in Female Hemodialysis Patients

Secondary hyperparathyroidism(SHPTH) is a common complication of chronic kidney disease and is characterized by elevated levels of serum parathyroid hormone (PTH) and abnormalities in bone and mineral metabolism. This serious disorder could be aggravated by metabolic acidosis which is a common consequence of advanced chronic renal failure and in maintenance dialysis patients. To investigate factors influencing the intensity of secondary hyperparathyroidism (SHPTH) in patients on chronic maintenance haemodialysis we tested the association of relative acidosis of hemodialysis patients with parathyroid gland activity. This is a cross-sectional study that was conducted on patients undergoing maintenance hemodialysis treatment with acetate basis dialysate and polysulfone membrane. Serum calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase (ALP) and intact serum PTH (iPTH) and plasma HCO were measured. A significant positive correlation of plasma HCO with duration and dosage of 3 3 hemodialysis were found. In all patients a significant inverse correlation of logarithm of serum iPTH with plasma HCO was seen while this association was very significant in female hemodialysis patients. A strong 3 inverse association between plasma HCO and serum PTH in female gender may show the more 3 aggressive form of SHPTH in this group.

An Anti-Inflammatory and Antioxidant Nutritional Supplement for Hypoalbuminemic Hemodialysis Patients: A Pilot/Feasibility Study

A low serum albumin concentration < 3.8 g/dL, a marker of malnutrition-inflammation complex syndrome, is observed in approximately half of all maintenance hemodialysis (MHD) patients in the United States and is strongly associated with increased mortality. We hypothesized that a novel oral nutritional intervention with anti-inflammatory and antioxidant properties taken during routine dialysis sessions is well tolerated and corrects hypoalbuminemia in MHD patients. Controlled clinical study. An outpatient dialysis facility affiliated with a tertiary care community medical center with six equally distributed hemodialysis shifts and 163 MHD patients. Among all MHD outpatients of three selected HD shifts (n = 81 patients), 21 subjects had a serum albumin level < 3.8 g/dL. One patient who was hospitalized before the intervention was excluded. The other three dialysis shifts, with 82 MHD outpatients including 20 hypoalbuminemic subjects, were observed as concurrent controls. The nutritional intervention included one can of Oxepa and one can of Nepro to be taken together orally during each routine hemodialysis session for 4 weeks. Each can contains 237 mL fluid. Oxepa provides 355 calories and 14.8 g protein per can, includes maltodextrin, medium-chain triglycerides, borage oil, and refined and deodorized fish oil, and is designed for critically ill patients with inflammation and oxidative stress. Each can of Oxepa includes 1,020 mg gamma-linolenic acid, 3,100 mg caprylic acid, 1,080 mg eicosapentaenoic acid, 75 mg taurine, 2,840 IU vitamin A activity, 75 IU vitamin E, and 200 mg vitamin C. Nepro provides 475 calories and 16.7 g protein per can; includes high-oleic safflower oil, corn syrup solids, and fructo-oligosaccharides; and is tailored for the nutritional needs of MHD patients. Oxepa and Nepro also contain L-carnitine, 43 mg and 62 mg, respectively. Serum albumin pretrial and posttrial. Studied outpatients (12 men and 8 women) were aged 60.4 +/- 13.0 (SD) years. Three patients had started MHD treatment between 1.5 and 3 months before the intervention. Nine patients were diabetic. Preintervention serum albumin, 3.44 +/- 0.34 g/dL (mean +/- SD) increased to 3.68 +/- 0.34 g/dL (P = .001) 4 weeks after the start of the intervention. In 16 patients, serum albumin level increased by 0.2 to 1.3 g/dL, whereas in 4 patients the serum albumin level decreased by 0.2 to 0.6 g/dL. Three patients reported diarrhea, and one diabetic patient had increased serum glucose values. No other side effects were noted. In 20 control outpatients not receiving nutritional intervention, serum albumin did not change from 3.46 +/- 0.20 to 3.47 +/- 10.44 g/dL (P = .47). In hypoalbuminemic MHD patients, a short-term in-center nutritional intervention with one can of Nepro and one can of Oxepa during HD is practical, convenient, well-tolerated, and associated with a significant increase in serum albumin level. Well-designed randomized placebo-controlled clinical trials are needed to verify the safety and effectiveness of this nutritional intervention and its impact on clinical outcome in hypoalbuminemic MHD patients.

The Effect of Hemodialysis and Dialyzer Biocompatibility on Erythrocyte Glutathione-Defense System in Chronic Hemodialysis Patients

Uremic patients, especially those receiving regular hemodialysis (HD) treatment, are at high risk of oxidative damage by noxious free radicals and reactive oxygen species (ROS). The erythrocyte glutathione-defense system (GSH-DS) is one of the major enzymatic means of scavenging and detoxifying ROS. This study aimed to elucidate the effect of HD and dialyzer biocompatibility on erythrocyte GSH-DS in uremic patients on maintenance HD treatment. Twenty-five healthy volunteers and 42 HD patients were enrolled in this study. Blood samples were drawn immediately before and after HD session, and erythrocyte glutathione (GSH) level as well as the activities of the enzymes glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-Rd), and glutathione S-transferase (GST) were measured. To evaluate the effect of dialyzer type on the studied parameters the patients were were subdivided into two groups: those who had dialysis with cuprophane (CU) membranes (n=23) and those who received dialysis with the aid of polysulfone (PS) membranes (n=19). The activities of G6PD and GSH-Px as well as GSH level were significantly decreased in HD patients as compared with controls. On the other hand, the activities of GSSG-Rd and GST were significantly elevated among HD patients in comparison with control values. A single HD session, regardless of the type of dialyzer, did not induce any significant effect on any of the measured parameters, although G6PD activity increased significantly after dialysis. CU membrane did not result in any change in GSH or its metabolizing enzymes, while PS dialyzers exerted a minor but significant restoration in GSH-DS. The antioxidant pool, as represented by GSH-DS, is significantly affected by dialyzer type in HD patients being significantly corrected with polysulfone dialyzer.

Effects of hemodialysis on serum lipids and phospholipids of end-stage renal failure patients

Patients with chronic renal failure undergoing periodic maintenance hemodialysis frequently present dyslipoproteinaemia which has been linked to the sharply increased risk of cardiovascular disease in these subjects. Reported defects on lipoprotein-related enzyme activities suggest a possible influence of hemodialysis not just to plasma lipid and lipoprotein levels but also to the composition of cell membranes. In this study, it was investigated whether the reported lipid abnormalities are accompanied by changes in serum phospholipids levels. Blood samples were obtained from 140 patients undergoing maintenance hemodialysis treatment and 122 normolipidemic healthy controls and analyzed for total serum phospholipids and their individual subclasses, as well as for total cholesterol and triglycerides, HDL-cholesterol and its subclasses. A significant decrease was observed in serum HDL cholesterol levels (p < 0.001) and its subclasses, HDL2-cholesterol (p < 0.01) and HDL3-cholesterol (p < 0.01) in patients when compared with healthy controls. A critical increase in the serum triglyceride content (p < 0.001) of patients was also observed. In addition, the serum levels of sphingomyelin (p < 0.01) and diphosphatidylglycerol (p < 0.001) were increased in the patient group, while the levels of phosphatidylcholine (p < 0.01) and phosphatidylinositol (p < 0.01) were significantly decreased in the patient group compared to healthy controls. In conclusion, this work clearly demonstrates that hemodialysis treatment contributes significantly to the dyslipidemic profile of end-stage renal failure patients by altering serum lipoprotein and phospholipids concentrations.

Interleukin-18 is a strong predictor of hospitalization in haemodialysis patients.

Morbidity and mortality rates are high among patients with end-stage renal disease (ESRD), and recent evidence suggests that this may be linked to inflammation. Current research has also demonstrated the crucial involvement of interleukin-18 (IL-18) in inflammation. In agreement, the activity of IL-18 has been markedly up-regulated in ESRD patients. However, it has not been established whether elevated plasma IL-18 predicts outcome in haemodialysis (HD) patients. To determine whether plasma IL-18 predicts overall hospitalization, we studied 184 ESRD patients (62% males, 58.5+/-1.0 years of age) undergoing maintenance HD treatment. The patients were followed for 12 months and were stratified by the tertiles of plasma IL-18 levels. Classic factors, such as age, body mass index, duration of HD, nutritional and inflammatory parameters, co-morbidity, dialysis adequacy, and lipid status were entered into a Cox regression model to predict hospitalization. The Kaplan-Meier method was used to analyse the cumulative proportion of hospitalization-free events. Significantly different hospitalization days and frequencies (P<0.05) were observed when patients were divided according to tertiles of plasma IL-18 levels. Patients were stratified according to IL-18 tertiles and analysed separately according to the hospitalization-free period. In the Kaplan-Meier model, the upper tertile of IL-18 had the highest probability of a hospitalization event during the entire follow-up period (P log rank = 0.027). In the Cox proportional hazard model, the relative risk for first hospital admission for each increase in Ln IL-18 (pg/ml) concentration was associated with a 1.709 (95% CI, 1.114 to 2.620; P = 0.014) increase in the risk for future hospitalization events. The present study demonstrated a strong predictive value of elevated IL-18 levels for poor outcome in HD patients.

Calcium-enriched bread for treatment of uremic hyperphosphatemia

Objective To assess phosphate-binding efficacy of a new food product, bread with unusually high calcium content (Ca-bread). Design and setting A randomized parallel group trial in the university hospital outpatient dialysis unit. Patients Fifty-three randomly selected uremic patients who met the following inclusion criteria: (1) required maintenance hemodialysis treatment, (2) were not to receive vitamin D throughout the study, (3) were nondiabetic, and (4) were diagnosed with hyperphosphatemia. Intervention Fifty-three patients were randomized into 2 groups: control group (n = 26), which received calcium acetate as a phosphate binder throughout the study, and Ca-bread group (n = 27), which, after a 2-week washout period, received Ca-bread containing 2.5% of elemental calcium (by weight), which served as a phosphate binder. Bread was made using wheat flour, calcium carbonate, and fermented buttermilk. The amount of elemental calcium used as a phosphate binder was similar in both groups. Observation of both groups lasted 14 weeks. Results Mean serum phosphate concentration at randomization was 2.11 ± 0.14 mmol/L in the control group and 2.20 ± 0.13 mmol/L in the Ca-bread group. Mean serum calcium concentration at randomization was 2.12 ± 0.21 mmol/L in the control group and 2.14 ± 0.11 mmol/L in the Ca-bread group. The Ca-bread group patients’ predialysis phosphate concentration decreased to a mean of 1.67 ± 0.18 mmol/L ( P < .05), and their mean calcium concentration increased to 2.27 ± 0.11 mmol/L ( P = NS). In the control group, neither value changed significantly from the original readings. After the hemodialysis session, the mean serum calcium concentration in the control group and the Ca-bread group increased by 7.5% and 7.9%, respectively ( P = NS). Mean phosphate concentration simultaneously decreased to nearly 1/2 its original predialysis value in both groups. Ca-bread group patients saw a decrease in the mean phosphate concentration (from predialysis to postdialysis values) that was 13.8% greater than that of the control group ( P = NS). Conclusion A new form of calcium-containing phosphate binder was developed: Ca-bread with an elemental calcium content of 2.5%. Ca-bread allows for effective amelioration of hyperphosphatemia without inducing hypercalcemia. Furthermore, patient compliance may increase if hyperphosphatemia can be treated by consuming bread with an elevated calcium content.

Potential cardiovascular risk factors in chronic kidney disease: AGEs, total homocysteine and metabolites, and the C-reactive protein

Total homocysteine (tHcy) and advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage. This study aimed to investigate whether elevated serum levels of the AGEs pentosidine, N(epsilon)-carboxymethyllysine (CML) and imidazolone; tHcy, cystathionine, methylmalonic acid (MMA), and 2-methylcitric acid (2-MCA), as well as C-reactive protein (CRP), are related to a higher risk for cardiovascular events. A total of 232 patients with chronic kidney diseases (mean age 57.6 +/- 13.1 years, 82 female and 150 male); 99 with chronic renal failure (CRF), 84 maintenance hemodialysis patients and 49 renal transplant recipients were followed for 2 years. The relationship between the parameters of interest, conventional risk factors and elevated levels of CRP with cardiovascular events was tested in all subjects by the Cox proportional hazards model. Mean serum levels of AGEs, tHcy, and of the metabolites were found to be significantly increased in all three groups compared to the healthy subjects (P < 0.01, respectively). Fifty-three cardiovascular events occurred during follow-up; a total of 40 patients died. Final multivariate analysis showed diabetes (RR 2.06, 95% CI 1.17-3.60, P= 0.013), end-stage renal disease (ESRD) (RR 4.88, 95% CI 2.40-9.89, P < 0.001) and elevated CRP levels (RR 2.00, 95% CI 1.11-3.60, P= 0.021) as independent risk factors for cardiovascular events. Data from a group consisting of patients with CRF, patients undergoing maintenance hemodialysis treatment, and renal transplant recipients provide evidence that conventional risk factors such as the presence of diabetes, ESRD, as well as elevated levels of the considered risk factor CRP, seem to play a more important role for cardiovascular outcome in patients with chronic kidney disease than elevated levels of AGEs, tHcy, and related metabolites. The evidence suggests that routine CRP measurement can be recommended in cases of chronic renal insufficiency.

Association of Serum Lipoprotein(a) with Left Ventricular Hypertrophy and Left Ventricular ejection Fraction in End-Stage Renal Failure Patients Under Hemodialysis

Background: The contribution of cardiovascular events to the extraordinary high mortality in end-stage-renal disease (ESRD) has generated some interest in non traditional athero sclerotic cardiovascular diseaserisk factors that are prevalent in ESRD , such as Lipoprotein(a) [Lp(a)]. In this study we aimed to consider the association of serum lipoproein(a)) with left ventricular hypertrophy (LVH) and hypertention (HTN) in ESRD patients under regular hemodialysis . Methods and patients: 61 unselected patients with end-stage renal disease (ESRD), undergoing maintenance hemodialysis treatment were studied. Lipoprotein (a) was measured by enzyme immuno assay (ELISA) test, all patients were echographied for left ventricular hypertrophy and left ventricular (LV) ejection fraction (EF). Hypertensive patients were stratified into no HTN, stage one to three HTN, as well as LVH was stratified to normal, mild, moderate and severe. Results: The total number of patients was 61(F=23 M=38). They consisted of 50 non diabetic hemodialysis patients (F=20 M=30) and 11 diabetic hemodialysis patients (F=3 M=8). Mean±SD of LP(a) of all patients was 58.5±19mg/dl. Mean±SD of LP(a) of the diabetic group was 62±12.3 mg/dl and for the nondiabetic group it was 57.7±20 mg/dl. There was a significant positive relationship between stages of LVH and stages of HTN, significant positive correlation between presence of chest pain and stages of LVH, significant reverse correlation of Lp(a) with percent of LV ejection fraction, as well as positive correlation of serum LP(a) with stages of HTN. A significant correlation between stages of LVH with serum LP(a) was observed this study. Conclusions: Lipoprotein(a) has an adverse effect on left ventricular hyperthrophy and hypertention of hemodialysis patients and needs more attention.

Relationship of Calcified Plaques of Carotid and Femoral Arteries with Left ventricular Hypertrophy in Maintenance Hemodialysis Patients

Objectives: Two Principle findings of cardiovascular disease in end-stage renal disease patients undergoing regular hemodialysis are left ventricular hypertrophy (LVH) and arterial disease due to rapidly progressive atherosclerotic vascular disease that can be characterized by arterial plaques. In this study we aimed to study the relationship of left ventricular hypertrophy with plaques of carotid-femoral artery in end-stage renal disease patients undergoing regular hemodialysis. Patients and Methods: 61 patients with end-stage renal disease (ESRD), undergoing regular and maintenance hemodialysis treatment (F=23 M=38), consisting of 50 non-diabetic hemodialysis patients (F=20 M=30) and 11 diabetic hemodialysis patients (F=3 M=8) were selected for this study. In all subjects echocardiography and B-mode ultrsonographic assessment of carotidfemoral arteries for plaque occurrence were performed. Results: In this study there was a positive correlation between stages of LVH and duration of hemodialysis treatment, a positive correlation between stages of LVH and stages of hypertension, significant association between stages of LVH with plaque score, and also a positive correlation between stages of LVH and presence of chest pain, as well as association of diabetes mellitus with the presence of chest pain and positive correlation between stages of HTN and plaque score. In addition, plaque score and percent of LV ejection fraction correlations were observed. Also, the association of plaque score with diabetes mellitus was demonstrated. Conclusions: The present study documents parallel cardiac and vascular adaptation in ESRD patients and demonstrates the potential contribution of structural and functional large artery alteration to the pathogenesis of left ventricular hypertrophy.

Initial body mass indexes have contrary effects on change in body weight and mortality of patients on maintenance hemodialysis treatment

Malnutrition is a relevant risk factor for mortality for patients on maintenance hemodialysis treatment. In a retrospective study including 377 patients who began hemodialysis treatment between 1986 and 2001, we assessed the prevalence of different statuses of nutrition and the impact of the initial status of nutrition on the change in body weight and patient survival. We found an inverse relationship between body mass index (BMI, kg/m 2) and the gain in body weight and BMI within 12 months of hemodialysis treatment. Underweight and normal weight patients had a substantial increase in these parameters, greatest in underweight subjects, whereas overweight and obese patients showed only a moderate increase or none ( P = .0019, P = .00036). Adjusted mortality rates showed an inverse correlation with the initial BMI ( P < .0001). There was a statistically significant difference in the mortality between patients with normal weight and overweight or obesity, respectively, showing a more favorable prognosis in overweight and obese patients ( P = .0007; P = .022; log-rank, normal versus overweight, P = .012). Weight loss was the greatest independent risk factor for mortality in general. Adjusted hazard ratio of death was highest in underweight patients (3.999; CI, 2.708 to 5.905; P < .0001) and decreased to 2.251 (CI, 1.795 to 2.822; P < .0001) in normal weight, 1.927 (CI, 1.390 to 2.670; P < .0001) in overweight, and 1.651 (CI, 0.841 to 3.236; P = .1439) in obese subjects when patients with weight loss were compared with patients who preserved their initial weight or gained weight. Overall, the initial BMI has an influence on the change in body weight as well as on patient survival in general and in the case of weight loss in particular.

Aldose reductase gene polymorphism is associated with progression of diabetic nephropathy in Japanese patients with type 1 diabetes mellitus.

The objective of this study was to investigate cross-sectionally and longitudinally whether polymorphism of the (A-C)n dinucleotide repeat sequence of the aldose reductase (AR) gene may modulate risk for diabetic nephropathy or retinopathy in Japanese patients with type 1 diabetes. We obtained DNA samples from 101 patients followed up after the onset of type 1 diabetes and analysed a (A-C)n dinucleotide repeat polymorphic marker in the AR gene by polymerase chain reaction (PCR) method. Ten alleles ranging from Z-10 (128 bp) to Z+8 (146 bp) in repeat number were identified. In cross-sectional studies, the prevalence of the Z+2 allele was higher than that of any other allele in patients with diabetic nephropathy (37.5% of patients in a microalbuminuria group, and 41.7% of those in a macroalbuminuria group including patients with chronic renal failure and maintenance haemodialysis treatment). Prevalence of the Z+2 allele was not increased in patients with diabetic retinopathy. In longitudinal Kaplan-Meier plots, the cumulative incidence of nephropathy was significantly associated with homozygosity for the Z+2 allele (log rank test, p = 0.031); respective prevalence of nephropathy after diabetes durations of 10 and 15 years was 42.9% and 100% in Z+2 homozygotes (n = 8), 17.6% and 27.4% in Z+2 heterozygotes (n = 44), and 6.1% and 17.4% in patients without the Z+2 allele (n = 49). However, occurrence of retinopathy was not influenced by the Z+2 allele (log rank test, p = 0.926). Homozygosity for the Z+2 allele was associated with accelerated early progression of diabetic nephropathy in Japanese type 1 diabetic patients.

Red blood cell fatty acid profile of chronic renal failure patients receiving maintenance haemodialysis treatment

The fatty acid profile of chronic renal failure (CRF) patients on maintenance haemodialysis treatment (MHT) is abnormal and results point towards an essential fatty acid (EFA) deficiency. However, controversies still exist as to which of the essential fatty acids (EFAs) or EFA-products are decreased. In this study, the results of a comprehensive analysis of the fatty acids, performed on the red blood cells of 14 CRF patients on MHT, are presented. The red blood cell membrane fatty acids determined in this study include a range of saturated fatty acids (SFAs), mono-unsaturated fatty acids (MUFAs) and poly-unsaturated fatty acids (PUFAs). Results confirmed the suggested presence of an essential fatty acid deficiency in CRF patients on MHT. It showed the total content of the n-6 fatty acids (31.66±3.21 vs 34.67±2.05), as well as the total content of the PUFAs (37.22±4.08 vs 40.93±2.35), to be significantly decreased. The total MUFA content was, in contrast, significantly increased (16.87±0.91 vs 15.49±1.18). The EFA deficiency profile seen in this study points towards that of a chronic inflammatory condition. This is borne out by the fact that all three precursors of the eicosanoids—the mediators of various inflammatory and immune responses—were reduced in the presence of an increase in MUFAs as well as SFAs. The possibility of the fatty acid profile of CRF patients on MHT being that of a chronic inflammatory condition is supported by the fact that continuous complement-dependent and complement-independent immune activation, due to bio-incompatibility between blood cells and the dialysis membranes, is known to occur during the dialysis process.

Intracellular free calcium in the neutrophils of maintenance haemodialysis patients.

Chronic renal failure has on occasion been referred to as a state of calcium toxicity. The aim of this study was to investigate the status of intracellular free Ca2+ in the neutrophils of chronic renal failure patients on maintenance haemodialysis treatment. Factors previously suggested to influence intracellular free Ca2+ were investigated including PTH levels, oxidative stress and recombinant human erythropoietin administration. The study involved 14 chronic renal failure patients on the haemodialysis programme of the Pretoria Academic hospital. Intracellular free Ca2+ and transmembrane Ca2+ fluxes were investigated by fluorescence spectrophotometry. Increases above control values were found in intracellular free Ca2+ (P-value 0.0242) and in the transmembrane Ca2+ flux upon fMLP stimulation (P-value 0.0002). The results showed significant differences in intracellular free Ca2+ between patients on rHuEPO and patients not on rHuEPO. The apparently rHuEPO-induced increase in intracellular free Ca2+ persisted in the presence of calcium channel blockers. No overt indications of oxidative stress could be detected by the antioxidant vitamin levels. It is concluded that factors other than those associated with uraemia, such as rHuEPO administration, might contribute to the often reported increase in intracellular free Ca2+ in these patients. Further studies to investigate the relationship between intracellular free Ca2+, rHuEPO and calcium channel blockers are suggested.

Incidence of Stroke among Chronic Hemodialysis Patients with Nonrheumatic Atrial Fibrillation

In general, nonrheumatic atrial fibrillation is associated with a high risk of stroke. However, its impact on stroke in the setting of chronic hemodialysis treatment is insufficiently addressed in the literature. We assessed the incidence of stroke among 430 chronic hemodialysis patients and the impact of atrial fibrillation and various other potential risk factors on stroke in a retrospective study covering 1,111.16 patient-years. The overall incidence of stroke was 3.78/100 patient-years. Among patients with chronic atrial fibrillation without any antithrombotic therapy besides regular dialysis anticoagulation, the stroke incidence was 1.0/100 patient-years and did not differ statistically significantly from the rate among patients without this arrhythmia, in whom the incidence was 2.8/100 patient-years (p = 0.220). Conversely, the overall rate of stroke incidence per 100 patient-years was statistically significantly higher in patients with diabetic nephropathy (6.46, p = 0.0036), age >65 years (5.90, p = 0.0001), moderate to severe hypertension (6.8, p = 0.0017), weight gain of >2 kg between dialyses as a marker of poor patient compliance (6.47, p = 0.0433), and antithrombotic therapy with salicylates or warfarin (8.33, p = 0.0002), as compared with corresponding groups without these risk factors. Our data suggest that in contrast to other risk factors nonrheumatic atrial fibrillation in itself is not associated with an increased risk of stroke in patients on maintenance hemodialysis treatment.

Responses of the skin microcirculation to acetylcholine and to sodium nitroprusside in chronic uremic patients

The aim of the present study was to assess the endothelial function of the microcirculation in chronic renal failure. We investigated the responses of the cutaneous blood flow to locally delivered acetylcholine and sodium nitroprusside in uremic patients. The study included 60 chronic uremic patients: 40 patients with a creatinine clearance of 4-25 ml/min were on conservative treatment and 20 patients were on maintenance hemodialysis. The changes in skin blood flow following iontophoretic delivery of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator) were measured by laser Doppler flowmetry. Acetylcholine induced a progressive increase in blood flow in both groups, reaching approximately 100% of the maximal hyperemic response obtained by sodium nitroprusside delivery. The percent increase in blood flow from baseline was lower in hemodialysis patients than in patients on conservative treatment, after both acetylcholine (550 +/- 44 vs. 718 +/- 61%, P < 0.05) and sodium nitroprusside (553 +/- 46 vs. 735 +/- 69%, P < 0.05) delivery. In the hemodialysis group, the hyperemic responses to acetylcholine and sodium nitroprusside did not improve after the hemodialysis session. Hence, the hyperemic responses of the skin microcirculation are lower in hemodialysis patients than in patients on conservative treatment, and did not ameliorate after hemodialysis. It seems to be independent of endothelial dysfunction, and associated with the severity of uremia and with the maintenance hemodialysis treatment. This microcirculatory abnormality is in keeping with the arterial stiffness and vascular wall damages described in dialysis patients, which contribute to the cardiovascular morbidity of chronic uremia.