Effect of phosphate binders on oxidative stress and inflammation markers in hemodialysis patients

It has been suggested that phosphate binders may reduce the inflammatory state of hemodialysis (HD) patients. However, it is not clear whether it has any effect on oxidative stress. The objective of this study was to evaluate the effect of sevelamer hydrochloride (SH) and calcium acetate (CA) on oxidative stress and inflammation markers in HD patients. Hemodialysis patients were randomly assigned to therapy with SH (n=17) or CA (n=14) for 1 year. Before the initiation of therapy (baseline) and at 12 months, we measured in vitro reactive oxygen species (ROS) production by stimulated and unstimulated polymorphonuclear neutrophils and serum levels of tumor necrosis factor α, interleukin-10, C-reactive protein, and albumin. There was a significant reduction of spontaneous ROS production in both groups after 12 months of therapy. There was a significant decrease of Staphylococcus aureus stimulated ROS production in the SH group. There was a significant increase in albumin serum levels only in the SH group. In the SH group, there was also a decrease in the serum levels of tumor necrosis factor α and C-reactive protein. Our results suggest that compared with CA treatment, SH may lead to a reduction in oxidative stress and inflammation. Therefore, it is possible that phosphate binders exert pleiotropic effects on oxidative stress and inflammation, which could contribute toward decreasing endothelial injury in patients in HD.     

Effects of l‐carnitine supplement on serum inflammatory cytokines,C‐reactive protein,lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia

Inflammation, oxidative stress, and high concentration of serum lipoprotein (a) [Lp (a)] are common complications in hemodialysis patients. The present study was designed to investigate the effects of l ‐carnitine supplement on serum inflammatory cytokines, C‐reactive protein (CRP), Lp (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was an unblinded, randomized clinical trial. Thirty‐six hyper Lp (a) hemodialysis patients (23 men and 13 women) were randomly assigned to either a carnitine or control group. Patients in the carnitine group received 1000 mg/d oral l ‐carnitine for 12 weeks, whereas patients in the control group did not receive any l ‐carnitine supplement. At baseline and the end of week 12, 5 mL of blood were collected after a 12‐ to 14‐hours fast and serum free carnitine, CRP, interleukin‐1β, interleukin‐6 (IL‐6), tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein were measured. Serum free carnitine concentration increased significantly by 86% in the carnitine group at the end of week 12 compared with baseline (P<0.001), while serum CRP and IL‐6 showed a significant decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes were observed in serum free carnitine, CRP, and IL‐6 in the control group. There were no significant differences between the two groups in mean changes of serum interleukin‐1β, tumor necrosis factor‐α, Lp (a), and oxidized low‐density lipoprotein concentrations. l ‐carnitine supplement reduces inflammation in hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.     

Mini mental status examination (MMSE) in stable chronic renal failure patients on hemodialysis: The effects of hemodialysis on the MMSE score. A prospective study

Cognitive impairment is common in hemodialysis (HD) patients. The mini mental status examination is a simple screening test for dementia. The objectives of this study were to (1) study and compare the predialysis and postdialysis mini mental status examination score and 2 subscores and compare them with those of a control group and (2) determine the factors affecting these scores. This was a prospective study of 54 HD patients, which involved calculation of their predialysis (PrHDSc) and (2–4 weeks later) postdialysis (PoHDSc) scores and comparison of these with the control scores (CoSc). The mean scores for PreHDSc and PoHDSc were 26.5±2.7 and 26.4±3.3, respectively. Both were significantly lower than CoSc, 28.4±1.6 (95% CI for score difference 0.99–2.97, P<0.001). The subscores for orientation, registration, and recall (ORR) and attention (ATT) before and after HD were 14.2±1.3, 14.3±1.8, and 3.5±1.7, 3.2±1.8, respectively. Both were significantly lower than the CoSc, 15.2±1.2 and 4.2±1.1 (P=0.001 and 0.004, respectively). There were no significant differences between the PrHDSc and PoHDSc (P values of 0.87, 0.63, and 0.45, respectively). Patients' PrHDSc correlated positively with PoHDSc and dialysis efficiency measured by the urea reduction ratio and Kt/V (r=0.58, 0.4, and 0.34, respectively). Education level correlated positively with PrHDSc r=0.41 but not PoHDSc. Hemodialysis duration correlated negatively with PrHDSc r=−0.3. There was no correlation among age, chronic renal failure duration, HD frequency, weight loss, systolic or diastolic blood pressure drop, and PrHDSc or PoHDSc. Hemodialysis patients scored significantly less than the control patients. Their score was not affected by HD. This may reflect the stable cognitive function/dysfunction or the mild sensitivity of the test.     

陶瓷膜用于气固分离的研究现状和前景

简要介绍陶瓷膜除尘分离的原理和应用技术的现状,并展望其应用和发展前景．陶瓷膜高温气体净化器和收尘、除尘技术及设备前途广阔,特别是在国内,是值得大力发展的一种高新技术。     

Cardiovascular disease on hemodialysis: Predictors of atherosclerosis and survival

Cardiovascular disease (CVD) is the leading cause of mortality in hemodialysis (HD) patients. This could not be explained by the known traditional CVD risk factors. In this study, we attempted to elucidate the factors influencing atherosclerosis, as measured by carotid artery intima-media thickness (IMT), in HD patients and their impact on cardiovascular mortality. A cohort of 50 patients started on HD was selected for this study. At baseline, IMT and the presence of atheromatous plaques were assessed. Plasma homocysteine (Hcy), malondialdehyde, total antioxidant capacity, von Willebrand factor, vitamins C, E, B₆, B₁₂, folate, and C-reactive protein (CRP) were also measured. Patients were followed up for 2 years to determine the impact of IMT and associated markers on mortality using survival analysis as well as Cox proportional hazard. At baseline, 40% of the patients had IMT>0.8 mm. They were older, had higher CRP (P<0.001), and lower serum albumin (P=0.03). Intima-media thickness >0.8 mm was associated with high calcium (risk ratio [RR]: 6.06; confidence interval [CI]: 0.75–12.25) and CRP (RR: 10.94 [CI: 2.56–46.74]). Fifteen patients (30%) died during the 2-year follow-up; the main cause of death was CVD (42%). The relative risk mortality was high with increased IMT (RR: 120.04 [CI: 4.18–3445.9]), Index of Coexistent Disease for CVD (RR: 4.04 [CI: 1.92–8.5]), and plasma Hcy (RR: 1.08 [CI: 1.02–1.13]). Markers of inflammation and increased serum calcium were significant predictors of increased carotid artery IMT. High IMT, Index of Coexistent Disease, and Hcy were associated with a high RR of all-cause mortality among a cohort of HD patients.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Looking at calcimimetics impact on hypercalcemia of immobilization: hypotheses and a case study

For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca x P). Hypocalcemia is a frequent finding during the correction phase of the HPTH-II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40-year-old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney-related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37-2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a hemodialysis patient.     

Correlates affecting survival in chronic hemodialysis patients: The combined impact of albumin and high hemoglobin levels on improving outcomes,local and national results

While national mortality rates for end‐stage renal disease (ESRD) patients remain high, for the past 4 years, lower than expected local mortality rates have been consistently seen in our facilities. Because of these progressive improvements in mortality rates, a study of 687 hemodialysis patients over a 4‐year period, 2003 through 2006, was undertaken to analyze which factors may be contributing to the enhanced survival rates. We also examined the partially overlapping United States Renal Data System clinical performance measures national data sets of hemodialysis patients for 2001 to 2004. Proportional hazards and logistic regression models were used to determine significant predictors of short‐term survival. Variables tested included hemoglobin (Hb), albumin, calcium, phosphorus, infections, hospitalizations, URR, Kt/V, erythropoietic stimulating agents (epoetin‐α) use, and comorbid conditions. The local and national models identified albumin, Hgb, and hospitalization as statistically significant predictors of survival. Local models also found years of dialysis as a significant predictor. Locally, there was a 69‐fold increase from 16.1 deaths/1000 patient years for albumin ≥4.0 with Hgb≥14.0 to 1115.9 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. The increase nationally is a 4‐fold increase from 96 deaths/1000 patient‐years for albumin ≥4.0 with Hgb≥14.0 to 406 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. There was no evidence that higher erythropoietic stimulating agents dose levels were associated with higher mortality rates, independent of the other significant factors. In conclusion, the findings indicate that individually higher Hgb and albumin levels are associated with increased survival, and when higher Hgb levels are in association with high albumin levels, the survival rates and hospitalizations are synergistically improved.     

Influence of platelet-activating factor,lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the single-chained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.