Low-density lipoprotein (LDL)-induced monocyte-endothelial cell adhesion, soluble cell adhesion molecules, and autoantibodies to oxidized-LDL in chronic renal failure patients on dialysis therapy

Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure patients undergoing dialysis. In this study, we compared autoantibodies to oxidized low-density lipoprotein (OX-LDL), soluble cell adhesion molecules (CAMs), and the effect of both LDL and OX-LDL on monocyte endothelial cell adhesion in chronic renal failure patients on hemodialysis (HD, n = 16) and peritoneal dialysis (PD, n = 17) compared with matched healthy control subjects (C, n = 17). In addition, we studied the effect of supplementation with RRR-alpha-tocopherol (AT) 800 IU/d for 12 weeks on the above measures. LDL and OX-LDL induced adhesion of U937 cells to cultured endothelium, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin); autoantibodies to OX-LDL and markers of lipid peroxidation were determined before and after AT supplementation. Native LDL from PD patients induced greater monocyte-endothelial cell adhesion than LDL from C subjects (43.8% +/- 17.0% v25.3% +/- 17.7%, respectively, P = .0028). OX-LDL from chronic renal failure patients on both PD and HD stimulated greater adhesion than OX-LDL from the C subjects (68.0% +/- 18.5% and 57.6% +/- 15.1% v 40.9% +/- 17.3%, respectively, P < .01); OX-LDL from PD patients induced greater adhesion than that from HD patients (P < .01). Plasma methylglyoxal levels were significantly increased in both HD and PD groups, with higher levels in the HD group. Chronic renal failure patients on HD and PD also had higher levels of plasma sVCAM-1 and sE-selectin than C subjects (P < .01), indicating endothelial activation. Titers of autoantibodies to OX-LDL were not elevated in renal failure patients. Supplementation with AT 800 IU/d for 12 weeks, while resulting in significant enrichment with AT in LDL, did not have a significant effect on any of the parameters studied. This study makes the novel observation that the LDL of chronic renal failure patients on HD and PD appears to be potentially more atherogenic, since it induces greater monocyte-endothelial cell adhesion.     

Effects of lovastatin therapy on susceptibility of LDL to oxidation during alpha-tocopherol supplementation.

A randomized, double-masked, crossover clinical trial was carried out to evaluate whether lovastatin therapy (60 mg daily) affects the initiation of oxidation of low density lipoprotein (LDL) in cardiac patients on alpha-tocopherol supplementation therapy (450 IU daily). Twenty-eight men with verified coronary heart disease and hypercholesterolemia received alpha-tocopherol with lovastatin or with dummy tablets in random order. The two 6-week, active-treatment periods were preceded by a washout period of at least 8 weeks. The oxidizability of LDL was determined by 2 methods ex vivo. The depletion times for LDL ubiquinol and LDL alpha-tocopherol were determined in timed samples taken during oxidation induced by 2, 2-azobis(2,4-dimethylvaleronitrile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation phase of conjugated-diene formation. alpha-Tocopherol supplementation led to a 1.9-fold concentration of reduced alpha-tocopherol in LDL (P<0.0001) and to a 2.0-fold longer depletion time (P<0.0001) of alpha-tocopherol compared with determinations after the washout period. A 43% prolongation (P<0.0001) was seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced alpha-tocopherol in metal ion-independent oxidation by 44% and shortened the lag time of conjugated-diene formation in metal ion-dependent oxidation by 7%. In conclusion, alpha-tocopherol supplementation significantly increased the antioxidative capacity of LDL when measured ex vivo, which was partially abolished by concomitant lovastatin therapy.     

Low density lipoprotein composition and oxidizability in coronary disease--apparent favourable effect of beta blockers.

The oxidative modification of LDL in vivo may have an important role in atherogenesis. To determine whether LDL fatty acid, anti-oxidant composition and sensitivity to oxidation in vitro is different in subjects with established atherosclerosis we compared 20 men with angiogram proven coronary disease with 25 controls without clinical evidence of arterial disease. LDL-cholesterol, total triglycerides and LDL fatty acid composition did not differ significantly between the groups. LDL oxidation lag time and oxidation rate in coronary patients (132 min, 0.02 absorbance units/min) and controls (140, 0.017) were not significantly different. However coronary disease subjects taking beta-blockers had evidence for reduced LDL oxidizability (lag time 148 +/- 7 min; oxidation rate 0.017 +/- 0.002 abs units/min) compared with those not on beta-blockers (lag time 114 +/- 7 min, rate 0.025 +/- 0.003, P < 0.005). LDL beta-carotene was significantly lower in coronary patients (0.92 mumol/mmol LDL cholesterol; controls 1.58; P = 0.001). LDL alpha-tocopherol appeared lower in coronary patients (2.8 mumol/mmol LDL cholesterol; controls 3.3; P = 0.056) and was significantly lower in smokers (2.56; non-smokers 3.24; P = 0.04). LDL oxidation rate was negatively correlated with LDL alpha-tocopherol (r = -0.51, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study

Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross‐sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre‐HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post‐HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre‐HD (β = ?0.8, P = 0.03) and similar to PD (β = ?0.5, P = 0.24) and post‐HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre‐HD, but not in PD and post‐HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.     

慢性肾功能衰竭患者血清低密度脂蛋白亚组分的分布及氧化易感性

为探讨慢性肾功能衰竭患者血浆低密度脂蛋白亚组分的异常特性,采用密度梯度超速离心直接分离血浆低密度脂蛋白亚组分,并对其分布及体外铜离子介导的氧化易感性进行分析。结果发现,慢性肾功能衰竭患者血浆低密度脂蛋白亚组分分布与对照组无差别,低密度脂蛋白氧化延滞时间缩短４８％,差异显著（Ｐ〈０．００１）,显示其易于氧化。血浆低密度脂蛋白氧化水平显著升高,氧化程度与低密度脂蛋白氧化延滞时间高度相关（ｒ＝－０．４５     

The prevalence of constipation in end-stage kidney disease patients: A cross-sectional observation study

The aim of our study was to determine the prevalence, distribution, and risk factors for constipation in peritoneal dialysis (PD) and hemodialysis (HD) patients in our center. In this cross-sectional study, 858 dialysis patients over 18 years of age (681 HD cases and 177 PD cases from our hospital) were enrolled. A constipation assessment scale (CAS) questionnaire was used to evaluate constipation status. Logistic regression analysis was performed to define independent risk factors for CAS scores. The prevalence of constipation in HD and PD patients was 52.7% and 77.4%, respectively. The mean CAS score in HD and PD patients was 1.73 ± 2.31 and 2.42 ± 2.34, respectively. Age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors associated with constipation in the HD population (OR = 1.67, 95% CI: 1.15–2.90, P = .019; OR = 3.31, 95% CI: 1.65–6.11, P < .001, respectively). In the PD population, only serum prealbumin was independently associated with constipation (OR = 0.88, 95% CI: 0.79–0.96, P = .007). The multivariable logistic regression analysis demonstrated that PD modality, age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors for constipation (OR = 2.15, 95% CI: 1.41–3.32, P < .001; OR = 1.65, 95% CI: 1.13–2.33, P = .003; OR = 3.19, 95% CI: 1.76–5.093, P < .001, respectively). The prevalence of constipation in PD patients was higher than that in HD patients in our center. PD modality for renal replacement therapy, age ≥ 65 and diabetic kidney disease for renal failure were closely associated with constipation in dialysis patients.     

Effect of thyroid function on LDL oxidation in hypothyroidism and hyperthyroidism

Oxidized low-density lipoproteins (LDL) are highly suspected of initiating the atherosclerosis process. Hypothyroidism is frequently associated with hypercholesterolemia and carries increased risk for atherosclerosis. In contrast to hypothyroidism, hyperthyroidism is not associated with increased LDL cholesterol, but is associated with increased oxidized LDL. This study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism or hyperthyroidism, and to reveal the effects of treatment in hypothyroidism and hyperthyroidism on LDL oxidation and lipid profiles. Thirty-two patients with hypothyroidism and 16 patients with hyperthyroidism were studied before the therapy and thereafter, when they were euthyroid with appropriate treatment. Plasma lipids and lipoproteins, and the oxidizability of LDL by determining the levels of malonaldehyde bis (dimethyacetyl) (MDA) and diene conjugation, were determined at baseline and after the patients were rendered euthyroid. The actual content of dienes in LDL particles was increased in hypothyroidism, with a decrease after T4 supplementation (p < .001). Dienes in LDL particles were increased in hyperthyroidism, with a decrease after treatment (p < .05). In hypothyroid patients, the lag phase was shorter in the pretreatment period than in the euthyroid period (p > .05). The lag phase of hyperthyroid patients was shorter in the pretreatment period than in the euthyroid period and hypothyroid state (p < .001). The Cu2+-catalyzed dienes of LDL and MDA oxidation in the hypothyroid state and the subsequent euthyroid states were decreased (p < .001). The Cu2+-catalyzed dienes of LDL (p < .01) and MDA oxidation (p < .001) in hyperthyroid patients after treatment were decreased. The enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.     

High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus

OBJECTIVE: To examine low-density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE). METHODS: Fifty-nine SLE patients and 59 healthy, age-matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A-I, and fatty acids were also measured. RESULTS: Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high-density lipoprotein cholesterol (HDL-C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL-C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels. CONCLUSION: SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.     

血透与腹透患者血清脂蛋白(a)的变化及意义

目的观察血透(HD)与腹透(PD)患者之间脂蛋白(a)[lipoprotein(a),Lp(a)]及脂质水平影响的差别及其临床意义.方法对68例HD患者及50例PD患者的临床及实验室资料作研究,比较两种透析方式对血Lp(a)及脂质水平影响的差别,分析血Lp(a)与其他相关因素特别是与心脑血管事件的关系.结果HD与PD患者血Lp(a)水平均较对照组呈显著性升高(P＜0.05),其中PD组较HD组更高(P＜0.01);HD组血Tch较对照组及PD组均呈显著性下降(P＜0.05)、血HDL-C较对照组呈显著性下降(P＜0.01);PD组血TG较对照组及HD组均呈显著性升高(P＜0.05);血ApoA、ApoB100与对照组间无统计学差异.HD与PD患者血Lp(a)水平与超声心动图异常(P＜0.05)、ECG异常(P＜0.001)及心脑血管事件的发生(P＜0.01)、24h腹水蛋白质浓度(P＜0.01)、血Tch及LDL-C浓度(P＜0.05)、纤维蛋白原(P＜0.05)呈正相关;而与血浆白蛋白浓度(P＜0.05)、24h腹水Lp(a)浓度(P＜0.05)呈负相关.结论HD与PD患者普遍存在严重的脂质代谢变化,其中以血Lp(a)、TG、HDL-C变化尤为显著,PD组由于长期吸收大量葡萄糖,因此脂质代谢紊乱更为明显.Lp(a)有可能是HD、PD患者并发心脑血管事件的危险因素之一.     

Quality of Life and Physical Function in Older Patients on Dialysis: A Comparison of Assisted Peritoneal Dialysis with Hemodialysis

Background and objectives

In-center hemodialysis (HD) is often the default dialysis modality for older patients. Few centers use assisted peritoneal dialysis (PD), which enables treatment at home. This observational study compared quality of life (QoL) and physical function between older patients on assisted PD and HD.

Design, setting, participants, & measurements

Patients on assisted PD who were >60 years old and on dialysis for >3 months were recruited and matched to patients on HD (needing hospital transport) by age, sex, diabetes, dialysis vintage, ethnicity, and index of deprivation. Frailty was assessed using the Clinical Frailty Scale. QoL assessments included Hospital Anxiety and Depression Scale (HADS), Short Form-12, Palliative Outcomes Symptom Scale (renal), Illness Intrusiveness Rating Scale, and Renal Treatment Satisfaction Questionnaire (RTSQ). Physical function was evaluated by Barthel Score and timed up and go test.

Results

In total, 251 patients (129 PD and 122 HD) were recruited. In unadjusted analysis, patients on assisted PD had a higher prevalence of possible depression (HADS>8; PD=38.8%; HD=23.8%; P=0.05) and higher HADS depression score (median: PD=6; HD=5; P=0.05) but higher RTSQ scores (median: PD=55; HD=51; P<0.01). In a generalized linear regression model adjusting for age, sex, comorbidity, dialysis vintage, and frailty, assisted PD continued to be associated with higher RTSQ scores (P=0.04) but not with other QoL measures.

Conclusions

There are no differences in measures of QoL and physical function between older patients on assisted PD and comparable patients on HD, except for treatment satisfaction, which is higher in patients on PD. Assisted PD should be considered as an alternative to HD for older patients, allowing them to make their preferred choices.     

Association Between Dialysis Modalities and Risk of Coronary Artery Disease: A Population‐Based Cohort Study in Taiwan

The hemodynamic effects of hemodialysis (HD) and peritoneal dialysis (PD) on end‐stage renal disease (ESRD) patients differ. The influence of dialysis modalities on the cardiovascular system has not been well investigated. We aimed to evaluate the association between dialysis modalities and risk of coronary artery disease (CAD) by using the claim data of Taiwan's Longitudinal Health Insurance Database. This study followed up a cohort of 1624 new onset ESRD patients (≥18 years old), who had started renal replacement therapy during 2000 to 2010; and was followed until 2012. After adjusting for potential confounders, patients who underwent HD had significantly higher risks of incidence of CAD, in comparison with patients who underwent PD (adjusted hazard ratio = 1.47; 95% confidence interval = 1.01–2.11). An increased risk of incident CAD was distinguished in patients receiving HD, compared with those on PD. Further studies are warranted to explore the underlying mechanism and improve dialysis outcomes.     

Comparison of mortality and its causes in patients with complicated systemic lupus erythematosus on hemodialysis versus peritoneal dialysis: A meta-analysis

Background:Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). Ten percent to 20% of patients with SLE progress to end-stage renal disease and would require renal replacement therapy or renal transplantation. In this analysis, we aimed to systematically compare mortality and the causes of mortality in patients with complicated SLE who were treated on hemodialysis (HD) versus peritoneal dialysis (PD).Methods:Cochrane Central, Medical Literature Analysis and Retrieval System Online, Google Scholar, Web of Science, Excerpta Medica dataBASE, and http://www.ClinicalTrials.gov were searched for studies that compared HD versus PD in patients with SLE. The RevMan software version 5.4 (RevMan software, Cochrane Collaborations, United Kingdom) was used to analyze data. Heterogeneity was assessed using the Q and the I² statistical tests. In this analysis, a random effects model was used during data assessment. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis.Results:A total number of 3405 SLE participants were included in this analysis, whereby 2841 were assigned to HD and 564 participants were assigned to PD. In patients with SLE who were on dialysis, our analysis showed that the risk of mortality was similar with HD and PD (RR, 0.69; 95% CI, 0.45–1.07; P = .10). When the cause of mortality was analyzed, cardiovascular death (RR, 0.63; 95% CI, 0.31–1.31; P = .22), death due to infection (RR, 0.74; 95% CI, 0.47–1.17; P = .20), death due to a respiratory cause (RR, 1.06; 95% CI, 0.18–6.21; P = .95), cause of death due to SLE flare up (RR, 2.54; 95% CI, 0.39–16.37; P = .33), and other causes of death (RR, 0.79; 95% CI, 0.35–1.77; P = .57) were not significantly different with HD and PD.Conclusion:This current analysis showed that in SLE patients who required dialysis, the risk of mortality between HD and PD was similar, and the causes of death including cardiovascular, infective, respiratory, SLE flare up, and other causes were not significantly different. Therefore, both dialysis methods were tolerable in these patients with SLE. Further studies with larger data would be required to confirm this hypothesis.     

Role of plasmalogens in the enhanced resistance of LDL to copper-induced oxidation after LDL apheresis.

Extracorporeal reduction of plasma low density lipoproteins (LDLs) by LDL apheresis was shown to attenuate the proatherogenic influences of LDL, such as impairment of vasodilation and increased monocyte adhesion to the endothelium. In 16 patients with familial hypercholesterolemia, we analyzed whether LDL apheresis by the heparin precipitation procedure affected the oxidative resistance of LDL. Plasma LDL cholesterol concentrations were reduced by 65% after the apheresis. The lag time of copper-mediated LDL oxidation was increased from 103 to 117 minutes (P<0.0005). The LDL contents of alpha-tocopherol and beta-carotene, as well as the ratio of monounsaturated to polyunsaturated fatty acids in LDL, were not altered. However, the LDL apheresis induced a 15% increase in the LDL contents of plasmalogen phospholipids (P<0.0005), a class of ether phospholipids that were recently shown to prevent lipid oxidation. The phosphatidylcholine (PC) to lysoPC ratio was elevated by 16% after the apheresis (P<0.0005). The percent increase in LDL plasmalogen phospholipids showed a close association with the increased lag time after apheresis (P<0.0005). The LDL plasmalogen contents of the blood samples from patients and from normolipidemic donors were also positively related to the lag time (P<0.005). In vitro loading of LDL with plasmalogen phospholipids resulted in a prolongation of the lag time and an increase in the PC/lysoPC ratio. In conclusion, the rapid rise in LDL contents of plasmalogen phospholipids most probably causes the increase in lag time after LDL apheresis. Plasmalogens appear to play an important role in the oxidation resistance of LDL in vivo.     

Lipoperoxidation and hemodialysis

It has been suggested that hemodialysis patients may be under increased oxidative stress and may therefore benefit from the long-term use of antioxidants (particularly for the reduction of the risk of heart disease). The aim of this study was, first, to evaluate the effect of hemodialysis by itself on lipid and lipoprotein oxidation profiles and, second, to analyze the effect of vitamin C supplementation in patients with end-stage renal disease starting hemodialysis. Forty-one patients with end-stage renal disease were enrolled and randomized to receive 1000 mg/d vitamin C or matching placebo before starting hemodialysis. We measured lipid profile and the susceptibility of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) to oxidation using copper ions at the moment of inclusion and after 1 year. All lipoperoxidation parameters were included. Hemodialysis by itself improved the lipid profile, lowering total cholesterol (176.4 ± 48.4 to 154.2 ± 28.8 mg/dL, P < .01), LDL cholesterol (94.1 ± 39.6 to 76.1 ± 26.6 mg/dL LDL, P < .03), and phospholipids levels (196.5 ± 36.7 to 182.9 ± 36.1 mg/dL, P < .05) in all patients on maintenance hemodialysis. The HDL cholesterol was also decreased (49.4 ± 19.8 to 43.4 ± 24.1 mg/dL HDL, P < .03). No significant differences were detected between patients receiving vitamin C and those receiving placebo. Thiobarbituric acid reactive substances (TBARS) and lipoperoxides increased in patients after a year of hemodialysis, but the difference was lower in those administered vitamin C for a year—TBARS LDL (in nanograms per gram LDL): 0.25 ± 0.20 to 0.38 ± 0.2 in vitamin C-treated subjects and 0.28 ± 0.17 to 0.46 ± 0.21 in those treated with placebo (P < .007); TBARS HDL (in nanograms per gram HDL): 0.22 ± 0.12 to 0.34 ± 0.30 in patients receiving vitamin C and 0.20 ± 0.18 to 0.28 ± 0.19 in those receiving placebo (P = .071). Hemodialysis by itself seems to improve the lipid profile in patients with a previous prooxidative state such as uremia. Although our results failed to demonstrate significant differences between vitamin C-treated and untreated patients, and despite the small number of patients, the trend toward a decrease in oxidation products due to vitamin C supplementation may be beneficial for oxidation parameters. This area remains controversial and under active investigation. Further research is necessary before a firm conclusion can be reached.     

Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability

BACKGROUND: Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil. METHODS: We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography. RESULTS: Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine. CONCLUSIONS: EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.     

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study

ABSTRACT: BACKGROUND: Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. METHODS: A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. RESULTS: Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024). CONCLUSION: Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.     

High insulin levels and increased low‐density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus

Objective

To examine low‐density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE).

Methods

Fifty‐nine SLE patients and 59 healthy, age‐matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A‐I, and fatty acids were also measured.

Results

Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high‐density lipoprotein cholesterol (HDL‐C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL‐C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels.

Conclusion

SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.

     

Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis

OBJECTIVE: The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF-I, whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD). DESIGN: A cross-sectional study in the setting of a dialysis unit of a general hospital. PATIENTS AND MEASUREMENTS: We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54, 31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were measured in all patients and control subjects. RESULTS: Fasting serum concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6 +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5 micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD, respectively). In both groups of dialysis patients, IGF-I correlated inversely with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P = 0.001). No correlation between insulin and IGFBP-1 was found in any of the groups studied. CONCLUSIONS: These findings demonstrate that adult dialysis patients have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I and IGFBP-3 are maintained in both groups of adult dialysis patients.     

Low-density lipoprotein (LDL) oxidizability before and after LDL apheresis.

Oxidation of low-density lipoprotein (LDL) plays a major role in the development of atherosclerosis. Hypercholesterolemia has been associated with enhanced in vitro oxidation of LDL, and lipid-lowering therapy reduces LDL oxidizability. In the present study, we investigated whether LDL apheresis performed with different techniques affects in vitro diene formation (lag phase) and modification of apolipoprotein B-100 (apoB). Baseline and posttreatment diene formation was correlated with the baseline pattern of plasma total fatty acids. We then performed a computer-simulation study to test the hypothesis that LDL apheresis-induced changes in LDL oxidizability are related to changes in the mass ratio between freshly produced and older LDL. In 19 patients aged 49+/-7 years with heterozygous familial hypercholesterolemia (FH) regularly treated with either immunoadsorption, heparin-induced LDL precipitation (HELP), or dextran sulfate (DS) adsorption, we determined lipoprotein levels, the lag phase, apoB modification, and the fatty acid pattern in plasma samples drawn at the onset and termination of one LDL apheresis. LDL apheresis significantly decreased total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglycerides by 50.4%, 14.9%, 62.6%, and 33.6%, respectively. The lag phase increased by a significant mean of 9.8%; the charge of apoB was not altered. The lag phase before treatment positively correlated with the baseline concentration of plasma total palmitic, myristic, and oleic acid. The increase in the lag phase during treatment correlated with a high pretreatment concentration of lauric, linoleic, and docosahexanoic acid. The simulation study indicates that a temporary imbalance between two LDL compartments, one representing freshly secreted LDL and the other representing older LDL, could explain the observed increase in the lag phase after LDL apheresis. In conclusion, in patients with heterozygous FH, LDL apheresis performed with different techniques decreases the susceptibility of LDL to oxidation. This decrease may be related to a temporary mass imbalance between freshly produced and older LDL particles. Furthermore, the baseline fatty acid pattern influences pretreatment and posttreatment susceptibility to oxidation.     

老年血液透析和腹膜透析患者蛋白质能量消耗的危险因素分析

目的:分析老年血液透析和腹膜透析患者的蛋白质能量消耗(PEW)的危险因素,为预防该类患者PEW以及预后改善提供依据。方法:根据国际肾脏营养与代谢学会关于PEW诊断标准共纳入上海市第八人民医院肾内科、复旦大学附属中山医院老年科、上海交通大学附属第六人民医院肾内科2016年5月至2020年6月行腹膜透析(PD)和血液透析(...