Cytokine induction in patients undergoing regular online hemodiafiltration treatment

End-stage renal disease (ESRD) patients are known to suffer from chronic inflammation as the result of an ongoing subacute cytokine induction, which may contribute considerably to dialysis-related, long-term morbidity and mortality. Preparation of infusate from cytokine-inducing dialysis fluid and its administration in large quantities as well as the use of high-flux membranes bear the risk of aggravating the chronic inflammatory response among online hemodiafiltration (online HDF) patients. In order to assess the inflammatory risk associated with online HDF, we compared the cytokine induction profile of ESRD patients receiving either online HDF or low-flux hemodialysis (low-flux HD). Specifically, we measured spontaneous and lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNFalpha) and interleukin-1 receptor antagonist (IL-1Ra) release during ex vivo incubation of whole blood. Ultrapure dialysis fluid and polysulfone membranes were used for both treatment modalities. LPS-stimulated release of TNFalpha and IL-1Ra was elevated for both online HDF and low-flux HD patients compared to healthy individuals (TNFalpha: 2,336 +/- 346 and 2,192 +/- 398 versus 1,218 +/- 224 pg/106 white blood cells [WBC]; IL-1Ra: 2,410 +/- 284 and 2,326 +/- 186 versus 1,678 +/- 219 pg/106 WBC). Likewise, spontaneous production of TNFalpha, but not IL-1Ra, was higher in online HDF and low-flux HD patients than in normal controls (37 +/- 32 and 22 +/- 19 versus 0.8 +/- 0.3 pg TNFalpha/106 WBC). There was no difference in spontaneous and LPS-stimulated cytokine release between both dialysis groups. In addition, intradialytic cytokine induction was not significant for either treatment modality as spontaneous and LPS-stimulated cytokine release were not increased postdialysis. These findings indicate that online HDF does not contribute to chronic leukocyte activation and, consequently, does not place ESRD patients at greater risk with respect to inflammatory morbidity and mortality.     

Reduction of Pro-Inflammatory Cytokines through Hemodiafiltration

Background. Hemodialysis (HD) prolongs the life of the patients with end stage renal disease (ESRD), but the survival rates are still lower than the general population. More than half of ESRD patients died from cardiovascular disease (CVD). Recent studies have revealed that CVD is a consequence of vascular inflammation, and that there are active inflammatory processes in ESRD patients. Reports have indicated that ESRD patients have fewer CVD events and better survival with hemodiafiltration (HDF), but the reasons for this remain unclear. This study attempts to prove that HDF reduces the CVD-related cytokines. Methods. Seventeen adult HD outpatients were put on HDF in our hospital from September 2004 to June 2006. We collected plasma samples before and six months after initiation of HDF. The target pro-inflammatory cytokines selected were interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Results. After six months of HDF, most of the biochemical parameters did not changed. Plasma IL-18 and TNF-α are decreased significantly (p?<?0.05) but IL-6 and CRP are not. Conclusions. IL-18 and INF-α decreased significantly after six months of HDF. These cytokines are key factors in atherosclerotic plaque formation and rupture, and a reduction of these inflammatory cytokines in HDF may reduce the CVD incidence and prolong life.     

Cellular interleukin-1 receptor antagonist production in patients receiving on-line haemodiafiltration therapy.

BACKGROUND: Repetitive exposure to cytokine-inducing substances (pyrogens) results in chronic inflammation, which may significantly contribute to some of the long-term complications in dialysis patients. On-line dialysis modalities, such as on-line haemodiafiltration (HDF), raise particular concerns because of the administration of infusate prepared from potentially contaminated dialysis fluid. Hence, great retention capability for pyrogens is of critical importance for the safe performance of on-line systems. METHODS: The microbiological safety of a novel on-line system, ONLINEplus(TM), was assessed in clinical practice in five centres for 3 months. Infusate and dialysis fluid were regularly monitored for microbial counts, endotoxins, and cytokine-inducing activity. Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in supernatants of whole blood incubated either under pyrogen-free conditions (spontaneous cytokine production) or following low-dose endotoxin exposure (LPS-stimulated cytokine production). RESULTS: We failed to detect microorganisms or endotoxin contamination of infusate during the entire study period. Moreover, neither infusate nor dialysis fluid demonstrated cytokine-inducing activity. Intradialytic IL-1Ra induction was not detected, as there was no difference between pre- and post-session values for both spontaneous and LPS-stimulated IL-1Ra production (115+/-26 vs 119+/-27 and 2445+/-353 vs 2724+/-362 pg/10(6) white blood cells (WBC), respectively). Neither the number of immunocompetent cells nor their capacity to produce IL-1Ra declined during this period, indicating that cells were not significantly stimulated during treatment. Spontaneous and LPS-induced exvivo IL-1Ra generation remained unchanged after 3 months of on-line HDF therapy as compared with the start of the study (71+/-30 pre- vs 48+/-14 post-study, and 2559+/-811 vs 2384+/-744 pg/10(6) WBC, respectively). CONCLUSIONS: The present on-line system performed safely from a microbiological view-point as both the dialysis fluid and infusate were consistently free of microorganisms, endotoxins, and cytokine-inducing substances. As a result, on-line HDF therapy had no effect upon the chronic inflammatory responses in end-stage renal disease patients.     

Hemodiafiltration and survival of end-stage renal disease patients: the long journey goes on

Survival of end-stage renal disease (ESRD) patients remains unacceptably poor. The excessive mortality of hemodialysis (HD) patients may result, at least in part, from the insufficient removal of medium or high molecular weight uremic toxins and from the systemic inflammatory response induced by the bioincompatibility of HD systems. Hemodiafiltration (HDF) combines diffusion and convection in a single modality, and it appears to be a promising method to improve ESRD patient outcomes. Emerging evidence suggests that this technique may be superior to classic diffusive HD in terms of patient morbidity. Despite the more widespread use of online HDF, evidence for survival benefits of HDF over other treatment modalities is scarce. Results of observational studies suggest lower mortality of HDF patients as compared to HD patients. Recent prospective randomized trials, however, failed to demonstrate any improvement in survival. Subanalyses of these trials, however, showed a significant survival benefit of HDF patients receiving high substitution volumes (17?L per session and more) compared to HD patients and to HDF patients receiving lower volumes. The explanation for this volume-dependent effect remains elusive. There is an urgent need for further randomized controlled trials to confirm previous findings and to identify those ESRD patients that are likely to benefit mostly from HDF.     

Can Dialysis Modality Influence Quality of Life in Chronic Hemodialysis Patients? Low-Flux Hemodialysis versus High-Flux Hemodiafiltration: A Cross-Over Study

Background: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. Methods: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 ± 13.34 years (mean ± SD), with the duration of dialysis of 31 ± 23.28 months (mean ± SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. Results: There were statistical significant differences in QoL for the total SF-36 [36.1 (26.7–45.7) and 40.7 (30.2–62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9–66.9) and 55 (35.6–87.5)], and for role limitations due to emotional functioning [0 (0–33.3) and 33.3 (0–100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. Conclusions: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.     

Clinical improvement by increased frequency of on-line hemodialfiltration.

BACKGROUND/AIMS: In spite of the better efficiency of on-line hemodiafiltration (HDF) compared with conventional hemodialysis (HD), it is relatively expensive. The aim of this study was to assess the advantages in the biochemical, hemodynamic and clinical effects in uremic patients treated with on-line HDF and with different frequencies of combination high-flux HD. METHODS: One hundred eleven patients were divided into four groups receiving different frequencies of on-line HDF (thrice, twice, once per week) and high-flux HD. RESULTS: Hemodynamic parameters including maximum drop of systolic blood pressure, episodes of symptomatic hypotension and mean saline infusion volumes during dialysis were reduced when frequencies of on-line HDF were increased. Significant improvements in urea kinetic were observed when frequencies of on-line HDF were increased. On-line HDF significantly reduced the amount of erythropoietin needed and improved intra- and inter-dialysis symptoms, physical well-being, menstruation and skin pigmentation when frequency of HDF is increased to three time per week. CONCLUSION: On-line HDF offers a better cardiovascular stability and clinical improvement. Thrice weekly on-line HDF offers a significant benefit when compared with lower frequencies of HDF per week and high-flux HD.     

Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS

Hemodiafiltration (HDF) is used sporadically for renal replacement therapy in Europe but not in the US. Characteristics and outcomes were compared for patients receiving HDF versus hemodialysis (HD) in five European countries in the Dialysis Outcomes and Practice Patterns Study. The study followed 2165 patients from 1998 to 2001, stratified into four groups: low- and high-flux HD, and low- and high-efficiency HDF. Patient characteristics including age, sex, 14 comorbid conditions, and time on dialysis were compared between each group using multivariate logistic regression. Cox proportional hazards regression assessed adjusted differences in mortality risk. Prevalence of HDF ranged from 1.8% in Spain to 20.1% in Italy. Compared to low-flux HD, patients receiving low-efficiency HDF had significantly longer average duration of end-stage renal disease (7.0 versus 4.7 years), more history of cancer (15.4 versus 8.7%), and lower phosphorus (5.3 versus 5.6 mg/dl); patients receiving high-efficiency HDF had significantly more lung disease (15.5 versus 10.2%) and received a higher single-pool Kt/V (1.44 versus 1.35). High-efficiency HDF patients had lower crude mortality rates than low-flux HD patients. After adjustment, high-efficiency HDF patients had a significant 35% lower mortality risk than those receiving low-flux HD (relative risk=0.65, P=0.01). These observational results suggest that HDF may improve patient survival independently of its higher dialysis dose. Owing to possible selection bias, the potential benefits of HDF must be tested by controlled clinical trials before recommendations can be made for clinical practice.     

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.     

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.     

Type 2 diabetes in patients with end-stage renal disease is not associated with further increased serum inflammatory parameters

BACKGROUND: Cardiovascular morbidity and mortality is markedly increased in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and is further pronounced when diabetes mellitus is also present. As atherogenesis is mediated by inflammation of vessel walls and as evidence evolves that atherosclerosis and diabetes mellitus share a common inflammatory basis, we considered whether ESRD patients with additional diabetes mellitus exhibit increased inflammation levels exceeding those of ESRD patients without diabetes mellitus. METHODS: The study included 20 ESRD patients with type 2 diabetes mellitus and 16 non-diabetic ESRD patients on long-term HD. The patients' clinical characteristics and serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor receptor I (sTNF-RI), neopterin and fibrinogen were assessed. RESULTS: There were no significant differences in serum levels of CRP, IL-6, neopterin, sTNF-RI and fibrinogen found in ESRD patients with and without diabetes mellitus. HD duration correlated significantly with neopterin (r=0.515, p<0.001) and sTNF-RI (r=0.429, p<0.05) serum levels. HD led to a significant reduction in neopterin levels whereas CRP, IL-6 and sTNF-RI levels did not change significantly. CONCLUSIONS: With the inherent limitations of a small number of patients studied, we observed that the presence of type 2 diabetes mellitus in addition to ESRD was not associated with further increased serum levels of the examined inflammatory parameters. Our observations suggest that the worsened prognosis of diabetic ESRD patients is probably not explainable by superimposing inflammatory processes.     

Ultrapure dialysate and inflammatory response in haemodialysis evaluated by darbepoetin requirements--a randomized study.

BACKGROUND: Dialysate quality has been suggested to influence inflammation status in patients subject to haemodialysis (HD). The aim of this study was to compare ultrapure dialysate (UPD) vs conventional dialysate (CD) with respect to darbepoetin requirements and other inflammation markers. METHODS: A controlled prospective randomized study was carried out on 78 patients from two HD units who were treated with low-flux polyamide dialysers. Patients were assigned to two groups by using different sized blocks per unit and dialysis session. One group received CD treatment while the other was treated with UPD over 12 months. From the groups, 37 patients started treatment with CD and 41 with UPD while 31 patients ended with CD and 30 with UPD. The main variables analysed were haemoglobin (Hb) and darbepoetin dose; other variables studied were C-reactive protein (CRP), albumin, interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1Ra). RESULTS: No significant differences were observed between the two groups for the variables analysed. At the beginning of the study the following values of CD and UPD were assessed: Hb 11.3 and 11.3 (g/dl); darbepoetin dose: 0.49 and 0.44 (microg/kg/week); CRP: 13 and 24 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 5.94 and 4.18; and IL-1Ra: 345 and 420 (ng/l), respectively. At the end of the study the values of CD and UPD were: Hb 12 and 11.9 (g/dl); darbepoetin dose: 0.47 and 0.48 (microg/kg/week); CRP: 14 and 14 (mg/l); albumin: 3.8 and 3.7 (g/dl); IL-6: 14.03 and 12.93 and IL-1Ra: 322 and 340 (ng/l). CONCLUSIONS: UPD does not improve the inflammatory status evaluated by darbepoetin requirements in conventional HD patients treated with low-flux polyamide dialyser. Further controlled studies are required to evaluate the clinical influence of UPD in HD with other low- and high-flux membranes.     

不同透析方式对终末期肾脏疾病患者钙磷代谢及炎症因子水平的影响

目的观察腹膜透析(PD)与血液透析(HD)对终末期肾脏疾病(ESRD)患者钙磷代谢及炎症因子水平的影响。方法筛选2016年1月至2019年2月在本院肾内科接受血液净化治疗的126例ESRD患者作为实验对象,应用分层随机分组法将所有患者分为两组,PD组(63例)给予非卧床持续性腹膜透析治疗,HD组(63例)给予血液透析治疗,观察两组患者治疗前、治疗后6个月后的钙磷代谢水平(血钙水平、血磷水平)、炎症因子水平[C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)]以及肾功能[肾小球滤过率(GFR)、血尿素氮(BUN)、血肌酐(Scr)]的差异情况,对比两组患者治疗期间的并发症发生情况。结果PD组和HD组治疗后的血钙水平、血磷水平差异无统计学意义(P>0.05);HD组的CRP水平高于PD组(P<0.05),但两组的TNF-α、IL-6水平差异无统计学意义(P>0.05);两组患者的CFR、BUN、Scr水平差异无统计学意义(P>0.05);PD组的感染、低蛋白血症、充血性心力衰竭的发生率高于HD组(P<0.05),心率失常低于HD组(P<0.05),两组的高血压发生率差异无统计学意义(P>0.05)。结论PD和HD都可以有效改善ESRD患者的钙磷代谢情况和肾功能状态,但PD、HD治疗后都有轻微的炎症反应,且HD的炎症反应高于PD;建议根据临床实际情况选择最适宜患者的血液净化方式。     

不同血液净化方式对尿毒症患者相关炎症因子及血清脂蛋白(a)的影响

目的 通过对比观察不同血液净化方式治疗前后血清相关炎症因子、脂蛋白(a)的变化及其之间的相互关系,探讨不同血液净化方式对尿毒症患者相关炎症因子及血清脂蛋白(a)的影响.方法 将75例初次透析的尿毒症患者随机分为血液透析组及血液透析滤过组,分别测定治疗前及治疗后3个月血清C反应蛋白、肿瘤坏死因子α、白细胞介素10、脂蛋白(a)浓度的变化.结果 血液透析组治疗前后血C反应蛋白、肿瘤坏死因子α浓度及白细胞介素10/肿瘤坏死因子α差异无统计学意义(均P＞ 0.05);血液透析滤过组治疗后血C反应蛋白、肿瘤坏死因子α浓度较治疗前及血液透析治疗后明显降低(P＜0.01),白细胞介素10/肿瘤坏死因子α较治疗前明显升高(P＜0.01),与血液透析治疗后比较有所升高(P＜0.05).血液透析组治疗后血清脂蛋白(a)浓度较治疗前有所降低,但差异无统计学意义(P＞0.05).血液透析滤过组治疗后血清脂蛋白(a)浓度较治疗前及血液透析治疗后明显下降(P＜0.01).脂蛋白(a)与C反应蛋白呈正相关(r=0.496),与白细胞介素10/肿瘤坏死因子α比值呈负相关(r=-0.369).结论 血液透析滤过可以通过清除部分炎症因子减轻微炎症状态,同时下调脂蛋白(a)水平,减少尿毒症患者相关并发症的发生发展.     

Impact of convective flow on phosphorus removal in maintenance hemodialysis patients.

OBJECTIVE: Hyperphosphatemia leads to increased risk of death in maintenance hemodialysis patients (MHD). This study investigated phosphorus (P) removal, P reduction rate (PRR), and P rebound, comparing on-line, high-volume hemodiafiltration in postdilution (HDF) and high-flux hemodialysis (HD) in a setting of an equal amount of produced dialysate solution in both modalities. METHODS: A total of 22 MHD patients, treated with regular 3 x 4 hours HDF weekly, were randomly dialyzed with one 4-hour session of HDF and of HD. In both modalities, an equal amount of produced dialysate solution of 800 mL/minute was used. The only variable was the fact that in HDF, 100 mL/min of this produced dialysate solution was used as replacement fluid. The other parameters were kept identical: blood flow rate, 350 mL/min; high-flux polysulfone F80 dialyzer; and 4800 E monitor, (Fresenius, Bad Homburg, Germany). The P removal was measured in total spent dialysate and ultrafiltrate volumes. Statistical analyses were done with the paired t-test. RESULTS: The mean total P removed with HDF was 1159 +/- 296 mg, and 972 +/- 312 mg with HD (P < .001), ie, 19% higher in HDF; PRR was significantly higher in HDF (63.3%) versus HD (58.6%) (P = .014). The mean serum P did not differ: 5.3 mg/dL in HDF and 5.2 mg/dL in HD. There was a linear correlation between serum P and P removal. With a serum P level up to 5 to 5.5 mg/dL, HDF achieved a higher P removal compared with HD. The difference gradually decreased as the serum P value increased. Above 7 mg/dL, no difference in total P removal was observed. There was a high but equal rebound percentage at 60 minutes in HDF (42%) and HD (39%) (P = .42). With HDF, no predialysis metabolic acidosis was noted. CONCLUSIONS: Treatment with on-line HDF in postdilution resulted in a higher P removal and higher PRR compared with HD. The long-term implementation of this modality may result in a more optimal serum P control, without an increase in the number of or lengthening of the dialysis sessions.     

Influence of a pre-dialysis education programme (PDEP) on the mode of renal replacement therapy.

BACKGROUND: The distribution of renal replacement therapy (RRT) modalities among patients varies from country to country, and is often influenced by non-medical factors. In our department, patients progressing towards end-stage renal disease (ESRD) go through a structured Pre-Dialysis Education Programme (PDEP). The goals of the programme, based on both individualized information session(s) given by an experienced nurse to the patient and family and the use of in-house audio-visual tapes, are to inform on all modalities of RRT, in order to decrease anxiety and promote self-care RRT modalities. METHODS: To evaluate the influence of our PDEP on the choice of RRT modalities, we retrospectively reviewed the modalities chosen by all consecutive patients starting a first RRT in our institution between December 1994 and March 2000. RESULTS: Two hundred and forty-two patients started a first RRT during the study period. Fifty-seven patients, median age 66 (24-80) years, were directed towards in-centre haemodialysis (HD) for medical or psycho-social reasons (seven of whom were not involved in the PDEP); the remaining 185 patients, median age 53 (7-81) years, with no major medical complications, went through our PDEP. Eight of them (4%) received a pre-emptive renal transplantation. The therapeutic options of the other 177 patients were as follows: 75 (40%) patients, median age 65 (20-81) years opted for in-centre HD, while 102 patients opted for a self-care modality; 55 (31%) patients, median age 56 (7-77) years, chose peritoneal dialysis, 30 (16%) patients, median age 49 (21-68) years, chose to perform self-care HD in our satellite unit, and 17 (9%) patients, median age 46 (19-70) years, opted for home HD. Interestingly, in the whole cohort of patients, the cause of ESRD was associated with the RRT modality: the proportion of patients with chronic glomerulonephritis or chronic interstitial nephritis on self-care therapy was significantly higher than that of patients with nephrosclerosis, diabetic nephropathy or unknown cause of ESRD. CONCLUSION: In our centre offering all treatment RRT modalities, a high percentage of patients exposed to a structured PDEP start with a self-care RRT modality. This leaves in-centre HD for patients needing medical and nursing care, or for patients refusing to participate in their treatment. Additional large studies, preferably with a randomized design, should delineate the cost-benefit of such a PDEP on the final choice of a RRT modality.     

Comparison of predilution hemodiafiltration and low-flux hemodialysis at temperature-controlled conditions using high calcium-ion concentration in the replacement and dialysis fluid

BACKGROUND: It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the hemodynamics of high-dose predilution hemodiafiltration (HDF) and low-flux hemodialysis (HD), under matched conditions and using high calcium-ion concentration in the replacement/dialysis fluid. METHODS: 13 stable hemodialysis patients were investigated in a randomized crossover, blinded controlled trial. The patients were allocated to one session of predilution HDF (substitution fluid 1.20 1/kg BW) and one session of HD at 4.5 hours. At the start of the dialysis the patient's core temperature was "locked" by an automatic feedback system regulating the dialysate temperature, thereby patient's temperature was kept stable throughout the whole treatment. The Ca ion concentration in the substitution/dialysis fluid was 1.75 mM. Cardiac output was measured hourly by the ultrasound velocity dilution method. RESULTS: Within treatments comparisons revealed that both treatments displayed stable mean blood pressure and equally reduced cardiac output. HDF showed decreased stroke volume and increased total peripheral resistance. The pulse rate decreased significantly only during HD. Arterial temperature was kept constant during both treatments. Ultrafiltration volume, cardiopulmonary recirculation, relative blood volume, Kt/V and total energy transfer were matched for HD and HDF. The overall between treatments comparisons revealed no significant differences. CONCLUSIONS: We have shown that during matched conditions and high calcium concentrations, the hemodynamic profiles of high dose predilution HDF and lowflux HD were similar. Both modalities showed stable mean blood pressure profiles. An acute circulatory benefit of convective solute removal over diffusive, could not be demonstrated.     

不同血液净化方式对尿毒症透析患者血中细胞因子清除的临床应用

目的 研究不同血液净化方式对尿毒症透析患者血中细胞因子的清除效果.方法 将2006年4月至2009年2月在我院血液净化中心透析的45例患者按随机数字表法分为(1)血液透析联合血液灌流组;(2)血液透析滤过组;(3)HD组,血液透析组,每组15例.血液透析联合血液灌流组、血液透析滤过组每周治疗1次,每组患者治疗3次,中间间隔1周,第1次及第3次治疗前、后各从动脉端采血5 ml,并留取正常健康对照组血液,整批送检.测定治疗前、后血清细胞因子的浓度.结果 血液灌流联合血液透析组、血液透析滤过组及血液透析组治疗前、后白细胞介素1β、白细胞介素6、肿瘤坏死因子α浓度与健康对照组比较差异有统计学意义(P＜0.01);血液透析组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(3±10)ng/L、(4±9)ng/L、(4±9)ng/L,治疗前、后差值比较分别为176.0%、141.0%、187.0%,血液透析滤过组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(39±15)ng/L、(36±14)ng/L、(45±16)ng/L,治疗前后差值比较分别为24.6%、22.1%、29.8%,血液灌流联合血液透析组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(48±16)ng/L、(38±15)ng/L、(50±14)ng/L,治疗前差值比较分别为27.8%、23.9%、32.3%,3组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平间比较差异有统计学意义(t分别=17.39、11.24、21.89,P均＜0.01).结论 不同的血液净化方式对各类细胞因子的清除效果不同,其中液灌流联合血液透析组及血液透析滤过组治疗埘细胞因子清除有效,血液透析组治疗对细胞因子清除基本无效,液灌流联合血液透析组及血液透析滤过组细胞因子清除效果与血液透析滤过组比较差异无统计学意义(P＞0.05).     

Impaired monocyte cytokine production in critically ill patients with acute renal failure

BACKGROUND: Plasma levels of pro- and anti-inflammatory cytokines are predictive of mortality in patients with acute renal failure (ARF). Anti-inflammatory strategies are postulated to be beneficial in treatment. However, there are few studies simultaneously examining monocyte cytokine production and plasma cytokine levels in patients with ARF. METHODS: Study populations consisted of 20 critically ill patients with ARF, 19 critically ill patients without ARF (CRIT ILL), 28 healthy subjects (HS), 19 patients with chronic kidney disease (CKD), and 15 patients with end-stage renal disease (ESRD). Monocyte intracellular content of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8, and tumor necrosis factor-alpha (TNF-alpha) was determined by flow cytometry in whole blood. Plasma interleukin 6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: At baseline, there were no differences in intracellular monocyte cytokine levels between groups. After lipopolysaccaride stimulation, monocyte production of IL-1beta, TNF-alpha, and IL-6 in ARF patients was reduced by 41%, 84%, and 45%, respectively, compared to healthy subjects (P < 0.01 in each case), and similarly reduced compared to CKD and ESRD patients, and were similar to CRIT ILL patients. Plasma IL-6 levels were significantly higher in ARF patients than healthy subjects, CKD, and ESRD patients (all P < 0.001). CONCLUSION: Critically ill patients with acute renal failure have impaired monocyte cytokine production and elevated plasma cytokine levels in a pattern that closely resembles critically ill patients without ARF, and that is dissimilar to CKD and ESRD patients.     

On-line haemodiafiltration: Effective removal of high molecular weight toxins and improvement in clinical manifestations of chronic haemodialysis patients

Summary: The aim of this study was to validate the purity of the injection fluid in an on-line haemodiafiltration (HDF) system, and to investigate whether the aggressive removal of high molecular weight toxins achieved by the on-line HDF will reduce symptoms such as shoulder pain and pruritus. the dialysate for substitution use contained no endotoxin, β-D-glucan, or peptidoglycan, suggesting that contamination with gram-negative/positive bacteria and fungi are kept clear or at extremely low levels. No deleterious complications occurred during the on-line HDF treatments. the improvement in shoulder pain and pruritus indicated by a decrease in patients' self-rating scores, was more apparent with treatment that removed both β2-microglobulin (β2-m) and α1-microglobulin (α-m) than with treatment removing either β2-m or α1-m alone. On-line HDF is much easier to operate and less costly than conventional HDF, and it may become one of the standard therapies for chronic renal failure patients.     

Skeletal muscle, cytokines, and oxidative stress in end-stage renal disease

BACKGROUND: End-stage renal disease (ESRD) is a state of microinflammation, with increased activation of cytokines and augmented oxidative stress. While peripheral blood mononuclear cells are an established source of reactive oxygen species and inflammatory cytokines during hemodialysis (HD), skeletal muscle is also capable of generating these biomolecules. METHODS: Femoral arterio-venous (A-V) balance of interleukin-1 (IL-1), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), malonyldialdehyde (MDA), and carbonyl protein (CP) were measured in 17 ESRD patients and 9 healthy volunteers. ESRD patients were studied before (pre-HD) and during HD. mRNA levels of cytokines, heme oxygenase-1 (HO-1), and suppressors of cytokine signaling-2 (SOCS-2) were quantitated in the skeletal muscle by real-time polymerase chain reaction (PCR). RESULTS: Arterial concentration of MDA (pmol/mL) was higher pre-HD (325.5 +/- 19.6) compared to controls (267.7 +/- 14.7), but decreased intradialysis (248.8 +/- 16.1) (P < 0.01). Dialysis clearance of MDA was 16.9 +/- 3.1 mL/min. CP concentration (nmol/mg protein) in the artery was significantly higher pre-HD (2.29 +/- 0.09) than in controls (1.92 +/- 0.05), and remained stable during HD (2.23 +/- 0.07). Plasma cytokines increased to a variable degree in the artery and vein during HD. A-V balance studies demonstrated that the MDA (17.8%) and CP (5.1%) concentrations increased significantly in the vein intradialysis. Venous concentration of IL-6 was higher than that in the artery during dialysis (16.27 +/- 2.42 vs. 11.29 +/- 2.17 pg/dL, P < 0.01). mRNA levels of IL-6 (0.028 +/- 0.02 vs. 6.69 +/- 0.21), HO-1 (0.96 +/- 0.01 vs. 5.08 +/- 1.11), and SOCS-2 (0.63 +/- 0.12 vs. 0.82 +/- 0.14) in the muscle increased during HD (P < 0.01). Immunohistochemical studies confirmed the increase in IL-6 protein in the skeletal muscle during HD. The intradialytic increase in IL-1, IL-10, and TNF-alpha gene expression was not significant. CONCLUSION: Skeletal muscle may also contribute to the circulating plasma IL-6 and increased oxidative stress during HD.