The effect of hemodiafiltration with on-line endogenous reinfusion (on-line HFR) on anemia: design of a European, open, randomised, multicentre trial. European Collaborative Study

The lack of backfiltration reduces plasma levels of C-reactive protein and interleukin-6. Paired filtration dialysis is the hemodialfitration technique that abolishes backfiltration. By physically separating convection from diffusion, it allows pure ultrafiltrate to be available during the entire session, so the ultrafiltrate can be regenerated and used as infusion fluid. On these premises, we have developed a European, open, randomised, multicentre study aimed at evaluating the effect of hemodiafiltration with on-line endogenous reinfusion (on-line HFR) on anemia. At least 130 chronically uremic hemodialysed (bicarbonate hemodialysis) stable patients with mild anemia (Hb between 9 and 11 g/dL) will be enrolled and normalized for iron stores by concomitantly repleting iron deposits (if ferritin <300 microg/L) and reducing the dose of erythropoietin to maintain Hb values within the range at enrollment (9-11 g/dL). Patients will be included in the study, randomized to the two treatments (test treatment: on-line HFR; control treatment: hemodiafiltration or modified forms) and followed up for nine months. Iron stores will be maintained within normal levels and the dose of erythropoietin will be kept constant. The primary question and response variable will be the mean monthly changes in hemoglobin levels over the period of nine months. As secondary questions and response variables, we will measure the nutritional status using a subjective global assessment, protein catabolic rate, urea generation rate and the dietician's assessment, serum concentrations of vitamins A, C, E and serum C-reactive protein.     

Four years' experience of long-term hemofiltration in a Swedish center

Thirty patients with end-stage renal disease were switched from maintenance hemodialysis to postdilution hemofiltration and observed for long-term effects. The study comprised totally 496 months of hemofiltration. Uremic and biochemical control was similar in the hemofiltration and in the hemodialysis period. Of the small molecules, only serum creatinine showed slight increase after 3 months. No other significant changes in creatinine, serum urea or potassium levels were associated with long-term hemofiltration. During each hemofiltration session there was significant decrease of serum parathyroid hormone (PTH) and serum beta 2-microglobulin, but over the first 8 months of hemofiltration the beta 2-microglobulin values did not fall, and significant PTH reduction was found only after 12 months. Although uremic control was similar with both methods, there were fewer complications of hemofiltration, which was preferred by the patients. Because it is currently more expensive, however, hemofiltration should be reserved for patients with dialysis related problems, that are not helped by other changes in the dialysis technique, such as sequential ultrafiltration changes in the dialysis membranes and in the dialysis buffer from acetate to bicarbonate.     

Correction of Hemodialysis Anemia is Associated with Significant Increase in Serum Concentration of IGF-I in Patients Treated with Erythropoietin: A Randomized Controlled Study

Background: The effect of erythropoietin (EPO) therapy on the serum level of IGF-I among hemodialysis patients is debated. The aim of this study is to study the effect of EPO on the erythropoiesis and the change of serum level of IGF-I among adequately hemodialyzed patients. Patients and methods: Forty patients (25 males and 15 females) who had an adequate level of both hemodialysis and nutrition were randomly allocated into two equal groups. Besides parenteral iron, the first group of patients received a conventional EPO dose regimen of 2000 U subcutaneously (SC) thrice weekly, the second group of patients remained on parenteral iron and ranked as a control group. The patients were subjected to thorough laboratory investigations. IGF-I concentration was measured before and at the end of the study. Results. Both groups were comparable in their demographic, laboratory, dialysis level, and nutritional status. There was no statistical differences in hemoglobin, hematocrit %, iron store indices and serum level of IGF-I at the study entry. We found a significant rise of both hemoglobin and hematocrit as well as IGF-I serum level in the EPO group at the end of the study in comparison to their values at the starting points in comparison to the control group (P< 0.001). Conclusion: Erythropoietin therapy enhances erythropoiesis and modulates the serum concentration of IGF-I.     

Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial.

BACKGROUND: HFR [double chamber haemodiafiltration (HDF) with reinfusion of regenerated ultrafiltrate] is a novel dialytic method which combines the processes of diffusion, convection and adsorbance. In this technique an adsorbent cartridge of resin and charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The aim of this multicentre randomized cross-over study was to compare HFR to online HDF in terms of inflammatory and nutritional parameters. METHODS: After a 1 month run-in period of standard bicarbonate dialysis (HD) with a synthetic membrane, 25 chronic dialytic patients were randomized (A-B or B-A) to be treated by HFR (A) with a two-chamber filter (SG 8 Plus - high permeability Polysulphone HF 0.7 m2 + SMC 1.95 sqm; Bellco, Mirandola, Italy) or by online sterile bicarbonate HDF. Each study period of 4 months was separated by 1 month of HD and the entire length of the study was 10 months. CRP levels were measured by a highly sensitive nephelometric assay (Dade, Behring) with a sensitivity of 0.1 microg/ml. Cytokine concentrations were determined by EIA [Interleukin (IL) 6, Biosource, USA and IL-10 Bender MED-Systems, Vienna]. The sensitivity thresholds were < 5 pg/ml for IL-6 and < 8 pg/ml for IL-10. Serum leptin was determined with a ELISA method (Biosource, USA). All parameters were determined monthly in patients starting a midweek dialytic session. RESULTS: Plasma CRP and IL-6 were significantly reduced during the 4 months of HFR and HDF: CRP from 8.0 +/- 3.2 to 5.6 +/- 3.4 mg/l with HFR (P < 0.05) and from 9.4 +/- 4.3 to 5.9 +/- 3.9 mg/l with HDF (P < 0.05). IL-6 decreased from 14.8 +/- 6.3 to 10.1 +/- 3.2 with HFR (P < 0.02) and from 12.1 +/- 4.2 to 9.6 +/- 3.7 with HDF (P = ns) with a percentage decrease after 4 months of 32% with HFR vs 21% with HDF. During the 1 month wash-out period with HD, CRP increased from 5.7 +/- 3.6 to 8.7 +/- 3.9 mg/l (P < 0.01) and IL-6 from 10 +/- 3.4 to 13.5 +/- 5.2 pg/ml (P < 0.01). A significant increase in IL-10 was detected either in HFR (from 4.8 +/- 2.1 to 6.89 +/- 1.7 pg/ml) and in HDF (from 3.3 +/- 1.7 to 8.95 +/- 4.3 pg/ml; P < 0.05) after 4 months. No significant variation in serum leptin levels were observed during the study. CRP and IL-6 were highly correlated (r = 0.54; P < 0.001) as was serum albumin and prealbumin (r = 0.39; P < 0.001). Serum albumin was negatively correlated with CRP (r = -0.26; P < 0.01) and IL-6 (r = -0.19; P < 0.05); serum prealbumin was correlated with IL-6 (r = 0.37; P < 0.001) and with CRP (r = 0.24; P < 0.01). CONCLUSIONS: Haemodiafiltration with online regeneration of ultrafiltrate and online HDF are highly biocompatible techniques and no significant difference between HFR and online HDF was observed in terms of reduction of inflammatory markers. Further studies with a longer follow-up are needed to evaluate the clinical relevance of the online endogenous reinfusion to counteract the chronic inflammatory state of the uraemic patient.     

Haemodiafiltration with sorbent-regenerated ultrafiltrate as replacement fluid: a multicenter study

BACKGROUND: Uncoated adsorbent charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The objective of this study was to assess the safety and the long-term clinical results. METHODS: Thirty-three chronic uraemic patients were dialysed for 1 year using two haemodialysers in series in order to separate convection from diffusion. At the outflow of the convective haemofilter, a cartridge containing 130 g of uncoated charcoal was inserted. The regenerated ultrafiltrate was then infused at the entrance of the diffusive dialyser. Ex vivo and in vitro studies were performed to analyse the adsorption characteristics and the release of aluminium, other trace elements, and microparticles. RESULTS: Passage through the charcoal left urea, phosphate, potassium, calcium, and bicarbonate concentrations unchanged. Creatinine, uric acid and beta 2- microglobulin were almost completely absorbed by the charcoal. Aluminium release was dependent upon time of storage, as inferred from studies on inter-lot variability. Washing with bicarbonate buffer (pH 7.0) allowed reduction of aluminium levels to within the pharmacopoeia requirements for intravenous fluids. No significant pre- or post- charcoal differences were observed for several trace elements such as manganese, selenium, arsenic, cadmium, mercury, lead, chromium and zinc. Copper was completely retained in the charcoal. Regenerated ultrafiltrate infused at the entrance of the diffusive dialyser was free of microparticles, bacteria, and endotoxin. Clinical tolerance was excellent and blood pressure control satisfactory. A significant decrease in serum values of beta 2-microglobulin was observed at 6 and 12 months of treatment. CONCLUSIONS: Reinfusion of ultrafiltrate through an uncoated charcoal cartridge proved to be a safe, well- tolerated and simple technique. Further potential benefits of regenerated ultrafiltrate may also include the maintenance of acid-base balance with reinfusion of endogenous bicarbonate.      

Benefits of preserving residual renal function in peritoneal dialysis

Residual renal function (RRF) is of paramount importance in patients with end-stage renal disease, with benefits that go beyond contributing to achievement of adequacy targets. Several studies have found that RRF rather than overall adequacy (as estimated from total small solute removal rates) is an essential marker of patient and, to a lesser extent, technique survival during chronic peritoneal dialysis (PD) therapy. In addition, RRF is associated with a reduction in blood pressure and left ventricular hypertrophy, increased sodium removal and improved fluid status, lower serum beta(2)-microglobulin, phosphate and uric acid levels, higher serum hemoglobin and bicarbonate levels, better nutritional status, a more favorable lipid profile, decreased circulating inflammatory markers, and lower risk for peritonitis in PD. As compared with conventional hemodialysis, PD is associated with a slower decrease in RRF. This highlights the usefulness of strategies oriented to preserve both RRF and the long-term viability of the peritoneal membrane. Several factors contributing to the loss of RRF have been identified and should be avoided. Renoprotective drugs and new glucose-sparing, more biocompatible PD regimes may prove useful tools to preserve RRF and peritoneal membrane function in the near future.     

Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.     

The role of hyperparathyroidism,erythropoietin therapy,and CMV infection in the failure of arteriovenous fistula in hemodialysis

BACKGROUND: Vascular access failure is the main cause of morbidity in hemodialysis. Venous stenosis and subsequent thrombosis, as the result of intimal hyperplasia, is the major cause of vascular access failure. Intimal hyperplasia of the arteriovenous fistula (AVF) closely resembles the main histopathologic feature of atherosclerosis. In addition to the classic atherogenic risk factors, recently, cytomegalovirus (CMV) infection and parathyroid hormone (PTH) have been suggested as a potential cause of vascular disease. METHODS: In the present study, we evaluated the relationship between AVF dysfunction and mean plasma PTH, cholesterolemia, high titer anti-CMV immunoglobulin G (IgG) (>250 U/mL), hematocrit, and mean erythropoietin (EPO) dose in 36 cases and 51 controls matched for age, time on dialysis, and type of AVF. RESULTS: A higher percentage of patients with AVF failure had a smoking habit and presented high anti-CMV IgG titer. Patients with AVF failure had significantly higher mean plasma PTH, whereas the groups did not differ for mean cholesterolemia and hematocrit. Mean EPO dose was slightly, but significantly, higher in the AVF failure group. Multiple logistic regression revealed that smoking, EPO dose, elevated mean plasma PTH and high titer anti-CMV antibodies, significantly increased the risk of AVF dysfunction. CONCLUSION: Our data suggest that hyperparathyroidism, smoking habits, CMV infection and EPO, independently of the hematocrit achieved, represent independent risk factors for hemodialysis access thrombosis.     

Recombinant human erythropoietin independence in chronic hemodialysis patients: clinical features, iron homeostasis and erythropoiesis

AIMS: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients can maintain high hemoglobin level without the need of r-HuEPO. The aim of this study is to investigate clinical features, iron metabolism and erythropoiesis of these r-HuEPO-independent HD patients. METHODS: r-HuEPO independence was defined in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for at least 6 months. An age- and sex-matched group was selected for comparison. Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C-reactive protein, serum iron, total iron binding capacity, transferrin saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were measured. Renal sonography was also performed in each patient to evaluate renal cyst formation. RESULTS: About 2.3% of all HD patients (21/888; M : F = 18 : 3) were r-HuEPO-independent. These patients had significantly longer HD duration and higher serum EPO and sTfR levels, and lower transferrin saturation rate than dependent groups. Correlation analysis revealed that hemoglobin level strongly correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were positively related with serum EPO levels and BMI. Multivariate regression analysis showed that level of sTfR was the only independent factor related to r-HuEPO independence. CONCLUSION: R-HuEPO independence is rare among chronic hemodialysis patients. Factors contributing to this dependence are complex and multiple. Level of serum sTfR parallels erythropoiesis and is the most significant factor associated with r-HuEPO independence in chronic HD patients.     

Vitamin B(6) therapy does not improve hematocrit in hemodialysis patients supplemented with iron and erythropoietin

BACKGROUND/AIM: Pyridoxine deficiency may be the cause of failure to respond appropriately to iron and erythropoietin (EPO) administration in hemodialysis patients. METHOD: We studied 36 patients on chronic hemodialysis amply supplemented with iron and EPO, who failed to raise hematocrit levels >33%. Patients were divided into three equal groups and evaluated for 6 months as follows: Group A -- no additional therapy; group B -- supplemented with oral pyridoxine 50 mg/day, and group C received 100 mg/day pyridoxine orally. RESULTS: In all our patients, erythrocyte pyridoxine levels were initially within reference range for a healthy population and did not vary significantly during the study period. Likewise, ferritin levels and iron saturation values remained normal and constant. Hemoglobin and/or hematocrit levels remained practically unchanged in all three groups. CONCLUSIONS: The results indicate that in hemodialysis patients with normal pyridoxine status who, despite appropriate supplementation of iron and EPO, fail to reach optimal hematocrit levels, additional pyridoxine treatment does not produce any hematocrit elevation.     

Factors related to erythropoietin hypo-responsiveness in patients on chronic peritoneal dialysis

Background The present study was aimed at investigating the factors related to hypo-responsiveness to erythropoietin in patients on chronic peritoneal dialysis (PD). Methods We studied 44 patients with end-stage renal disease who had been on PD for more than 6 months and on erythropoietin (EPO) ≥6,000 U/week for more than 3 months. We expressed EPO resistance index (ERI) as weekly EPO dose per hematocrit (Hct) per body weight. The dose of EPO was titrated to maintain a target Hct level between 33% and 36%. Patients were divided into two groups according to weekly EPO dose. We compared the various factors in those two groups and, by using correlation and linear regression analysis, investigated factors that might predict EPO resistance. Results There were 13 patients in the EPO <150 U/kg per week group and 31 patients in the EPO ≥150 U/kg per week group. Among those 31 patients, there were five patients on EPO ≥300 U/kg per week. Compared to the EPO <150 U/kg per week group, the EPO ≥150 U/kg per week group had a lower normalized protein catabolic rate (nPCR), lower level of serum albumin and higher C-reactive protein (CRP). Correlation analysis showed that the ERI had a statistically significant correlation with CRP (r = 0.303, P < 0.05), serum albumin (r = −0.26, P < 0.05), parathyroid hormone (PTH) (r = −0.307, P < 0.05) and nPCR (r = −0.259, P < 0.05). These results show that CRP, serum albumin, PTH and nPCR are factors related to hypo-responsiveness. Multiple stepwise linear regression analysis showed that CRP was the most important independent predictor of EPO hypo-responsiveness. Conclusion CRP, serum albumin, nPCR and PTH are factors related to hypo-responsiveness. Inflammation contributes significantly to EPO hypo-responsiveness.     

Alpha-interferon therapy increases serum beta2-microglobulin levels in hemodialysis patients.

BACKGROUND/AIMS: Beta2-microglobulin is the main component of dialysis-associated amyloid. Interferons (IFNs) have the ability to induce an increase in the formation and release of this protein. The aim of this study was to evaluate serum beta2-microglobulin levels in 11 hemodialysis patients with chronic hepatitis C treated with IFNalpha. METHODS: Eleven hemodialysis patients with chronic hepatitis C that received IFNalpha treatment were included in this study. No patient had residual renal function. High-flux membranes were used in 5 patients, and low-flux membranes in the remaining 6 patients. Beta2-microglobulin was analyzed at baseline, during IFNalpha treatment and after IFNalpha was stopped. RESULTS: Serum beta2-microglobulin concentration rose in all patients during the IFNalpha therapy. Compared with baseline values (43 mg/l, range 22-59) the median beta2-microglobulin levels increased significantly at one month (65 mg/l, range 37-142, p = 0.008) and at 12 months (59 mg/l, range 42-137, p = 0.003) after the beginning of IFN therapy. One month after IFNalpha was discontinued, beta2-microglobulin decreased significantly (median 48, range 34-75 mg/l, p = 0.05) in comparison with that obtained at the end of the therapy. The increase observed during IFN therapy was lower in patients treated with high-flux membranes than in those with low-flux membranes, although it was not statistically different. CONCLUSION: Our results show that IFNalpha therapy increases serum beta2-microglobulin levels in hemodialysis patients. Further studies are needed to clarify whether the use of high-flux membranes should be recommended in hemodialysis patients requiring IFN treatment.     

The effect of hematocrit on peritoneal transport

Eight stable patients, from our institution, on continuous ambulatory peritoneal dialysis (CAPD) were entered into a multicenter, randomized, double-blind, placebo-controlled study with erythropoietin (EP]. To assess the effect of hematocrit on peritoneal solute transport, we performed peritoneal equilibration tests (PET) on each patient on a quarterly basis throughout the study. Patients on EPO had a significant increase in hematocrit at 3 (32% +/- 5%), 6 (32% +/- 2%), and 9 (38% +/- 3%) months compared with baseline (22% +/- 4%). The D/P creatinine (Cr) at 4 hours was also significantly reduced in the patients on EPO at 3 (.70 +/- .1), 6 (.66 +/- .12) months when compared with baseline (.76 +/- .11). No significant change in D/Do glucose at 4 hours or in the 4-hour ultrafiltrate (except at 9 months) was found. Based on mixed-effects regression analysis, the 4-hour D/P Cr, peritoneal Cr clearance, and Cr mass transfer area coefficient significantly decreased as hematocrit levels increased. The 4-hour D/Do glucose and the 4-hour ultrafiltrate both demonstrated a positive correlation with increasing hematocrit levels, but this did not reach statistical significance. Although larger studies are needed, it appears that increasing hematocrit levels may negatively affect peritoneal solute transport in CAPD patients as determined by PET.     

Serum erythropoietin levels and their correlation with the erythropoietic system in hemodialysis patients and renal allograft recipients

BACKGROUND: Following renal transplantation, serum erythropoietin (EPO) levels gradually increase during the first 2 to 3 months. However, some transplant recipients continue to remain anemic. The aim of the present study was to correlate serum EPO concentrations with hematocrit (Hct) and hemoglobin (Hb) levels in hemodialysis (HD) patients and renal allograft recipients. METHODS: In a comparative cross-sectional study, serum EPO concentrations and Hb and Hct levels were measured in 35 chronic HD patients and 40 transplant recipients who had stable kidney function for at least 6 months after transplantation (group 1). The HD patients were further divided based on their recombinant human (rHu) EPO supplementation into those who received rHu EPO during dialysis (group 2A, n=15) and those who were not on rHu EPO (group 2B, n=20). Data are presented as mean values +/- SD. The statistical analysis was performed by SPSS version 11.0 using chi-square, ANOVA, and Pearson correlation tests. A general linear model (GLM) was used to compensate for the effects of age. The P value for significance was set at .05. RESULTS: Group 2B patients tended to be older than groups 1 and 2A (P=.014). The sex ratios were comparable among groups. Mean EPO level was 17.09 +/- 10.99 mIU/mL in recipients, which was comparable with that of HD patients (18.54 +/- 26.18 mIU/mL; P>.05). No significant correlation was observed between the serum EPO concentrations and Hb and Hct levels in recipients (P>.05). When comparing the 3 groups, EPO was not correlated with Hct and Hb in any group. Hb and Hct were significantly higher among HD patients not on rHu EPO therapy (P=.02). GLM, with age as a covariate, did not yield a significant difference between EPO levels of the studied groups (P=.36). CONCLUSIONS: This study showed that serum EPO level was in the normal range in recipients and HD patients. We were not able to find any correlation between Hb and Hct levels and EPO concentrations in any group of patients irrespective of rHu EPO supplementation. Hence, impaired EPO stimulatory effects may be considered a potential contributor to anemia in these patients.     

Beta-2-microglobulin in hemodiafiltered children: long-term efficiency follow-up

Data of beta 2-microglobulin (beta 2M) levels are not well known in hemodialyzed children. We analyzed 28 children, all maintained on thrice weekly hemodiafiltration (HDF) with highly permeable membrane (mean age 8 years 7 months, mean time on dialysis 32 months). beta 2M is significantly elevated: 34 + 8.5 mg/l without differences for sex but correlated to residual urinary volume. The kinetics of beta 2M removal during HDF with different dialysis membranes (polysulfone, polyacrylonitrile), and with the same membrane (polysulfone) used in diffusive (hemodialysis), in convective (hemofiltration) and in diffusive and convective (HDF) modes reveals that polysulfone membranes in HDF mode allow the greatest beta 2M serum level drop over dialysis session time (-60 +/- 12%). Five children, anuric, mean time on dialysis 75 months (65-94), chronically on thrice weekly (3 x 3 h) HDF with first polyacrylonitrile then polysulfone membranes are investigated regarding beta 2M levels and amyloidosis risks. Despite the high removal rate of beta 2M with these dialytic modes, beta 2M serum levels do not decrease during this five-year study. High beta 2M serum extraction seems to be compensated by high beta 2M cell generation. Further investigation is necessary for the explanation of the presumed high beta 2M generation rate in the HDF with polysulfone membranes before recommendation of safe long-term use of such highly permeable membranes for prevention of amyloidosis risks in dialytic patients.     

Clinical outcomes for maintenance hemodialysis patients using a high-flux (FX60) dialyzer

Abstract

Aims: To investigate the clinical outcomes of maintenance hemodialysis (HD) patients using a high-flux (FX60) dialyzer. Method: Thirty patients undergoing dialysis for at least 2 years with a low-flux dialyzer were switched to the FX60 dialyzer for 3 years. Clinical and biochemical analysis was performed monthly for each patient. The parameters monitored included blood pressure, hemoglobin, albumin, intact parathyroid hormone (iPTH), calcium and phosphorus levels, the adequacy of dialysis (Kt/V), beta2-microglobulin (β2-MG) clearance rate, as well as antihypertensive and erythropoietin (EPO) medications. Results: After 3 years of dialysis with an FX60 dialyzer, the mean arterial blood pressure fell, hemoglobin increased, serum phosphate level decreased, iPTH declined and medication doses decreased. Conclusions: Dialysis with the FX60 dialyzer has a better clinical outcome for rectifying renal anemia, controlling hypertension and lowering serum phosphate levels making it a better choice for long-term HD patients.     

不同频率血液透析滤过对维持性血液透析患者促红细胞生成素疗效的影响

目的:探讨不同频率血液透析滤过(hemodiafiltration,HDF)对维持性血液透析(maintenance hemodialysis,MHD)患者促红细胞生成素(erythropoietin,EPO)疗效的影响。方法:回顾性研究2017年06月~2019年06月杭州市中医院肾内科留治的MHD患者151例,按照在常规血液透析(hemodialysis,HD)基础上增加不同频率的HDF治疗分为HD组34例(常规HD治疗,不进行HDF治疗)、HDF1组25例(每月1次HDF)、HDF2组47例(每月2次HDF)、HDF4组45例(每月4次HDF)。所有入组患者每4周复查一次血红蛋白,根据血红蛋白水平调整EPO用量,分别于治疗前和治疗24周后测定血红蛋白、红细胞压积、超敏C反应蛋白、血清尿素氮、甲状旁腺素、干体重等指标。结果:治疗24周后,各组患者较入组时血红蛋白水平均明显上升(P均<0.05);HDF1组患者较入组时红细胞压积水平上升(P均<0.05);HDF1、HDF2、HDF4组患者较入组时ERI值、甲状旁腺素水平、超敏C反应蛋白水平下降(P均<0.05)。相关性分析显示,ERI值与铁蛋白、KT/V呈负相关关系,与甲状旁腺素、超敏C反应蛋白呈正相关关系。结论:不同频率的HDF治疗均能提高患者EPO的疗效,但提高HDF治疗的频率不能明显改善EPO疗效,就有效纠正MHD患者肾性贫血而言,可在常规HD基础上联合每月1次HDF治疗。     

L-carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients.

Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis (MHD) or chronic peritoneal dialysis patients. We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status. MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg (n = 48) or placebo (n = 65) thrice weekly at the end of each hemodialysis treatment for 6 months. The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin, blood hemoglobin, and body mass index. Conversely, in the placebo-treated group, a significant decrease was reported for serum albumin, serum transferrin, and body mass index, whereas the other considered measures did not change significantly. These preliminary findings suggest that in MHD patients, L-carnitine therapy may suppress inflammation, particularly among those patients with C-reactive protein > or =3 mg/dL, and may improve protein-energy nutritional status.     

Occult infection of old nonfunctioning arteriovenous grafts: a novel cause of erythropoietin resistance and chronic inflammation in hemodialysis patients

BACKGROUND: Occult infection of old nonfunctioning arteriovenous grafts (AVGs) is frequent among hemodialysis patients. It is a recognized cause of bacteremia and other infectious complications. Additionally, old nonfunctioning AVGs may be harbingers of other noninfectious complications. The aim of this study was to investigate whether occult infection of old nonfunctioning AVGs is a cause of a chronic inflammatory state in hemodialysis patients. METHODS: This study was performed in two phases: In the first phase (study 1), 22 patients with clinically proven occult infection of old nonfunctioning AVG were identified, and data on hemoglobin, weekly erythropoietin dose, and albumin levels were collected retrospectively. Comparisons were made between values obtained pre- and post-AVG resection. In the second phase (study 2), we examined whether the presence of a chronic inflammatory state is associated with occult AVG infection in old nonfunctioning AVGs. Twenty hemodialysis patients were identified with chronic inflammatory state based on erythropoietin dose (units/wk)/hematocrit ratio>470, serum albumin <3.3 g/dL, and CRP>25 mg/L. Among these patients, we found eight with old nonfunctioning AVGs. We then performed indium-labeled white blood cell (WBC) scans on the eight patients to screen for occult infection of old nonfunctioning AVGs. The AVGs with positive indium scan were resected and cultured. Data on hematocrit, erythropoietin dosing, serum albumin, ferritin, and CRP were obtained at 2 months following AVG resection and compared to pre-resection values. RESULTS: In study 1, the 22 patients with occult infection of old nonfunctioning AVG exhibited profound anemia and hypoalbuminemia. Their mean hemoglobin was 9.2 +/- 1.2 g/dL which improved to 11.6 +/- 0.8 g/dL (P < 0.05) 3 months after AVG resection. Their mean serum albumin was 3.3 +/- 0.5 g/dL which improved to 3.8 +/- 0.2 g/dL (P < 0.05) 3 months after AVG resection. Their mean erythropoietin dosages (units/patient/wk) fell from 14,240 +/- 350 to 6,675 +/- 455 (P < 0.05). In study 2, among the 8 patients with chronic inflammatory state and old nonfunctioning AVG, 6 (75%) had positive indium scans and underwent surgical resection that proved bacterial infection. Upon follow-up, the 2-month data showed a remarkable improvement in the following parameters: weekly erythropoietin dose/hematocrit ratio from 622 +/- 137 to 254 +/- 28 (P < 0.05), plasma ferritin values from 690 +/- 126 ng/mL to 247 +/- 42 ng/mL (P < 0.01), and plasma CRP from 56.7 +/- 9.0 to 14.5 +/- 3.8 mg/L (P < 0.01). Serum albumin values also improved from 3.07 +/- 0.08 g/dL to 3.34 +/- 0.14 g/dL (P = 0.13). Percent plasma iron saturation did not appreciably differ from baseline (20.5% +/- 4.4% to 19.8 +/- 1.9%, P = 0.89). CONCLUSIONS: Occult infection of old nonfunctioning AVG is a common cause of erythropoietin resistance and chronic inflammatory state among hemodialysis patients. Resection of old nonfunctioning AVGs with occult infection is associated with resolution of markers of chronic inflammatory state.     

Effect of hemodialysis on serum complexed prostate-specific antigen levels

OBJECTIVE: The measurement of prostate-specific antigen (PSA) is a useful tool in the screening and follow-up of prostate cancer, but its diagnostic validity is uncertain in hemodialysis patients. The aim of this study was to evaluate the effects of hemodialysis on serum complexed PSA (cPSA) levels. MATERIAL AND METHODS: A total of 36 men (mean age 62.54+/-8.20 years) with end-stage renal disease were enrolled in a prospective study. Serum total PSA (tPSA), free PSA (fPSA) and cPSA, and hematocrit levels were measured before and immediately after dialysis using low-flux membranes in the serum and in the dialysis ultrafiltrate. RESULTS: After hemodialysis, cPSA, fPSA and the fPSA:tPSA ratio increased significantly (p<0.05). However, there was no significant increase in tPSA. fPSA, cPSA and tPSA were not detected in ultrafiltrate. Hematocrit levels increased significantly (p<0.0001) due to hemoconcentration. Of patients with initial serum tPSA and cPSA values and fPSA:tPSA ratios below the cut-off values, none had a post-hemodialysis value greater than the cut-off point. There were weak correlation between the difference in values after and before hemodialysis of hematocrit and cPSA (p=0.035), and between the percentage change in levels before and after hemodialysis of hematocrit and cPSA (p=0.041). CONCLUSIONS: Hemodialysis induced elevations in all forms of PSA, but tPSA was the least affected form. cPSA did not show any diagnostic superiority over other forms of PSA. Thus, serum tPSA remains a reliable parameter for follow-up of prostate cancer in uremic patients receiving long-term dialysis. However, further research is needed to explain the pathophysiology of alterations in the concentrations of different forms of PSA.