Ultrapure dialysate improves iron utilization and erythropoietin response in chronic hemodialysis patients - a prospective cross-over study

BACKGROUND: The impact of ultrapure dialysis on dialysate-related chronic inflammatory status and anemia in uremic patients on maintenance hemodialysis (HD) remains uncertain. We evaluated ultrapure dialysate effects on erythropoietin (EPO) response and inflammatory status in a prospective, randomized, cross-over study. METHODS: Thirty-four HD patients were divided into two groups. One group was treated with conventional dialysate and the other group with ultrapure dialysate for 6 months and crossed over for another 6 months. Bacteria growth and dialysate endotoxin were examined. Parameters including C-reactive protein (CRP), recombinant human erythropoietin (rHuEPO) dose, ferritin, iron saturation and serum albumin were measured at the start, and at 6 and 12 months. RESULTS: The endotoxin levels reduced significantly in the ultrapure dialysate by adding a dialysate ultrafilter. After a 6-month treatment with ultrapure dialysate, there were statistically significant differences in the systemic inflammation markers between both groups. Changing from conventional to ultrapure dialysis fluid significantly reduced CRP (7.01 +/- 5.059 to 4.461 +/- 3.754 mg/L, p<0.05), and resulted in reduced rHuEPO doses (12500 +/- 7060 to 10440 +/- 7050 U/month, p<0.05). Continuous conventional dialysate use was not associated with significant alternations in CRP (from 5.849 +/- 7.744 to 6.187 +/- 7.997 mg/L, p=0.456) and rHuEPO dose (14060 +/- 6210 to 15060 +/- 7250U/month, p>0.05). The ferritin level reduced significantly (422 +/- 183 to 272 +/- 162 mcg/L, p<0.05) in the ultrapure dialysate group. After another 6-month cross-over, the study parameters were reversed among the two groups indicating the beneficial effect of ultrapure dialysis. CONCLUSIONS: Through endotoxin reduction in conventional dialysate, ultrapure dialysis in dialysis patients manifested a reduced inflammatory parameter, reduced rHuEPO dose and improved iron utilization; and therefore, could be beneficial in anemia treatment.     

The Beneficial Effect of Low Initial Dose and Gradual Increase of Erythropoietin Treatment in Hemodialysis Patients

Abstract: It is well known that the effects of human re-combinant erythropoietin (rHuEPO) are dose-dependent. However, when higher doses of rHuEPO are used, the frequency of the side effects also increases. The aim of our study was to analyze the hematologic parameters and blood pressure response in hemodialysis patients treated with low initial and gradually increased rHuEPO. Sixteen regular hemodialysis patients were treated with 3 times 20 U/kg/week of rHuEPO subcutaneously during the first month. Every fourth week the dose was increased by 3 times 20 U/kg/week if the hematocrit did not rise by 2%. If the elevation was 2% or more, the dose of the rHuEPO was not changed. Blood count and blood pressure were checked every week. The antihypertensive treatment was also reviewed weekly. The hematocrit increased significantly from the second week, and 11 patients achieved the target level (30%) between Weeks 8 and 24. Two patients reached the 30% hematocrit level between Weeks 2 and 8, and another 2 patients reached the target level between Weeks 25 and 28. There was 1 nonresponder. The average rHuEPO dose needed to achieve the target hematocrit was 56.3 U/kg/week. We did not observe significant changes in the mean arterial or diastolic blood pressure. It was necessary to increase the doses of anti-hypertensive drugs, namely nifedipine and captopril, to control blood pressure. Encephalopathy occurred in none of the cases. The low initial dose and the gradual increase of rHuEPO treatment were beneficial to the hemodialysis patients. Although the target hematocrit took longer to achieve, high blood pressure and encephalopathy were prevented by close monitoring and administration of suitable antihypertensive treatment.     

Safety and efficacy of erythropoietin in children with chronic renal failure

 A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks (mean±SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. Received: 12 March 1998 / Revised: 24 June 1998 / Accepted: 6 July 1998     

Complete switch to darbepoetin in a hemodialysis unit

AIMS: In March 2003, our hemodialysis unit switched all patients from subcutaneous (s.c.) rHuEPO to intravenous (i.v.) darbepoetin. The primary outcome was to assess the efficacy of i.v. darbepoetin to maintain target serum hemoglobin (Hb) compared to s.c. rHuEPO. Secondary outcomes were to evaluate the manufacturer's recommend guidelines for conversion of rHuEPO to darbepoetin, and to assess the cost implications of darbepoetin therapy. METHODS: This was an 18-month open-label observational study of 95 hemodialysis patients. At the time of the switch to darbepoetin (baseline), data were collected retrospectively for six months and prospectively for 12 months, at three-month intervals. The first six months of darbepoetin therapy was considered a dose titration phase, thus, data were analyzed comparing two six-month periods: (-) six months to baseline (rHuEPO phase) and (+) 6-12 months (darbepoetin phase). Doses were titrated to a target Hb of 120-135 g/l. RESULTS: There was no significant difference in Hb between phases at any time point. Mean Hb ranged from 119.6-121.5 g/l for rHuEPO and 121.9-123.4 g/l for darbepoetin. The median darbepoetin dose remained stable throughout the analysis at 30 microg/week while the median dose of rHuEPO rose from 8,000 U/week at minus six months to 9,000 U/week at baseline. Median 12-month cost savings associated with the administration of darbepoetin were estimated at 212,000 dollars. The recommended darbepoetin dose from the manufacturer's conversion table was deemed too low for baseline rHuEPO doses above 17,000 U/week. A more simplified dose conversion nomogram was created. CONCLUSION: Darbepoetin was able to maintain similar serum Hb levels compared to rHuEPO at a substantially reduced cost.     

The evaluation of postdialysis L-carnitine administration and its effect on weekly requiring doses of rHuEPO in hemodialysis patients

BACKGROUND: In this study, our aim was to evaluate the effect of postdialysis administration of parenteral L-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. MATERIAL AND METHODS: The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80-120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n=17) and Group 2, rHuEPO therapy + L-carnitine (n=17). L-carnitine (L-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe(+2)), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. RESULTS: In group 1 (n=17, 13 female, four male), the mean age was 38.8 +/- 12.1 years, mean period time on HD therapy was 18.1 +/- 14.9 months, and mean Kt/V value was 1.48 +/- 0.28. In group 2 (n=17, 13 male, four female), the mean age was 48.1 +/- 15.4 years, mean period time on HD therapy was 34.4 +/- 23.0 months, and mean Kt/V value was 1.29 +/- 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9-10.8 g/dl, Hct: 25.3-32.5%; in group 2, Hgb: 10.2-11.8 g/dl, Hct: 30.6-35.4%, respectively (p < 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe(+2) markers (p > 0.05). But unlike serum Fe(+2) markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/ week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/ kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p < 0.05). CONCLUSIONS: If other factors related to anemia are excluded, the postdialysis parenteral L-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients

Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.     

The Evaluation of Postdialysis l-Carnitine Administration and Its Effect on Weekly Requiring Doses of rHuEPO in Hemodialysis Patients

Background. In this study, our aim was to evaluate the effect of postdialysis administration of parenteral l-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. Material and Methods. The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80–120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n = 17) and Group 2, rHuEPO therapy +l-carnitine (n = 17). l-carnitine (l-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe^{+ 2}), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. Results. In group 1 (n = 17, 13 female, four male), the mean age was 38.8 ± 12.1 years, mean period time on HD therapy was 18.1 ± 14.9 months, and mean Kt/V value was 1.48 ± 0.28. In group 2 (n = 17, 13 male, four female), the mean age was 48.1 ± 15.4 years, mean period time on HD therapy was 34.4 ± 23.0 months, and mean Kt/V value was 1.29 ± 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9–10.8 g/dl, Hct: 25.3–32.5%; in group 2, Hgb: 10.2–11.8 g/dl, Hct: 30.6–35.4%, respectively (p< 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe^{+ 2} markers (p > 0.05). But unlike serum Fe^{+ 2} markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p< 0.05). Conclusions. If other factors related to anemia are excluded, the postdialysis parenteral l-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.

Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hyperparathyroidism on response to erythropoietin in children on dialysis

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits <25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was <100 ng/ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30% – 33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6±1; 6 HD patients treated intravenously reached target at week 11±3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P <0.005); 3 of 6 later reached a hematocrit of 30% – 33% after the rHuEPO dose was increased to 120 – 130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed. Received May 8, 1997; received in revised form September 16, 1997; accepted September 19, 1997     

Low-dose erythropoietin is effective and safe in children on continuous ambulatory peritoneal dialysis

Hypertension is one of the most important complications of erythropoietin (rHuEPO) therapy in dialysis patients. In this study, the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [BP] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis (CAPD). Patients were randomized to receive rHuEPO 50 U/kg, either once a week (group 1, 50 U/kg per week) or three times a week (group 2, 150 U/kg per week). At the beginning of the study, 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy. In group 1, the hematocrit increased gradually and significantly from 18.98%±1.79% to 30.1%±1.62% after 6 months, while in group 2 it rapidly increased from 19.53%±1.86% to 32.4%±1.11% after 3 months. A significant increase in the mean arterial BP was observed in group 2. Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group. None of the patients in group 1 required a change in antihypertensive medication. We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD, and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension. Received December 11, 1995; received in revised form September 16, 1996; accepted September 19, 1996     

The influence of vitamin E supplementation on erythropoietin responsiveness in chronic hemodialysis patients with low levels of erythrocyte superoxide dismutase

About 12–15 % of hemodialysis patients have a poor response to recombinant human erythropoietin (rHuEPO). The aim of this prospective study was to examine the influence of oxidative stress and vitamin E supplementation on rHuEPO responsiveness in chronic hemodialysis patients. Sixty-five hemodialysis patients treated with rHuEPO were studied. Those with iron deficiency, blood loss, malignancy, vitamin B12 and folate deficiency, severe hyperparathyroidism, liver cirrhosis, and congestive heart failure were excluded. Twenty-one healthy volunteers served as a control group. Malondialdehyde, carbonyl proteins, erythrocyte superoxide dismutase (SOD), ceruloplasmin, and serum antioxidant capacity were measured. Values of SOD > 150 U/ml were considered as normal. Patients with SOD < 150 U/ml were divided in two groups: group A (n = 11): treated with vitamin E 400 mg/day (600 IU/day) for 8 weeks; group B (n = 13): not treated. A third, group C consisted of patients with normal SOD. rHuEPO doses (U/kg/week) were recorded. rHuEPO responsiveness index was calculated as rHuEPO U/week/hematocrit. A poor response was defined as a rHuEPO responsiveness index >200. SOD positively correlated with hemoglobin (p = 0.0018, R = 0.337) and negatively with rHuEPO responsiveness index (p = 0.0122, R = 0.319). Vitamin E-treated patients from group A exhibited significantly increased hemoglobin levels as compared to initial values (10.5 ± 0.3 vs. 8.6±0.4, p = 0.002). In comparison with group B, the vitamin E-treated patients displayed a higher hemoglobin (10.5 ± 0.3 vs. 9.4 ± 0.3, p = 0.04), had a lower rHuEPO dose (85.7 ± 7.4 vs. 136.8 ± 13.8, p = 0.025), and a significantly improved rHuEPO responsiveness (rHuEPO responsiveness index 177.9 ± 28.6 vs. 314.1 ± 34.0, p = 0.006). Patients from group A significantly improved their rHuEPO responsiveness after vitamin E therapy as compared to baseline (rHuEPO responsiveness index 177.9 ± 28.6 vs. 271.7 ± 30.3, p = 0.034). We conclude that lower values of SOD correlate with lower hemoglobin, higher rHuEPO dose and poor response to rHuEPO in chronic hemodialysis patients. Vitamin E supplementation significantly improves rHuEPO responsiveness, increases hemoglobin level, and decreases rHuEPO dose.     

Reduction of recombinant human erythropoietin maintenance dose by supplementation with a low-dose iron preparation, given intravenously

Background. In chronic hemodialysis patients who showed iron deficiency, we investigated whether the maintenance dose of recombinant human erythropoietin (rHuEPO) could be reduced by long-term intravenous supplementation with a low-dose iron preparation. Methods. In 26 chronic hemodialysis patients who were receiving treatment with a maintenance dose of rHuEPO, without an iron supplement, who showed iron deficiency, the intravenous administration of 40 mg of chondroitin sulfate-iron colloid once per week after dialysis was initiated. We observed the patients' course for 1 year and investigated the reduction in the rHuEPO dose. Results. In the 26 patients, the rHuEPO dose was reduced by 25% after 6 months, and the reduction increased to 32% in the twelfth month. The patients were divided, according to the maintenance dose of rHuEPO received before the iron supplementation into high-, intermediate-, and low-dose groups (9000, 4500, and 2250 IU/week, respectively), and the results were analyzed. A marked reduction of the rHuEPO dose, of 46% in the twelfth month, was obtained in the intermediate-dose group. In the high- and low-dose groups, the reductions of the rHuEPO dose were low. Conclusions. In chronic hemodialysis patients with iron deficiency who are being treated with a maintenance dose of rHuEPO, the intravenous administration of a low dose of iron (40 mg/week) led to a reduction in the rHuEPO dose. This effect was marked in patients in the intermediate-dose rHuEPO group, i.e., 4500 IU/week, which is the most frequently employed maintenance dose in Japan. This therapeutic method can be recommended from a health-care economics perspective. Received: April 5, 2001 / Accepted: August 22, 2001     

Epoetin omega for treatment of anemia in maintenance hemodialysis patients

After the synthesis of epoetins alpha and -beta, a third molecule of recombinant human erythropoietin (rHuEPO) was synthesized and was named epoetin-omega. The molecule of epoetin-omega is a sialoglycoprotein with smaller amounts of O-bound sugars, less acidic and with different hydrophylity than the other 2 epoetins. The purpose of the study was to assess the efficacy, safety and clinical tolerance of epoetin-omega for treatment of renal anemia. In an open-label, uncontrolled prospective clinical study, 22 end-stage renal disease patients (9 male and 13 female) were followed for 6 months. They all had a hemoglobin (Hb) value below 85 g/l, and were on regular hemodialysis therapy 3 times a week, 4 hours per session. The initial weekly dose of epoetin-omega was 90 units per kg of body weight (b.w.) divided in 3 equal portions and administered subcutaneously after each dialysis session. After correction of the hemoglobin, the dose of rHuEPO was individualized to keep Hb within target limits of 100-120 g/l. To follow efficacy and safety, a number of clinical and laboratory parameters were monitored. All patients responded well to the therapy with corrected hemoglobin after the 10th week of the study. The mean dose of epoetin-omega during the correction period never exceeded 100 U/kg b.w. per week. The average maintenance dose of rHuEPO was 50-60 U/kg b.w. per week. Iron was, where needed, supplied intravenously. We noted no change in serum urea. creatinine, phosphorus, and heparin dose per dialysis session. The prothrombin time improved during the study. Serum albumin increased. No change was observed in urea reduction ratio (URR), body weight and mean arterial pressure. One serious adverse event was noted: worsening of hypertension in 1 patient, with the development of hypertensive encephalopathy and severe headache. rHuEPO treatment was stopped. The blood pressure was effectively controlled by reducting her body weight by 5%. Thereafter, rHuEPO therapy was resumed with good blood pressure control. We could conclude that recombinant human erythropoietin-omega was an efficient and safe therapeutic agent for the treatment of renal anemia.     

A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove bacteria and endotoxin.

Pyrogenic reactions (PR) are a well-recognized complication of hemodialysis and have been associated with dialyzer reuse, high-flux dialysis, and bicarbonate dialysate. However, the roles of bacteria and endotoxin in dialysate for producing PR are not well defined. To determine the effect of removing most bacteria and endotoxin from the dialysate on the incidence of PR, a cohort of chronic hemodialysis patients receiving high-flux, high-efficiency, or conventional hemodialysis at three centers with bicarbonate dialysis fluids that had been filtered with a polysulfone high-flux hemodialyzer was prospectively studied. Unfiltered bicarbonate concentrate had median bacterial and endotoxin concentrations of 479,000 CFU/mL and 39,800 pg/mL, respectively. After filtration of the bicarbonate concentrate at the central proportioner, dialysate had a median 9.2 CFU/mL of bacteria and 17.8 pg/mL of endotoxin. Dialysate filtered at individual proportioning dialysis machines had a median 0.001 CFU/mL of bacteria and 0.19 pg/mL of endotoxin. Nine PR were identified among 303 patients after 28,007 hemodialysis treatments (0.3 PR/1,000 treatments). The rate of PR was similar for the three hemodialysis treatment modalities and for first-use compared with reused dialyzers. Although the PR rate in this study was lower (P = 0.046) than the PR rate of a previous study with unfiltered dialysis fluids (0.7 PR/1,000 treatments), it represents a difference of only 10 PR in over 28,000 treatments. It was concluded that filtration of hemodialysis fluids is efficacious in removing bacterial and endotoxin contamination and can result in a lower incidence of PR in patients receiving high-flux, high-efficiency, or conventional hemodialysis.     

Use of recombinant erythropoietin in thalassemic patients on dialysis.

We studied the therapeutic benefit of recombinant human erythropoietin (rHuEPO) in dialysis patients with thalassemia minor. Four of the 40 randomly selected patients (22 on hemodialysis [HD], 18 on continuous ambulatory peritoneal dialysis [CAPD]) were identified to be thalassemic prior to a trial of rHuEPO (alpha-thalassemia trait in three and beta-thalassemia minor in one). All patients were initially treated with rHuEPO at a dose of 100 +/- 25 U/kg/wk subcutaneously depending on the hemoglobin level. EPO injections were continued for 16 weeks with further adjustments of the doses according to the hemoglobin level increases attained. All nonthalassemic patients reached a target hemoglobin of 10 g/dL at week 16, with an average maintenance dose of 120 +/- 7.8 U/kg/wk, but the hemoglobin was increased by only 1 g/dL in the thalassemic patients receiving 175 U/kg/wk. Following cessation of rHuEPO therapy for 6 weeks, all four thalassemic patients and 18 randomly selected nonthalassemic patients received a fixed dose of rHuEPO 4,000 U/wk (equivalent to 80 U/kg/wk) for 16 weeks. The hemoglobin remained unchanged in the thalassemic patients, but a progressive and significant increase of hemoglobin was observed in the nonthalassemic patients. At the last phase of the study, the thalassemic patients received rHuEPO at a dose of 100 or 125 U/kg/wk with 4-weekly increments of 25 U/kg/wk until their hemoglobin reached 10 g/dL. One patient developed uncontrolled hypertension with a dose of 150 U/kg/wk, and one reached the target hemoglobin at a dose of 200 U/kg/wk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacterial Challenge of NISSHO Ultrafilter ETF 609: Results of In Vitro Testing

Abstract: In hemodialysis, a certain degree of bacterial contamination on the dialysate side is a regular finding. Concern has been growing that this contamination may lead to a chronic inflammatory response in the patient. Ultrafiltration of dialysate can be used to reduce bacterial content and levels of cytokine-inducing substances upstream of the patient's dialyzer. The aim of this study was to test in vitro the rejection capacity of a polysulfone hollow-fiber ultrafilter (ETF 609, NISSHO Co., Osaka, Japan) challenged with bacterial filtrates derived from Pseudomonus aeruginosa PA 103. Results showed a reduction of interleukin-Iβ-inducing activity (measured on peripheral blood mononuclear cells) from 5,035 ± 394 pg/ml prefilter to nondetectable levels postfilter and endotoxin levels (limulus amebocyte lysate assay) of 4,167 ± 1,079 versus 12 ± 2 pg/ml, respectively. In conclusion, ultrafiltration of dialysate with the polysulfone ultrafilter ETF 609 leads to a potent reduction of cytokine-inducing activity.     

Ultrapure versus standard dialysate: A cost‐benefit analysis

Low‐level bacterial and endotoxin contamination of water used to generate dialysate propagates chronic inflammation in patients with a wide‐range of potential adverse consequences, including erythropoietin hyporesponsiveness. Advancements in hemodialysis systems now allow for the generation of ultrapure dialysate that has lower bacterial and endotoxin levels than the standard dialysate. The cost associated with ultrapure dialysate is thought to be a major barrier to its widespread adoption. In this report, we conduct a cost‐benefit analysis examining the excess cost of generating ultrapure dialysate and the potential cost saving from a lower erythropoietin dose requirement. Our analysis suggests a potential cost saving of approximately $371 to $425 million per year with full adoption of ultrapure dialysate in the United States.     

Relationship among catheter insertions, vascular access infections, and anemia management in hemodialysis patients

BACKGROUND: Arteriovenous fistulas are the recommended permanent vascular access (VA) for chronic hemodialysis. However, in the United States most patients begin chronic hemodialysis with a catheter. Recent data suggest that VA type contributes to recombinant human erythropoietin (rHuEPO) resistance. We examined catheter insertions, VA infections, and anemia management in Medicare, rHuEPO-treated, chronic hemodialysis patients. METHODS: We compared hemoglobin values and rHuEPO and intravenous iron dosing with concurrent catheter insertions and VA infections in 186,348 period-prevalent patients in 2000. We studied anemia management after catheter insertions and VA infections in 67,410 incident patients from 1997 to 1999. Multiple linear regression models examined follow-up hemoglobin and rHuEPO dose per week (rHuEPO/wk) by numbers of catheter insertions and hospitalizations for VA infection. RESULTS: In the prevalent cohort, increasing temporary and permanent catheter insertions and VA infections were associated with slightly lower hemoglobin, higher rHuEPO doses, and higher intravenous iron doses. In the incident cohort, compared to patients with no VA infections or no catheter insertions (temporary or permanent), respectively, patients with 2+ VA infections or 2+ catheter insertions had 0.12 g/dL and 0.06 g/dL lower mean hemoglobin (P = 0.0028 and P < 0.0001), and 25.7% and 12.2% higher mean rHuEPO/wk (P < 0.0001). CONCLUSION: Higher rHuEPO doses may be required to maintain similar or slightly lower mean hemoglobin values among chronic hemodialysis patients with higher numbers of catheter insertions and VA infections, compared to patients without any.