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.     

Prevalence of anemia in erythropoietin-treated pediatric as compared to adult chronic dialysis patients

BACKGROUND: Recent guidelines recommend a target hemoglobin range of 11 to 12 g/dL in pediatric and adult dialysis patients. We compared anemia prevalence in United States Medicare pediatric and adult dialysis patients. METHODS: Prevalent hemodialysis patients (0 to 19 years, pediatric: N= 1692; adult: N= 352,291) and peritoneal dialysis patients (pediatric: N= 597; adult: N= 39,136) treated with recombinant human erythropoietin (rHuEPO) from 1996 to 2000 were selected. Mean annual hemoglobin values were calculated by modality, age, sex, and race. RESULTS: Among hemodialysis patients, mean annual hemoglobin values less than 11 g/dL were present in pediatric and adult patients during 54.1% versus 39.8% patient years, respectively (P < 0.0001); for peritoneal dialysis patients, 69.5% versus 55.1% (P < 0.0001). Mean hemoglobin values increased over time and were 11.2, 11.5, 10.8, and 11.2 g/dL for pediatric and adult hemodialysis and peritoneal dialysis patients, respectively, in 2000. Pediatric hemodialysis patients received intravenous iron less frequently than adults (66.3% vs. 82.5% patient years; P < 0.0001). CONCLUSION: Hemoglobin values in rHuEPO-treated pediatric dialysis patients lagged behind those of adult patients, with pediatric patients achieving target hemoglobin values only a minority of the time (45.9% and 30.5% patient years, respectively, for hemodialysis and peritoneal dialysis). Trends show recent improvement in anemia treatment of children on dialysis. Still, further attention to and analysis of rHuEPO and iron therapy in pediatric dialysis patients is warranted.     

Changes in anemia management and hemoglobin levels following revision of a bundling policy to incorporate recombinant human erythropoietin

In April 2006, Japan's health insurance system instituted a bundling policy that included recombinant human erythropoietin (rHuEPO) in outpatient hemodialysis therapy. To evaluate outcomes of this, we analyzed a prospective cohort of hemodialysis patients in the Japan Dialysis Outcomes and Practice Patterns Study, in 53 facilities using prevalent cross-sections of 1584 patients before and 1622 patients after the rHuEPO reimbursement change. Patient data included hemoglobin levels, iron management profiles, and anemia treatment with rHuEPO and intravenous iron. No significant differences were found in pre- or post-policy cross-sections for hemoglobin distributions or the percentage of patients prescribed rHuEPO. Among patients receiving rHuEPO, the mean dose significantly decreased by 11.8 percent. The percentage of patients prescribed intravenous iron over 4 months significantly increased; however, the mean dose of iron did not significantly change. Thus, this bundling policy was associated with reduced rHuEPO doses, increased intravenous iron use, and stable hemoglobin levels in Japanese patients receiving hemodialysis.     

Randomized trial of darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients

BACKGROUND: Darbepoetin alfa is a glycoprotein with a three-fold longer terminal half-life than recombinant human erythropoietin (rHuEPO). We aimed to determine whether darbepoetin alfa is as effective and well tolerated as rHuEPO for treating renal anemia in dialysis patients when administered at a reduced dose frequency. METHODS: A total of 522 European and Australian hemodialysis and peritoneal dialysis patients receiving stable rHuEPO therapy by either the intravenous (IV) or subcutaneous (SC) route were randomized, open-label in a 1:2 ratio to continue rHuEPO or to receive an equivalent dose of darbepoetin alfa at a reduced dose frequency. Patients receiving rHuEPO once weekly changed to once every other week darbepoetin alfa, and those receiving rHuEPO two or three times weekly changed to once-weekly darbepoetin alfa. The doses of rHuEPO and darbepoetin alfa were titrated to maintain hemoglobin close to the patient's baseline level for up to 52 weeks. The primary endpoint was the change in hemoglobin between baseline and the evaluation period at weeks 25 to 32 of treatment. RESULTS: The mean change in hemoglobin from baseline to the evaluation period was similar in the darbepoetin alfa (-0.03 g/dL; SE 0.11) and rHuEPO (-0.06 g/dL; SE 0.13) groups, and the difference between the two treatments was 0.03 g/dL (95% CI -0.16, 0.21). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. At the end of the evaluation period, >/=95% of patients had their hemoglobin successfully maintained on their assigned dose frequency for darbepoetin alfa (once weekly and once every other week) and rHuEPO (once, twice and three times weekly). The safety profiles of darbepoetin alfa and rHuEPO were similar, and no antibodies to either treatment were detected. CONCLUSIONS: Darbepoetin alfa maintains hemoglobin as effectively as rHuEPO, but with a reduced dose frequency.     

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)     

Total dose infusion iron dextran therapy in predialysis chronic renal failure patients

BACKGROUND: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. METHODS: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. RESULTS: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 +/- 0.57 and 9.22 +/- 0.44 respectively (p < 0.001). The mean serum ferritin (ng/mL) increased from 29.73 +/- 9.38 at baseline to 218.43 +/- 15.66 at 12 weeks (p < 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 +/- 23.4 (p < 0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. CONCLUSION: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.     

Efficacy and safety of once-weekly intravenous epoetin alfa in maintaining hemoglobin levels in hemodialysis patients

BACKGROUND: Although an erythropoiesis-stimulating agent (ESA) is most frequently administered intravenously for treatment of anemia in patients with chronic kidney disease who are on dialysis, few studies have compared the efficacy of different intravenous (i.v.) dosing schedules. METHODS: This multicenter, phase IIIb, open-label, controlled study randomized 289 stable hemodialysis patients to continue with conventional dosing of i.v. epoetin alfa or darbepoetin, or to switch to once-weekly i.v. epoetin alfa at the same cumulative weekly starting dose, to maintain hemoglobin levels at 11.0-13.0 g/dL, and within 1.0 g/dL of the baseline value. Hemoglobin levels and ESA doses were recorded every 4 weeks for 28 weeks. RESULTS: Hemoglobin levels fell significantly and ESA doses increased significantly between baseline and week 28 (mean of week 16-28 values) in the once-weekly epoetin alfa group, compared with the conventional treatment group (p< 0.001). The adjusted difference in mean hemoglobin levels between the groups was 0.73 g/dL (greater than the threshold for therapeutic equivalence of 0.5 g/dL). The changes between groups from baseline was significant at all time points for hemoglobin levels (0.36, 0.46, 0.81, 0.87, 0.78, 0.62 and 0.49 g/dL) and from week 12 for ESA dose (718.5, 1,326.5, 1,732.0, 1,839.7 and 1,959.1 IU/week; p=0.005). Hemoglobin was maintained at the target level in 78% and 84% of patients on conventional dosing, and 67% and 64% of those on once-weekly epoetin alfa in the intention-to-treat (p=0.1) and per protocol (p=0.016) populations, respectively. CONCLUSIONS: This study did not show therapeutic equivalence of once-weekly i.v. epoetin alfa with conventional dosing regimens.     

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.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthorpometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.     

Intravenous iron treatment of renal anemia in children on hemodialysis

Treatment of anemia in children with end-stage renal disease (ESRD) has been greatly facilitated by the introduction of recombinant human erythropoietin (rHuEPO). A major limiting factor in the treatment of renal anemia is sufficient iron supplementation. Eight children (aged 10–17 years) receiving hemodialysis were treated with intravenous iron (1 mg/kg per week) for 3 months. Hemoglobin (Hb), hematocrit (Hct), and serum ferritin levels were measured regularly. The mean Hct increased from 25% to 30%, the mean Hb increased from 7.8 g/dl to 9.2 g/dl, and the mean ferritin level from 200 to 395 mg/dl. The mean EPO dosage could be tapered from 6,500 IU to 6,150 IU. No adverse side-effects were noted. Hence, in this uncontrolled study intravenous iron was an effective treatment for iron deficiency during rHuEPO therapy in children with ESRD on hemodialysis. Received: 30 October 1997 / Revised: 17 November 1998 / Accepted: 18 November 1998     

Effect of weekly or successive iron supplementation on erythropoietin doses in patients receiving hemodialysis

AIMS: To conduct a 3-month prospective study to determine the optimal way for intravenous iron supplementation in hemodialysis (HD) patients with resistance to recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage. METHODS: Thirty-five HD patients with iron deficiency were divided into three groups: (1) patients receiving an intravenous infusion of 40 mg of iron during the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected once a week for 10 weeks (n = 12), and (3) patients without any iron supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. RESULTS: In group 1, the hemoglobin levels were significantly increased after 4 weeks and remained increased until the end of the study (p < 0.01). In group 2, the hemoglobin levels were gradually increased until the end of the study (p < 0.01). There was no difference in the final hemoglobin values between both groups. The rHuEPO dosage was significantly decreased from 131 +/- 18 to 90 +/- 17 U/kg/week in group 1 (p < 0.01), but could not be changed in group 2 during the observation period despite a similar elevation of the serum ferritin level. In group 3, the rHuEPO doses were rather increased at the end of the study (p < 0.05). CONCLUSION: Aggressive iron supplementation for the short term may be effective to restore rHuEPO hyporesponsiveness in HD patients with functional iron deficiency.     

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.     

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients

BACKGROUND: The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. METHODS: Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. RESULTS: Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). CONCLUSION: The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.     

Hemoglobin predicts long-term survival in dialysis patients: a 15-year single-center longitudinal study and a correlation trend between prealbumin and hemoglobin

BACKGROUND: Dialysis patients have much higher mortality rates than the general population. Anemia is a common complication of uremia and a major contributor to morbidity and mortality in dialysis patients. The benefits of anemia correction using recombinant human erythropoietin (rHuEPO) are well established. Optimum hemoglobin level for dialysis patients remain controversial. We have investigated the association of enrollment hemoglobin with long-term survival in hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: We enrolled 529 HD and 326 PD patients from 1987 and followed them to April 2003. Demographics, enrollment, and clinical and laboratory data were recorded. The Kaplan-Meier method was used to compute observed survival, and the multivariate Cox regression analysis was used to identify the independent predictors of mortality risk. RESULTS: Mean ages of HD and PD patients were 60 +/- 16 (SD) and 54 +/- 16 (SD) years, respectively. Forty-seven percent of HD patients and 41% of PD patients were diabetic. Mean enrollment hemoglobin levels of HD and PD patients were 9.44 +/- 1.9 and 9.61 +/- 1.77 g/dL respectively. Cumulative 15 year observed survivals of HD (P = 0.05) and PD (P = 0.032) patients with hemoglobin levels greater or equal to 12 g/dL were higher than those with hemoglobin levels less than 12 g/dL. Hemoglobin <12 g/dL was a better predictor of mortality in nondiabetics than diabetics, particularly in HD patients. Both in HD and PD diabetic patients, hemoglobin was not a significant predictor of mortality. By Cox regression analysis, after adjusting for age, race, gender, and months on dialysis at enrollment, the relative risk of mortality of patients with hemoglobin <12 g/dL was 2.13-fold (P = 0.008) higher for HD and 1.85-fold (P = 0.06) higher for PD compared to those with hemoglobin >/=12 g/dL (P = 0.035). A logistic regression analysis revealed a strong inverse relationship between the hemoglobin level and the odds risk of death in HD (OR = 0.83, P = 0.008) and in PD (OR = 0.85, P = 0.02) patients. CONCLUSION: Enrollment hemoglobin is a predictor of long-term survival in HD and PD patients. Patients with hemoglobin levels that are higher than current treatment recommendations (>12 g/dL) may benefit from long-term survival. Survival of dialysis patients may be improved by better management of malnutrition and anemia.     

Iron supplementation in adolescent hemodialysis patients

AIMS: Iron supplementation is necessary in children on hemodialysis, but the optimal protocol remains unknown. We studied the effects of changing our unit's protocol from oral iron with periodic doses of parenteral iron dextran to routine administration of parenteral sodium ferric gluconate on anemia and iron parameters. METHODS: We followed seven hemodialysis patients aged 15 20 years (mean 17 years). Hemoglobin, hematocrit, serum iron, transferrin saturation, ferritin, erythropoietin dose, total elemental iron dose and total iron cost for the six months prior to the protocol change were compared to the same variables during the six months following the change. RESULTS: There was no statistically significant difference between the doses of parenteral iron between the two protocols; however, the total dose of elemental iron administered in the oral iron plus iron dextran protocol was greater than in the sodium ferric gluconate protocol (19.6+/-13.1 (mean+/-SD) mg/kg/week versus 1.1+/-0.3 mg/kg/week; p = 0.03). Both protocols had equivalent efficacy with respect to hemoglobin, ferritin and other measures of iron stores. On the other hand, the costs of sodium ferric gluconate were significantly higher than those of oral iron plus intermittent iron dextran (157.75+/-45.94 $/patient/month versus 52.08+/-49.88 $/patient/month; p = 0.01). CONCLUSIONS: Routine administration of sodium ferric gluconate is equivalent if not superior to use of oral iron plus iron dextran for maintenance of iron stores in adolescents on hemodialysis, but more expensive.     

Possible influence of vitamin D receptor gene polymorphisms on recombinant human erythropoietin requirements in dialysis patients

BACKGROUND: Vitamin D receptor (VDR) gene polymorphisms have been widely studied, especially to analyze their effects on calcium-phosphorus metabolism and secondary hyperparathyroidism in patients on dialysis. In this study, we sought to investigate the possible effects of these polymorphisms on the anemia of renal failure and recombinant human erythropoietin (rHuEPO) responses among patients receiving hemodialysis. METHODS: One hundred twenty-eight patients (52 females/76 males) underwent genotyping for the insertion/deletion Bsml (B-->b, restriction site, exon VIII-->IX) and Tagl (T-->t, 352 exon IX) VDR gene polymorphisms. The mean value of the last 6 months' monthly evaluated laboratory values (C-reactive protein, hemoglobin, iron indices, PTH, and albumin) and clinical findings (rHuEPO requirement, cumulative iron supplementation doses, and body weight) were analyzed retrospectively excluding patients with chronic inflammation, hemolytic anemia, or active blood loss such as gastrointestinal bleeding. RESULTS: Mean age and dialysis durations were 41.5 +/- 11.8 years and 91.8 +/- 45.3 months, respectively. Polymorphism percentages were as follows: Bsml; BB/Bb/bb: 32.2/63.6/4.2 and Tagl; TT/Tt/tt: 40.5/55.4/4.1%, respectively. BB variant of Bsml gene was related to lower rHuEPO needs (P < .05) and also higher hemoglobin levels (P < .005) when compared with the Bb/bb variant. Considering Tagl variants, transferrin saturation levels were lower (P < .03) among patients with the Tt/tt variant, but there was no other significant difference in the mean values of other data between TT and Tt/tt variants. CONCLUSION: The BB variant of Bsml was related to decreased rHuEPO requirements to achieve higher hemoglobin levels among maintenance hemodialysis patients without chronic inflammation.     

Influence of oxidative stress and inflammation on rHuEPO requirements of hemodialysis patients with CRP values "in normal range"

AIMS: We sought to evaluate influences of oxidative stress (OS) on rHuEPO requirements in hemodialysis patients without chronic inflammation. METHODS: Sixty-eight hemodialysis patients and 46 healthy controls underwent measurements plasma levels of antioxidative agents, such as glutathione peroxidase (GPX), superoxide dismutase (SOD), and oxidative compounds including malonyldialdehyde (MDA). We retrospectively analyzed the last 3 months' rHuEPO requirements, iron indices, and CRP levels. RESULTS: Plasma levels for SOD, GPX, and MDA were 974.4+/-216.4 U/gHb, 44.4+/-13.6 U/gHb, 10.0+/-2.0 nmol/mL, respectively yielding results that were different from healthy controls (P<.0001). Increased OS negatively correlated with hemoglobin levels (P<.0001) and positively correlated with rHuEPO requirements (P<.01). Increased antioxidative capacity positively correlated with hemoglobin levels (P<.0001) and negatively correlated with rHuEPO requirements (P<.0001). For further analyses, hemodialysis patients were subgrouped according to rHuEPO requirements as group I (lowest 1/3, n=23), group II (moderate 1/3, n=23) and group III (highest 1/3, n=22). Group III displayed the highest MDA (P<.05), the lowest SOD (P<.0001), and comparable GPX (P<.05) levels. Group III also had the highest CRP and the lowest albumin levels compared with the others (P<.01). CONCLUSION: OS has strong adverse influences on rHuEPO responses of HD patients with "normal" CRP levels, but it should not be forgotten that CRP levels in the "normal" range may still reflect ongoing microinflammation.     

Erythropoietin requirements increase following hospitalization in end-stage renal disease patients.

The effect of hospitalization on an ESRD patient's hemoglobin (Hgb) level and erythropoietin (Epo) requirement has not been investigated. We postulated patients with end stage renal disease required an increased Epo dose to maintain stable Hgb during hospitalization and for a period following discharge. To evaluate this hypothesis, we conducted a retrospective chart review on 65 hemodialysis patients. All hemodialysis patients admitted for more than 2 days who did not have more than the index hospitalizations for 2 months prior to and following discharge were included. Multiple parameters including Hgb, Epo dose, intravenous iron dose, serum iron, TIBC, and ferritin during the 2 months before and the two months after hospitalization, Hgb at admission and discharge, Hgb trough, surgery, blood transfusions and co-morbid factors were evaluated. Statistical significance was evaluated using ANOVA or rank-sum testing, as appropriate. In 65 hemodialysis patients (24 M/41 F, age 58 +/- 2.2 years, mean +/- SEM), Hgb levels following discharge and for 2 subsequent months were significantly lower than 2 months prior to admission (11.4 +/- 0.25 vs. 10.7 +/- 0.22 g/dl, p < 0.01). This occurred in spite of an increase in Epo dose (128 +/- 14 vs. 185 +/- 21 U/kg/week, p < 0.0001) over this 2-month period. There was no difference in the iron saturation before and after hospitalization (22 vs. 23%,p > 0.05). There were also no apparent effects of comorbid factors, including surgery, or discharge diagnosis on the changes in Hgb or Epo requirements. However, patients who required a blood transfusion during the hospitalization had lower Hgb levels and higher Epo doses both prior to and after hospitalization, as well as lower Hgb trough levels. In addition, females had lower Hgb levels than males both prior to and after hospitalization, and were receiving a higher Epo dose 191 +/- 18 vs. 129 +/- 20 U/kg/week at 1 month and 215 +/- 18 U/kg/week vs. 134 +/- 22, p < 0.005 at 2 months after hospitalization. CONCLUSION: This study points out that hemodialysis patients experience a significant and prolonged decrease in Hgb levels after hospitalization, even despite a moderate increase in Epo dosing.     

Significance of parenteral iron administration for HCV-positive hemodialysis patients

BACKGROUND: It is well recognized that parenteral iron administration is recommended for hemodialysis (HD) patients treated with rHuEPO. On the other hand, hepatic iron concentration increases in chronic hepatitis C, and iron reduction improves serum transaminase levels in these patients. METHODS: We compared the rHuEPO doses with hematological parameters in HCV-positive (n = 7) and HCV-negative (n = 32) HD patients when parenteral low-dose iron was administered for one year (target ferritin level: 200-300 ng/ml, target hematocrit level: 30-33%). RESULTS: None of the parameters was significantly different between the groups at the start of the study. One year later, levels of hematocrit and serum ferritin significantly increased compared with those at the start in each group (HCV-positive group: 28.0 +/- 2.7-->31.3 +/- 1.5%, p < 0.01, 119.3 +/- 171.9-->303.3 +/- 77.7 ng/ml, p < 0.05, respectively, HCV-negative group: 26.8 +/- 2.2-->30.0 +/- 3.5%, p < 0.01, 69.8 +/- 100.5-->278.4 +/- 66.4 ng/ml, p < 0.01, respectively). Serum transaminase levels were not significantly different between the start and end points in the HCV-positive group, but 2 patients showed an increase in these levels. In the HCV-negative group, the rHuEPO dose at the end point was significantly reduced compared with that at the start (4,875 +/- 2,089-->4,031 +/- 2,203 IU/W, p < 0.05). In the HCV-positive group, however, it was difficult to reduce the rHuEPO dose in order to maintain the target hematocrit level (4,071 +/- 1,134-->3,857 +/- 1,464 IU/W, NS). CONCLUSION: We suggested that rHuEPO should be used together with parenteral iron administration, even in HCV-positive HD patients, because it is safe at low doses under careful observation.