A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.     

Diagnostic value of iron indices in hemodialysis patients receiving epoetin.

BACKGROUND: Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However, considerable controversy exists regarding the best strategies for diagnosis and treatment. METHODS: As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin, we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation, and serum ferritin. If a patient had serum ferritin <100 ng/mL or the combination of serum ferritin <400 ng/mL and a transferrin saturation <20%, he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial, the effect of its administration on iron indices and epoetin dose, and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. RESULTS: Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin <200 ng/mL had the best positive predictive value (76%) for predicting a response to parenteral iron administration, but it still had limited clinical utility. CONCLUSIONS: Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility.     

Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients

BACKGROUND: Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial. METHODS: We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels. RESULTS: After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients. CONCLUSION: We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.     

Efficacy of hepatic computed tomography to detect iron overload in chronic hemodialysis

The diagnostic efficacy of hepatic computed tomography density (HCTD) in comparison with serum ferritin for the detection of iron overload was investigated in uremic patients on maintenance hemodialysis (HD) and in patients with idiopathic hemochromatosis (IHC). Ten IHC patients, 38 HD patients and 40 healthy subjects underwent the CT scanning of the liver and determination of percent saturation of transferrin, serum ferritin concentration and HLA typing. Liver iron content was determined by histochemical grading and direct measurement of liver iron concentration either in IHC patients or in HD patients. Nineteen HD patients were considered to have iron overload on the basis of liver iron concentration exceeding 3.6 mumol/100 mg dry weight. The mean +/- SD values of HCTD in healthy subjects, IHC patients, HD patients with iron overload and without iron overload were 60.2 +/- 5.6, 79 +/- 5.6, 71.4 +/- 3.6, 58 +/- 3.8 Hounsfield units, respectively. HCTD showed positive correlations with liver iron concentration and serum ferritin either in IHC patients or in HD patients. The analysis of the diagnostic efficacy of HCTD in comparison with serum ferritin for the detection of excessive hepatic iron in HD patients demonstrated that HCTD had higher sensitivity, specificity, positive and negative predictive values. Cut-off points were arbitrarily fixed to 66 Hounsfield units for HCTD, 400 micrograms/liter for serum ferritin and 3.6 mumol/100 mg dry weight for liver iron concentration. Seventeen HD patients who possessed the histocompatibility antigens associated with IHC, namely HLA-A3 and/or HLA-B7 and/or HLA-B14, had liver iron concentration, serum ferritin and HCTD values higher than those of the HD patients without these "hemochromatosis alleles".(ABSTRACT TRUNCATED AT 250 WORDS)     

Anemia management and treatment response in patients on hemodialysis: the MAR study

BACKGROUND: Anemia management guidelines describe the importance of anemia as a risk factor in hemodialysis and the need for clinical prospective studies focused on this role of anemia. Response to treatment with iron and epoetin is multifactorial, and results are still far from the targets set by the guidelines. The Morbidity and Mortality Anemia Renal study (MAR) is a multicenter prospective cohort study of hemodialysis (HD), designed to assess the burden of anemia on morbidity and mortality. We report here a cross-sectional analysis of the management of anemia, and response-to-treatment factors. METHODS: A total of 1,710 patients were included (60% male, mean age 64.4 +/- 13.6 years, mean 16.2 +/- 11.1 months on HD) with a high comorbidity (hypertension 75.8%, diabetes 25.9%, heart failure 13.9% and coronary disease 16.7%) and a mean Charlson Index of 6.5 +/- 2.3. RESULTS: There were 28.7% of patients who had started epoetin before end-stage renal disease (pre-ESRD), 81.4% of patients displayed Hb <11 g/dL when initiating HD with a mean Hb of 9.7 g/dL. Only 67.9% of prevalent HD patients attained a hemoglobin (Hb) level above 11 g/dL, 89.5% achieved a ferritin level above 100 ng/mL, 76.7% a transferrin saturation index (TSI) above 20%, and 61.1% met all 3 objectives. The multivariate analysis identified the following risk factors for Hb <11g/dL: low albumin (odds ratio, OR = 1.75), HD efficacy below objectives (OR = 1.44) and female sex (OR = 1.36), corrected for comorbidity, epoetin treatment, transfusion, surgery or hospital admission. CONCLUSIONS: As compared with previous surveys, we found an improved but still inadequate anemia management in Spanish HD patients. Our results are comparable with those of Euro-DOPPS. Several modifiable factors related to a lower Hb concentration were assessed. On behalf of the MAR Study Group.     

Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients.

BACKGROUND: Haemodialysis patients need sustained treatment with intravenous iron because iron deficiency limits the efficacy of recombinant human epoetin therapy in these patients. However, the optimal intravenous iron maintenance dose has not been established yet. METHODS: We performed a prospective multicentre clinical trial in iron-replete haemodialysis patients to evaluate the efficacy of weekly low-dose (50 mg) intravenous iron sucrose administration for 6 months to maintain the iron status, and to examine the effect on epoetin dosage needed to maintain stable haemoglobin values in these patients. Fifty patients were enrolled in this prospective, open-label, single arm, phase IV study. RESULTS: Forty-two patients (84%) completed the study. After 6 months of intravenous iron sucrose treatment, the mean ferritin value showed a tendency to increase slightly from 405 +/- 159 at baseline to 490 +/- 275 microg/l at the end of the study, but iron, transferrin levels and transferrin saturation did not change. The haemoglobin level remained stable (12 +/- 1.1 at baseline and 12.1 +/- 1.5 g/dl at the end of the study). The mean dose of darbepoetin alfa could be reduced from 0.75 to 0.46 microg/kg/week; epoetin alfa was decreased from 101 to 74 IU/kg/week; and the mean dose of epoetin beta could be reduced from 148 to 131 IU/kg/week at the end of treatment. CONCLUSIONS: A regular 50 mg weekly dosing schedule of iron sucrose maintains stable iron stores and haemoglobin levels in haemodialysed patients and allows considerable dose reductions for epoetins. Low-dose intravenous iron therapy may represent an optimal approach to treat the continuous loss of iron in dialysis patients.     

Australian haemodialysis patients on intravenous epoetin alfa or intravenous darbepoetin alfa: How do they compare?

AIM: The purpose of the present study was to determine whether Australian haemodialysis patients receiving intravenous epoetin alfa are comparable to those receiving darbepoetin alfa with respect to a range of demographic and clinical characteristics. METHODS: Data on haemodialysis patients were extracted from the Renal Anaemia Management database for the period from July 2003 to March 2004. RESULTS: Patients on haemodialysis were more likely to receive epoetin alfa than to receive darbepoetin alfa (n = 1898 vs n = 603, respectively). Patients receiving epoetin alfa were marginally older than patients receiving darbepoetin alfa (61 +/- 15 vs 59 +/- 15, mean +/- SD; P < 0.05). Patients were similar in terms of proportion of males, incidence of diabetes, and angiotensin-converting enzyme inhibitor and antihypertensive use. However, patients receiving epoetin alfa had higher haemoglobin (116 +/- 13 g/L vs 113 +/- 15 g/L), serum ferritin (582 +/- 414 mug/L vs 461 +/- 350 mug/L) and transferrin saturation levels (29 +/- 13% vs 26 +/- 14%), and better dialysis adequacy test results, as measured by urea reduction ratio (URR) or Kt/V, than patients on darbepoetin alfa (P < 0.001 in all cases). The frequency of dosing was higher in the epoetin alfa group (1.7 +/- 0.7 doses/week vs 1.0 +/- 0.4 doses/week, P < 0.001). Using the 240:1 dose ratio recommended in the Australian prescribing information for darbepoetin alfa, epoetin alfa was administered at a lower dose compared with darbepoetin alfa (164 +/- 116 IU/kg per week vs 192 +/- 152 IU/kg per week, P < 0.001). CONCLUSION: This cross-sectional sample of Australian clinical practice suggests that there are differences in the haematological parameters of patients receiving epoetin alfa compared with patients receiving darbepoetin alfa.     

Assessment of iron status by erythrocyte ferritin in uremic patients with or without recombinant human erythropoietin therapy.

Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-dose intravenous iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin

We conducted a prospective study to determine the effect of intravenous low-dose iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin (rHuEPO). Sixteen hemodialysis patients (8 males and 8 females; mean age 63.1+/-9.8 years) on maintenance rHuEPO therapy were included in the study. Patients with <100 ng/ml of ferritin received 50 mg iron during every hemodialysis session. Patients with 100-200 ng/ml of ferritin were given 50 mg iron fortnightly. Iron was not supplemented in patients with ferritin levels >200 ng/ml. Mean hematocrit, serum iron levels and transferrin saturations were significantly higher at 6 and 12 months. There was a significant reduction in weekly rHuEPO doses between the start and the 6th and 12th months. Our study shows intravenous iron administration of 100 mg/month may be sufficient to achieve a satisfactory iron status in dialysis patients on maintenance rHuEPO therapy.     

Soluble transferrin receptor is correlated with erythropoietin sensitivity in dialysis patients.

BACKGROUND: Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability. PATIENTS AND METHODS: To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures. RESULTS: While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements. CONCLUSION: Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.     

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial.

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.     

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.     

Achievements of kidney disease outcomes quality initiative goals in hemodialysis patients at Jordan University Hospital

This study was conducted to assess the current practice patterns of care for hemodialysis (HD) patients at the Jordan University Hospital Dialysis Center using Dialysis Outcomes Quality Initiative Guidelines as the reference. In a cross-sectional study, we assessed 61 patients on HD. The Kt/V was calculated, and data on serum levels of hemoglobin, iron, ferritin, transferrin saturation, calcium, phosphate, and intact parathormone (PTH) were collected. The values were compared with the dialysis outcomes quality initiative (K/DOQI) recommended target values. Forty-one patients (67.2%) had an arteriovenous fistula as the primary access. The mean hemoglobin level was 10.8 ± 1.4 g/dL, 9.8% of patients had mean serum ferritin < 100 ng/dL and 14.7% had transferrin saturation < 20%. The mean serum calcium level was 9.1 ± 0.9 mg/dL and serum calcium level between 8.5 and 10.5 mg/dL was found in 82% of HD patients. The mean serum phosphorus was 3.9 ± 1.1 mg/dL and 59% of patients had serum phosphorus between 3.5 and 5.5 mg/dL. The mean serum PTH was 364 ± 315 and 14 patients (23%) had serum PTH between 150 and 300 pg/mL. The achieved standard of HD among our study patients was acceptable and, in many aspects, comparable with the NKF-KDOQI guidelines. However, there is still need to improve the management of anemia and control of hyperparathyroidism.     

Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.     

The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease

BACKGROUND: Provision of adequate iron to support erythropoiesis in patients with chronic kidney disease (CKD) is time consuming and may present adherence problems for patients in the outpatient setting. We studied an accelerated regimen of high-dose intravenous iron sucrose therapy in a cohort of iron-deficient, anemic CKD patients. METHODS: Intravenous iron sucrose 500 mg was infused over three hours on two consecutive days in 107 CKD patients (glomerular filtration rate, 32.3 +/- 19.6 mL/min/1.73m2, baseline hemoglobin 10.2 +/- 1.7 g/dL). Iron indices (transferrin saturation, ferritin) were measured at baseline and at two and seven days after completion of the iron regimen. Blood pressures were monitored immediately prior to, and hourly throughout the iron sucrose infusions. RESULTS: Transferrin saturation and serum ferritin increased from 18.5 +/- 8.5% and 177 +/- 123.8 ng/mL at baseline to 40.2 +/- 22.3% and 811 +/- 294.1 ng/mL in 102 evaluated patients (P < 0.015). In 55 patients with additional measurements at 7 days post-dosing, the transferrin saturation and ferritin had fallen to 26.3 +/- 10.6% and 691 +/- 261.8 ng/mL (P < 0.015 compared to two days' post-dose). Blood pressure rose slightly, but not significantly, throughout the infusions, and altering the infusion rate was not necessary. Two patients had seven adverse events that were considered related to iron sucrose. CONCLUSION: An accelerated regimen of high-dose intravenous iron sucrose therapy in CKD patients is safe and effective in restoring iron stores, and may potentially save time and improve patient adherence.     

Erythropoietin therapy in pre-dialysis patients with chronic renal failure: lack of need for parenteral iron

BACKGROUND: During erythropoietin therapy, scant information exists regarding the optimal target percent saturation of transferrin (TSAT), ferritin and the mode and amount of iron supplementation in pre-dialysis patients with anemia due to chronic kidney disease (CKD). HYPOTHESIS: Pre-dialysis CKD patients may have different needs for iron supplementation than end-stage renal disease subjects during erythropoietin therapy. METHODS: Retrospective analysis of pre-dialysis CKD subjects (n = 31) treated with erythropoietin at our institution. RESULTS: In this population our results showed that target hematocrit (33-36%) was achievable with erythropoietin (mean subcutaneous dose 86 +/- 17 [SD] units/kg/week) without parenteral iron therapy. The hematocrit increased from a mean baseline value of 28.4 +/- 2.7 to 33.6 +/- 3.4% at time 1 (4-9 weeks, p < 0.0001), and to 37.7 +/- 4.5% at time 2 (10-20 weeks, p < 0.0001). The hemoglobin concentration increased from 9 +/- 0.9 g/dl at baseline to 10.7 +/- 1.1 g/dl at time 1 (p < 0.0001) and to 12 +/- 1.5 g/dl at time 2 (p < 0.0001). Subgroup analyses of patients prescribed <200 mg oral elemental iron per day (n = 10), those with TSAT <20% and/or ferritin <100 ng/ml (n = 19), and those prescribed erythropoietin <80 units/kg/week (n = 12), all showed a significant increase in hematocrit and hemoglobin. CONCLUSIONS: Our data show that pre-dialysis CKD subjects respond adequately to erythropoietin at or lower than recommended erythropoietin doses without parenteral iron. This response extends even to subgroups with TSAT and/or ferritin levels deemed to indicate iron deficiency in CKD subjects, and may be due to lack of existence of functional iron deficiency in this group of patients.     

Predictors of the response to treatment in anemic hemodialysis patients with high serum ferritin and low transferrin saturation

Treating hemodialysis patients to combat anemia corrects hemoglobin but exacerbates iron deficiency by utilizing iron stores. Patients needing iron should receive this by intravenous (i.v.) means. The Dialysis patients' Response to IV iron with Elevated ferritin (DRIVE) trial investigated the role of i.v. iron in anemic patients with high ferritin, low transferrin saturation, and adequate epoetin doses. We examined whether baseline iron and inflammation markers predict the response of hemoglobin to treatment. Patients (134) were randomized to no added iron or to i.v. ferric gluconate for eight consecutive hemodialysis sessions spanning 6 weeks with epoetin increased by 25% in both groups. The patients started with hemoglobin less than or equal to 11 g/dl, ferritin between 500 and 1200 ng/ml, and transferrin saturation of less than 25%. Significantly, patients with a reticulocyte hemoglobin content greater than or equal to 31.2 pg were over five times more likely to achieve a clinically significant increase in hemoglobin of greater than 2 g/dl. Lower reticulocyte hemoglobin contents did not preclude a response to i.v. iron. Significantly higher transferrin saturation or lower C-reactive protein but not ferritin or soluble transferrin receptor levels predicted a greater response; however their influence was not clinically significant in either group. We conclude that none of the studied markers is a good predictor of response to anemia treatment in this patient sub-population.     

Content of reticulocyte hemoglobin is a reliable tool for determining iron deficiency in dialysis patients

BACKGROUND: The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). METHODS: In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. RESULTS: Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. CONCLUSIONS: CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.     

A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.