Efficacy of erythropoietin on dialysis in patients with beta thalassemia minor

BACKGROUND: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with beta-thalassemia minor (beta-thal). METHODS: In 12 hemodialysis (HD) patients with beta-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11-12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). RESULTS: In the year before the study, patients required 3.3 +/- 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 +/- 73 U/kg/week i.v. was 8.2 +/- 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 +/- 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 +/- 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 +/- 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 +/- 12 to 124 +/- 11 g/m2 in the first year and normalized in all patients at month 24 (109 +/- 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). CONCLUSIONS: In HD transfusion-dependent patients with beta-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.     

Improvement of anemia in hemodialysis patients treated by hemodiafiltration with high-volume on-line-prepared substitution fluid

BACKGROUND: Hemodiafiltration (HDF) is associated with a lower incidence of neuropathy, carpal tunnel syndrome, joint pain, and partial correction of anemia. HDF with on-line-prepared substitution fluid (OL HDF), as compared with conventional hemodialysis, increases the treatment tolerance and, as compared with standard HDF, avoids storage problems and allows a higher substitution volume at low cost. METHODS: Thirty-two hemodialysis patients treated by OL HDF for at least 9 months were studied. Hemoglobin, hematocrit, iron metabolism, serum albumin, dialysis dose and dry body weight were determined under a settled condition with regular hemodialysis 3 months before the transfer to OL HDF. The same parameters were analyzed 3, 6 and 9 months after the beginning of the new treatment modality. RESULTS: During OL HDF, hemoglobin values significantly increased in patients without addition of recombinant human erythropoietin (rHuEPO): baseline vs. 6 months 11 +/- 1.7 vs. 12 +/- 1.8 g/dl (p < 0.01); baseline vs. 9 months 11 +/- 1.7 vs. 12 +/- 1.6 g/dl (p < 0.05). In patients on a maintenance dose of rhuEPO, this could be significantly reduced, while the target hemoglobin levels were maintained (10.6 +/- 0.9 g/dl): baseline 99.8 +/- 50.4 U/kg/week, 3rd month 76.2 +/- 43 U/kg/week, 6th month 64.3 +/- 37 U/kg/week, and 9th month 59.4 +/- 38.6 U/kg/week (p = 0.007, p = 0.0006, and p = 0.0007, respectively, vs. baseline). Iron metabolism, dialysis dose, dry body weight and serum albumin levels did not significantly change during the follow-up period. Further, a stability of the rHuEPO supplementation was observed in 14 patients followed up for 24 months. CONCLUSIONS: OL HDF influences anemia and rHuEPO dose. It allows considerable anemia correction in patients without rHuEPO treatment, while it significantly reduces rHuEPO doses in those on rHuEPO treatment as compared with standard hemodialysis. The rHuEPO costs are consequently reduced.     

Effect of erythropoietin treatment on blood pressure and intracellular cation concentrations in maintenance hemodialysis patients.

To assess the effect of recombinant human erythropoietin (EPO) on the factors regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide (ANP), and serum and intracellular concentrations of cations before and after 3 months of EPO treatment (40 units/kg/week of EPO intravenously after each hemodialysis session) in 11 patients undergoing maintenance hemodialysis. Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with flame photometry. EPO treatment was associated with significant increases in Hgb (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9 mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By multiple regression analysis, delta[Na+]q and deltaBV independently contributed to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These data suggest that intracellular sodium accumulation as well as increased blood viscosity may be independently involved in the blood pressure elevation after EPO treatment in patients under maintenance hemodialysis. We found no evidence supporting a role of circulating hormonal factors, such as the renin-angiotensin system, adrenaline, or ANP, in the change in blood pressure.     

Effects of parathyroidectomy on iron homeostasis and erythropoiesis in hemodialysis patients with severe hyperparathyroidism

AIMS: Secondary hyperparathyroidism (HPT) worsens anemia and may cause hyporesponsiveness to recombinant human erythropoietin therapy (r-HuEPO). To investigate the effect of parathyroidectomy (PTX) on iron homeostasis and erythropoiesis, we conducted a prospective study in chronic hemodialysis patients who underwent PTX. METHODS: Thirty-two patients were enrolled in this study. Based on the increases in hemoglobin level after PTX, patients were divided into responders and nonresponders. Iron homeostasis and erythropoiesis were assessed before and 1 and 3 months after PTX, hemoglobin and parathyroid hormone levels were monitored until 6 months after PTX. RESULTS: In the responders, increased hemoglobin levels were observed in 15 patients at 1 and 3 months after PTX (8.0 +/- 0.8 g/dl vs. 9.2 +/- 1.3 and 10.1 +/- 0.9 g/dl, p < 0.05). The nonresponders had higher pre-PTX hemoglobin levels than the responders (10.3 +/- 1.6 g/dl vs. 8.0 +/- 0.8 g/dl, p < 0.05). There was no further increase in hemoglobin at 6 months compared to 3 months after PTX in both groups. In neither group did PTX affect serum ferritin, transferrin saturation and serum erythropoietin level. Serum soluble transferrin receptor (sTfR) concentration was found to be higher in responders than in nonresponders (3.32 +/- 1.28 mg/l vs. 1.70 +/- 0.31 mg/l, p < 0.05). CONCLUSIONS: We conclude that PTX can improve anemia in hemodialysis patients with severe hyperparathyroidism and greater resistance to r-HuEPO therapy. The reversing of anemia does not involve altering iron mobilization. Pre-PTX hemoglobin and serum sTfR levels can predict the effect of PTX on correcting anemia.     

Study of immutable variables determining rHuEPO dose requirements on hemodialysis patients

Patients receiving recombinant human erythropoietin (rHuEPO) therapy show wide variability in their responsiveness to the drug. Variables that affect rHuEPO dose requirements can be broadly divided into modificable and immutable characteristics. Most of the scientific research on rHuEPO hyporesponsiveness has focused on modificable variables (iron status, dialysis adequacy), while immutable variables such as gender, etiology of chronic renal failure (CRF) and age have been insufficiently explored. A cross sectional study was performed in order to evaluate if immutable patient characteristics determine rHuEPO dose requirements among 215 patients (52% males; mean age 66 +/- 14 years) on hemodialysis (HD) for more than twelve months. Data were collected at 10 hemodialysis units in Aragon. Patients were divided into three groups according to their gender, their cause of CRF (diabetic nephropathy, vascular nephropathy, tubulointerstitial nephropathy and primary glomerulonephritis) and their age (younger than 60 years, from 60 to 75 years, older than 75 years). Despite a similar dose of rHuEPO, women had lower mean hemoglobin (11.1 +/- 1.5 versus 11.6 +/- 1.7 g/dl; p = 0.0258) than men. The greater hemoglobin in men than women may be attributed to greater serum albumin in men (3.5 +/- 0.3 versus 3.7 +/- 0.3 mg/dl; p = 0.0001). Requirements of rHuEPO were higher in the patients with etiology of primary glomerulonephritis compared with those with the other etiologies, even those with diabetic nephropathy (p = 0.0374). The rHuE-PO doses required to obtain similar hemoglobin levels were higher in patients younger than 60 years (p = 0.0249). We conclude that women, patients with primary glomerulonephritis as cause of CRF, and patients younger than 60 years showed the highest requirements of rHuEPO doses.     

Improved iron utilization and reduced erythropoietin resistance by on-line hemodiafiltration

BACKGROUND: Recent investigation has shown that on-line hemodiafiltration (HDF) can reduce the amount of recombinant human erythropoietin (rhEPO) deemed necessary to reach the target hematocrit. The aim of this study was to analyze the potential effect of on-line HDF on rhEPO resistance in relation to iron utilization and anemia-related parameters, when compared to conventional hemodialysis (HD). METHODS: Ninety-two chronic uremic patients were treated with conventional HD and then shifted to on-line HDF. Measurements of various erythropoiesis-related parameters were collected during HD and on-line HDF periods for statistical analysis for erythropoietin resistance. RESULTS: Patients treated with on-line HDF switching from conventional HD significantly contributed to the reduction of EPO dose to reach a higher mean hematocrit level (31.8 +/- 4.4% vs. 29.5 +/- 3.9%, p < 0.001) and a reduction of the serum ferritin level (322.5 +/- 268.4 vs. 544.9 +/- 642.4, p < 0.001). The median EPO/Hct ratio was greater in the HD period (504.6 +/- 310.1) than in the on-line HDF period (307.6 +/- 334.4) (p < 0.001). These results indicated a reduced EPO resistance and improved iron utilization by on-line HDF. By multiple regression analysis, the significant predictors of EPO resistance are ferritin, transferrin, albumin, and TACurea (Time average concentration of urea) in HD treatment. In on-line HDF modality, in addition to ferritin and albumin, the duration of on-line HDF is a negative predictor in EPO resistance. CONCLUSION: When on-line HDF is recommended to chronic dialysis patients, long-term use of this technique provides an efficient means of achieving the goal of an elevated hemoglobulin by reducing EPO resistance, improved iron utilization and may further improve the quality of life.     

Daily ambulation activity and task performance in community-dwelling older adults aged 63-71 years with preclinical disability

BACKGROUND: The purpose of this study was to examine differences in daily ambulation activity and task modification between community-dwelling older adults above and below an empirically derived physical threshold that has been linked to independence. METHODS: 20 community-dwelling older adults (72.8 +/- 6 years) were categorized into groups based on functional performance using the Continuous scale Physical Functional Performance Test total score (Cs-PFP). Individuals with Cs-PFP > or =57 were assigned to the high functioning group (HIGH; n=10) with all others assigned to the lower functioning group (LOW; Cs-PFP<57; n=10). Dependent variables included steps/day, number of tasks reported with difficulty, and number of tasks reported with modification. RESULTS: HIGH took significantly more steps/day (HIGH: 9503 +/- 4623; LOW: 5048 +/- 2917, p=.019) compared to LOW. Groups reported having difficulty with a similar number of tasks (HIGH: 0.4 +/- 1; LOW: 1.0 +/- 1, p=.092) but LOW reported modifying a significantly larger number of tasks (HIGH: 0.3 +/- 1; LOW 1.4 +/- 1, p=.049). CONCLUSIONS: Older adults with preclinical disability have reduced daily ambulatory activity compared to older adults with high function despite a similar independent living status. Individuals compensate for reduced physical reserves by modifying the method of performing a task. Identifying early declines in physical ability through task modification and daily ambulation will provide the opportunity for timely intervention to older adults desiring to remain independent within a community-dwelling environment.     

Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial.

OBJECTIVES: We performed a study to determine whether prophylactic hemodialysis reduces contrast nephropathy (CN) after coronary angiography in advanced renal failure patients. BACKGROUND: Pre-existing renal failure is the greatest risk factor for CN. Hemodialysis can effectively remove contrast media, but its effect upon preventing CN is still uncertain. METHODS: Eighty-two patients with chronic renal failure, referred for coronary angiography, were assigned randomly to receive either normal saline intravenously and prophylactic hemodialysis (dialysis group; n = 42) or fluid supplement only (control group; n = 40). RESULTS: Prophylactic hemodialysis lessened the decrease in creatinine clearance within 72 h in the dialysis group (0.4 +/- 0.9 ml/min/1.73 m(2) vs. 2.2 +/- 2.8 ml/min/1.73 m(2); p < 0.001). Compared with the dialysis group, the serum creatinine concentrations in the control group were significantly higher at day 4 (6.3 +/- 2.3 mg/dl vs. 5.1 +/- 1.3 mg/dl; p = 0.010) and at peak level (6.7 +/- 2.7 mg/dl vs. 5.3 +/- 1.5 mg/dl; p = 0.005). Temporary renal replacement therapy was required in 35% of the control patients and in 2% of the dialysis group (p < 0.001). Thirteen percent of the control patients, but none of the dialysis patients, required long-term dialysis after discharge (p = 0.018). For the patients not requiring chronic dialysis, 13 patients in the control group (37%) and 2 in the dialysis group (5%) had an increase in serum creatinine concentration at discharge of more than 1 mg/dl from baseline (p < 0.001). CONCLUSIONS: Prophylactic hemodialysis is effective in improving renal outcome in chronic renal failure patients undergoing coronary angiography.     

Red blood cell density distribution in uremic patients on acetate and bicarbonate hemodialysis

Renal anemia is the result of reduced erythropoietin (EPO) biosynthesis in the diseased kidney and also in part the result of a reduced life span of red blood cells (RBCs). An increase in density and a decrease in enzyme equipment (aspartate aminotransferase; GOT) of RBCs reflect cell age. In the following study, the density distribution (median density D50; determined by Percoll density gradients) and GOT activities of RBCs were measured in patients on acetate (HDA; n = 15) and bicarbonate (HDB; n = 51) hemodialysis. Hemoglobin (Hb) concentrations were: in the HDB group, 9.1 +/- 3.4 g/dl; in the HDA group, 6.2 +/- 1.2 g/dl, and, in a control (C) group of healthy persons, 14.0 +/- 1.5 g/dl. 14 HDB patients with severe anemia received EPO therapy during 1 year. D50 were found as follows: group C, 1.0674 +/- 0.0016 g/ml; HDB, 1.0674 +/- 0.0015 g/ml, and HDA, 1.0660 +/- 0.0012 g/ml (HDA vs. group C: p less than 0.05; HDA vs. HDB: p less than 0.05. D50 were elevated in the subgroups of HDA and HDB patients with severe anemia (Hb less than 8 g/dl). During activated erythropoiesis by EPO therapy, D50 decreased from 1.06739 +/- 0.0015 to 1.0656 +/- 0.0014 g/ml. The GOT activities in RBCs demonstrated a rejuvenation of the RBC population in the HDB group (6.4 +/- 2.5 U/g Hb) and HDA group (5.9 +/- 3.1 U/g Hb) compared to group C (3.9 +/- 1.3 U/g Hb).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin.

BACKGROUND: Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second. PATIENTS AND METHODS: Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks. RESULTS: During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl). CONCLUSION: Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.     

Impact of the change in CMS billing rules for erythropoietin on hemoglobin outcomes in dialysis patients

On April 1, 2006, new Centers for Medicare and Medicaid Services (CMS) rules for billing erythropoietin (EPO) for dialysis patients went into effect. Two key provisions of the rules were to cap the dose for a single patient at 500,000 IU/month and to mandate a 25% reduction in dose for patients whose latest hemoglobin (HGB) or hematocrit (HCT) in the prior month exceeded 13 g/dl or 39%, respectively. The purpose of this article is to document the effect of the rules change on HGB outcomes in a single large dialysis provider whose computer system was modified to enforce the rules. HGB and EPO doses for 5 months following the implementation were analyzed retrospectively. The most noteworthy observation is that while the rule appears to have reduced the percentage of patients with an HGB of >13 g/dl slightly, it has also increased the percentage of patients with HGB in the medically undesirable range of <11 g/dl.     

Serum erythropoietin levels in the elderly.

We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 +/- 15.2 mU/ml), was significantly higher than that in younger controls (15.8 +/- 5.0 mU/ml, p less than 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = -0.559, p less than 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.     

Management of disease-related anemia in patients with multiple myeloma or chronic lymphocytic leukemia: epoetin treatment recommendations

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients often develop anemia due to the disease process and effects from disease therapy. Blood transfusion, the established treatment, has an immediate effect in improving patients' hemoglobin levels. However, this effect is transient and transfusion is associated with several risks, including infections and mild to life-threatening immunologic reactions. A newer option is recombinant human erythropoietin (epoetin); a biological treatment that leads to increased hemoglobin levels over an extended time without the risks of blood transfusion. Extensive evidence has shown that epoetin is effective in the treatment of cancer-associated anemia. An international expert panel met to develop treatment recommendations for the use of epoetin in MM and CLL patients. Based on the available data, it is recommended that treatment be initiated only after other possible causes of anemia are eliminated. Epoetin should be administered to any patient with hemoglobin < or=10 g/dl. Patients with hemoglobin 10-12 g/dl should receive epoetin if they suffer from significant symptoms of anemia and/or have progressively decreasing hemoglobin values. Dosage should be initiated at 10 000 IU three times/week or 40 000 IU once/week and be titrated to maintain hemoglobin at 12 g/dl. Nonresponsive patients (<1 g/dl increase over four weeks) may have their dose increased to 20 000 IU three times/week or 60 000 IU once/week, respectively. Epoetin treatment should be discontinued if there is no response to the increased dosage, or hemoglobin >14 g/dl. Treatment should resume for patients who exceed 14 g/dl, at a reduced dosage, if their hemoglobin falls below 12 g/dl.     

Long nocturnal dialysis

BACKGROUND/AIMS: The continuous growth of the dialysis pool in our unit induced us to organize a third long nocturnal dialysis (LND) session, considering the excellent survival and rehabilitation results reported with this method. This paper analyzes the results and assesses the role of LND among the different dialytic treatment options. METHODS: Out of 18 patients on LND, 13 (12 males and 1 female, mean age 52 +/- 13 years, time on dialysis 21.8 +/- 23.8 months) with >6 months' experience were studied, and 9 underwent a further metabolic evaluation. LND was performed using 1- to 1.4-m(2) Hemophan membranes, bicarbonate buffer, 200-250 ml/min blood flow, and 300-500 ml/min dialysate flow, 8 h three times a week. Kt/V and protein catabolic rate (3-point classic urea kinetics), postdialytic weight, serum albumin, total protein, hemoglobin, Ca(2+), phosphate, intact parathyroid hormone, bioimpedance body water, blood pressure, and drug use (antihypertensives, phosphate binders, erythropoietin, vitamin D, hypnotics) were evaluated in each patient during hemodialysis and LND. In the metabolic study (done twice), sodium (compared with the Kimura model), potassium, phosphate, and urea were analyzed in blood and inlet and outlet dialysate after 0, 2, 4, 6, and 8 h. RESULTS: The mortality was low (1 death every 247 patient-months). After 19 +/- 8.1 months of LND, the postdialytic weight rose from 68.5 +/- 9.6 to 70.8 +/- 10.7 kg (p < or = 0.01), and the hemoglobin concentration rose from 10.8 +/- 2.2 to 11.8 +/- 1.8 g/dl (p < or = 0.05); phosphate dropped from 5.6 +/- 2.0 to 4.4 +/- 1.3 mg/ dl (p < or = 0.01) and the systolic blood pressure from 152 +/- 15 to 143 +/- 19 mm Hg (p < or = 0.05). In the metabolic study, the sodium profile was significantly lower during the last 4 h than in the Kimura model. The potassium concentration, stable between 4 and 6 h, rose against the gradient during the last 2-hour period. The behavior of sodium and potassium during the last part of the dialysis session can be taken to indicate exhaustion of the sodium/potassium pump. Phosphate showed a gradual reduction with no intradialytic and only a moderate postdialytic rebound. The postdialytic urea rebound was 23.4%. CONCLUSIONS: LND is a useful additional tool for nephrologists in treating chronic renal failure, it is easy to organize, and it shows overall good results. Together with other dialysis methods, this schedule permits individualized treatment for each uremic patient.     

Huesca and Teruel survey on hemodialysis management

A cross sectional study was performed in order to evaluate the treatment conditions and medical outcomes among 131 prevalent hemodialysis patients (57% males; mean age 66 +/- 12 years) in Huesca and Teruel. Data were collected at 5 hemodialysis units in Huesca and Teruel. Diabetes mellitus, at 30 percent, was the most common cause of renal insufficiency. The mean (+/- SD) urea-reduction ratio (URR) was 66.0 +/- 8.8%. We observed that 56.5% of the population reached an URR higher than 65%. The duration of dialysis session was 220 +/- 24 minutes, with a rate of blood flow 297 +/- 47 ml/min. 36% of patients used high-flux membranes. The patterns of vascular access were: 69% arteriovenous fistula, 5% synthetic graft and 26% catheter. Eighty nine percent of patients were treated with erythropoietin. The mean dose of erythropoietin was 109 +/- 62 UI/Kg weight/week. Thirty nine percent of patients had haemoglobin below 11.0 g/dl (mean 11.2 +/- 1.4 g/dl). Ferritin levels were below 100 ng/ml in 24% of the patients and 25% showed a transferrin saturation index below 20%. Fifty percent of patients were receiving vitamin D. Serum calcium 9.3 +/- 0.8 mg/dl; phosphorous 5.5 +/- 1.5 mg/dl; calcium-phosphorous product 51.5 +/- 14.3 mg/dl; PTHi 433 +/- 459 pg/ml; and aluminium 26.8 +/- 14.5 mcg/l were the mean of main biochemical markers of mineral metabolism. Sixty eight percent of patients had phosphorous levels below 6.0 mg/dl. Thirty seven percent of patients had aluminium levels lower than 20 mcg/l. The mean serum albumin was 3.4 +/- 0.4 g/dl. Forty five percent of patients had albumin below 3.5 g/dl.     

Prevalence, prognostic importance and therapeutic implications of anemia in heart failure

BACKGROUND: Despite advances in its management, heart failure, once established, remains highly prevalent and lethal. Anemia can exacerbate the hemodynamic burden in heart failure. The present study was undertaken to assess the presence of anemia and analyze how its control impacts the outcome in heart failure patients. METHODS AND RESULTS: From a cohort of 238 heart failure patients, 55 (231%) patients were found to be anemic. Twenty-nine patients (Group A) were given recombinant human erythropoietin for 12 weeks along with iron, and followed up for a mean period of 24 +/- 6 months. The patients improved substantially in terms of functional capacity (6 min walk test improved from 232 +/- 35 m to 278 +/- 41 m, p < 0.001), hemoglobin level from 10.1 +/- 0.90 gm/dl to 12 +/- 0.7 gm/dl, (p < or = 0.001), and ejection fraction from 33 +/- 7.1% to 41 +/- 6.9% (p < or = 0.001). Twenty-six patients (Group B) who were age- and sex-matched with Group A and had similar degree of functional disability and left ventricular dysfunction as that of Group A were not given erythropoietin and iron. Thus, Group B patients served as controls. In comparison to Group B, Group A patients demonstrated not only higher hemoglobin level (12 +/- 0.7 gm/dl v. 9.8 +/- 0.9 gm/dl, p < or = 0.001), and ejection fraction (41 +/- 6.9% v. 26 +/- 7%, p < or = 0.05), but also better survival (16/29 v. 7/26, p < 0.05, odds ratio 1.27). CONCLUSIONS: Anemia is a significant predictor of poor outcome in patients with heart failure. Administration of erythropoietin can correct anemia and help improve survival.     

Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure

OBJECTIVES: This study aimed to investigate the prognostic importance of plasma erythropoietin (EPO) levels in chronic heart failure (CHF) patients. BACKGROUND: Anemia is common and is associated with an impaired survival in patients with CHF. Erythropoietin is a hematopoietic growth factor, upregulated in anemic conditions. Little is known about the pathophysiology of anemia in CHF and the prognostic importance of plasma EPO levels in CHF patients. METHODS: In 74 patients with CHF (age, 61 +/- 2 years; left ventricular ejection fraction, 0.31 +/- 0.01; peak oxygen consumption, 19.1 +/- 0.6 [mean +/- SEM]) and in 15 control patients, hemoglobin levels and plasma concentrations of EPO and brain natriuretic peptide were measured. RESULTS: During a mean follow-up of 3.0 years (range, 2.3 to 5.3 years), 22 patients (30%) died. Anemia was present in 24% of the patients. Multivariate analysis showed that plasma EPO (p = 0.026) and hemoglobin levels (p = 0.005) were independent predictors of survival in this CHF population. We observed only a mild inverse correlation between the logarithm of EPO and hemoglobin levels (r2 = 0.08, p = 0.02) in CHF patients, whereas the control group showed a clear significant inverse correlation (r2 = 0.44, p = 0.007). CONCLUSIONS: Elevated plasma EPO levels are associated with an impaired prognosis independent of hemoglobin levels and other established markers of CHF severity. Furthermore, in the CHF patients, EPO levels poorly correlate with the hemoglobin levels, in contrast with the control group.     

Improved short-term cardiovascular profile after simultaneous pancreas-kidney transplantation

The prognosis of type 1 diabetes mellitus (T1DM) patients with chronic renal failure (CRF) improves after simultaneous pancreas-kidney (SPK) transplantation. In order to evaluate the changes in cardio-vascular risk (CVR) factors after SKP, we studied nine recipients before and 6 months after SPK. There were five females and four males, with a mean age of 37 +/- 8 years, duration of diabetes of 24 +/- 5 years, three of them before starting dialysis, and six on dialysis (hemodialysis = 5; peritoneal dialysis = 1). Before SPK, all patients received anti-hypertensive therapy (1-4 drugs; mean 2.2 +/- 0.9) and eight received statins. At 6 months after SPK, all patients were under triple immunosuppressive therapy (steroids + tacrolimus + MMF) without statins. They had normal renal function (Plasma Creatinine = 1.2 +/- 0.3 mg/dl) and pancreatic endocrine function (glycemia = 80 +/- 8 mg/dl). HbA1c decreased significantly (8.4 +/- 1.2 vs 4.7 +/- 0.6%; p < 0.007) with a value > 7% in seven patients before SPK and in none 6 months after SKP transplantation (p < 0.001). Although Body Mass Index increased (23 +/- 2 vs 25 +/- 3 kg/m2; p < 0.05), plasma triglycerides decreased (130 +/- 51 vs 88 +/- 33 mg/dl; p < 0.05), and total cholesterol, LDL-cholesterol and HDL-cholesterol were similar. Systolic and diastolic blood pressure (BP) decreased (156 +/- 7 vs 133 +/- 15; p < 0.01 and 96 +/- 7 vs 79 +/- 9; p < 0.007) with only two patients on anti-hypertensive therapy (1 drug). Likewise, before transplantation all patients were hypertensive (six grade 1 and three grade 2) while this was observed in only two at the end of follow-up (both grade 1) (p < 0.001). In conclusion, SPK transplantation with good renal and pancreatic function is associated with a short-term improvement in CVR profile.     

Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure.

AIMS: An erythropoietin (EPO)-deficient anaemia is recognized in Type 1 diabetic patients with early nephropathy and symptomatic autonomic neuropathy (DN). The aim of this study was to determine whether the EPO response to hypoxia was deficient in order to clarify the mechanisms involved in this process. METHODS: Five Type 1 diabetic patients DN (age 39 (28-48) years (mean (range))) with EPO-deficient anaemia (haemoglobin, Hb 10.6 (9.5-12.0) g/dl, EPO 5.0 (3.2-6.5) IU/l) and early diabetic nephropathy (persistent proteinuria 1161.6 (130-2835) mg/day, serum creatinine 97.6 (63-123) micromol/l)) were compared with nine normal subjects (age 31 (24-39) years, Hb 13.4 (11.8-15.7) g/dl, EPO 7.6 (5.6-10.3) IU/l) and four patients with non-diabetic advanced chronic renal failure RF (proteinuria 2157.5 (571-4578) mg/day, serum creatinine 490.2 (406-659) micromol/l, Hb 10.3 (9.0-11.3) g/dl, EPO 4.6 (2.9-8.5) IU/l). The subjects were exposed to 6 h of hypoxia (inspired oxygen 11.6-12.6%) by breathing a gas mixture via a hood. Hourly serum EPO levels were measured. RESULTS: All groups showed a rise in EPO production after 2 h. The diabetic DN group achieved a similar maximal response to the normal subjects at 6 h (EPO 17.3 +/-5.4 vs. 17.8 +/-7.9 IU/l). The renal failure patients mounted an EPO response to hypoxia but at lower EPO levels. CONCLUSIONS: Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia. The mechanism underlying the EPO-deficient anaemia present in some diabetic patients remains unclear.